a Tuatha an Soa tes aes st ‘ Bone Bei chst Gahneeraines asnetones set site aah SAS iS act BCR st AOR sy Fea, a SOs T ss es ; Hee i Bx RA See ane iAH Sn a : satis Rat HBAS he Sam HRs : Pe hua ti eet a ee ‘ sea ERR i et ie {HMR Hai howitn i eas hat raven vi Se arbi be Senet i ute Rett rekts RS mi Sean Erni peta i ty a bt ; ae Ra er a i ine i Pits a ea fe aati LIBRARY OF THE NEW YORK STATE COLLEGE OF HOME ECONOMICS CORNELL UNIVERSITY ITHACA, NEW YORK Cornell University Library QP 171.B46 THAT 2 5D! 303 136 888 THE GASEOUS METABOLISM OF INFANTS WITH SPECIAL REFERENCE TO ITS RELATION TO PULSE- RATE AND MUSCULAR ACTIVITY fod BY FRANCIS G. BENEDICT anp FRITZ B. TALBOT WASHINGTON, D. C. PUBLISHED BY THE CARNEGIE INSTITUTION OF WASHINGTON 1914 Ww CARNEGIE INSTITUTION OF WASHINGTON Pusuication No. 201 hae POS ROD? PRESS OF GIBSON BROTHERS, INC. WASHINGTON, D. C. PREFACE, These observations were made in the Children’s Department of the Massachusetts General Hospital with an apparatus belonging to the Nutrition Laboratory. The experimental technique was exclusively under the charge of Miss Alice Johnson, of the Nutrition Laboratory staff. For her extraordinarily painstaking skill and fidelity we are under great obligations. Of the numerous co-workers in this research we wish especially to mention Doctors 8. Morgulis and J. L. Gamble, and of the various house officers and nurses, Dr. R. E. Eustis, Dr. Clifford B. Sweet, and the Misses Trainer, Sullivan, and Richardson. The obtaining of subjects for observation was much facilitated by the kindness and assistance of Dr. F. A. Washburn, the superintendent of the Massachusetts General Hospital, and various members of his staff. Our thanks are due to Dr. J. H. Wright of the Pathological Depart- ment, who placed an excellent room in his laboratory at our disposal. We are particularly indebted to Dr. Hans Murschhauser of Diissel- dorf, Research Associate of the Carnegie Institution of Washington, attached to this laboratory, for his reading of the entire manuscript and for numerous helpful suggestions. The labor of preparing much of the material in this report has fallen upon Miss A. N. Darling and Mr. W. H. Leslie, whose assistance we gratefully acknowledge. Nutrition LABORATORY OF THE CaRNeEGIE INSTITUTION OF WASHINGTON, Boston, Massachusetts, February 7, 1914. 3 CONTENTS. Part I, Page. ANTOMUCHON i. gs Sendai ieee Paes bade a oe eed ee ad eed esis 11 Basic principles yes: i:s dea ses. x ive gos 8:5 bo 5- 5d alaiaed eeu Maal ssc hlgua tevok wou Wie a scusd acksi evade S48 23 The respiratory quotient and its significance..............0.0cc ccs eeeeeeees 23 Indirect: calorimetiy 5s sass gscig chines 4 ae os wah ya OL a Rew ne SaT EAS 27 Basal: meta bolisin soc. sacise:oicase desies Ste dussbuaid Seay tueratd doh Gaapsl ochanBsdaaye. 6-5 Geepeie cia deepak 30 Apparatus and methods used in this research.............. 00-0 cc eee cence eens 31 Respiration apparatus. ........0.. cece c cece eee ene e een n eee te teeters 82 Methods of testing the respiration apparatus............... cece eee neces 44 Pests for tiehtnesss ain2 3 heehee cenies 6 Gidley EME GS aE ee eRe Eee IR 44 Alcohol check tests i... .o0ic gs gaiaia! da aiesned aces divi traasia disp mieno dae Suciard eo waeee ew wee 46 Complete short-period alcohol check tests.............0 2. ccc eens 47 Details of typical quantitative alcohol check test....................65. 51 Method of determining the degree of muscular repose.................-00: 55 Apparatus used in the respiration experiments..................0-0s00e 55 ‘Ward crib recorders: +. as2234 eek ose pase skeen tier beeede eee eee eras 59 Method of recording the pulse-rate........... 0.0... cece cece eeee 61 General technique of respiration experiments with infants................... 62 Part II, Statistics of observations...........0. 00. ccc cece eee eee ee eee e teen ete eeeees 67 Selection Of stbbjects sci i.. seen det haces wou eid Qc tani dace kPa dove aera, ue cues a ela 67 Hospital:records). eg tree ee sea aS aiek aes eased > AoE aalse Pe ERR Tas Lai 68 Ty plea record 'ssiijs hs dsctncdsae sede tees VRS Beans OE IAD SE Ra See eReE 68 Summarized hospital records for the other subjects..................... 72 Clinical ‘status‘of infants wos .sccug os cass ca ed ena abo bes caw CS eo dees 83 Results of observations on the gaseous exchange...............-0seeee reece 83 Part III. Discussion of results. i... eo. cca es cece eed Gowan we soma Rel wees Senate atone whale 105 Pulse-raterss:s Ged sic ries Saas Hee ae Dod wena eee er abe was 106 Preliminary observationS.......... 2.00. sce c cece cece e cnet e sete eens 107 Records obtained during observations with the respiration apparatus..... Relationship between pulse-rate and muscular activity..................000% Ais Effect of changes in activity on the pulse-rate at different ages with the : Same dufan tes siecces deaiaia aed eecseu ogee, wees cic cas yA ee eta eaa ae aba tee 126 Effect of changes in activity on the pulse-rate with infants of the same weight but different ages.... 2.0.0... 6 cece cece eee eee eee nes 127 Effect of changes in activity on the pulse-rate with infants of the same age but with different body-weights.......... 2.0.5 c cece eee eee eens 128 Relationships of the muscular activity, pulse-rate, and metabolism........... 130 Observation with J. V., February 27, 1913. .............. eee e cece eee 130 Observation with J. V., April 22, 1918......... 0... c cece cece eee eens 132 Observation with A. L., June 28, 1913......... 0.0.00. cece cece eee eee 133 Observation with F. M., February 20, 1913.....................00005. 134 Observation with M. M., June 5, 1918........... 002... cece e eee 135 Observation with F. K., May 2, 1913.......... 0... cece cece eee 136 Significance of the relationships. ........-..- 6. see eee eee e eee eee eee 137 Relationship between pulse-rate and metabolism................0...00 eens 138 Basal metabolism of infants studied.............. 2... cece cece e eee e eee 141 Selection of data used for comparison............... 00: c cece eee ences 142 Minimum extraneous muscular activity.............. 0.0.0 cece eee 144 Minimum influence of food............. ccc c eee e eee eee eeeneee 145 CONTENTS. Parr IJI—Continued. Discussion of results—Continued. Normality of infants studied... .....00000 00 c cc cece cece eee e eevee anes Relationship between body-weight and metabolism..................2..0005 Comparison of the body-weight of infants and the total heat-production in DE DOUTB .. bcsceris sti gana Gunde a Fae eee ee RAS OE EL ab BS Heat-production per kilogram of body-weight.................00000005 pees tad of normal body-weight and total heat-production in 24 OUTS ao have shes aes 4 deg Sones Sewanee aia ean meine Seem ee Comparison of normal body-weight and heat-production per kilo- gram of actual body-weight............ 00.00 cece eee eee eens Comparison of expected body-weight and total heat-production in 24 TOURS ci. 2 Sco ca steed cut va anceala tang aavavents Worse alata rnonasesh sia eean ae SWAT Wee Comparison of expected body-weight and heat-production per kilo- gram of actual body-weight.......0..0.0. 0... ccc cece cece eee tees Comparison of the age and heat-production per kilogram of body-weight. Relationship between body-surface and metabolism................ 00000005 Methods used for measurement of body-surface...................2.-4. Comparison of age and heat-production per square meter of body- SUE A oases 2a: Steph ch lain Soa daes heaith.d Soe Ties we had GM MILO GARE PNM Comparison of actual body-weight and heat-production per square meter of body-surface.. 0.2.0... cece eee eee eens Effect on metabolism of possible disturbance in relationship between body- surface and body-weight............. 0.0 c eee cee eee eee eee Influence of variations in the composition of the body upon total heat-production. Fig. ILLUSTRATIONS. . Schematic outline of respiration apparatus....................000 cee eee . Detailed scheme of respiration apparatus. ..............00 ccc eee ip MPIPOMObENs 67 hen se ig bale Hig ts Sec 8 GAS eeghed Ses Laas s hesk eee pas oe er HRS . Method of introducing alcohol in the alcohol check tests of the respiration SPPALatuUBiicccs os cawalcs sexe oe ek Lee Geeky eee ee des see ees sede . Method of obtaining graphic record of muscular activity................ . Typical kymograph curve, showing record of the muscular activity and the SENSILIVILY LeSbeecvee ovcade av sade oeedae MEG a aoe ee eee EA eee OES o Ward) criby TeCOrd G8 -c3i2i5 5:2: waees cscs cous acts eaten Rte ila clave tint aan aed Rept ea Revolution counter used in the later form of the ward crib recorder...... . Typical kymograph curves obtained with the ward crib recorder......... . Hospital chart for F.B.. 0... cent eee eee eens . Pulse-rate curve for S——ns, July 1, 1911.............00.. cee eee ee . Pulse-rate curve for S——ns, July 6, 1911............ 0... ee . Pulse-rate curve for Dow, July 1, 1911......... 00... e cece eee eee . Pulse-rate curve for Weldon, July 6,1911........... 0.0... cece eee . Pulse-rate curve for Herbert W., July 13, 1911....................0045 . Pulse-rate curve for Rita McL., July 14,1911......................00. . Pulse-rate curve for Paul, July 12, 1911.......... 0.0.0.0... cece eee eee . Pulse-rate curve for Tremballe, July 12, 1911......................000. . Pulse-rate curve for Christine D., July 18, 1911...................0.0.. . Pulse-rate and kymograph curves for E. R., April 12, 1913.............. . Pulse-rate and kymograph curves for E. N., May 23, 19138.............. . Pulse-rate and kymograph curves for F. B., April 24, 1913.............. . Pulse-rate and kymograph curves for F. K., May 3, 1913............... . Pulse-rate and kymograph curves for F. K., May 3, 1913............... . Pulse-rate and kymograph curves for E. L., May 20, 1913.............. . Pulse-rate and kymograph curves for E. L., May 21, 1913.............. . Pulse-rate and kymograph curves for D. M., March 26, 1913............ . Pulse-rate and kymograph curves for J. M., April 2, 1913............... . Pulse-rate and kymograph curves for M. M., June 2, 1913.............. . Pulse-rate and kymograph curves for M. M., June 7, 1918.............. . Pulse-rate and kymograph curves for M. M., June 7, 1913.............. . Pulse-rate and kymograph curves for E. N., May 21, 1913.............. . Pulse-rate and kymograph curves for E. N., May 22, 1913.............. . Pulse-rate and kymograph curves for W. P., January 31, 1913........... . Pulse-rate and kymograph curves for E. §., March 22, 1913............. . Pulse-rate and kymograph curves for J. S., June 18, 1918............... . Pulse-rate and kymograph curves for J. V., April 22, 1913.............. . Pulse-rate curves with J. Vi... ee teens . Pulse-rate curves with infants of like weight but of different ages........ . Pulse-rate curves with infants of like weight but of different ages........... . Pulse-rate curves with infants of like age but of different weights......... . Pulse-rate curves with infants of like age but of different weights........ . Kymograph curve for J. V., February 27, 1913...................02.0., . Kymograph curve for J. V., April 22, 1913...................0-...0005. . Kymograph curve for A. L., June 28, 1918...............- cee eee eee . Kymograph curve for F. M., February 20, 1913....................... . Kymograph curve for M. M., June 5, 1913................-..0.0.0000, . Kymograph curve for F. K., May 2, 1913............ 000 ec c eee eens . Pulse-rate and kymograph curves for L. B., February 1, 1913........... . Pulse-rate and kymograph curves for A. D., May 19, 1913.............. . Pulse-rate and kymograph curves for J. M., April 4, 1913............... . Pulse-rate and kymograph curves for E. N., May 26, 1918.............. . Chart showing actual body-weight of infants and the total heat-production Pers DANMOUTS! ssid eased Bek ase 54s 9S Sa iee w epsiets sania an? Adud dea baggie Bodvdadidungeaonevatss . Chart showing the actual body-weight of infants and the heat-production per kilogram of body-weight per 24 hours............--. esse eseee eae 112 127 128 129 8 Fia. 55. 56. 57. 58. 59. 60. 61. 62, 63. 64. 65. ILLUSTRATIONS. Chart showing the normal weights for the ages of the infants under obser- vation and the total heat-production per 24 hours.................0+- Chart showing the normal weights for the ages of the infants under obser- ae and the heat-production per kilogram of actual body-weight per QUIS eariiacee Sis suing eee ana woe sine ed eae y a mines nea eet esas Eos Chart showing the expected weights for the infants under observation and the total heat-production per 24 hours..............00ceseeeeee Chart showing the expected weights for the infants under observation and heat-production per kilogram of actual body-weight per 24 hours. . Chart showing the age of infants and heat-production per kilogram of body-weight per 24 hours............0 002 c cece cece cece cece ceeeeees Chart showing the age of infants and heat-production per square meter of body-surface (Meeh formula) per 24 hours.........0....0.0.00 cece cence Chart showing age of infants and heat-production per square meter of body-surface (Lissauer formula) per 24 hours..................+-- Chart showing age of infants and heat-production per square meter of body-surface (Howland curve) per 24 hours................-...000- Chart showing actual body-weight of infants and heat-production per square meter of body-surface (Meeh formula) per 24 hours............- Chart showing actual body-weight of infants and heat-production per square meter of body-surface (Lissauer formula) per 24 hours....... Chart showing actual body-weight of infants and heat-production per square meter of body-surface (Howland curve) per 24 hours........ Page. 153 154 154 155 156 159 160 161 162 162 163 THE GASEOUS METABOLISM OF INFANTS WITH SPECIAL REFERENCE TO ITS RELATION TO PULSE-RATE AND MUSCULAR ACTIVITY BY FRANCIS G. BENEDICT anp FRITZ B. TALBOT PART I. INTRODUCTION. Observations on the metabolism of infants have for the most part been confined to records of food intake, changes in body-weight, and analyses of urine and feces. Studies of the gross metabolism of the body, necessitating either direct calorimetric observations or meas- urements of the gaseous exchange, demand elaborate apparatus and unusual technique and hence they have been precluded in most clinics and laboratories. Before entering into a discussion of our researches in this field, it is desirable to cite briefly the evidence on the gaseous exchange of infants thus far published. The earliest record that we have been able to find of the measurement of the gaseous metabolism of an infant is that reported by J. Forster, of Munich, in 1877.1. In an effort to explain the well-known fact that children consume a larger amount of food in proportion to their body- weight than do adults, this investigator made determinations of the carbon-dioxide excretion in 14 experiments on children varying in age from 14 days to 9 years. His results all showed that 10 or 12 grams of carbon dioxide were given off per hour for every 10 kilograms of body-weight. With adults on the same basis, the carbon dioxide given off under conditions of rest and approximate hunger was 4 to 5 grams per hour; with an average diet, 5 to 6 grams; and with food and work, 7 grams. The author points out that the youthful organism, even in the condition of hunger, produces per unit of weight at least twice the amount of carbon dioxide which is produced by the adult body. The fact is also recognized that the infant can develop aconsiderable amount of work, as will be seen by the following quotation: “Bedenkt man noch die relativ grossen Arbeitsleistungen, welche die meist lebhaften kindlichen K6rper ausfiihren, so ergibt sich, dass eine relative Mehr- zufuhr von Speisen fiir den kindlichen Organismus eine durch innere Verhdlt- nisse bedingte Nothwendigkeit ist.” The experiments were made with the large Pettenkofer-Voit respi- ration chamber in Munich, but the protocols were never published, and aside from the statement that the children were at rest, no further details are given as to the muscular activity or the pulse-rate. In 1885 Richet,? in describing his calorimeter, states that he has two chambers, one of which, having a capacity of about 1,500 liters of air, is used for experiments with infants. He cites an experiment with an infant of 9 kilograms, who was in the chamber for 1 hour and 10 minutes, 1Forster, Amtl. Ber. d. 50. Versammlung deutsch. Naturforscher u. Aerzte in Munchen, Munich, 1877, p. 355. 2Richet, Archives de Physiol. norm. et path., 1885, 15, 3d ser., p. 237. 11 12 GASEOUS METABOLISM OF INFANTS. and gives protocols for another experiment, 1 hour in length, presum- ably with the same infant. In summing up his averages he refers to numerous experiments on infants weighing from 6 to 9 kilograms and includes observations made with environmental temperatures ranging from 18° C. to 25°C. He concludes that the infant produces on the average 4 calories per kilogram of body-weight per hour. Richet dis- cusses especially the relationship between the body-surface and the heat-production. Two years later, Langlois! conducted experiments on children with Richet’s calorimeter, in which only the heat-production was measured. From 17 controlled experiments, all with infants weighing about 7 kilograms, Langlois concludes that the heat-production is increased as the environmental temperature is lowered. As a result of a study on the influence of the time of day upon the heat-production, he also concludes that there are two maximum values at approximately 11 a.m. and 3 p. m., corresponding to the values for the absorption of oxygen found by Fredericq.? Tasie 1.—Relationship between heat-production and body-weight of infants (Langlois). Heat-production Body-weight. per kilogram of body-weight. kilos. cals. Two children at 1.8 6.40 Child of 2.5 4.80 Children from 3.0t0 4.0 4.20 Children from 7.0 to 8.0 4.12 Children from 9.0 to 10.0 3.93 TaBLe 2.—Relationship between heat-production and body-surface of infants (Langlois). Heat-production. Body-weight. | Body-surface. Per kilogram of | Per unit of! Per sq.meter of body-weight. surface. | body-surface.? kilos. cals. cals. cals. 10 9,142! 3.920 17 1,690 9 2.106 3.900 16 1,620 7 1.778 4.120 16 1,580 6 1.638 4.200 15 1,500 4 1.135 4.300 15 1,370 2 0.780 6.000 15 1,510 1This figure is quoted from Langlois and as his discussion of body-surface is very confusing, it is impossible to make a correction which is obviously much needed. 2As calculated by Camerer, using Meeh’s formula (Camerer, Der Stoffwechsels des Kindes, Tubingen, 1896, p. 109). Langlois’s discussion of therelationships between the heat-production and the body-weight and the heat-production and the body-surface is of special interest in connection with our research. As will be seen 1Langlois, Centralbl. f. Physiol., 1887, 1, p. 237. *Fredericq, Arch. de Biol., 1882, 3, p. 731. INTRODUCTION. 13 from his figures given in table 1, the smaller the child the larger was the heat-production per kilogram of body-weight. The author points out, however, that if the heat-production and body-surface are com- pared, as is done in table 2, the uniformity is remarkable. He gives a very unsatisfactory explanation of his unit of surface, but brings out the fundamental idea that the heat per unit of body-surface is essentially the same for an infant as for an adult weighing 65 kilograms, namely, 14 to 17 calories. No information is given regarding the muscular activity, the age, or the pulse-rate of these infants. In another paper, Langlois! refers to Richet’s observations on normal children weighing from 7 to 10 kilograms with a heat-production of approximately 4,000 calories per kilogram per hour, and reports his own results with sick infants in which he finds a direct yelationship between the body-temperature and heat-production. Infants having temper- atures below 37.5° C., which he takes as normal, had a heat-production less than 4 calories per kilogram of body-weight per hour, while those with temperatures above 37.5° C. had a higher heat-production; thus, with a body-temperature of 35.5° C., the heat-production was equal to 2,900 calories, while with a body-temperature of 40.5° C., it was equal to 4,600 calories. Langlois’s calorimeter was subsequently used by Variot and Saint- Albin? in studying the calorimetry of atrophic infants. The tests of this calorimeter published by Saint-Albin® show a possible error of plus or minus 10 per cent, thus indicating that the apparatus can hardly be considered an instrument of precision. As Saint-Albin himself points out, his check tests differ considerably from those of Langlois. Variot and Saint-Albin studied a large number of atrophic infants; their conclusions, reported by Saint-Albin, are especially interesting in connection with this report of our researches, as they show that (using their terminology) out of 33 atrophic infants, there were 11 “hyperray- onnants,”’ 16 ‘“hyporayonnants,” and 6 “‘rayonnants normalement.’4 Of the numerous forms of calorimeters reported to the French scien- tific societies by d’Arsonval, one’ was employed by Bonniot* in 1898 for a study of the heat-production of infants with temperature disturb- ances, but he found no regular relationship between heat radiation and rectal temperature. A detailed presentation of Bonniot’s results may be found in his thesis for 1900.’ lLanglois, Compt. rend., 1887, 104, p. 860. 2Variot and Saint-Albin, Bull. de la Soc. de Pediatre. 1903, 5, pp. 246 and 307. See, also, an extensive discussion of these researches in the thesis by Saint-Albin, Etude sur la calorimétrie des infants atrophiques, Paris, 1904, No. 295. 3Saint-Albin, loc. cit., p. 25. 4Ibid., p. 39. 5See note on this particular calorimeter by d’Arsonval, Mem. de la Soc. de Biol., 1898, p. 248. 6Bonniot, Mem. de la Soc. de Biol., 1898, p. 249. Fora critique of the Richet and d’Arsonval calorimeters, see Bonniot, Calorimetrie infantile. Etat dela question. Clinique Infantile, 1906, 4, p. 289. TBonniot, De l’hyperthermie dans la fiévre; essai de calorimétrie clinique, Paris, 1900, No. 419. 14 GASEOUS METABOLISM OF INFANTS. The most recent contribution from French laboratories on direct calorimetry with which we are familiar is that of Variot and Lavialle! in 1912. In this interesting communication, in which the fundamental principles of infant calorimetry are well considered, the authors state that they used the modified form of the d’Arsonval calorimeter which was calibrated by electrical resistance. The gaseous metabolism was not studied and no statement was made as to the muscular activity of the infants. The authors conclude that the heat-output of infants increases in proportion as the weight decreases and lay great emphasis upon the effect of clothing upon radiation. They likewise believe that the supply of adipose tissue may materially modify the radiation. Mensi? of Turin, without stating the apparatus employed or even the fundamental principle, reports a series of observations on 5 new-born infants varying in age from 6 hours and 5 minutes to 7 days, 17 hours, and 54 minutes. In these experiments the oxygen consumption was determined as well as the carbon-dioxide production. The results are given in table 3. The statement is made that the infants were quiet in each case, but no pulse records are given. TasLe 3.—Summary of experiments on respiratory exchange of new-born infants (Mensi). Oxyaen consumed Carbon dioxide Length : produced. Respir- Body- of atory Age. | Sex weight. | experi- Per | Per kilo- Per | Per kilo- | quo- ment. | Total.) min- | gram per; Total.| min- | gram per | tient. ute. | minute. ute. | minute. 1 1 d.h.m. kilos. mans. | ¢.t. C.c. C.c. C.c. c.c. | c.c.| mg. 6 5| M.| 2.70 173 | 5,707) 32.9 | 12.18 | 4,174] 24.1 |8.92/16.08) 0.73 1 247| M.| 3.— 173 | 6,470) 37.4 | 12.46 | 3,844) 22.2 |7.40)13.34) 0.593 3.155|/ M.| 2.92 159 | 6,216) 39.09) 13.38 | 3,442) 21.64/7.41/13.36) 0.55 3 722) F. 2.47 171 | 5,463) 31.9 | 12.91 | 3,586) 20.9 |8.46/15.25) 0.655 71754|} M.| 2.32 149 | 4,997) 33.5 | 14.43 | 2,979) 19.9 |8.57/15.45) 0.59 A very interesting series of experiments on infants was carried out by Scherer, in the institute of Professor Mares in Prague,’ with an apparatus on the Regnault-Reiset principle, the oxygen being supplied from a bomb. The author states that the infants found themselves in “‘complete physiological conditions” inside the chamber. In this series, 55 experiments were made in the spring and summer and 30 experiments in the winter, each one being about 2 hours long. No information is given regarding the activity of the infants or the pulse- rate. The fact that the average respiratory quotients were consider- ably below 0.6 points strongly to an error in the method. The author concludes that the intensity of the respiratory exchange is dependent upon the body-weight and is inversely proportional to it. 1Variot and Lavialle, Bulletins and Mémoires Soc. Med. des H6épitaux de Paris, 1912, 3d ser., 33, p. 410. See also Clinique Infantile, 1912, 10. p. 229, and Report of the Congrés National des Gouttes de Lait ténu 4 Fécamp les 26, 27, et 28 Mai, 1912, p. 79, for abstracts of this work. 2Mensi, Giorn. d. R. Accad. di Med. di Torino, 1894, 57, p. 301. 3Scherer, Jahrb. f. Kinderheilk., 1896, N. F., 43, p. 471. INTRODUCTION. 15 Two years later the classic monograph of Rubner and Heubner! appeared. In discussing the earlier observations of Forster, they add the significant fact that Forster’s experimental periods were but one hourlong. As their own work was done with the Pettenkofer chamber, they criticize adversely the closed-circuit apparatus used by Scherer and particularly the fundamental principle of using experiments with short periods, their paper setting forth fully the arguments in favor of the long experimental period and the Pettenkofer type of respiration chamber as compared with the short period and the Regnault-Reiset chamber. The Pettenkofer chamber, which had previously been de- scribed, was slightly modified for the studies of Rubner and Heubner, a small chamber being used. The fundamental question studied by Rubner and Heubner was the nourishment of an infant from a practical standpoint; and they were accordingly more interested in the average daily requirement of an infant for nourishment than in the physiological fact of the minimum requirement for comparison with other individuals. The subject—a “normal” infant—was 9 weeks old at the time of the observation and weighed 5,220 grams. The infant was placed in the respiration chamber and removed and fed from 6 to 8 times each day, the time thus lost being carefully recorded. Ocular observations of the muscular activity were made and a general impression for each day recorded. Muchof the time, the infant was awake but not crying. On the basis of 24 hours the authors found a difference of 22 per cent between minimum and maxi- mum carbon-dioxide production. They state that this difference is due to the unequal activity of the infant, emphasizing especially the fact that disturbance of sleep during the night influences the total daily average of the metabolism. Using Meeh’s formula’ (S=11.9¥/W) and a body-weight of 5.1 kg. they compute the body-surface to be equal to 3,500 sq. cm. and find a carbon-dioxide production of 13.5 grams per square meter of body- surface per hour. Comparing this value with those found with adults, they state that the infant excreted less carbon dioxide per square meter of body-surface than did the adults and explain this by the fact that the infant was asleep a part of the time while the determinations with adults were made only when the subjects were awake. Having pointed out that their results contradict those of Sondén and Tigerstedt,* which showed an increased production of carbon dioxide in youth, they em- phasize the fact that the carbon dioxide is essentially proportional to the body-surface with human individuals of any size. Shortly after the publication of their investigations with a normal, breast-fed infant, Rubner and Heubner’ reported a comparative study 1Rubner and Heubner, Zeitschr. f. Biol., 1898, 36, p. 1. 2Wolpert, Archiv f. Hyg., 1896, 26, p. 32. 3Meeh, Zeitschr. f. Biol., 1879, 15, p. 425. 4Sondén and Tigerstedt, Skand. Archiv f. Physiol., 1895, 6, p. 1. 5Rubner and Heubner, Zeitschr. f. Biol., 1899, 38, p. 315. 16 GASEOUS METABOLISM OF INFANTS. with a normal and an atrophic infant, neither being breast-fed. This study was carried out on the same plan as that used for the former experiment. The ‘normal’ infant weighed 7.57 kilograms, was 7} months old, and appeared to be in good health. She was fed on milk and milk sugar and throughout the observation was said to be in general “‘recht ruhig.”” The results were compared with those obtained with the breast-fed infant in the previous experiment, the hourly excre- tion of carbon dioxide per square meter of body-surface being but 13.5 grams for the breast-fed infant, which weighed but 5 kilograms, and 17.3 grams for the artificially fed infant, which weighed 7.6 kilograms. TaBLE 4.—Resulis of experiments with a normal infant and an atrophic infant. (Rubner and Heubner). i Calories per Description Food. Period. | square meter of of subject. body ody-surface. Normal... ...{Breast-fed. ¥Nas 1,006 Cow milk. I 1,143 me II 1,233 Il 1,378 Atrophic.... = I 1,090 “ II ATs Meal. aces 1,036 The second portion of the paper deals with the metabolism of the atrophic infant, artificially fed with cow’s milk and “ Kindermehl.”’ Their results are given in table4. The authors conclude that there was nothing abnormal in the metabolism of the atrophic infant. TaBLe 5.—Results of experiments on the respiratory exchange of atrophic infants (Poppi). Carbon dioxide produced. Oxygen produced. Ree Dura-| Body- ratory Name.| Date. tion. | weight. Age. Per kg. Per kg.| quo- Per 24 Per 24 : Total. hours per | Total. ours per | tient. * |minute. *) minute. 1899. |h. m. | kilos. | mos.| c.c. | liters. C.c, cc. liters.| c.c. P.L July 11 | 115] 3.425] 9 | 2,166) 40.62 | 8.237 | 2,084) 40.02 | 8.114 |1.015 N.B 20/2 0O| 3.865} 10 | 3,900) 46.80 | 8.409 | 3,820] 45.84 | 8.236 |1.021 C.F Nov. 10! 2 0| 5.500] 16 | 4,125) 49.50 | 6.25 | 4,621) 55.452) 7.002 |0.893 A.F. 12/2 0] 3.465] 7 | 3,177| 38.13 | 7.642 | 3,027) 36.324] 7.280 {1.050 M.G 15|2 0] 5.450] 12 | 4,071) 48.852) 6.225 | 4,186) 50.232) 6.40 [0.973 F.G Dec. 8|2 0O| 2.780 | 383 | 2,667) 32.004] 8.07 | 2,642) 31.704) 7.92 /1.019 1900. E.N. | Feb. 3|2 0] 3.940] 4 | 3,009) 36.108) 6.364 | 3,223) 38.676) 6.818 (0.933 The first extensive study exclusively with atrophic infants was made by Poppi.! A respiration apparatus of the closed-circuit type was probably used, as both the carbon-dioxide production and the oxygen consumption were measured, though little is said of the method. An abstract of the results obtained with 7 infants is given in table 5. 1Poppi, Il ricambio materiale e il ricambio respiratorio nell’atrofia infantile, Bologna, 1900. INTRODUCTION. 17 The respiratory quotients all seem unusually high, and this fact throws doubt upon the accuracy of the research. It is probable, however, that the carbon-dioxide determinations are well within the limits of accuracy, as is usual with methods of this type. From the protocols of one of Poppi’s studies it appears that the experiments were each 2 hours long, but no estimations are given regarding the muscular activity or the pulse-rate. In 1904 Rubner and Heubner' reported another series of experiments covering a period of 5 days. The subject was a breast-fed infant, 5} months old and weighing 9.7 kilograms. Notwithstanding the appar- ently large changes in the activity from day to day, the investigators found that the carbon-dioxide output on the last 4 days was fairly constant—a fact which puzzled the authors, who suggest a compensa- tory influence in the life of the infant. They compare the results found in this observation with those secured with other infants in the previous work done by them, and find an increase in the carbon-dioxide output of 21 per cent over the results obtained with the breast-fed infant previously studied. (See table 6.) This increase they explain by saying that it is due to the greater activity of the infant in the last experiment. Taste 6.—Metabolism of infants compared (Rubner and Heubner). Calories per ‘ ‘ Body- | square meter of Subjects and diet. weight. | body-surface per day. kilos. Atrophie child (cow milk)............... 3 1,090 Bredist: Child's: <5 %6c:0 esis gees caroteriaiars. 5 1,006 Child (cow milk)...... 2... ce cee eee eees 8 1,143 Child (breast, of this experiment)........ 10 1,219 In 1908 a report appeared of the first in a remarkable series of experi- ments carried out by Schlossmann and Murschhauser in Diisseldorf.? The protocols of this experiment were given in connection with a description of the testing of the modified Regnault-Reiset apparatus constructed by Zuntz and Oppenheimer. The authors, Schlossmann, Oppenheimer, and Murschhauser, emphasize the importance of obser- vations when the infant is asleep; they accordingly preferred to make their observations the first half of the night, feeding the infant with a large amount of breast milk in the early evening. The measurements of the metabolism of the infant during this experiment are given in table 7. During the experimental period the infant weighed 5.79 kilo- grams, the calculated body-surface being 0.384 square meter (using Meeh’s formula given on page 15). 1Rubner and Heubner, Zeitschr. f. exp. Path. u. Therapie, 1904-05, 1, p. 1. °8chlossmann, Oppenheimer, and Murschhauser, Biochem. Zeitschr., 1908, 14, p. 385. 18 GASEOUS METABOLISM OF INFANTS. The same infant was subsequently studied by Schlossmann and Murschhauser! at the ages of 144 days, 284 days, and 380 days. They found no difference in the metabolism per square meter of body-surface and conclude that Rubner’s law is correct and that the metabolic processes are proportional to the body-surface. Taste 7.—Metabolism of an infant (Schlossmann and Murschhauser). (Per square meter of body-surface per hour.) Oxygen Carbon-dioxide consumption. production. gms. gms. Average during 8 hours sleep. . . 11.0 137 Shortly after feeding.......... 11.88 15.52 Three hours after feeding...... 10.42 12.68 Waking and sleeping.......... 12.85 15.75 The report of the first extensive research made by Schlossmann and Murschhauser appeared in 1910.2. This is of special interest, inasmuch as the authors recognize at the outset the importance of muscular repose and of determining the basal metabolism. Many valuable sug- gestions as to the selection of infants for such study are incorporated in the report. Observations were made on 3 female infants; the results of these are given in table 8. The authors conclude that the carbon- dioxide production and the oxygen consumption depend upon the body- TasLe 8.—Results of fasting experiments with infants during approximately absolute rest (Schlossmann and Murschhauser). Carbon-dioxide] Oxygen per Respi Subject. Age. | Weight. | Body-surface. per square square meter espiratory : meter per hour. per hour. quotient. days kilos. 8g. m. grams. grams. ise evacciccns 174 5.010 0.3505 12.27 10.56 0.847 180 5.115 .3553 12.22 10.81 -824 DP eiccier erecauars 149 4,220 .3124 12.35 10.52 . 856 169 4.430 3228 12.64 11.08 - 832 Dos ctaseveseee 87 4.980 .38491 12.33 12.22 -730 93 5.040 .3519 11.48 10.93 - 760 surface, being wholly independent of the age of the subject, and draw the general conclusion that the infant produces per square meter of body-surface about 12 grams of carbon dioxide and consumes about 11 grams of oxygen per hour. Recognizing the possibility that the environmental temperature may have an effect upon the metabolism of the infant, Schlossmann and Murschhauser discussed this point in 1911,’ giving the results of exper- iments with an infant in which the temperature of the surrounding atmosphere varied from 16.3° C. to 23.4° C. Another infant was 18chlossmann and Murschhauser, Biochem. Zeitschr., 1909, 18, p. 499. 2Zbid., 1910, 26, p. 14. 4[bid., 1911, 37, p. 1. INTRODUCTION. 19 studied with temperatures varying from 16.9° C. to 23.4° C. The results of this second experiment substantiated those obtained with the first infant, and the authors feel justified in concluding that the slight temperature changes found in experiments with an apparatus of the Regnault-Reiset type are entirely without influence upon the metab- olism of the individuals studied. The same investigators, with a keen appreciation of the influence of muscular activity upon metabolism, compared the results of observa- tions with an infant who cried continuously for an hour with those obtained when the infant was approximately quiet. They estimated that the crying increased the carbon-dioxide production 59.4 per cent and the oxygen consumption 44 per cent. In still another paper Schlossmann? discusses the general principles involved in the measurement of the respiratory exchange of infants and emphasizes the necessity of muscular repose and the absence of food, and the importance of measuring the basal metabolism. He again asserts that the heat per square meter of body-surface is constant and maintains that this is a proof that the metabolism of young individuals is not variable. In this paper, also, he discusses the amount of work the infant does, basing the discussion upon results obtained in his experiments with crying infants. In many of his experiments Schloss- mann measured the skin-temperature of the infant by electrical methods and found that there was no increase in the temperature. In a paper discussing his earlier experiments on infants of varying ages and particularly those with an atrophic infant, Schlossmann opposes the views defended by Kassowitz? that the metabolism in smaller animals is more intense than in the large animals and that there is no relationship between the metabolism and the body-surface.‘ Schlossmann maintains that atrophic infants have a higher metabolism per unit of body-surface than normal infants, but that this points to the correctness of the Rubner law, since with these infants the relation between body-surface and body-weight is abnormal. As he made no measurements of the body-surface of these infants—a procedure that necessitated an enormous amount of work—no direct evidence is offered to show that there was an actual disproportion between the body-surface and the body-weight. In a paper which appeared after the publication of Schlossmann’s criticism, Kassowitz® sums up his arguments against the belief that the metabolism is proportional to the body-surface and using Schloss- mann’s own protocols criticizes adversely the latter’s deductions. 18chlossmann and Murschhauser, Biochem, Zeitschr., 1911, 37, p. 23. °8chlossmann, Deutsche med. Wochenschr., 1911, 37, p. 1633. 3Kassowitz, Allgemeine Biologie, Vienna, 1904, 3, p. 221. 4Schlossmann, Zeitschr. f. Kinderheilk., 1912-13, 5, p. 227. ®Kassowitz, Zeitschr. f. Kinderheilk., 1913, 6, p. 240. 20 GASEOUS METABOLISM OF INFANTS. In a paper which has only recently appeared! Schlossmann again discusses the degree of activity and the amount of work done by infants in crying. He strongly emphasizes the necessity of noting the degree of repose during the observation, either by the ocular method used by himself or the graphic record devised in this laboratory. Unfortunately at the time this paper was written, Schlossmann had not been able to compare the two methods. Two later communications by Schlossmann and Murschhauser? on the metabolism of fasting infants have particular significance in connection with this report, as they discuss the ideal conditions for obtaining the basal metabolism. Using a Pettenkofer-Voit respiration apparatus* in the Kaiserin Auguste Victoria-Haus in Charlottenburg, Birk and Edelstein‘ studied the respiratory exchange of a healthy, new-born infant weighing 3.2 kilograms and having a length of 50 cm. The infant was completely wound in cotton wool so as to keep the body-temperature at a normal level. Although he was removed from the respiration chamber several times during the day, the infant remained in the apparatus for the greater part of the 24 hours. On the second day the carbon-dioxide production per 24 hours was 55.6 grams, or 18.2 grams per kilogram; on the third day the total amount was 47.59 grams, or 15.76 grams per kilogram per 24 hours. The authors criticize the use of short experi- ments with a respiration apparatus by which the oxygen consumption can be determined and the respiratory quotients calculated, but they express regret that with their method the oxygen consumption can not be determined. In a study made by Carpenter and Murlin of the energy metabolism of pregnant women before and after the birth of the child,® the energy metabolism of three new-born infants was also found per unit of weight and per unit of body-surface. The values were obtained by subtracting the measured metabolism of the mother from that of the mother and infant. The metabolism of an atrophic infant was studied by Niemann,‘ who used a Pettenkofer-Voit respiration apparatus in the children’s clinic of the University of Berlin. The observation continued 6 days, the infant remaining in the chamber the greater part of each day. The measurements of the carbon-dioxide production on the basis of 24 hours are given in table 9. When these results are computed on the basis of carbon dioxide produced per square meter of body-surface, 1§chlossmann, Monatsschr. f. Kinderheilk., 1918, 12, p. 47. See also Am. Journ. Diseases of Children, 1913, 6, p. 15. 2Schlossmann and Murschhauser, Biochem. Zeitschr., 1913, 56, p. 355, ibid., 1914, 58, p. 483. *Bahrdt and Edelstein, Jahrb. f. Kinderheilk., 1910, 72, p. 43. 4Birk and Edelstein, Monatsschr. f. Kinderheilk., 1910, 9, p. 505. 5Carpenter and Murlin, Arch. Internal Med., 1911, 7, p. 184. *Niemann, Zeitschr. f. Kinderheilk., 1913, 6, p. 375. INTRODUCTION. 21 using the formula of Meeh and the constant 11.9, the author finds that this infant with an average body-weight during the 6 days of 3.28 kilograms had a body-surface corresponding to 0.2626 square meter, and that the carbon-dioxide excretion per square meter of body-surface was 18.5 grams per hour. TABLE 9.—Results of an experiment with an atrophic infant (Niemann). Carbon- | Average dioxide | tempera- Day. production ture per day. of air. grams. On Lincs ce wees 108.0 20.5 Dives tend bas 110.4 20.0 Gein ees cadaee 117.6 21.0 Broo eing 5% 115.2 21.0 Dis iagee tenes 120.0 21.0 Gece secswass 127.2 21.0 Maximum... D272 lacusceceats ats Minimum... LOS.0; © leccsaawtevarvend Average..... BIG 4 lncenshauns The metabolism of another atrophic infant was studied in the Univer- sitéts-Kinderklinik, Berlin, by Frank and Wolff.t Using the Petten- kofer-Voit respiration apparatus modified by Rubner, they made two series of experiments of 4 days each. The average values for carbon dioxide are given in table 10. The authors especially comment upon Taste 10.—Average carbon-dioxide excretion in experiments with an atrophic infant (Frank and Wolff). Period I. | Period II. Total 24 hours.............. 127.61 148.81 Per hour..........20e cece 5.317 6.151 Per kilogram per 24 hours.... 34.44 38.95 Per kilogram per hour....... 1.435 1.623 Per square meter per hour... 18.76 21.26 the unusually high figures for the carbon-dioxide excretion and attempt to explain them by the disturbance between the computed body-surface and body-weight and the effect of a protein-rich diet, but expressly maintain that muscular activity played no réle, as the infant, except on the first day, was ‘‘ sehr ruhig.”’ Bahrdt and Edelstein? also report an experiment with an atrophic infant, in which they used the respiration apparatus in Langstein’s laboratory in the Kaiserin Auguste Victoria-Haus. The observation was made in three periods of four days each. In the first and last periods, the infant remained inside the chamber for the greater part of the 24 hours, being removed periodically, as is customary in experiments with this type of apparatus. Their final conclusion was that the heat- 1Frank and Wolff, Jahrb. f. Kinderheilk., 1913, 78, p. 1. : 2Bahrdt and Edelstein, Festschrift Dr. Otto L. Heubner, Berlin, 1913. 22 GASEOUS METABOLISM OF INFANTS. production of atrophic infants can be abnormally high aside from any effect which the environmental temperature or the body activity may have upon it. Finally the direct calorimetric and gasometric researches of Howland! in Lusk’s laboratory should be especially noted. In discussing the calculation of the body-surface, Howland cites the use of the factor 12.3 as a constant for infants, but we are not aware of any writers who have previously used this factor. The experiments were made with the respiration calorimeter? at the Cornell University Medical College in New York. Three infants under one year of age were studied and ocular observations of the activity of the infants were recorded. Howland’s experiments were subsequently published in detail and the results more fully discussed.’ In this paper therelationship between body-surface and body-weight is extensively treated and the various factors and formulas are considered. A curve is proposed which is represented by the algebraic expression y = mz + b, in which y is the surface area of the infant, x the weight of the infant in grams, m the constant 0.483, and b 730 sq. cm. TABLE 11.—Heat-production of infants, directly and indirectly measured, as reported by Howland. Calories per square : meter per day. Difference Subject. Food. (per cent). Measured. | Calculated. 1,046 1,084 Child 1....... Ordinary....... 1,113 1,174 2 1,196 1,164 DOiine cs Nutrose added. . 1,218 1,179 3 1,204 1,180 Do sccasalevies Gis ise csveeds 1,235 1,212 Less than 1 1,181 1,250 1,106 1,177 DO jei/6 sce Fasting........ 1,226 1,156 Less than 1 1,301 1,243 Child 3....... Ordinary syeies: { a ies 2 Dosis. cs sens OO scci aac 825 840 2 The last portion of the paper, which is of most significance, compares the direct and indirect computation of the heat-production of the infants observed. This comparison is of such value to workers in metabolism that it is given here in table 11. The agreement between the heat-production as directly measured and as indirectly computed is striking, to say the least, and justifies for the present the utilization of the indirect method of computing the calorimetry of infants. 1Howland, Proce. Soc. Exp. Biol. and Med., 1911, 8, p. 63; Hoppe-Seyler’s Zeitschr. f. Physiol. Chem. 1911, 74, p. 1. 2Williams, Jour. Biol. Chem., 1912, 12, p. 317. ?Howland, Trans. 15th Int. Congress on Hygiene and Demography, Washington, 1913, 2, p. 438. BASIC PRINCIPLES. 23 BASIC PRINCIPLES. Though Howland, using Lusk’s calorimeter, has been eminently suc- cessful in experiments on the direct calorimetry of infants, experience with such researches in the Nutrition Laboratory has led us to believe that a type of calorimeter with less mass, less heat capacity, and prob- ably not of the continuous-flow type could most advantageously be em- ployed for the short periods necessitated by experiments with infants. Several types or modifications of calorimeters have been in process of testing for some time, and pending the satisfactory development, con- struction, and testing of an infant calorimeter with the qualifications referred to, we have actively undertaken the study of infant metabolism as determined by indirect calorimetry. In these observations we have devoted our energies to the accurate measurement, in relatively short periods, of the carbon dioxide produced and oxygen consumed by infants less than one year of age. There is at present in Americaastrong movement toward the develop- ment of hospital clinics liberally endowed for scientific research and it is fair to assume that in the next decade the study of infant metabolism will be more actively prosecuted in this country than ever before. Clinicians with whom we have conferred have especially requested that in publishing the results of our observations we should discuss the gaseous metabolism of infants somewhat in detail. Accordingly at this point it seems desirable to define a few of the principles under- lying the method of study. This is done, first, to make clear the methods and technique used in our investigation; and, second, to serve as a guide for those clinicians or experimenters who are interested in actively following this line of research. THE RESPIRATORY QUOTIENT AND ITS SIGNIFICANCE. The oxygenation of the blood—which, prior to the birth of an infant, was effected by the lungs of the mother—is after birth at once begun through the lungs of the infant. The oxygen is carried by the blood to the various tissues and there enters into the katabolic processes, oxidizing the protein, fat, and carbohydrates. The resulting carbon dioxide is carried by the blood to the lungs and thence excreted into the air which passes though the lungs in respiration, while the partially oxidized nitrogenous products resulting from protein disintegration are excreted through the kidneys. With normal life both the carbohy- drates and fat of the body-material are converted into carbon dioxide and water; protein, also, is in large part changed to carbon dioxide and water, the nitrogenous portion being excreted in the urine in the form of urea, uric acid, and allied compounds. The chemical composition of the chief constituents of the body has been determined by analysis and is given in table 12. These values 24 GASEOUS METABOLISM OF INFANTS. represent the average of a large number of analyses, and have been exten- sively used in computations of the indirect calorimetry of men. TaBLe 12.—Chemical composition of the constituents of the body. Mineral Body material. N. Cc. H. Oo. matters (including §.). per cent. | percent. | per cent. | per cent. per cent. ProteinShs cieaaue sx s ro ten eeu 16.67 52.80 7.00 22.00 1.53 Pats stcardesarren aoe ties 8 45 RE Rea ee ace BO 76.10 11.80 12810) liens eeieeeeees Carbohydrate (glycogen) .........|......005 44.40 6.20 WOUAO no aaeeeenees 1While these values were determined on carefully isolated and purified materials obtained from the animal body, they may be considered as approximate values for all proteins and fats. Innumerable analyses have been made of the ordinary food sub- stances, but the composition of starch, cane sugar, glucose, and lactose can be computed from the chemical formulas directly. For the com- position of normal fat, the average values given by Koenig are ordi- narily used.1 When these substances are burned inside the body, a definite volume of oxygen combines with their carbon and hydrogen to produce carbon dioxide and water. The amount of carbon dioxide produced per gram of a substance, the amount of oxygen required for the oxidation, and the total heat evolved can be determined exactly by burning a known amount of various fats and carbohydrates outside of the body, as, for instance, in a calorimetric bomb. The carbon dioxide is excreted in a gaseous form, while the water may be excreted through the kidneys, vaporized through the lungs and skin, or added to the residual water always present in the body. Since there is so large a storage of water in the body, it is obviously impossible to distinguish between water formed by the oxidation of organic mate- rial and water existing preformed in the body, but the relationship between the oxygen consumed and the carbon dioxide produced has a great physiological value and plays an important réle in indicating the character of the material burned in the body. The importance of this relationship was early recognized by Pfliiger and the ratio was designated by him as the “respiratory quotient.” The theoretical respiratory quotient for the combustion of a pure substance of definite chemical composition may be easily computed. If we consider, for example, one of the chief foods of an infant—lactose or milk sugar, with a chemical formula of Ci:2H22O1 -- HxO—we see that the hydrogen and oxygen are present in the molecule in the exact proportions to form water. Since there is in the molecule sufficient oxygen to oxidize the hydrogen completely, the oxygen which enters into the combustion burns only the carbon. It is, of course, obvious that the complete combustion does not proceed in this sharply defined manner, but this alters in no wise the trend of our reasoning. 1Koenig, Chemie der menschlichen Nahrungs- und Genussmittel, 3d ed., 1, p. 198. BASIC PRINCIPLES. 25 The chemical reaction may be expressed as follows: CreHosOre + 12 O. = 12 CO, + 12 H.0O That is, for every 12 molecules of oxygen absorbed, there are produced 12 molecules of carbon dioxide. Accordingly, for every liter of oxygen absorbed, there is produced one liter of carbon dioxide, so that the volume ratio may be expressed: Volume CO, Volume O2 We can say, therefore, that the respiratory quotient of lactose is 1.00, This is also true of all carbohydrates, including starch, cane sugar, levulose, and dextrose. Furthermore, it can be computed from the molecular composition that 1 gram of human fat requires 2.844 grams of oxygen in its com- bustion and that as a result of the combustion 2.790 grams or 1,420.4 c.c. of carbon dioxide are produced. There is, therefore, an absorption of 1,990.8 c.c. of oxygen to form 1,420.4 c.c.1 of carbon dioxide; hence the respiratory quotient would be: Volume CO, 1420.4 Volume O, 1990.87 0°13 k The calculation of the theoretical respiratory quotient of protein is less simple, owing to the fact that protein is only incompletely oxidized, a portion of the protein molecule being excreted unburned in the form of urea, uric acid, and allied compounds in the urine. The calculation of this quotient has been made in a number of ways by different writers on the subject, each assuming a somewhat different molecular compo- sition for protein and each ascribing in turn various values to the =1.00 TABLE 13.—Assumed apportionment of elements after oxidation. Cc. H. O. N. 8. grams. | grams. | grams. | grams. | grams. In the urine..... 9.406 2.663 | 14.099 16.28 1.02 In the feces...... 1.471 | 0.212 | 0.889 0.37 | 0.00 Remainder...... 41.500 | 4.400] 7.690 0.00} 0.00 unoxidized portion of the protein excreted in the feces as well as in the urine. Furthermore, observers differ as to what degree the sulphur of protein is oxidized, for unoxidized as well as completely oxidized sulphur may be found in the urine. The following calculation is taken directly from Loewy,? in which he assumes that 100 grams of fat-free, dry substance of flesh contain 52.38 grams of carbon, 7.27 grams of hydrogen, 22.68 grams of oxygen, 16.65 grams of nitrogen, and 1.02 grams of sulphur. The assumed apportionment after oxidation is given in table 13. 1Frroneously stated as 1,240.4 c.c. by Benedict, Am. Journ. Physiol., 1909, 24, p. 348. 2Loewy, Oppenheimer’s Handbuch der Biochemie, Jena, 1911, 4, (1) p. 156. 26 GASEOUS METABOLISM OF INFANTS. In the combustion of 41.5 grams of carbon and 4.4 grams of hydrogen, 145.87 grams of oxygen are used. Deducting from this the 7.69 grams originally in the protein and not excreted in the urine or feces, 138.18 grams of oxygen additional are required. During the process of oxida- tion, 152.17 grams of carbon dioxide areformed. Reducing these values to volumes, we then have the ratio: Volume CO, 77.39 Volume O; ~ 96.63 The oxygen required for combustion, the products of combustion, and the respiratory quotient for several typical materials have been calculated and are given in table 14. TaBiLE 14.—Respiratory quotients for protein, fats, and carbohydrates. = 0.801. Oxygen tequired to Produced in the oxidation of 1 gram. Respicatory Materials. eeerene Carbon dioxide. i Heat COz c.c. Weight. | Volume. Weight. Volume. Or c.c. grams. £.C. grams. Cx, cal. Starch.......... 1.185 829.3 1.629 829.3 4,20 1.000 Cane sugar...... 1.122 785.5 1.543 785.5 3.96 1.000 Milk sugar!..... 1.066 756.2 1.466 746.2 3.75 1.000 Animal fat...... 2.876 2013.2 2.811 1431.1 9.50 0.711 Human fat...... 2.844 1990.8 2.790 1420.4 9.54 0.713 Protein?........ 1.367 956.9 1.520 773.8 4,403 0.809 1These values apply likewise to dextrose and levulose. ? While this computation is based upon meat protein, the values will be essentially the same for all proteins. These values represent quantities found when burning protein not in a calori- metric bomb, but in the animal body. 3 The heat of combustion of protein averages 5.65 calories per gram; deducting the unoxidized material in the urine, the heat per gram would be 4.40 calories. For discussion of this point, see Atwater and Bryant, Storrs (Connecticut) Agr. Expt. Sta. Rept., 1899, p. 73. The carbohydrates have a respiratory quotient of 1.00; fat in general, of 0.71; and protein of 0.81. From these factors, therefore, we can see that during inanition, when the subject is subsisting for the greater part upon body-fat and protein, the respiratory quotient would tend to approach 0.71. On the other hand, if a diet is taken consisting largely of carbohydrates, the respiratory quotient tends to approach 1.00. Since the metabolism of the protein remains relatively constant from day to day and from hour to hour and is but a small proportion of the whole, the errors involved in its calculation are not of sufficient magni- tude to influence seriously any deduction drawn from the results in which these calculations occur. Usually the disintegration of the protein is about 15 per cent of the total katabolism. Magnus-Levy' has calculated that if the remaining 85 per cent is wholly from carbo- hydrates, the respiratory quotient would be 0.971; if, on the other hand, the remainder of the energy is derived solely from fat, the respiratory 1Magnus-Levy, von Noorden’s Handbuch der Pathologie des Stoffwechsels, Berlin, 1896, 1, p. 217. BASIC PRINCIPLES. 27 quotient would be 0.722... Under ordinary conditions, the respira- tory quotient would lie between these two figures, and values above or below these points might reasonably be considered as due to faulty technique, to distinctly abnormal metabolism, or to a possible forma- tion of fat from carbohydrate or carbohydrate from fat. It is thus clear that when the respiratory quotient is carefully deter- mined, considerable light may be thrown upon the character of the materials burned in the body. It should be considered, however, that to determine accurately the respiratory quotient calls for an extraordi- narily skilful technique, since any errors affecting either the determina- tion of the carbon dioxide or the determination of the oxygen likewise affect the respiratory quotient. The absolute values for the amounts of carbon dioxide exhaled and oxygen absorbed in a given time, usually 1 minute, 1 hour, or 24 hours, are also of importance in indicating the quantitative relations of the total katabolism. For example, it is possible to strike a daily balance from the amounts determined for 24 hours and show the adequacy or inadequacy of the ration for maintenance by determining or computing the carbon in the diet. INDIRECT CALORIMETRY. A number of physiologists have used the respiratory exchange to compute the total calorimetry by the method of so-called ‘indirect calorimetry,’” and obtained results of still moreimportance. The total katabolism may be apportioned between protein, fat, and carbohy- drates by using the determination of nitrogen in the urine (protein katabolism) and the respiratory exchange. Since in calculating the materials katabolized in experiments with respiration calorimeters, it is generally assumed that all of the food materials are first transformed into similar substances found in the body, the calculation of the total energy may with propriety be based upon the values of body-protein, human fat, and glycogen. As each of these materials, when burned, supplies definite amounts of heat, the total energy resulting from the oxidation may be computed by multiplying the number of grams of each katabolized material by certain factors, that customarily used for protein being 5.65, or after deducting the potential energy in the urine, 4.4; for fat, 9.54; and for carbohydrates, 4.19. Definite information regarding the calorific output of an infant is of great importance in studying infant nutrition in order that a calculation may be made of the amount of food required to provide a suitable quota of calories for the day. The caloric losses from the body, therefore, 1frroneously reported as 0.772 by Benedict, Am. Journ. Physiol., 1909, 24, p. 351. 2This method is not to be confused with the usage of certain French writers who consider “‘indi- rect calorimetry” as indicating the computation of material consumed by noting the weights of food eaten, excreta, and gain or loss of body-weight. 28 GASEOUS METABOLISM OF INFANTS. require careful consideration in studies of infant metabolism. With normal metabolism and normal digestion, thelossof unoxidized material in the feces and urine may be considered as essentially constant. The feces represent not merely the undigested residues of food but the epithelial débris, the residues of digested juices, and bacteria; with normal digestion, these remain essentially a constant percentage of the total amount digested. It is not the loss of energy through the urine and feces, however, that is of special interest in studying infant metabolism, but the losses resulting from the katabolism of materials in the body, namely, the loss through the combustion of organic substances by virtue of the oxygen taken into the system and there combined with carbon and hydrogen to form carbon dioxide and water. The carbon dioxide thus formed has been considered so close a measure of the total amount of material burned that for years it served as the index of the total combustion of the materials in the body. It may be computed from the data given in table 14 that if the combustion in the body were exclusively of carbo- hydrate, the production of 1 liter of carbon dioxide would be equivalent to the liberation of approximately 5.05 calories of heat. If, on the other hand, the carbon dioxide resulted exclusively from the combus- tion of fat, it can be computed that 1 liter of carbon dioxide corresponds to 6.7 calories of heat. While with an infant on a normal diet the proportions of protein, fat, and carbohydrate in the oxidized material may remain relatively constant, it is certainly true that in pathological cases these proportions may be greatly disturbed, and the calorific value of the carbon dioxide may vary considerably with different conditions. Inasmuch as infor- mation regarding the diet and treatment of infants is more especially required in pathological conditions, it is evident that a better method for estimating the total heat output than by the carbon-dioxide excre- tion is to be desired. If the relationship between the heat-output and the oxygen consumption is closely examined, it will be seen that the ratio is much more constant than is the ratio between the carbon dioxide and the heat. Thus, for every gram of lactose burned, 1.066 grams of oxygen are consumed, each gram of oxygen thus used being equivalent to 3.51 calories of heat. Likewise, for every gram of fat burned, 2.85 grams of oxygen are consumed, each gram of oxygen resulting in the production of 3.35 calories of heat. It will be seen from these figures that while the calorific equivalent of carbon dioxide varies some 25 per cent according to whether carbohydrate or fat is burned in the body, the calorific equivalent of oxygen varies only about 6 per cent. It is clear, therefore, that the best measurement of the caloric output of the body is the amount of oxygen consumed rather than the amount of carbon dioxide produced. BASIC PRINCIPLES. 29 With modern apparatus it is possible to arrive at an even more exact knowledge of the energy output by determining both the oxygen con- sumption and the carbon-dioxide production and calculating the respi- ratory quotient. Zuntz, to whom we are especially indebted for the introduction of this method for computing the heat output, has pains- takingly computed the calorific value of oxygen with different respira- tory quotients, and these figures may be considered to-day as the best data that we have for the computation of the energy output from the measurement of the gaseous exchange. In the Zuntz laboratory, where practically all of the experiments carried out have been made upon adults with a mouthpiece or upon animals with tracheal fistulas, the Taste 15.—Calorific equivalents of carbon dioxide. . Calorific value of Calorific value of ; Calorific value of Respira-| carbon dioxide. | ResPiT@-| carbon dioxide. || ResPir@-| carbon dioxide. tory tory ae melee OER tory fics Se oe oo tens e quotient. Per liter. | Per gram. quotient. Per liter. | Per gram. quotient. Per liter. | Per gram. cals. cals. cals. cals. cals. cals. 0.70 6.694 3.408 0.80 6.00 3.05 0.90 S.ATL 2.785 71 6.606 3.363 81 5.942 3.025 .91 5.424 2.761 72 6.531 3.325 .82 5.884 2.996 .92 5.378 2.738 .73 6.458 3.288 .83 5.829 2.967 .93 5.333 2.715 74 6.388 3.252 .84 5.774 2.939 .94 5.290 2.693 to 6.319 S217 -85 5.721 2.912 -95 5.247 2.671 76 6.253 3.183 . 86 5.669 2.886 — -96 5.205 2.650 77 6.187 3.150 oe 5.617 2.860 .97 5.165 2.629 .78 6.123 Bile .88 5.568 2.835 -98 5.124 2.609 .79 6.062 3.086 .89 5.519 2.810 -99 5.085 2.589 1.00 5.047 2.569 determinations of the oxygen consumption are as accurate as are those of the carbon-dioxide production; consequently Zuntz has utilized the calorific values of oxygen, and these have been given in tabular form in one of the publications from his laboratory.!_ Knowing the respira- tory quotient, the calculation of the calorific value of carbon dioxide is a simple one. Since, in our respiration apparatus, the carbon-dioxide determinations for short periods are even more exact than are the deter- minations of the oxygen, we give in table 15 the calorific equivalents of carbon dioxide with the varying respiratory quotients, particularly as this table will be used extensively in the computation of our own researches. Since any form of indirect calorimetry must of necessity be somewhat speculative,” one must always rely for fundamental values upon direct heat measurements. Such measurements have been extensively made 1Zuntz and Schumburg, Physiologie des Marsches, Berlin, 1901, p. 361. 21t will be noted that in this publication the computation of the energy derived from protein is neglected and that the total energy output is computed only from the amounts of carbon dioxide and oxygen. ‘The possible error in neglecting the protein has been computed by Magnus-Levy to be somewhat under 1 per cent, and as the determinations of nitrogen were not feasible in our studies, we have used the method of simple computation from the gaseous exchange as recommended by A. Loewy. (Loewy, Oppenheimer’s Handbuch der Biochemie, Jena, 1911, 4, p. 281. See also, Magnus-Levy, von Noorden’s Handbuch der Pathologie des Stoffwechsels, Berlin, 1896, 1, p. 207.) 30 GASEOUS METABOLISM OF INFANTS. with men by Atwater and his associates at Wesleyan University, Middletown, Connecticut, where it was shown in experiments of long duration that the heat output as measured directly by the respiration calorimeter and the heat output as computed from the respiratory exchange agreed remarkably well. It should be pointed out, however, that these computations were based upon 24-hour periods. In certain experiments the computation has likewise been successful for periods as short as 6 hours, but it remained for Howland! to demonstrate with Lusk’s calorimeter the complete agreement of the direct calorimetric measurements and of the computation from the gaseous exchange for short periods and particularly with an infant as subject. Howland has, temporarily at least, forsaken direct calorimetric research, as he is not now supplied with a respiration calorimeter, but it is much to be hoped that these few observations, which imply such a remarkable agreement between the direct and indirect calorimetry, may be extended in the near future to cover other cases. Until later evidence disproves this assumption, workers in this field are perfectly justified in assuming that the comparison between direct and indirect calorimetry has been made with infants with more than ordinary scien- tific accuracy. This being the case, the field is open for making a large number of metabolism experiments with the respiration apparatus in laboratories and institutions where a respiration calorimeter for direct calorimetry is not available. BASAL METABOLISM. While the normal life of the infant is a relatively simple and constant one, yet it does include periods of muscular activity which vary greatly, the extremes ranging from perfect muscular repose during deep sleep to the violent exercise incidental to vigorous crying. As a result of these changes in muscular activity, the output of heat would likewise vary largely, with a minimum output during sleep and quiet and a maximum during the period of crying. An attempt has been made to find the average value for the heat output of an infant by experiments with 24-hour periods, thus securing an average for the life of the day; but when one considers that the difference between the heat output in complete muscular repose during sleep and the heat given off when the infant is crying vigorously may be as great as 60 or more per cent, it will be seen that this method of averaging does not furnish information with regard to the minimum metabolism. With adults, the best condition which has been found for a basis of comparison has been when the subject was in complete muscular repose and in the so-called “‘post-absorptive”’ state, 7. e., when absorption of material from the alimentary tract had ceased, this being with adults generally 12 hours after the last meal. With an adult who is capable of a certain degree of muscular relaxation and repose, suitable experi- 1Howland, Trans. 15th Int. Congress on Hygiene and Demography, Washington, 1913, 2, p. 451. APPARATUS AND METHODS USED IN THIS RESEARCH. 31 mental conditions can be obtained without great difficulty. With an infant this condition may only be approximated during sleep. It thus becomes necessary to consider seriously a fundamental change in the principle of studying infant metabolism and, instead of attempting to average the life during a 24-hour period, to use only selected periods with complete muscular repose. The muscular activity of infants is twofold: (1) internal muscular activity, consisting of muscular tonus, the movements of the organs of circulation and respiration, and possibly the processes of digestion; and (2) external muscular activity such as the movements of the limbs or vigorous body movement incidental to crying. The internal move- ments can be controlled only by minimizing the after-effects of digestion through the absence of food; the regular involuntary muscular activity of the respiratory and circulatory system and the muscular tonus can not be altered. On the other hand, the external muscular activities are at a minimum only during complete muscular repose, as in deep sleep. It is thus seen that the ideal conditions for studying the basal or minimum metabolism of infants would be the post-absorptive state— that is, sufficiently long after the last meal to insure that there was no longer an absorption of food materials from the alimentary tract, and during deep sleep when there is complete muscular repose. With very young infants, periods of complete muscular repose can not be expected for any great length of time, probably not for more than twosuccessive hours. The difficulties incidental to securing these conditions have prevented researches in this line for many months, if not years; the best method for obtaining them is still to be demonstrated. We have, then, two factors to deal with, first, the heat elimination incidental to the specific katabolic stimuli of the food materials accom- panying the digestion and absorption of food; and, second, the internal muscular activity of the infant. If the first of these factors can be eliminated, we have what may properly be termed the basal metabolism unaccompanied by extraneous muscular activity of any kind. APPARATUS AND METHODS USED IN THIS RESEARCH. Certain inherent difficulties in conducting experiments with infants have undoubtedly delayed the accumulation of a large amount of material in regard to infant metabolism. While researches have been actively prosecuted with domestic animals and with men for many years, the technique for the study of the metabolism of infants has been but slowly developed. Nevertheless, the natural difficulties incidental to the separation of the urine and feces of children have been for the most part overcome by careful technique, so that in hospital wards, at least, experiments on the total urine and fecal secretions can now be satisfactorily made. But in a more extensive study of infant metabolism certain difficul- ties occur which are not encountered in a study of the metabolism 32 GASEOUS METABOLISM OF INFANTS. of an adult. The infant is incapable of giving intelligent assistance in the experiment, neither can its muscular activity be controlled. Furthermore, in adult life, growth has been attained and the energy required is mainly for maintenance and for definite external muscular work, while infancy is a period of rapid growth, at least if normal metab- olism is progressing; the infant, therefore, requires energy both for growth and for maintenance. While the amount of effective mechan- ical work is nil, nevertheless it has been clearly demonstrated that, during the periods of muscular activity incidental to the active life of the infant, there may be a large increase in the total metabolism. This simultaneous requirement for growth and for maintenance makes the study of infant metabolism a doubly complicated problem. On the other hand, in studying the metabolism of an adult, one of the greatest difficulties we have to contend with is the complex life of the normal individual—the irregular or intermittent ingestion of food and the various degrees of muscular activity contributing to the sum total of the metabolic changes of the day. It is possible, by means of large respiration chambers, to approximate the normal life of a man of sedentary occupation or even with some degreeof muscular activity, but it is practically impossible to duplicate the life of an ordinary individual with its different environments and activities. Consequently with adults it is necessary to secure periods for observation when the subject is without food in the stomach and when there is a minimum amount of activity. With an infant who spends the greater part of his day in the crib, the life complexes can be much more easily studied. The daily life is divided first into eating, sleeping, and crying; later, as the special senses and the intellect develop, to these divisions are added playing and exercise. Throughout the infantile period, therefore, the daily routine is monotonous and regular, with hours of sleep and waking time relatively constant. The diet of the infant is also unchanging in character, consisting for the most part of milk. In summing up, we may say that the normal infant is more nearly constant as to its body activity, daily routine, and diet than the normal adult with his higher life complexes. The inability of the infant to assist materially in metabolism experiments, the difficulty of carrying out definite well-known tests with mathematical accuracy, and the impossibility of regulating the muscular activity must therefore be offset by this constancy in diet and daily routine. Hence it is by no means impossible to reproduce the daily routine of infants inside of a specially constructed chamber. RESPIRATION APPARATUS. Jn the Nutrition Laboratory and previously in the chemical labora- tory of Wesleyan University, Middletown, Connecticut, various types of apparatus for studying the respiratory exchange have long been in the process of development. Since practically all of the earlier work APPARATUS AND METHODS USED IN THIS RESEARCH. 33 had to do with the metabolism of men, there was very little demand for a small respiration apparatus. There are, however, many physiological laboratories and laboratories in hygienic institutes and medical clinics that wish to utilize an apparatus, not only for experiments with men but also with animals. Such a possibility has already been demon- strated, notably by Grafe! in Heidelberg and by Rolly? in Leipsic. A small apparatus, which is based upon the principle of the large respira- tion calorimeters used in this laboratory, has been here devised for experiments with men; this has already been described in detail. While the fundamental principle has not been altered in any way, the apparatus has from time to time been modified and improved, and a cage or respiration chamber added, thus making observations possible with small animals and with infants. Its use with animals was first described by Benedict and Homans; it was later referred to in a paper by Benedict and Talbot® as being used for observations with infants. In these earlier descriptions, it was stated that the apparatus had been only so far perfected as to permit the measurement of the carbon-dioxide excretion and did not permit the measurement of the oxygen consumption. Since these publications have appeared, a newer type of this apparatus has been devised and at least two investigations® have been reported from this laboratory in which the apparatus was used. The large number of respiration apparatus devised in the Ameri- can and foreign laboratories make it practically impossible to contribute any fundamentally new features to the study of animal metabolism along this line. Nevertheless, as the main object in devising the appa- ratus used in this laboratory was to make it so flexible that it could be employed not only for men but likewise for infants and for large and small animals, a description of this later form seems desirable before further investigations are reported. While the new feature in this modified apparatus is the direct deter- mination of the oxygen consumption, opportunity is again taken here to emphasize strongly the importance of graphic records of the muscular activity in experiments with all classes of subjects, including not only men but infants and small animals, and also to emphasize the import- ance of the pulse-rate as an index of the intensity of the metabolism. Every respiration experiment conducted in this laboratory consists always of two parts, each indispensable to the other and each valueless without the other; first, the chemical division, 7. ¢., the measurements of the carbon-dioxide excretion and the oxygen consumption; and, 1Grafe and Graham, Zeitschr. f. physiol. Chem., 1911, 73, p. 7. 2Rolly and Rosiewicz, Deutsch. Archiv f. klin. Med., 1911, 103, p. 58. See also discussion of Rolly’s apparatus by Grafe, Abderhalden’s Handbuch der biochemischen Arbeitsmethoden, 1913, 7, p. 524. 3Benedict, Deutsch. Archiv f. klin. Med., 1912, 107, p. 156. 4Benedict and Homans, Journ. Med. Research, 1912, 25, p. 409. 5Benedict and Talbot, Am. Journ. of Diseases of Children, 1912, 4, p. 129. ®Benedict and Pratt, Journ. Biol. Chem., 1913, 15, p. 1; Morgulis and Pratt, Am. Journ. Physiol., 1913, 32, p. 200. At this point it is a pleasure to acknowledge the helpful assistance of Dr. S. Morgulis in developing the technique of determining oxygen with the apparatus. 34 GASEOUS METABOLISM OF INFANTS. second, the graphic records of the muscular activity or muscular repose and the pulse-rate. The main object of the apparatus and its acces- sories is, therefore, to give an accurate measurement on small animals or infants of the carbon dioxide produced and the oxygen consumed, and an interpretable record of the degree of muscular activity or repose, accompanied by pulse observations. The carbon dioxide produced by the animal is completely absorbed, the amount excreted being determined by the increase in weight of the absorbing vessels. Gas analyses, with their attendant difficulties of technique, are therefore unnecessary. RESPIRATION CHAMBER CO> produced O> consumed i ~ OXYGEN INTRODUCED Carson Dioxide WaTER So ABSORBED bead os deficrent o pizsshyen Fic. 1. Schematic outline of respiration apparatus. The oxygen is determined directly by noting the amount it is neces- sary to introduce into the respiration chamber in order to secure the same volume of air in the chamber at the beginning and end of the experiment, making due allowance for changes in temperature, pressure, and water-vapor. While usually the amount of oxygen used is deter- mined by allowing oxygen to flow into the respiration chamber from a previously weighed cylinder of the highly compressed gas and noting the loss in weight, it may likewise be accurately determined by passing the gas from a compressed cylinder through a carefully calibrated gas- meter which is submerged in water to prevent gross temperature fluctu- ations. The general plan of the apparatus is shown in the schematic outline given in figure 1. As the infant gives off carbon dioxide and consumes oxygen, the air leaving the chamber is rich in carbon dioxide and water-vapor from the lungs and skin of the infant, contains a normal amount of nitrogen, APPARATUS AND METHODS USED IN THIS RESEARCH. 35 and is deficient in oxygen. By means of a rotary pump, the air is carried from the chamber and forced through sulphuric acid, which absorbs the water, then through soda lime toremove the carbon dioxide; oxygen is next introduced and when the air returns to the chamber it is free from carbon dioxide and water and contains a normal percentage of nitrogen and oxygen. A somewhat more elaborate scheme of the respiration apparatus, giving in considerable detail some of the special connections, may be seen in figure 2. The chamber, C, in which the infant remains, with Fig. 2. Detailed scheme of respiration apparatus. C, chamber; W, W, water jacket; O, outgoing air-pipe; Z, psychrometer; N, muffler; P, blower; A, acid trap; B and C, Williams water-absorbers; Vi and V2, 2-way valves; D: and Dz, carbon-dioxide absorbers; Ei and Ep, air-dryers; F', sodium bicarbonate can; J, by-pass; R, valve; K, air moistener; L, oxygen cylinder; J, ingoing air-pipe; S, spirometer; 7; and T2, thermometers; M, manometer; U, spiral spring; H, pneumograph. its surrounding water jacket, W, W, for temperature control, is shown at the upper left-hand corner of the figure. The air leaves the chamber near the right-hand end at O, and is drawn by the rotary pump over a wet- and dry-bulb psychrometer, Z, which gives the amount of moisture in the air of the chamber. A can, N, filled with dry cotton-batting is also placed in the air-current between the blower and the chamber to act as a muffler. After leaving the exhaust side of the blower, P, the air is forced through an empty glass bottle, A, which serves as a trap should any back pressure take place and sulphuric acid be forced back from the water-absorbing vessels Band C. These latter vessels, which are of peculiar construction, were designed by Dr. H. B. Williams, of the department of physiology of Columbia University, and will here- after be designated as ‘‘ Williams bottles.” The air passes along a pipe 36 GASEOUS METABOLISM OF INFAN'TS. to a 2-way valve, V:, where it may be deflected through either of the soda-lime bottles D; or D2, in which the carbon dioxide is absorbed. Since the reagent must be somewhat moist to facilitate the absorption, it gives up water-vapor to the dry air-current, which must in turn be absorbed by sulphuric acid in the Williams bottles E, or Ez. The air next passes through the 2-way valve, V2, and enters a small can, F, which contains dry sodium bicarbonate, the unweighable but noticeable sul- phuric-acid odors being effectually removed by this means. The air then returns to the chamber through the by-pass J; or, if it is desired to moisten the air, the current can be deflected by closing the valve R in the by-pass J, so as to pass all of the air through distilled water in the Williams bottle, K. The air is now free from carbon dioxide and con- tains the water-vapor added in passing through K, but is still deficient in oxygen. This deficiency is made up by admitting oxygen from a cylinder, L, of compressed gas. The air thus enters the respiration chamber at J, somewhat moist and with approximately the normal percentage of oxygen. Either series of absorbers may be used as desired, for if the air-current has been passing through the series D, and £, for a given experimental period, the air can be instantly deflected through the series D, and E,, by turning simultaneously valves Vi and V>. As actually constructed, V; and V, are connected by a long rod, so that they may be thrown simultaneously by one movement of the hand. Since the air-current is entirely closed, a small spirometer, S, is attached at the upper right-hand corner of the respiration chamber, thus providing for any expansion or contraction of the air. A ther- mometer, 7, in the cover of the chamber, and a second thermometer, T., in the outgoing air, serve to indicate the temperature changes, while the manometer, M, shown below the spirometer, indicates the pressure of the air in the chamber. By noting the increase in weight of the absorbers, D, and FE, or Dz and E;, the amount of carbon dioxide absorbed is known. It is possible that the amount of water-vapor given up by D, to the dry air passing through it may be actually more than the amount of carbon dioxide absorbed, so that the bottle D: may lose in weight; on the contrary, the water-vapor given up is immediately absorbed by #1, and hence the algebraic sum of the weight of the two bottles gives the weight of the carbon dioxide absorbed. Usually both bottles are weighed on a balance at the same time. The loss in weight of the cylinder L indi- cates the amount of oxygen absorbed, corrections being made for any variations in temperature and barometric pressure, or in the composi- tion of the air inside the respiration chamber. In figure 2 a general idea is given of the method of suspending the crib upon a stout spiral spring, U, at one end and a knife-edge, G, at the other. Alongside of the spring U is a pneumograph, H, the disten- APPARATUS AND METHODS USED IN THIS RESEARCH. 37 sion or contraction of which compresses the air inside of the pneumo- graph tube, thus transmitting, to a delicate tambour outside, a record of the slightest motion of the cage resulting from the movements of the infant. This method of obtaining a graphic record of the muscular activity is shown in more detail in figure 5 (p. 57 Je While the general features of this apparatus have already been dis- cussed in considerable detail, with increased experience and with the facilities for modifying the technique to suit the conditions to be met, certain fundamentally important variations from the previously estab- lished technique have been found necessary. In this type of respira- tion apparatus the infant is lying in a crib inside of a small respiration chamber constructed of galvanized iron or copper and 77 cm. long, 25 em. deep, and 37 cm. wide. To insure temperature control, the whole respiration chamber is surrounded by a water-jacket consisting of a second shell of galvanized iron or copper with a space of 5 cm. between the two shells. To withstand the pressure exerted by the weight of water, the two walls are separated by brass studs at approxi- mately 5.5 cm. from each other, distributed all over the respiration chamber. This water jacket, which is filled with water to within a few centimeters of the top, acts also as a seal when the cover is placed upon the apparatus. Through this double-walled jacket pass the two pipes for the ventilating air-current, a pipe communicating with the spiro- meter or tension equalizer, a small pipe for the stethoscope tube, and a small pipe to connect the pneumograph of the body-movement regis- tering device with the tambour outside. In the cover of the chamber are a window securely sealed and an opening for the air-thermometer. In discussing the details of this apparatus, it seems best to follow in a general line the course of the ventilating air-current as shown in figure 2, from the time it leaves the respiration chamber until it returns. It should be stated at the outset that the general description of the apparatus previously referred to! gives a number of details that we can not enter into here, and that at this point we will discuss only such modifications as are essential for the successful prosecution of experi- ments with infants and small animals. Psychrometer.—The psychrometer is essential for indicating the degree of moisture inside the respiration chamber. This is of value not only for the comfort or discomfort of the infant, but also for computing the amount of gas, particularly oxygen, inside the chamber at the end of the experimental period, since for these computations an exact knowl- edge of the water-vapor in the air is essential. Formerly in the large respiration chambers it was necessary to aspi- rate a definite volume of air over pumice-stone drenched with sulphuric acid and note the increase in weight. Experiments carried out more 1Benedict, loc. cit. 38 GASEOUS METABOLISM OF INFANTS. recently have shown that in a specially constructed and very delicate psychrometer the depression of the wet-bulb thermometer can be measured with great accuracy and the amount of water-vapor in the air computed with an exactness sufficient for all practical purposes. The construction of this psychrometer, Z, is very simple. Two ther- mometers, each graduated in 0.1 degree and capable of being read with a lens to 0.01 degree, are placed in the air-circuit leading from the respiration chamber. The thermometer nearest to the chamber is the dry-bulb thermometer; around the bulb of the other thermometer is lightly attached a piece of fine linen which is continually kept moist with water drawn from a small reservoir by capillary attraction. By the use of the well-known psychrometric tables, it is possible to compute from the depression of the temperature the tension of the water-vapor, the degree of humidity, and the actual amount of moisture in the air. With the large respiration calorimeters, this has been carefully con- trolled both by the aspirator method—that is, by the aspiration of a certain volume of air over pumice-stone—and more particularly by the use of the extraordinarily ingenious and accurate psychrometer' of Dr. Klas Sondén of Stockholm. The wet- and dry-bulb psychrometer as thus constructed gives most satisfactory results. It is, however, of the highest importance to make sure that the cloth around the wet-bulb thermometer is kept thoroughly drenched with distilled water, also that the capillarity of the fiber is good, as otherwise the cloth may become partially dried and inaccurate results obtained. Prior to each experiment, the wet bulb is drenched by using an elongated medicine dropper filled with distilled water. Muffier.—Since a rotary pump is used to keep the current of air in motion, which rapidly draws in successive small portions of air, a puffing sound is produced which has proved somewhat disturbing to certain infants. To eliminate this, a small muffler, N, consisting of a brass can filled with cotton batting, is placed between the psychrometer and the blower. Blower.—After experimenting with many different types of blowers, we have found the most satisfactory to be that furnished by the Crowell Manufacturing Company of Brooklyn, New York, under the specifica- tion No. O-D Rotary Compressor. This can be secured from the manufacturers in a surrounding iron box, which is suitable for an oil- immersion bath. It is a positive blower in that the air withdrawn from the chamber may be forced through a considerable number of layers of sulphuric acid and soda lime contained in suitable vessels. The blower (P) is connected by a leather belt to a small electric motor and can be provided with a safety clutch to prevent the reversing of the wheel through carelessness and the drawing over of sulphuric acid from the 1Sondén, Bihang till K. Svenska Vet.-Akad. Handlingar, 1891, 17, p. 3; see also Meteorologische Zeitschr., 1892, p. 81. APPARATUS AND METHODS USED IN THIS RESEARCH. 39 water-absorbers. This latter feature has been found of advantage, although the insertion of the safety trap (A) has prevented this. The speed of the blower may easily be altered by a simple lamp resistance, these blowers usually giving a suitable ventilation—not far from 35 liters per minute—when rotating at the speed of 270 revolutions per minute. Even with this rate of ventilation, it has been shown by careful experi- menting, with a portable alcohol lamp placed in different parts of the chamber, that there is no draft which would be noticed by the infant. The fact that the relative humidity does not become unduly low is further proof that the infant is sojourning in an atmosphere approxi- mately normal. Acid trap.—To prevent the possibility of sucking strong sulphuric acid into the delicate mechanism of the blower, an empty glass bottle (A) is inserted into the series. While almost any form of bottle can be used for this purpose, it has been convenient for us to employ an empty reversed ‘‘ Williams bottle.” Water absorber.—The air leaving the respiration chamber contains a large amount of water-vapor from the lungs and skin of the infant and from the moisture of the incoming ventilating air-current. Before the carbon dioxide produced by the infant is absorbed, it is important to remove this water-vapor entirely from the air. The current is there- fore first passed through two or more bottles containing concentrated sulphuric acid. Usually one large-sized Williams bottle (B) is sufficient to collect nearly all of the moisture, but this is followed by a second bottle (C),which retains the last traces of water-vapor.! To facilitate the hand- ling of the bottles and to prevent breakage, they are usually inclosed in a small wire basket with a handle, by means of which they may be suspended directly from a hook on the arm of the balance. When these two Williams bottles are used, it is possible to retain the first bottle in the circuit until the acid has so far accumulated as to render it liable to be carried over mechanically into the second bottle. Indeed, 100 or 200 grams of water-vapor may be absorbed; it is fundamentally important, however, to note that the second Williams bottle must not increase in weight more than 15 grams before being renewed. As a matter of experimental routine, it has been found advantageous to replace the first Williams bottle each day with another which has previously served in the quantitative absorption of carbon dioxide, replacing these bottles with new ones every other day. The second Williams bottle should be controlled by weighing every few days. Tubing and piping—The Williams bottles, as well as the soda-lime bottles for absorbing the carbon dioxide, are fitted with short lengths of rubber tubing of good quality, to which are attached respectively male and female parts of ordinary garden hose couplings of the standard 1The Williams bottles are made for us in Berlin by the Vereinigte Fabriken f. Laboratoriums- bedarf. 40 GASEOUS METABOLISM OF INFANTS. #-inch size (approximately 16 mm. internal diameter). The couplings are therefore interchangeable with different forms of apparatus. With a standard rubber hose gasket, the couplings can be made air-tight by a simple twist of the hand. All of the piping throughout the apparatus is of standard $-inch (16 mm. internal diameter) galvanized iron pipe. Two-way valve-——In order to deflect the main air-current from one set of purifiers to the other, it is necessary to have a 2-way valve, but unfortunately this can not be purchased in the open market. For this purpose we have taken an ordinary 3-way 3-inch gas cock and soldered up one of the ports, then ground it again to fit the valve body. When properly done and the valve lubricated with a little cerate or vaseline, the result is very satisfactory. The valves V; and V; are of this type. A long steel rod connects these two valves so that by throwing the handle at one valve both valves are simultaneously closed and the air-current instantly deflected from one set of purifiers to the other. Soda lime and containers.—The most effective absorbent for carbon dioxide that we have found is slightly moist soda lime. So important is the preparation of this reagent that we consider it fitting to republish the method here. The soda lime is prepared in a round-bottom iron kettle, holding about 3 liters. For this purpose 1,000 grams of commercial caustic soda of good quality are dissolved in approximately 600 c.c. of water. When completely dissolved, 1,000 grams of finely pulverized quicklime are rapidly stirred into the hot lye and the stirring continued with a long-handled iron rod. The lime is immediately slaked, a large amount of heat and steam being given off. If the operation is carried on out of doors or under a good hood, soda lime may be readily made by unskilled labor. For infants and for animals weighing not less than 3 to 5 kilograms the ordinary soda-lime containers are used (D, and D.), these being wide-mouthed glass reagent bottles of the usual type. Each bottle contains 2 kilograms of soda lime, capable of absorbing not less than 75 grams of carbon dioxide, and weighs when filled about 4 kilograms. The moisture in the soda lime is essential to its efficiency, but the air after passing through the absorbent must again be dried by passing it through the Williams bottles H, or E:. Sodium-bicarbonate can.—In order to absorb the traces of acid fumes which may remain in the air after it has been carried through the Williams bottles, it is necessary to insert in the air-circuit a small can filled with dry sodium bicarbonate (F). This completely removes the acid fumes and does not affect the determination of the carbon dioxide or of the oxygen in any way. Air-moistener.—With very small infants and with a fairly rapid flow of air, it is quite possible that the humidity inside the chamber may be too low for comfort and hence it is advisable to secure some means for APPARATUS AND METHODS USED IN THIS RESEARCH. 41 rapidly and accurately moistening the air to a suitable degree. For this purpose a Williams bottle (K), containing pure distilled water, is placed in the circuit in such a manner that, by closing a valve in the by-pass, the entire air-current may be forced through the water in this bottle or as little thereof as may be desired. Oxygen.—The direct determination of oxygen may be made either by weighing a small cylinder of gas (Z) and noting the loss in weight during the experiment or by using an exceedingly delicate and accurate gas meter. Small cylinders of compressed oxygen which can readily be weighed may be secured from the Linde Air Products Company of Buffalo, New York. These cylinders weigh when filled about 3 kilo- grams and contain about 150 grams of oxygen with a purity of about 97 per cent. The oxygen supplied by this company is made from liquid air and consequently the residual gas, instead of being nitrogen, as has commonly been supposed, is as a matter of fact in large part argon,} so that to the volume of oxygen measured, about 1 per cent should be added for the argon.” One of the greatest difficulties in using these cylinders has been the selection of a suitable valve, that furnished on the cylinder by the manufacturer being difficult to utilize owing to the high pressure under which these cylinders are filled. Formerly recourse was had to one of the numerous types of reduction valves, but a thorough test of these did not result in securing such a valve as would functionate properly for any long period of time. One or two types of needle valves have been found which are much less expensive and give a satisfactory closure. Such a needle valve is coupled to the exit of the cylinder, then closed, and the main valve on the cylinder is opened to its fullest extent. The issuing gas may then be very delicately regulated by means of the needle valve. With so high a pressure it is obvious that the packing around the main valve stem should be excellent, so as to give no opportunity for leakage of air. The valves may be tested by immersing the cylinder and valve under water or by weighing the cylinder carefully on a balance and then again an hour later, when any loss of oxygen will be instantly apparent. Gas meter—From many standpoints the use of a small weighable cylinder of oxygen is to be recommended. On the other hand there are certain advantages in favor of using an accurately calibrated gas- meter under such conditions as to preclude excessive temperature fluctua- tions. Inour experiments with infants we have almost always employed a large cylinder of oxygen with a valve, conducting the gas through a carefully calibrated meter of the type devised by Bohr and manu- factured by the Dansk Maalerfabrik of Copenhagen. This gas meter registers one liter for each complete revolution of the drum. Being 1Claude, Comptes rendus, 1909, 151, p. 752; Morey, Journ. Am. Chem. Soce., 1912, 34, p. 491. 2For a discussion of this point, see Carnegie Inst. Wash. Pub. No. 187, 1913, p. 74. 42 GASEOUS METABOLISM OF INFANTS. constructed of britannia, it may without injury be completely immersed in water in a large aquarium vessel and so leveled as to be easily read. The corrections for temperature changes are minimized by this immer- sion in water. It is not possible, of course, to control the barometric fluctuations, and the meter readings should therefore be corrected not only for the average of the temperature fluctuations obtaining through- out the experimental period, but also for the average changes in the barometer. For relatively short periods this can best be done by using the temperature readings taken at the beginning and end of the period, and the barometer readings taken at the same time. The meter is calibrated by the method of weighing the gas delivered from an oxygen cylinder.1. Many tests of this type of meter show that, when properly installed, it gives admirable results and when a long series of experiments is contemplated, its use is strongly to be recom- mended. A small, weighable cylinder of oxygen is required in either method, since such a cylinder is necessary for the calibration of the gas meter. Temperature measurements.—In the dog apparatus, the volume of air inside the respiration chamber is about 250 liters; in the infant appa- ratus it is about 75 liters. It is clear, therefore, that correct tempera- ture measurements of this air are necessary in order to determine the actual volume of the air in the chamber at the end of every experimental period. We have thus far employed two carefully calibrated mercury thermometers to measure the average temperature of the air in the chamber, one in the cover of the chamber (71), the other the dry-bulb thermometer of the psychrometer (72). While the two thermometers rarely read alike, their fluctuations in temperature are usually parallel; consequently, for lack of better measurement, the average of the readings of the two thermometers is taken as representing the average tempera- ture of the air in the chamber. Experiments are now in progress seek- ing a better record of the average temperature of the air by means of electrical-resistance thermometers. Temperature control of the respiration chamber.—The importance of temperature measurement has just been outlined, but it is likewise important to conduct the experiments so that the respiration chamber shall not be subjected to sharp and sudden fluctuations of temperature during the experimental period. It has therefore been found necessary to construct the water-jacket entirely around the chamber, except on the top. The space between the two metal walls is filled with water. During cold weather, with a mercury thermo-regulator and a small burner beneath, temperature control can be very readily secured. In the excessively warm days of summer, when the temperature of the laboratory is considerably higher than that of the chamber, it is neces- sary to place ice in the water-tank. The ice floating on the water melts 1Benedict, Physical Review, 1906, 22, p. 294. APPARATUS AND METHODS USED IN THIS RESEARCH. 43 and the cold current of water descends, thus tending to equalize the temperature of the whole system. By judicious use of i ice, a reasonably good control of the temperature can be obtained, even in the warmest weather. Spirometer or tension equalizer.—Although an absolute temperature control is theoretically possible with this apparatus, thus securing a constancy in the apparent volume of the air in the closed spect it is practically impossible to prevent slight tem- perature fluctuations, and these, together with the unavoidable and uncontrollable fluctu- ations in barometric pressure, demonstrate the necessity for some form of tension equalizer which will insure atmospheric pressure in the chamber. For this purpose a small spirometer ; (S)isused. The spirometer regularly attached to the “universal” respiration apparatus is provided with sundry devices for graphically tracing the volume of each respiration and indicating the total ventilation of the lungs when employed with adults. When the infant or dog respiration chamber is employed, the spirometer is used solely as a tension equalizer and accordingly, in figure 3, only those parts are shown which are essential to its use under such conditions. The upper part of this spirometer consists of a bell, c, constructed of very light copper or aluminium, suspended by a delicate cord, d, over a pulley, e, and counterpoised by a brass rod, g,g,g. This bell dips into a bath of water or oil in the annular space, b, between the two walls of the lower part of the spirometer. The pipe, a, connects directly with the respiration Fig. 3. Spirometer. apparatus. By noting the position of the ¢, bell of spirometer; d, suspension pointer on the millimeter scale at the right, the Sat aes ar eer exact height of the bell can be seen at any air-pipe connecting with the moment. Thereisnoparticular compensation 7*?"4t#on apparatus. device used in connection with this spirometer to allow for the variations of the metal displaced as the bell enters or leaves the liquid ; consequently there are, theoretically at least, slight alterations in the tension with the different positions so that it is advantageous to have the bell in nearly the same position at the beginning and end of each experimental period. It is our practice at the beginning of an experiment, after taking an initial reading of the height of the bell, to introduce a volume of oxygen approximately that which it is assumed that the infant will Lem eel «il beets 44 GASEOUS METABOLISM OF INFANTS. use during the period. The oxygen supply is then shut off and the bell gradually sinks. Itis highly desirable that at the end of each period the bell should always be sinking, thus in part compensating for the slight alteration in tension. More recently we have found it advantageous to move the counterpoise rod, g, g, g, up or down by hand at the exact end of the period until the very delicate petroleum manometer indicates that there is no pressure. At this point the reading is taken. Manometer.—The small oxygen consumption and the large volume of the respiration chamber with its accessory parts make the influence of slight changes in temperature and pressure of great moment in measuring the total oxygen consumption. Consequently it is essential to note the exact pressure inside the chamber. This is assumed to be atmospheric, but it is possible that the spirometer does not respond instantly to slight changes in pressure; accordingly it is more efficacious to use a very delicate manometer. This manometer (JM) is of the type employed by Pettersson and Sondén in their gas-analysis apparatus and indicates the slightest alteration in atmospheric pressure. It con- sists of a glass tube bent in the form of an are and containing a few drops of petroleum oil. Balance.—The soda-lime bottles weigh, together with the Williams bottles, approximately 6 kilograms. The necessity for determining the amount of carbon dioxide produced in a half-hour period to within 0.01 gram makes it imperative to secure a balance with a large carrying capacity and extreme sensitiveness. Such balances we have as yet been able to obtain from only one manufacturer. Fortunately they are quite inexpensive. These balances—of which there are many sizes, all of which have been tested in this laboratory—give very accurate results, for with a load of 10 kilograms 1 centigram is easily recorded. The balances are substantially mounted and surrounded by a glass case for protection against any disturbing drafts. METHODS OF TESTING THE RESPIRATION APPARATUS. The respiration apparatus just described, though extremely simple in principle, nevertheless has certain complexities. For experiments with infants, therefore, it is necessary to test completely the feasibility of the apparatus for measuring or indicating the several factors. For this purpose it is of prime importance to know that the apparatus is absolutely air-tight, so that when the cover is properly in place, no air can enter or leave the circulating air-current. Fortunately this is very readily tested in this type of apparatus. TESTS FOR TIGHTNESS. By a consideration of the diagram given in figure 2, it will be seen that the entire ventilating current is a closed circuit, the tension equal- izer or spirometer allowing it to expand or contract according to the 14, Sauter, Ebingen, Wiirttemberg, Germany. The specifications are as follows: No. 7 Ila, with aluminium beam and iron support, black enameled, in glass case, with carrying power 10 kilograms. APPARATUS AND METHODS USED IN THIS RESEARCH. 45 variations in temperature, pressure, or actual volume of air inside the system. By reading the millimeter scale over which the pointer from the counterweight of the spirometer bell passes, it can easily be seen whether or not the apparent volume of air in the chamber is altered during a test. To make such a test, all of the various parts of the apparatus are connected as in an experiment with an infant, and the ventilating air- current started. After the first moment or two, during which the air throughout the whole system will be attaining equilibrium, the bell on the spirometer should reach a constant level, and thereafter the air should remain absolutely constant unless affected by changes in tem- perature or atmospheric pressure, these being indicated by the readings of the barometer and the two air thermometers. If the changes in the position of the spirometer bell can not be accounted for by temperature or barometer changes, there is obviously a leakage of air into or out of the system, usually the latter. To test the efficiency of the apparatus and the absence of a defect in any individual part, especially when assembling the parts or when trying to locate a leak, a water manometer, consisting of two glass tubes connected at the bottom by a short bit of rubber tubing and attached to a suitable standard, is found advantageous, inasmuch as the slightest leak in any individual portion of the apparatus can readily be detected by applying pressure with a bicycle pump. When the apparatus has been properly installed, with accurately fitting rubber gaskets and connections, and suitable inspection given from time to time, there is no occasion for leakage, so that such an occurrence can invariably be ascribed to faulty technique. Since the experiments with infants instantly follow the test of the apparatus, the only disturbance there- after being the removal of the cover which fits into the water seal, it will be seen that these tests should prove an admirable index of the condition of the apparatus during the experimental period. Tests for the efficiency of the absorbing vessels.—The amount of carbon dioxide given out by the infant is determined by noting the increase in weight of the soda-lime vessel (D, or D2) with its attendant Williams bottle (EZ, or E.); the degree of absolute moisture in the air when it enters the soda-lime bottle and leaves the Williams bottle should be identical. If, however, the sulphuric acid in the Williams bottle, EZ, or E>, following the soda-lime container, is allowed to accumulate water to such an extent that its efficiency as a water-absorber is somewhat less than that of the Williams bottle, C’, preceding the soda-lime con- tainer, it is obvious that there would be a loss of water from the system as a whole and the amount of carbon dioxide thus measured would actually be too small. Conversely, if the air is not as dry before it enters the soda-lime bottle as when it leaves the Williams bottle fol- lowing, there will be an undue increase in the weight of the carbon- 46 GASEOUS METABOLISM OF INFANTS. dioxide absorbing system owing to the excess water absorbed. If the routine with the Williams and the soda-lime bottles is carried out as previously outlined, no difficulty is experienced, but it is advantageous occasionally to test the efficiency of the apparatus for absorbing carbon dioxide and water-vapor. Consequently, in testing for leaks it is advisable to weigh the sulphuric-acid and soda-lime vessels separately, and continue passing the air through the system for a half hour. Under these conditions, the loss in weight of the soda-lime vessel should of course be exactly counterbalanced by the increase in weight of the accompanying Williams bottle. With all of the experiments with infants here reported, this procedure was followed out every morning. It is needless to say that such precautions are no longer necessary, but inasmuch as this was the first year that the apparatus was used in the present form we considered it advisable to obtain this control before each experiment. ALCOHOL CHECK TESTS. The large respiration calorimeters in this laboratory have all been controlled by alcohol check tests as to their capability for measuring the carbon dioxide and the water-vapor produced, oxygen absorbed, and heat eliminated by the subject inside the chamber; we therefore hoped to secure as satisfactory control tests for this small respiration apparatus when used for infants. One of the greatest difficulties which immediately presented itself was that of developing inside the respira- tion chamber a known amount of carbon dioxide and absorbing a known amount of oxygen. A simple method for this would have been to place inside the respiration chamber an alcohol lamp and let it burn for several hours, noting the loss in weight of the lamp. It should be observed, however, that this respiration chamber is used for the most part during experiments with half-hour periods. We considered it unfair, therefore, to make an alcohol check experiment covering several hours and assume that the results showed that the apparatus would be equally as satisfactory for half-hour periods. The same problem arose in connection with the development of our first respiration apparatus for man,! and the difficulty was then overcome by burning a known amount of ether vapor. By reference to this earlier test, it will be seen that the special form of combustion chamber then used was perfectly comparable with the respiration chamber employed for infants. But the difficulties incidental to cooling the intense ether flame and making all the connections satisfactory rendered it practically impossible for us to carry out these tests in the hospital. For many years an attempt has been made to secure some method for obtaining the actual amount of alcohol burned in a small lamp inside the respiration chamber in periods as short as 30 minutes. In lieu of 1Benedict, Am. Journ. Physiol., 1909, 24, p. 372. APPARATUS AND METHODS USED IN THIS RESEARCH. 47 this ideal test, we had to content ourselves with alcohol check tests of the following character: A small lamp, which was constructed from a 100 ¢c.c. Erlenmeyer flask and partially filled with alcohol, was ignited and placed inside the respiration chamber. After a preliminary period of several minutes the air-current was deflected to the second set of purifiers, the proper readings taken, and several periods of 30 to 45 minutes each were carried out. Irrespective of the absolute amount of carbon dioxide absorbed by the soda lime or the total amount of oxygen admitted from the cylinder or measured by a meter, the relation between these two should be that obtaining in the perfect combustion of alcohol by oxygen. The respiratory quotient of alcohol, which can readily be computed, is found to be 0.666. Consequently the relationship between the amount of carbon dioxide absorbed and the amount of oxygen delivered through the meter or from the weighed cylinder was deter- mined and if this was found to be approximately 0.666, it was assumed that the apparatus was functionating perfectly. As a matter of fact, such an alcohol check test was made usually once a week throughout the whole experimental year with values varying but little from the theo- retical amount. Deferring for the moment the description of the method of calcula- tion, we give in table 16 the respiratory quotient for every alcohol check test carried out with this apparatus, the results being, for the most part, within the limits of experimental error. TasLe 16.—Respiratory quotients obtained in alcohol check experiments with the respiration apparatus for infants. Date. Quotient. Date. Quotient. Date. Quotient. 1913. 1913. 1913. Jams Sicx 0.67 Apr. 10... 0.68 June 24... 0.68 TB: 34 .68 Iisa 9 «67 206 2% . 66 16... .68 Os a 5 oF Sept. 27... 67 Shee. . 66 May 9... .67 SU s-2u -66 Boas .67 15... .68 Oct. 4... .66 Feb. 25... -66 Vea 65 Cie 67 Mar. 1... .68 DB as - 66 Qe).53 - 66 14... .69 June 5... 66 ae .67 215 .68 14... .70 Dee. 11... . 66 28... .67 18... .71 1914. Apr. 4... -65 19... .69 Jan. 1... .65 ae Y - 66 COMPLETE SHORT-PERIOD ALCOHOL CHECK TESTS. Although the observations on infants reported in this publication were based upon the accuracy of alcohol check tests involving only the determination of the respiratory quotient, it is desirable to record at this point the development of a method which provided for the testing 48 GASEOUS METABOLISM OF INFANTS. of this identical apparatus and the proof of its accuracy for measuring the results of half-hour periods after an amount of carbon dioxide had been developed approximately equal to that produced by an infant. From the experience with the large respiration chambers in the Nutri- tion Laboratory, it became increasingly evident that the discrepancies shown in the alcohol check tests for short periods were to be ascribed not to errors in the absorption of carbon dioxide or to the calculation of the amount of oxygen produced, but to discrepancies in the meas- urement of the small quantities of alcohol necessary for the control test. The alcohol required for producing (when burned inside the respiration chamber) an amount of carbon dioxide equivalent to that given off by a small infant corresponds to about 1.00 or 1.50 grams per half hour. To measure this with an accuracy of 1 per cent and to insure that the measurement represents not only the amount of alcohol introduced but the actual amount consumed, involves much experi- mental work. Mr. T. M. Carpenter, of the Laboratory staff, has recently conducted experiments in which this second difficulty has been overcome. In these experiments a small piece of capillary copper tubing was carried through the walls of the respiration chamber by means of the tube commonly used for the stethoscope, and then bent upward to form a minute lamp. The exterior end of the copper tube was connected by capillary rubber tubing to a glass burette of very fine caliber which could easily be read to 0.01 ¢.c. The burette and the capillary rubber tubing were suspended by a cord running over a pulley, so that both the burette and the rubber tubing hung free in the air. When this burette was very slowly and gradually raised, alcohol flowed with great regularity through the copper tube into the chamber, where it burned quietly. By reading the level of the alcohol in the burette at the beginning and the end of any given experimental period, the absolute amount of alcohol introduced could be accurately determined. A small wooden pulley attached to the vertical upright of a Porter kymo- graph was used for raising the burette regularly. An extremely even elevation of the burette could be secured by adjusting the speed of the rotating fan so that the amount of alcohol introduced per half hour ranged not far from 1.00 to 1.25 grams. The whole apparatus is shown in figure 4, in which may be seen the copper tube extending through the two walls of the respiration chamber, the flexible rubber tubing, one end of which is attached to the copper tube and the other to the burette, and the wooden pulley and kymograph in position to raise the burette as desired. When beginning the experiment, the lamp was lighted, the kymo- graph set in motion, and after the lamp had burned a few moments and regularity of combustion was assured, the cover was put in place. At the end of a preliminary period of not far from 15 to 20 minutes, the APPARATUS AND METHODS USED IN THIS RESEARCH. 49 level of the alcohol in the burette was accurately read and the experi- ment proper began. Thereafter it was only necessary to read this burette accurately with a lens at the end of each experimental period of 30 to 40 minutes. VY Fie. 4. Method of introducing alcohol in the alcohol check tests of respiration apparatus. The ventilating air-current was passed through the chamber at the rate of approximately 35 liters per minute, and with a flame of this size and regularity in the introduction of alcohol the amount of carbon dioxide residual in the chamber at the end of each experimental period was usually very constant. Since, however, we were dealing with quantities of carbon dioxide amounting to 0.01 gram, it was necessary in this exceedingly exact work to determine the residual amount of carbon dioxide. This was obtained by drawing a sample of the air at the end of each period, and determining the amount of carbon dioxide by means of a modified! Pettersson-Palmquist gas-analysis apparatus, which permits measurements of 0.5 or less per cent of carbon dioxide to the third significant figure. Its manipulation is very simple and has been rapidly acquired by a number of workers in the laboratory. It should be stated that these residual analyses were not required in the observations on infants at the hospital, but were necessary only to secure the greatest degree of refinement in establishing the accuracy of 1Anderson, Journ. Am. Chem. Soc., 1913, 35, p. 162. 50 GASEOUS METABOLISM OF INFANTS. the apparatus for measuring minute quantities of carbon dioxide and oxygen. Method of computing the carbon-dioxide production.—In these alcohol check experiments, the carbon-dioxide production is found by weighing the soda-lime container with its accompanying Williams bottle, the increase in weight giving the amount of carbon dioxide produced during the period, assuming no change in the amount of carbon dioxide residual in the chamber. If extreme accuracy is desired, determina- tions of the residual amount of this gas are made as outlined above and any variations corrected for. Method of computing the oxygen consumption.—The computation of the oxygen consumption is much more elaborate than that of the carbon-dioxide production, for while a rough measurement of the total oxygen consumption can readily be obtained by noting the loss in weight of the cylinder of gas or by reading directly the volume of gas passing through the Bohr meter, there are nevertheless a number of factors which affect these determinations, all of which must be taken into consideration. For example, the spirometer bell is at a certain height at the beginning of an experiment; if at the end this bell is either above or below this point, a correction therefor must be applied. If above, an excessive amount of oxygen has been added, and if below, the amount of oxygen is deficient. As each millimeter difference in the height of the spirometer bell corresponds to 23 c.c. of gas, the com- putation is very simple. On the other hand, if there is an increase in the temperature inside the chamber, the air expands and even if the spirometer bell is in the same position at the end of the period as at the beginning, less oxygen has evidently been introduced than if the tem- perature had remained constant. Conversely, if the temperature has fallen, more oxygen has been introduced. Similarly, if the barometric pressure has altered materially, it has likewise affected the introduction of the oxygen. For an exact computation of the amount of oxygen consumed by the subject, therefore, not only is it necessary to know the amount introduced from the weighed cylinder or through the Bohr meter, making due corrections on the readings of the gas meter for the factors of temperature and pressure and the mechanical factor of the meter itself, but likewise a correction for the alterations in the total volume of air inside the ventilating air system should also be made, since any alteration of the volume of the air inside the system represents a corresponding error in the oxygen introduced. For this purpose, it is necessary to note, first, the volume of air inside the chamber, which is roughly found by a simple computation; second, the temperature of the air in the chamber as shown by the readings of the two thermometers; third, the barometric pressure; fourth, the degree of humidity as obtained from the wet- and dry-bulb psychrometer, since the water-vapor in the chamber may also vary ; and fifth, in exceed- APPARATUS AND METHODS USED IN THIS RESEARCH. 51 ingly refined experimenting, the amount of carbon dioxide present in the residual air. The protocol of a single alcohol check test by this later quantitative method may serve to illustrate simultaneously the method of calculation and the accuracy of the apparatus. DETAILS OF TYPICAL QUANTITATIVE ALCOHOL CHECK TEST. Measurement of the residual carbon dioxide and oxygen.—This experi- ment consisted of two periods, the first from 115 30™ a. m. to 125 11™ p. m., and the second from 125 11™ p.m. to 12851™p.m. At the begin- ning and end of each period of the experiment, observations were made of the humidity conditions, the temperature of the apparatus, and the barometric pressure. By means of these observations and the deter- mination of the carbon-dioxide content of the air in the chamber, the volumes of oxygen and nitrogen and of the carbon dioxide residual in the apparatus were obtained for the standard conditions of 0° C. and 760 mm. pressure. The observations made at the end of the first period are given in table 17. TaBiLe 17.—Observations at end of first period of alcohol experiment of October 9, 1913. Psychrometer: Dry bulb (é) 19.80° C.; wet bulb (t) 15.91° C. Temperature at top of chamber (f,) 21.63° C. Temperature of apparatus (t,): 4 = 19.80°C.; t, = 21.63°C.; average, (t,) 20.72° C. Barometer: Reading at end of period.............. 767.05 mm. Tension of aqueous vapor in chamber... 11.10 mm. Corrected barometer (p)........ 755.95 mm. Residual carbon dioxide and oxygen: Logs. Total volume of apparatus..... 81.5 liters = 91116 1 Temperature of apparatus..... 1-10.00367 t = 96817 Corrected pressure............ za = 99768 Corrected volume COz + O2 + No.........655 = 87701 = 75.364 liters. Per cent CO, (by analysis) 0.098 ............. = 99123 Residual CO gisele distis atin eo eeniiniaenedanteun wares = 86824 = 0.07 liter. Residual Op + Nav... cece cece cece cece tence eee eeeennee 75.27 liters. The temperature of the air in the chamber of the apparatus was not determined with absolute certainty. The thermometer placed in the top of the apparatus (¢, in table 17) recorded temperatures which, because of the position of the lamp and the warm air rising to the bulb of the thermometer, were without doubt too high. The record obtained from the dry-bulb thermometer (é, of table 17) shows the temperature of the air immediately after it left the chamber. It is believed that the average of these two records (20.72° C. in table 17) gives an approximate value for the temperature of the air in the appa- ratus at the time the records were made and that the change in tempera- ture from the beginning to the end of the period may by this means be obtained. 52 GASEOUS METABOLISM OF INFANTS. The barometer record in millimeters is also shown in table17. From the psychrometer observations the humidity of the air within the appa- ratus is known. Deducting from the barometric pressure the tension of aqueous vapor (11.1 mm.) for this observed humidity, allowance is made for the volume of water-vapor present within the apparatus. The corrected barometer reading, 7, is then used. The total volume of the apparatus is 81.5 liters. In order to deter- mine the total volume of water-free air under standard conditions of temperature and pressure, 7. e., 0° C. and 760 mm., to the logarithm of this total volume is added, first, a logarithmic factor for the average temperature recorded and, second, a logarithmic factor for the corrected pressure. These factors are obtained from tables which have been prepared for the purpose. The standard temperature reduction is rep- resented by the formula a t, representing the temperature of the ‘4 apparatus. The reduction factor of pressure for standard conditions is obtained from the ratio a0) in which p represents the corrected barometer. The total volume of oxygen and nitrogen is then obtained from the total volume of water-free air by deducting the volume of carbon dioxide as determined by the analysis with the Pettersson- Palmquist apparatus. No attempt is made to separate the volume of nitrogen, since the amount of this gas remains unchanged and the absolute amount of oxygen is not desired. Measurement of the carbon dioxide absorbed and the oxygen admitted.— The records of the carbon-dioxide production and oxygen consumption for the first period of the experiment are given in table 18. The carbon Taste 18.—Carbon dioxide absorbed, oxygen admitted, and alcohol burned in the first period of alcohol check experiment. Oxygen admitted. Alcohol burned. Weights of oxygen cylinder: One gram 92.56 p. ct. absolute alcohol yields Mier ds yy keameeen 3408.41 gm. 1.769 gm. CO: and requires 1.930 gm. O». ENG 22s pase seeer es 3405.00 gm. O2 = 3.41 gm. Impurity correction....... —.01 gm. | Burette readings: Spirometer correction...... -—- .03 gm: 115 30™a.m.... 0.590 cc. _— 12 11 p.m... 2.770 ex. Total Oo = 3.37 gm. ———. Difference..... 2.180 c.c. at 21.05° C. = ° Carbon dioxide absorbed. 2.169 c.¢, at 15.6° C. Weights of absorbers, G+44: 2.169 c.c. (sp. g. 0.81576) = 1.769 grams Wad) soarav weed teks ee 5125.90 gm. (C2H;OH). Start. pactvas tice soeas 5122.78 gm. 1.769 X 1.769 = 3.13 gm. CO: produced. 1.769 XK 1.930 = 3.41 gm. Oz» used. CO, = 3.12 gm. 1The calculations are here made on weight. For a method of determining the oxygen con- sumption by volume, see Benedict, Deutsch. Archiv f. klin. Med., 1912, 107, p. 181. APPARATUS AND METHODS USED IN THIS RESEARCH. 53 dioxide absorbed from the ventilating air-current was determined from the amount collected in the absorbing vessels, which were weighed at the beginning and end of each period. The amount of oxygen admitted to the apparatus was found from the change in weight of a cylinder of oxygen, which was also weighed at the beginning and end of each period, correction being made for the known impurities contained in the oxygen. Correction was also made for the change in volume of the spirometer, which, in the period represented by table 18, rose 1 mm. corresponding to 23 c.c. or 0.03 gram of oxygen. This, for convenience, is deducted from the corrected amount admitted from the cylinder. Measurement of the alcohol burned and the calculation of the products of combustion.—The records of the alcohol burned and the calculation of the products of the combustion during the first period of the experi- ment are also given in table 18. The alcohol used in this experiment was 92.56 per cent ethyl hydroxide by weight, the combustion pro- ducing 1.769 grams of carbon dioxide for each gram of alcohol burned and requiring 1.930 grams of oxygen for the oxidation. The readings of the burette at the beginning and end of the period were respectively 0.590 c.c. and 2.770 c.c. at the average temperature of 21.05° C., or 2.169 c.c. at 15.6° C. The multiplication of this amount by the specific gravity at 15.6° C. (0.81576) gives 1.769 grams as the weight of alcohol burned. This amount, in turn multiplied by the factors 1.769 grams for carbon dioxide and 1.930 grams for the oxygen, gives respectively the theoretical amounts of carbon dioxide produced and oxygen con- sumed as a result of the combustion. Comparison of the theoretical amounts of carbon dioxide produced and oxygen consumed with those measured by the apparatus.—The amounts of carbon dioxide produced and oxygen used as measured by the appa- ratus are found by correcting the amounts of carbon dioxide absorbed and the oxygen admitted for the change in the residual amounts present in the chamber. Comparison ofthe amounts found with the theoretical amounts as calculated from the weight of alcohol burned shows that for the entire experiment 98.7 per cent of the carbon dioxide produced was measured and 100 per cent of the oxygen used. The comparison is given in table 19. As supplementary evidence on the alcohol check tests, measurements made in four other experiments with the baby respiration apparatus and one check test of two periods with another respiration apparatus of exactly the same type but used for dogs are presented in table 20. In considering the data for the experiment with the dog respiration apparatus, it should be stated that the volume of air in the chamber is over three times as large as the volume of air in the baby respiration apparatus; hence the errors incidental to accurate oxygen determinations are greatly magnified. In spite of this, however, it can be seen that the results for both forms of apparatus are very satisfactory, showing that 54 GASEOUS METABOLISM OF INFANTS. measurements having a high degree of accuracy may be secured with either. At this point emphasis should be laid upon the necessity of selecting a chamber of suitable size for the animal or the individual to be studied. The chamber having the smallest inner dimensions compatible with the comfort of the subject is to be preferred. TaBLE 19.—Summary of measurements in alcohol check test of October 9, 1913. Carbon dioxide. Oxygen. Respi- Resid- | Carbon dioxide | Resid- ratory | Carbon AAD ual in produced. ual in Oxygen used. quo- | dioxide. Oxygen. cham- cham- tient. ber. |Found.| Theory.| ber.! | Found.} Theory. First period.| gram. | grams.| grams. | liters. | grams.| grams. p. ct. p. ct 115 30™a.m.| 0.20 ‘ Reese 75.30 7 ee || SES 115 307 a.m. to 12 11™ p.m. .15 3.07 3.13 oT 3.41 3.41 0.65 98.1 100.0 Second period. 12 11™ p.m. to 125 51™ p.m. .20 2.96 2.98 75.18 3.25 3.25 .66 99.3 100.0 Total...J .... 6.03 GiTh > avnseas 6.66 6.66 - 66 98.7 100.0 1Residual oxygen + nitrogen. TaBLE 20.—Summary of measurements in alcohol check tests of the baby respiration apparatus and the dog respiration apparatus. (Carbon dioxide ; Percentage produced. Oxygen used. Respi- found. Date. Apparatus and time. ratory . 3 | s/s] 6 ime] as | g g 3 g S tients. 2 g sa 5 a } a 8 Fy HH Fe H os 6 1913. Baby. gm. gm. | gm. gm. Sept. 30 | 25 23™ p.m. to 2553™p.m.| 2.20 | 2.22 | 2.44 | 2.42 | 0.655] 99.1 | 100.8 2 53 a 23 2,24 | 2.30 | 2.49 | 2.51 | 0.655 97.4 99.2 a 23 3 49 1,88 | 1.93 | 2.05 | 2.10 | 0.655 97.4 97.6 Baby. Oct. 4 |12549™p.m. tol" 20™p.m.| 2.33 | 2.31 | 2.57 | 2.52 | 0.660 | 100.9 | 102.0 1 20 . oo 2.15 | 2.19 | 2.39 | 2.39 | 0.655 98.2 100.0 Baby. Oct. 7] 1542™p.m. to 2h18™p.m.| 2.70 | 2.76 | 2.94 | 3.01 | 0.665 | 97.8 97.7 2 18 2 54 2.66 | 2.69 | 2.87 | 2.93 | 0.670 98.9 98.0 Baby. Oct. 9 | 3518"p.m. to 358™p.m.| 2.65 | 2.61 | 2.86 | 2.85 | 0.675 | 101.5 | 100.4 3 58 4 38 2.58 | 2.64 | 2.82 | 2.88 | 0.665 | 97.7 97.9 Dog. Sept. 26 | 8553™ a.m. to 95 33™a.m.| 2.92 | 2.99 | 3.22 | 3.26 | 0.660 97.7 98.8 9 33 10 13 2.79 | 2.83 | 3.06 | 3.09 | 0.665 98.6 99.0 APPARATUS AND METHODS USED IN THIS RESEARCH. 55 METHOD OF DETERMINING THE DEGREE OF MUSCULAR REPOSE. The intimate relationship between minor muscular activity and metabolism was soon recognized in experimenting with men in the large respiration calorimeter at Wesleyan University, Middletown, Connecticut, and all of the earlier publications of researches with this apparatus accentuate the importance of having a regular life routine throughout the experimental period. The first attempt to secure such regularity was the preparation of a program for each experiment, to be rigidly adhered to by the subject. This was followed by a record, made directly on the protocol sheets, of both the major and minor muscular movements which were noted by the physical observer through the window of the respiration calorimeter—a routine that was carried out for a number of years in all of the experiments. In the later experiments made at the Nutrition Laboratory in Boston, a pneumograph was placed about the chest of the subject, primarily to record the respiration and the pulse-rate. These curves showed not only the rise and fall of the chest in respiration, but also any other muscular movements of the subject. This record was the first step towards a graphic representation of muscular activity during metabolism experi- ments, and played a very important part in an extensive research on dia- betes! in comparing the metabolism of normal individuals and diabetics. APPARATUS USED IN THE RESPIRATION EXPERIMENTS. The success of this method of graphic registration in experiments on man led to the development of a method for the registration of the movements of animals. The first apparatus used in this laboratory was that devised by Benedict and Homans,’ in which one end of the cage containing the animal was supported by a knife edge and the other by a stout spiral spring; the slightest change in the center of gravity of the animal changed the tension upon the spiral spring, causing the suspended end of the cage to move up or down. By means of a rod connected with the end of the cage and carried out through the top of the chamber, the movements of the cage were traced directly upon a kymograph. The mechanical difficulties of passing this rod through the cover of the chamber, which must be air-tight, were overcome, but later a tube pneumograph was substituted. This pneumograph was attached to the cage and the wall of the chamber parallel to the spiral supporting the free end of the cage. The slightest lengthening or shortening of the pneumograph produced a change in the tension of the confined air, these varying air tensions being transmitted by a tube through the walls of the chamber to a delicate tambour and pointer which gave graphic records on a kymograph drum. 1For a reproduction of these curves, see Benedict and Joslin, Carnegie Inst. Wash. Pub. No. 136, 1910. . 2Benedict and Homans, Am. Journ. Physiol., 1911, 28, p. 29. 56 GASEOUS METABOLISM OF INFANTS. This method proved admirable for use with animals and was subse- quently added by us to the respiration apparatus for infants. We have in an earlier publication pointed out the advantages of securing such records and have likewise given some characteristic tracings. The same principle has been applied to the bed calorimeter in use in the Nutrition Laboratory.2 For this apparatus, however, we have recognized the fact that while infants when moving usually change the center of gravity lengthwise of the body, the muscular movements of adults are apt to be in a lateral rather than a longitudinal direction, so that the center of gravity is changed across the body. Accordingly the knife edges are placed on one side of the bed and spiral springs on the other when used for adults, rather than at the foot or head as when used with the crib or cage for infants or animals. Certain details of the crib suspension have already been given in figure 2, but the exact connection between the crib and the tambour is shown in figure 5. One end of the crib, L, rests on a knife edge, O, while the other is supported by the spiral spring, M. A tube pneu- mograph, NV, has its lower end attached to the crib, the upper end being fastened to a stout support soldered to the wall of the respiration chamber. The changes in tension of the air in the pneumograph are transmitted through the tube to a tambour, P, whose pointer traces the record upon the kymograph drum. A glass tee, 7, with rubber tube and pinchcock, serves to equalize the tension in the tambour if there should be any permanent contraction or distention of the pneumograph. The careful and frequent testing of both the pneumograph and the tambour for tightness is of practical importance. The pneumograph being inside the respiration chamber, and connected by a rubber tube to the outside, would obviously furnish a path for leakage of air out of the chamber, provided a leak in both the pneumograph and tambour should occur. Tests are readily made by immersing them in water and employing slight pressure with the mouth on the connecting rubber tube. The pneumograph is of the type regularly furnished by the Harvard Apparatus Company, but for use in the infant chamber it is somewhat shortened. The tambours, which are likewise supplied by the Harvard Apparatus Company, are covered with very delicate tambour rubber, which is liable to deterioration and should thus be frequently renewed and tested. 1Benedict and Talbot, Am. Journ. Diseases of Children, 1912, 4, p. 129. 2After the observations reported in this publication had been completed, information was received from Dr. Paul Roth, of Battle Creek, Michigan, that in recording the body movements of men or women lying on beds, he had replaced the pneumograph with a small Politzer bulb, so adjusted as to be somewhat compressed by the bed frame. The bulb was connected to the tambour and kymograph. Preliminary tests made in the Nutrition Laboratory with the Politzer bulb arrangement have shown that the results of the variation in pressure on the Politzer bulb by variation in muscular activity are most satisfactory, not only with adults but also with small animals—a fact of special interest in connection with the research on infants. Two serious objections to the pneumograph, 7. e., the danger of leaks through the rubber and the difficulty of renewing the rubber, are thus obviated by the use of this bulb. A flexible rubber bulb of small size is best used. APPARATUS AND METHODS USED IN THIS RESEARCH. 57 A major change in position of the body of infants during the respira- tion experiment is not ordinarily to be expected. With animals there may be a change in the center of gravity of the body from one part of the cage to the other, and consequently a distension or shortening of the pneumograph with a corresponding increased or decreased ten- sion on the tambour. Under these conditions it has been found advan- Hay lyrblye tpl | Fic. 5. Method of obtaining graphic record of muscular activity. L, crib; O,"knife-edge support; M, spiral spring; N, pneumograph; P, tambour; 7’, tee for equal- ‘izing tension; H, cover of apparatus; K, water bath; G, ingoing air-pipe; G’, outgoing air-pipe. tageous to place in the rubber tube leading from the respiration chamber to the tambour a glass tee tube, with a short rubber tube and pinch- cock on the open end. When the animal or infant has permanently or temporarily settled down in a new position and the tambour shows a distension or contraction, by opening the tee tube the normal pressure can again be secured and the curves will proceed at the normal level. 58 GASEOUS METABOLISM OF INFANTS. For the graphic record we have used extensively the simple Porter kymograph manufactured by the Harvard Apparatus Company, the most advantageous speed of rotation corresponding to one complete revolution of the drum in about 30 minutes. It has been found desirable to precede the experiment with a test of the sensitivity of the apparatus for giving a good graphic record of the movements of the crib to make sure that the tambour rubber is intact and that there is a reasonably constant tension upon the tambour. For this purpose a weight is placed in the center of the crib approxi- mately equivalent to the weight of the infant upon whom the observa- tions are to be made. The tambour and pneumograph are then con- nected as usual and the kymograph set in motion, the speed being the same as that used in the experiment following. A 50-gram weight is next dropped from a definite height (21 cm.) so as to strike the crib a blow at a certain distance (32 cm.) from the knife-edge bearing upon which the crib rests. This imparts a slight impulse to the whole suspended system and a series of vibrations takes place. The ampli- tude of the vibrations as well as the number of the vibrations which continue after the first impulse indicate the sensitivity of the apparatus. This test is of great significance, accompanying as it does the kymo- graph record for each experiment and proving positively that the recording apparatus is in excellent condition. It also gives a rough estimate of the degree of muscular activity and the true value of the magnitude of the excursions of the pointer as the result of any restless- ness on the part of the infant. The tambour was usually adjusted in the observations with infants so that the distance between the end of the writing point and the center of the tambour rubber was 190 mm. and from the center of the tambour to the fulerum 25 mm.; all of the magnifications were there- fore on the same basis. The curves may be made to show motions that would otherwise be imperceptible to the eye by altering the magnitude of the multiplication and the sensitivity of the apparatus. For example, it has frequently been observed with both dogs and infants that when the animal or the infant is very quiet, even the slight change in the center of gravity produced by the respiratory movement has been sufficient to give a clear and regular record of the respiration- rate. Ordinarily such a degree of sensitivity is not at all necessary and is not regularly employed. A typical kymograph curve, which was obtained with D. M. on March 26, 1913, is given in figure 6. This also shows a record of the sensitivity test which preceded the experimental periods. The vibra- tions of the crib after the weight had fallen are shown by typical curves which gradually decrease; the small disturbances of the line following, also resulting in curves, are due to the lifting of the weight. After the first test, the speed of the kymograph was increased and three tests were made at the higher rate of speed. }NO ploj APPARATUS AND METHODS USED IN THIS RESEARCH. 59 The apparatus was so sensitive that even the slight movements due to respiration are clearly indicated, especially in the quiet period between 45 12™ p. m. and 4"45™ p.m. It will be seen by this curve that there were several major changes in the position of the infant’s body which resulted in a total displacement of the level of the curve. Shortly afterward, air was released through the tee tube and the pointer was brought back to the original level. In any attempt to quantify the values of the different periods, these displacements of the curve due to major movements should be taken into consideration. A move- ment may not be sufficiently great to produce a considerable amplitude of the pointer and yet be produced by ashifting of the whole body, thus establishing a new, permanent center of gravity of the system. Obvi- ously, in this case, a greater displacement could reasonably be supposed to have taken place than when the line returned to the same level. It should be stated that the ocular method of observation of infants or animals during respiration experiments is most illusive and unsatis- factory. We have repeatedly seen experimental periods when a careful observer, even though watching the infant continuously, was unable to record a perceptible movement other than those of respiration, and yet the suspended crib, pneumograph, and tambour have recorded distinct and persistent muscular tremors, accompanied in all cases by an increasing pulse-rate and increased metabolism as measured by the oxygen consumption and the carbon-dioxide production. While, there- fore, careful ocular observations, such as were made in the earlier experimenting at Wesleyan University in Middletown, Connecticut, are of great value in interpreting the gross metabolism, for extremely accurate observations the graphic method alone insures scientifically exact results. It is furthermore obvious that the sensitivity of the graphic method makes the continuous attention of an observer unnec- essary, as the record of body movement is directly written without bringing the personal equation in any way into play. WARD CRIB RECORDER. The relationship observed between the graphic tracings of the muscu- lar activity and the katabolism indicated the possible value of recording the activity of the infant throughout the day when it was not inside the respiration chamber. Accordingly, to assist in settling some com- plicated problems of nutrition, a special apparatus was devised and set up in the children’s ward of the hospital in order to obtain a con- tinuous graphic record of the muscular activity of the infant. This apparatus, which was designated the ‘‘ward crib recorder,”’ consisted of a small crib, one end of which rested on two hardened steel points and the other was suspended by a strong spiral spring. The movements of the crib due to the activity of the infant were graphically 60 GASEOUS METABOLISM OF INFANTS. recorded by means of a pneumograph, tambour, and kymograph as used for the same purpose with the respiration apparatus (see figure 7). For these 24-hour observations, the kymograph was set at a very much slower speed than in the short-period observations with the respiration apparatus to avoid the necessity of changing the kymograph frequently. The curves were therefore not so sharply defined as those secured when the infant was in the respiration chamber. Numerous curves were obtained with the ward crib recorder during the winter of 1913. The kymograph was adjusted by the nurses in charge, often- times during the night, so that certain irregularities in the time record are to be expected. When the infant was removed from the crib for bathing, nursing, or any other cause, the kymograph was of course stopped and a break in the record occurred. Such records as these, which were frequently obtained with infants who were supposed to be lying quietly in the crib throughout the night, are particularly helpful in estimating the needs for energy. More recently another form of this recorder has been devised and successfully used. In this later apparatus the adjustment of the crib by means of the spiral spring remains the same. Instead of using the pneumograph and rubber tambour, however, the measurements and manipulation are simplified by substituting an ordinary mechanical counter. This consists of a small revolution counter, such as a Veeder counter, to the axle of which is attached a thin aluminium wheel 119 mm. in diameter, with a milled edge. A lever and spring pawl are attached to this toothed wheel in such a way that each upward move- ment of the crib causes the wheel to move slightly in the direction of the hands of a clock. As the crib returns to its original position, any back movement of the wheel is prevented by a second pawl fast- ened to the base of the recording device, but the spring pawl which engages in the teeth of the wheel slides back to its original position without material resistance. Since every upward movement of the crib produces a rotary motion of the wheel, it will be seen that the total movement for any period can be obtained from the number of revolutions of the wheel as recorded by the counter. The wheel is divided into 10 equal divisions and provided with a pointer, so that the readings may be obtained in hundredths of a revolution if desired. The details of the later device are shown in figure 8. Two curves obtained with this form of the ward crib recorder are given in figure 9, one of these being for a very restless infant, J. P., November 14-15, 1913, and the other for one much less restless, M. A., November 17-18, 1913. With the restless infant, the toothed wheel made 18.4 complete revolutions during the period from 6 p. m. to 7 a. m. In the curve obtained with the less restless infant, the wheel made 5.2 complete revolutions in approximately the same time, 7. ¢., from 5 p. m, to 7 a. m. Fig. 7. Ward crib recorder. Fig. 8. Revolution counter used in later form of the ward crib recorder. [batch GOOP.M, APPARATUS AND METHODS USED IN THIS RESEARCH. 61 As yet no attempt has been made to measure the amount of increase in metabolism incidental to one complete revolution of the wheel, and it is a question whether quantitative values can be obtained with this device, especially for the comparison of results with different infants. But this method, which is inexpensive and simple, gives a general index of the degree of restlessness or muscular repose of infants, which should prove of value for ward use. This has already been shown in our more recent observations. 7OOAM J.P NOV. 14 = NOV.15,1913 At Ul by ae i ford | ees M.A, NOM.17 — NOV.18, 1913. Fie. 9. Typical kymograph curves obtained with the ward crib recorder. METHOD OF RECORDING THE PULSE-RATE. Previous experiments with adults in the Nutrition Laboratory, in which the large respiration chambers were used, showed a striking relationship between the pulse-rate and the metabolism. Attempts were accordingly made to secure accurate pulse records in our observa- tions with infants. For this purpose we attached the bell of a small Bowles stethoscope to the infant over the apex beat of the heart by means of strips of adhesive plaster. A rubber tube connecting with the bell led to a pipe in the wall of the chamber, a piece of rubber tubing and the earpieces being attached to the outer end of the tube. Even with a total length of some 2 or 3 meters from the bell to the earpieces, it was possible to count the pulse-rate of the weakest infant. Since here again there is a direct connection between the inside of the chamber and the outside air, it is of the highest importance that the stethoscope and the rubber tube leading from it be tested for tightness. For this test, the stethoscope bell is immersed in water, and a slight pressure is put upon the diaphragm by blowing through the rubber tube. If it is not found absolutely tight, a thin coating of vaseline on the edge of the diaphragm usually insures a complete closure. The importance of these pulse observations is so strongly impressed upon us that a special assistant is at present detailed in all of the experi- ments with infants for the sole purpose of recording the pulse-rate. The major muscular movements of the infant and any abdominal or chest sounds, such as grunting, sneezing, coughing, etc., may readily be heard through the stethoscope-and are likewise regularly recorded upon the protocol sheet. It is also perfectly feasible to secure the respiration-rate in this way from time to time. 62 GASEOUS METABOLISM OF INFANTS. We are far from satisfied with this as a permanent method for securing a record of the pulse-rate, and it is our hope, in connection with the hospital or with the laboratory, to secure records either with the string galvanometer or with the Bock-Thoma oscillograph. It is clear that the records of the pulse-rate should be more objective than they can be even with a specially detailed assistant. During the experi- mental period, it is necessary to have the room absolutely quiet, and hence the assistant is not distracted by extraneous sounds. We regret, however, that a better method was not at the time practicable for recording a factor which is of such great significance in determining the general tonus of the body and therefore the basal metabolism. GENERAL TECHNIQUE OF RESPIRATION EXPERIMENTS WITH INFANTS. Previous to an observation, the length of the baby was measured by placing it upon a board with a head-board at right angles and a sliding foot-board. Subsequent to May 1, 1913, the infant was measured while flat on his back. Measurements were likewise taken of the cir- cumference of the head above the ears, the chest over the nipples, and the abdomen over the umbilicus, as well as the greatest circumference of the thighs and the calves. The baby was also weighed naked. The rectal temperature was taken and recorded and the baby was given its food, except in certain instances when boiled water sweetened with saccharine was substituted. The infant was then immediately taken to the room in which the respiration chamber was placed. Preliminary to the respiration experiment, the kymograph was wound, the wet bulb of the psychrometer thoroughly moistened with distilled water, the tambour tested under water to make sure that there was no defect in the rubber, and the pneumograph likewise tested for tightness. A sensitivity test of the apparatus was then made as previously described. In the bottom of the crib a small mattress or folded blanket was laid. The stethoscope was next prop- erly adjusted by means of small strips of adhesive plaster and as soon as the infant was placed in the crib, the stethoscope tube Was connected with the copper pipe in the wall leading to the earpieces outside. If the crib did not swing freely, the tension of the spring could readily be adjusted by raising or lowering a screw. In most instances, after placing the infant in the crib, it was found advantageous to pin the blanket in which it was wrapped at both the top and the bottom in the same manner that infants are wrapped when they are put to bed. The cover of the apparatus was then put on, the thermometer inserted in the top, the window covered with a black cloth, the ventilating current set in motion, and the time recorded. The usual preliminary period sometimes lasted a considerable length of time, for it is obviously unwise to begin the first period of observation until the infant has been quiet for at least 15 minutes. The tempera- APPARATUS AND METHODS USED IN THIS RESEARCH. 63 ture of the water in the water jacket around the chamber was recorded and, if necessary, controlled by cooling during the period until the air inside the chamber, as recorded by the thermometer in the cover and by the thermometer in the outgoing air, had a temperature not far from 20° C. During this preliminary period, the air-current passed through one of the two sets of purifiers, the other set having previously been weighed and connected into position ready for use. Just prior to the end of the period, air was allowed to escape through a pet-cock in the system until the bell of the spirometer was about 30 mm. above the lowest point; the spirometer was then about half filled with oxygen, ‘thus avoiding any possibility of there being a deficiency in the oxygen content of the air. While the rate of ventilation should be approxi- mately constant, 7. e., about 35 liters a minute, it is practically impos- sible to regulate this unless a very constant electrical current is available. With the Crowell blower, as here used, about 270 revolutions a minute gives a suitable ventilation. When the infant was perfectly quiet and the preliminary period was nearing the end, records were made of the readings of the wet- and dry- bulb thermometers, the thermometer in the top of the chamber, and the thermometer showing the room temperature. Air was then released from the system through the pet-cock until the spirometer pointer read about 30mm. Inasmuch as there is a slight tension due to the uncom- pensated spirometer bell, the counterweight of the spirometer was taken in the hand and the bell gradually raised until the delicate petroleum manometer read zero. While the valves were turned to deflect the air-current from one set of air-purifiers to the other, the manometer was held at zero and the readings of the spirometer level taken imme- diately before and afterward. The beginning of the new period was marked on the kymograph record by the assistant, who then recorded the barometer reading and the temperature of the barometer. The readings on the oxygen meter having previously been taken or the oxygen cylinder carefully weighed, about one-half liter of oxygen was introduced or even more if the infant was very large or restless. This of course raised the spirometer bell. By determining the time in which the infant utilizes the half liter of oxygen, the oxygen supply can be regulated with considerable exactness, so that the spirometer reading will be nearly the same at the beginning and end of each period. The length of a period of observation depends altogether upon the muscular repose of the infant, as only quiet periods, accompanied by a low pulse-rate, are of value. With a small, quiet infant, the periods may vary in length from 20 to 30 minutes, but with a large infant they may be as short as 15 minutes. About a minute and a half before the close of the period, the dry- and wet-bulb thermometers were again read, also the thermometer in the cover of the chamber, and the temper- ature of the room was recorded. The manometer was then adjusted 64 GASEOUS METABOLISM OF INFANTS. to zero, the spirometer read, and the valves turned, thus deflecting the air through the original set of absorbers, which in the interim had been weighed and again connected. In the middle of the period, a test for possible unabsorbed carbon dioxide was made by deflecting a small part of the air-current for a few moments through a solution of barium hydroxide in a small flask, returning the air to the system again to insure no loss of air from the chamber. Throughout the entire period of observation, the pulse-rate was recorded every two minutes by a nurse, who made this her sole duty. Likewise other body movements distinguishable by means of the stetho- scope, such as coughing, crying, or a deep breath, were noted and an occasional record made of the respiration-rate, which was counted directly from the stethoscope. Occasionally the observations had to be interrupted because a change in position of the baby displaced the stethoscope and the pulse-rate could no longer be counted. Under such conditions, it was necessary to remove the cover of the chamber and reapply the adhesive plaster. The stethoscope caused the baby no discomfort at any time. The ward records were consulted to determine the normal or minimum normal pulse-rate and when the record reached this point and the kymograph showed that the infant was quiet, a period was started. At first the infant was observed through the window in the cover of the apparatus to see whether or not he was quiet, but in many instances it was found that infants which appeared absolutely quiet to the eye showed slight movements on the kymograph and the pulse-rate remained high. The visual estimation was therefore discontinued as being too inaccurate and unreliable a record of the degree of quiet. The conduct of such an observation as has been outlined is not unlike the actual technique involved in a short-period alcohol check test, although the results of the short experimental periods with an infant are by no means as satisfactory. The temperature distribution throughout the chamber is more uneven in observations with infants; furthermore, the slightest movement of the infant may so disturb the temperature equilibrium that at the end of the period the temperature will be some- what different from that at the beginning. Such changes, of course, affect the determination of the oxygen; as a result, the respiratory quotients for successive periods do not often agree. It is perfectly feasible, however, to determine the respiratory quotient during the entire period that the infant is inside the respiration chamber, inde- pendent of whether the subject is quiet or restless; as so determined, the respiratory quotient is an accurate indication of the character of the combustion. On the other hand, the determinations of the carbon dioxide for each individual period are extremely exact. It is possible, therefore, to utilize the carbon-dioxide measurements as an index of the total katabolism for each individual period and the respiratory APPARATUS AND METHODS USED IN THIS RESEARCH. 65 quotient for the whole sojourn inside the chamber as an index of the character of the combustion. It is thus perfectly logical to compute the indirect calorimetry from the measurements of the carbon dioxide and the calorific value of carbon dioxide for the particular respiratory quotient determined at the time. This is the exact reverse of the method employed by Zuntz, who measures the oxygen consumption with great accuracy and computes the heat-output by indirect calorimetry, using the calorific value of oxygen with the various respiratory quotients. Theoretically either method gives reliable results and is without criticism. On the other hand, in experiments made with the respiration chamber, a rapid change in the value of the respiratory quotient is always possible. This is particularly true after feeding, since there may be a considerable rise in the respiratory quotient immediately after the food is taken, followed by a relatively rapid fall, thus materially affecting the indirect determination of the heat-output. Strictly speaking, therefore, the respiratory quotient should be determined for each individual period. As a matter of fact, in observations made a considerable time after the food had been taken, the respiratory quotient would remain relatively constant throughout the whole period of an hour or an hour and a half. In most of our observations the measurements of oxygen did not begin until some time after food was taken, and the preliminary period is not considered in our discussion of the respiratory quotient. While a gradual falling of the quotient would be expected as the time increased after food was taken, we have every reason to believe that, with the conditions obtaining in our observations, the actual fall in the quotient was very slight and could but rarely, if at all, affect the calculation of the indirect calorimetry. In this series of observations we have com- puted the indirect calorimetry from the direct measurements of the carbon dioxide, using the calorific values of carbon dioxide! for the respiratory quotients obtained during the experimental period. The fact should again be emphasized here that tests for tightness and efficiency preceded every individual observation and check tests for determining the respiratory quotient with alcohol were made once a week. The later method for determining the absolute amount of alcohol burned and the respiratory quotients for short periods approximating the periods of observation with infants was not perfected until the fall of 1913; nevertheless we feel confident that the number of control tests made with the older method in connection with these researches is fully justified in order to secure absolute accuracy in this, the first extensive use of the apparatus for studying infant metabolism. 1See table 15, p. 29. PART II. STATISTICS OF OBSERVATIONS. SELECTION OF SUBJECTS. The infants studied were all kept in the children’s ward of the Massa- chusetts General Hospital and were selected for the most part from those coming to the Out-Patient Department; a few came directly from the Boston Lying-in Hospital. In many instances they were placed in the wards for the purpose of having their digestion studied; in a few cases they came because of some slight indigestion or because they were not gaining weight satisfactorily. Each infant that enters the children’s ward of the Massachusetts General Hospital has a complete physical examination, including an examination of the ear drums; careful notes are also made as to the general appearance, actions, and digestion. When the physical exami- nation of the infants selected for observation was normal—in most instances the records were naturally of a negative nature, as for example “no enlargement of the peripheral lymph nodes’’—and the infant led a regular and uneventful life, it was considered a normal infant. In some instances the subjects were below weight but appeared normal in other ways. In such cases, the fact is recorded in the statistics. The infants were under the general care of one of us who saw them each day, but the immediate care was detailed to the house physician and excellent trained nurses. The routine throughout the day was regular. They were weighed naked at the same hour each day by the same nurse. The nurses also recorded carefully how much food was eaten; the percentages of the food components given and the number of calories in the food taken were roughly calculated for each day. Notes were kept as to the character of the dejections, and the pulse-rate and body-temperature were recorded twice a day. The clothing was the ordinary clothing used in hospitals for infants of their age; the beds were the usual hospital cribs. The house officer took careful histories of all the infants, his physical examination and bed- side notes being verified by one of us. These records were made and the infant studied before any observations were made of the metab- olism in order to control all factors so far as possible. Infants who were quiet and comfortable were considered to be the most favorable subjects for observation, but we were frequently dis- appointed in the results, as many infants who were supposed to be absolutely quiet during the 24 hours did not prove to be so. This 67 68 GASEOUS METABOLISM OF INFANTS. led us to install in the ward a crib so adjusted as to give kymographic records of the degree of activity or quiet, like those obtained with the respiration chamber.! The infant selected for observation was placed in this crib for 24 or 48 hours and a graphic record of his muscular activity secured for the whole period. In one instance an infant who was said to be the “quietest baby in the ward, hardly moving all day,” gave a surprising record in that it showed that she actually moved a great deal and that there were only a few hours out of the whole 24-hour day in which she was truly quiet. HOSPITAL RECORDS. The routine histories, records of the physical examinations, notes regarding the urine, stools, blood, and temperature, the pulse and respi- ration charts, and detailed records of the food were kept for all of the infants. The Wassermann reaction and the von Pirquet skin tests were also made in many of the cases noted in the statistics. It does not seem desirable to publish the complete hospital record of each infant that came under observation, as such an amount of detail would make it impossible to find the essential points without too much labor. This is particularly true because most of the evidence is negative as to whether or not an infant is normal. One complete record of a typical case will therefore be given and only such information recorded for the other cases as has a bearing on the metabolism or is pathological in character. TYPICAL RECORD. Subject, F.B. Male; date of admission to hospital, April 22, 1913; age, 53 months. Preliminary diagnosis. Feeding. Family history. Father and one other child living and well. Mother lame from an old infantile paralysis. She was operated on in the Massachusetts General Hospital a year ago for “intestinal obstruction” which came on when she was 2 months pregnant. Past history. Full term, instrumental delivery. Birth-weight, 4.54 kg. Breast-fed, 6 days, then mother had blood poisoning and infant was weaned. Present illness. From the age of 10 days until admission to the hospital, has had recurring boils on different parts of the body. Was fed for two months on modified milk and lactose and after that a proprietary food was substituted for lactose because he was not doing well. Is now getting 2.7 per cent of fat, 8 per cent of sugar (extra sugar in the proprietary food), 2.1 per cent of protein, 6 feedings of 5 ounces. Takes bottle well, does not vomit. Is very constipated in spite of magnesia and orange juice. Physical examination. Fairly developed, poorly nourished. Bright and intelligent. Strong cry. Almost no subcutaneous fat. Muscles small but firm. Holds head up and sits up without support. Skin of trunk shows scars of old furuncles and on scalp are two which have almost healed. There is a fine papular eruption on back of neck and between shoulders. Head well shaped. Anterior fontanelle depressed and measures 2X2 cm. in diameter. 1For description see p. 59. STATISTICS OF OBSERVATIONS. 69 Posterior fontanelle closed. Suturesclosed. Nocraniotabes. Parietal bones not prominent. Eyes: No discharge; pupils equal and react to light; external ocular movements normal. Ears: No discharge; tympanicmembranes normal. Nose: No discharge; ale nasi do not move with respiration. Mouth: Mucus membrane, good color; no teeth; in center of hard palate is an oval ulcer about 1 em. long in diameter, which is shallow and apparently filled with granulations; tonsils not prominent or reddened; pharynx normal. Glands: Axillary normal; epitrochlears normal; submaxillary, cervical, posterior auri- cular, occipital, inguinal, and femoral glands all enlarged and vary in size from a pea to a large bean; are hard and non-tender. Chest: Symmetrical; expan- sion equal; very slight rosary; no Harrison’s groove. Heart: Apex impulse felt in fourth space, 4. cm. from midsternum; dulness corresponds; right border 1 cm. from midsternum; upper border at third rib; sounds regular and of good quality; no murmurs; pulmonic second louder than aortic second. Lungs: Normal resonance, fremitus, and breath sounds; no rales. Abdomen above level of thorax, soft, very tympanitic. Moderate diastasis of recti. No masses or tenderness. Liver dulness extends from fifth space to 1 cm. below costal margin, where smooth edge is felt. Smooth edge of spleen is felt 3 cm. below costal margin. Genitalia normal. Extremities normal. No paralysis, contractures, or edema. Epiphyses of long bones not enlarged. Reflexes: knee-jerks present and equal. No Kernig sign. No stiffness of neck or neck sign. April 22. Blood: Hemoglobin, 70 per cent (Talquist); white count, 10,000. Smear normal. Polynuclears, 32 per cent; small lymphocytes, 20 per cent; large lymphocytes, 47 per cent; endothelial cells, 1 per cent. Wasser- mann reaction suspicious. April 23. Urine: Pale; clear; acid; albumin, slightest possible trace. No sugar. Urobilinogen absent. Sediment, a few round cells. Stool: Greenish brown; pasty; normal odor; acid to litmus paper; few soft curds, no tough curds; little finely divided mucus. April 24, X-ray examination immediately after bismuth feeding, and every hour thereafter for several hours. April 25. Von Pirquet skin tuberculin, negative 48 hours. Stool: Greenish yellow and black; crumbly; acid; no curds. Bismuth in large amount. Total fat in moderate excess. April 26. X-ray examination as before. April 27. Stool: Yellowish-white and black mixed (bismuth) ; acid; normal odor; few soft curds; total fat in moderate excess. April 28. Stool: Soft yellow; acid; many small soft curds, few tough curds; no mucus; total fat in moderate excess. X-ray examination as before. Takes bottle well; gaining weight in spite of starvation. May 2. Summary: Underfed; under-weight; bright, happy infant; very active; always hungry for bottle; takes it quickly; not quite satisfied. Dis- charged, relieved, Out-Patient Department. Diagnosis: Feeding; syphilis (?). 70 GASEOUS METABOLISM OF INFANTS. The chart for this infant during his stay in the hospital is given in figure 10. This shows curves for records of the body-temperature, the pulse-rate, the respiration-rate, the body-weight, and the calories per kilogram of body-weight contained in the food. APRIL MAY 22 23 24 25 26 27 28 29 30 I 2 Fic. 10. Hospital chart for F. B. One dejection in evening is indicated by —; one dejection during day by |; two dejections during day by ||. The records of the temperature were taken in the rectum. This infant weighed about 2 kilograms less than the average weight for the age, and 3 kilograms less than he would have weighed had he developed in the normal manner. He was very much under weight, but gained consistently while in the hospital. He was considered to be in the convalescent stage of infantile atrophy. The daily records of the food, dejecta, and body-weight are given in table 21. STATISTICS OF OBSERVATIONS. TaBLE 21.—Record of food, dejecta, and body-weight. 71 7 Body- Date. Food. Dejecta. weight. 1913. kilos. Apr. 22-23 .| 3 p.ct. fat;6 p. ct. lactose; 1.4p.ct. protein. | 2 greenish yellow and brown | 4.750 180 c.c. at 3,6,and 10 p.m., 2530™ and stools with many small soft 6 a.m. curds and little mucus. 23-24.) 3 p. ct. fat; 6 p. ct. lactose; 1.6 p.ct.|1 small constipated stool |4.825 protein. Extrasugarlactose. 180c.c. with fat curds. at 9 and12a.m.;210¢.c.at 2515™p.m.; 195 c.c. at 6 and10p.m., 2 and 6 a.m. Total amount for day, 1350 c.c. 24-25 .| One feeding water, 90 c.c., whole milk, 120 | llarge constipated stool with | 4.750 e.c., bismuth, 30 gm. total (210c.c.) at many soft curds. 1 large 9am. Water, 210 c.c.at 2>20™ p.m. dark green dry _ stool. Regular formula as on Apr. 23-24: 195 Acid. c.c. at 8 a.m., 90 c.c. at 10 a.m.; 195 ¢.c. at 2and 6p.m. Total for day, 1095 c.c. 25-26.) Regular formula: 195¢.c.at9and12a.m., | 1 large soft dry yellowish | 4.815 2515™ and 6 p.m.; 180 ¢.c. at 10 p.m.; green stool with many soft 195c.c. at2 and6a.m. Total amount for curds. Acid. day, 1350 c.c. 26-27 .| One feeding whole milk, 120¢.c., bismuth, | 1 large green and white | 4.825 30 gm., lime water, 24 c.c., water, 64¢.c. movement with many soft (total, 210 cc.) at 9 a.m. Regular curds. Acid. formula: 195 c.c. at 2515™, 6 and 10 p.m., 2 and 6 a.m. Total for day, 975 c.c. 27-28.| Regular formula: 195 c.c. at 9 and 12] 1 large spongy yellowish | 4.850 a.m.; 210 c.c. at 3,6, and 10 p.m., 2 and green stool with many soft 6a.m. Total amount for day, 1440 c.c. curds. Acid. 28-29.) Regular formula: 195 c.c. at 9 a.m. and | 1 large soft formed yellow | 4.925 10 p.m.;210c.c. at 12a.m., 3 and 6 p.m., stool with many soft curds. 2 and 6 a.m. Total amount for day, Acid. 1440 c.c.; vomited about 30 c.c. 29-30.| 1 feeding of whole milk, 120 c.c., bismuth, | 2 large yellowish gray stools | 5.100 30 gm., lime water, 60 c.c., water, 30 c.c. with many soft curds. (total,210 c.c.)at9 a.m. Regular formula: 1 large yellow and very 210 c.c. at 2515™,6and 10p.m., 2and dark green stool with curds. 6 a.m. Total amount for day, 1260 c.c. Acid. April 30 | Regular formula: 210 ¢.c. at 9 and 12 | 2 somewhat constipated yel- | 5.025 to May 1. a.m.; 3, 6, and 10 p.m., 2 and 6 a.m. low stools with specks of Total amount for day, 1470 c.c. mucus. Acid. May 1-2..| Regular formula: 210 c.c. at 9 and 12 | 2 large yellow rather consti- | 5.050 a.m.; 3, 6, and 10 p.m., 2 and6a.m. pated stools with soft curds Total amount for day, 1470 c.c. and little mucus. Acid. SUMMARIZED HOSPITAL RECORDS FOR OTHER SUBJECTS. Instead of giving the detailed records for each subject, as in the case of F. B., summaries of the hospital records are presented herewith which include all data of value in studying the results of the metabolism observations. and may thus be readily referred to. These summaries are arranged in alphabetical order, Subject, M.A. Male; born February 11, 1913; birth-weight, 3.75 kilograms. Previous to coming to the hospital, this infant had been breast-fed at inter- vals of 2to 3 hours. Although never acutely ill, he had not gained weight as rapidly as the average infant, and had never been very strong. He usually 72 GASEOUS METABOLISM OF INFANTS. passed 4 to 6 stools a day. An analysis of his mother’s milk showed that it was very weak. He entered the hospital when 9 months old (November 3, 1913), with a severe secondary anemia. His weight at that time was 5.70 kilograms. When the blood was examined, it was found that while the dif- ferential count of the white cells was normal, there was but 35 per cent of hemoglobin (Talquist), 18,000 white blood corpuscles, and 2,712,000 red cells. The Wassermann reaction was negative. The physical examination showed that the infant was well developed and fairly nourished. The skin and mucous membrane were of a pale lemon color. The edge of the liver was felt 2 cm. below the edge of the ribs and the spleen was hard, extending down to the crest of the ileum. There was but a small amount of subcutaneous fat. The digestion was normal, but it was often necessary to feed him with a stomach tube. When discharged from the hospital on December 27, 1913, he weighed 5.60 kilograms. The case was diagnosed as splenic tumor with a severe grade of secondary anemia. His weight on entering the hospital was 2.8 kilograms less than the average for an infant of his age. Subject, J. B. Male; born October 19, 1912; birth-weight unknown. This infant entered the skin ward of the Massachusetts General Hospital on February 21, 1913; his weight at that time was 3.06 kilograms. He was described as a poorly developed and nourished infant with an eruption typical of congenital syphilis. After inunctions of mercury were given him, the external evidence of syphilis disappeared. The physical examination was otherwise normal. During the 5 weeks this infant remained in the hospital he gained very little until the week preceding his discharge, when he gained approximately 0.5 kilogram, weighing when discharged 3.74 kilograms. His case was diagnosed as one of hereditary syphilis. He was very much under- weight, weighing about 3 kilograms less than the average weight for his age. During the last week he was gaining weight and therefore may be considered as in the convalescent stage of infantile atrophy with syphilis. Subject, L. B. Female; born at full term in September, 1912; birth-weight, 3.86 kilograms. She was breast-fed for the first 2 months and subsequently fed on a mixture of milk, a proprietary food, and water. Her digestion was poor and she lost a little weight. She entered the hospital January 24, 1913, age 4 months, to have her metabolism determined. At this time she was a small, thin, but healthy- looking infant, with but little subcutaneous fat. She was not emaciated, however, and appeared well. She held up her head, but could not sit up with- out support. Her physical examination was normal. She was fed on modi- fied milk in the usual proportions, her weight increasing from 3.89 kilograms to 4.07 kilograms, after which she ceased to gain. She was moderately under weight, as the average weight for an infant of 4 months is 6.25 kilograms. If she had grown in the usual way from birth, she would have weighed about 0.5 kilogram more than the average weight for an infant of this age. The hospital diagnosis was “regulation of feeding.” Subject, L. R. B. Female; born June 24, 1913; birth-weight, 4.08 kilograms. This infant had always been breast-fed and had gained in the usual manner. She entered the hospital when 4 months old (October 31, 1913), to have her metabolism determined, and for weaning, as the mother was obliged to work. The physical examination showed that she was a well-developed, well-rounded infant, with the normal musculature and subcutaneous fat. The organs were all normal. On November 1 and November 3, modified milk was given her STATISTICS OF OBSERVATIONS. 73 containing about 88 calories per kilogram of body-weight. On November 5, she was given milk containing 103 calories per kilogram of body-weight. The temperature was normal. Her weight was 6 kg; the average weight for an infant of her age is 6.25 kg.; she was therefore a perfectly normal infant. Subject, A.C. Female; born February 2, 1913; birth-weight, 3.09 kilograms. Her history was unimportant, and her physical examination normal. When she entered the hospital March 19, 1913, at the age of 63 weeks, she was a strong, well-developed, and well-nourished infant. During her stay in the hospital she was fed with modified milk of the ordinary proportions and showed no signs of indigestion other than the occasional spitting up of small amounts of food. Her diet contained about 100 calories per kilogram of body-weight; with this diet her weight decreased in one week from 3.02 kilograms to 2.92 kilograms. Her temperature was normal except for two instances when it rose for no cause that could be discovered. She was to all appearances a normal infant. She weighed 0.4 kilogram less than the average weight for the age, but since she weighed 0.3 kilogram less than the average at birth this may be deducted from the average weight to show her expected weight for the age. Subject, M.C. Female; born August 31, 1913; birth-weight, 4.09 kilograms. She was breast-fed for a month and a half after birth and was then given modified milk; she had always been well. When 4 months old (January 1, 1914), she entered the hospital to have her metabolism determined; her weight at this time was 6 kilograms. The physical examination was normal and there was a normal amount of subcutaneous fat and muscle. Her temperature was normal throughout her stay. The average weight for an infant of this age is 6.25 kilograms; she was therefore approximately the weight of the average infant and on this basis may be considered a normal infant. As she weighed 0.68 kilogram more at birth than the average infant, she was approximately 0.75 kilogram below the weight she would have been had she gained in the usual manner. Subject, A.D. Female; born December 28, 1912; birth-weight, 2.36 kilograms. Previous to coming to the hospital she had always been fed on modified milk. She cried considerably and vomited immediately after almost every feeding. The milk formula had been changed, a month previous, to equal parts of cream, water, and lactose in amounts that gave her about 50 calories per kilogram of body-weight. She entered the hospital when 4 months old (April 26, 1913), with the provisional diagnosis of starvation. Her weight at that time was 2.55 kilograms, which was less than half of what she would have weighed had she gained in the normal manner, and 3.70 kilograms less than the average for an infant of that age. She was a poorly developed, poorly nourished, emaciated, and “dried up”’ infant, with a fairly strong cry and afeeble grasp. There was no subcutaneous fat and the muscles were small and weak. After coming to the hospital, she was fed on modified milk and gained rapidly in weight from May 1, when she weighed 2.60 kilograms, to June 5, when she weighed 3.70 kilograms. On May 18 it was noted that she was gaining very rapidly in weight and strength, and that her general appear- ance was improving. The digestion and temperature were normal except on the afternoon of May 24, when the temperature was 36.1° C. (97° F.). At the time of her discharge from the hospital, she weighed about 2 kilograms less than she would have if she had gained weight in the usual manner, and 3 kilo- grams less than the average weight of an infant of her age (5 months). She 74 GASEOUS METABOLISM OF INFANTS. was therefore markedly under weight as a result of improper food and was on the border line of infantileatrophy. When her food was regulated, her digestion became good and she gained weight rapidly. She could be considered as being in the stage of convalescence. Subject, M.D. Male; born February 23, 1913; birth-weight unknown. He entered the hospital March 8, 1913, at the age of 2 weeks, to have his metabolism determined. Before coming to the hospital he had been fed partly on modified milk and partly at the breast. His history was negative. He was a well-developed, strong, well-nourished infant, who was normal in every way. While in the hospital, he was given modified milk. His digestion remained good but he did not gain in weight, presumably because he only received 80 to 90 calories per kilogram of body-weight. He weighed 4.05 kilograms, which was about the average weight for an infant of his age. Subject, R. H. Male; born July 22, 1913; birth-weight, 2.27 kilograms. His history was negative except for the fact that he had twice had jaundice. Previous to coming to the hospital, he had been fed on modified milk; his digestion was normal. He entered the hospital when 43 months old (December 4, 1913), for the purpose of having his metabolism determined. The physical examination showed that he was well-developed and nourished, with firm mus- culature and considerable subcutaneous fat, though not an excessive amount. He was otherwise physically normal. The temperature varied between 36.4°C and 38.0° C. (97.6° F. and 100.4° F.). On entering the hospital, he weighed 5.1 kilograms; as the average weight for an infant of his age is 6.5 kilograms, he was 1.4 kilograms under weight, but since he weighed 1.1 kilograms less than the average at birth he was only 0.3 kilogram below his expected weight. He was otherwise a physically normal infant. Subject, H. F. Male; born September 3, 1913; birth-weight, 4.22 kilograms. He had always been breast-fed and thrived in every way. He was brought to the Out-Patient Department of the hospital, when 3 months old, for the purpose of having his metabolism determined. The physical examination showed that he was a well-developed, well-rounded infant, with a normal amount of subcutaneous fat. The average weight of an infant of his age (3 months) is 5.56 kilograms. At birth he was 0.8 kilogram heavier than the average infant, and with normal development he would be expected to weigh 6.36 kilograms at this age. He actually weighed 7.05 kilograms, or approxi- mately 1.5 kilograms above the average weight for this age and 0.7 kilogram above what he would have weighed with normal development. He was there- fore a perfectly normal infant. Subject, E. G. Male; born January 23, 1913; birth-weight, 3.63 kilograms. For the first 8 months after birth he was breast-fed and subsequently fed on modified milk. He had always thrived on this food. When 10 months old, he entered the hospital on November 25, 1913, to have his metabolism deter- mined and for weaning. On physical examination he was found to be a normal well-developed and very well-nourished infant, with firm muscles and deep layers of subcutaneous fat. He had 4 teeth. His temperature was normal. His weight was 9.55 kilograms; the average weight for an infant of this age (10 months) is 8.75 kilograms; he was therefore 0.8 kilogram above the average weight and 0.6 kilogram above the expected weight. He may be characterized as a large, fat, normal infant. STATISTICS OF OBSERVATIONS. 75 Subject, E. K. Male; born at full term July 18, 1912; birth-weight unknown. He was breast-fed for 2 months; subsequently he was given modified milk, and more recently was fed from the family table. He had never been well and when brought to the hospital on November 29, 1913, he was found to have broncho-pneumonia and rachitis. The metabolism was determined a week after he had recovered from the pneumonia. He was physically a fairly well- developed and nourished infant with a moderate amount of subcutaneous fat. When his metabolism was determined, his weight was only 8.03 kilograms, which is the average weight for an infant of 8 months, so that for an infant of 17 months he was very much under weight. Subject, F. K. Male; born October 4, 1912; birth-weight, 3.54 kilograms. For the first 3 months he was fed at the breast; he vomited considerably, was cross and fretful, and did not gain in weight. He was then weaned, and at first given modified milk, and later condensed milk, but without improve- ment, as he continued to vomit and to pass 6 to 8 loose green stools a day. He entered the hospital on May 1, 1913, at the age of 7 months. At that time he was a fairly developed and nourished infant, with a considerable amount of subcutaneous fat and firm muscles. The physical examination was normal. He was fed with modified milk having a caloric value of about 140 calories per kilogram of body-weight. His digestion and temperature were normal; he did not vomit during his stay in the hospital. His weight was 5.65 kilograms when he entered the hospital and 5.75 kilograms at the time of his discharge on May 11. He was about 1.5 kilograms lighter than the average for his age, but was otherwise perfectly normal. Subject, A. L. Female; born at full term Mar. 2, 1913, birth-weight, 3.64 kg. Previous to entering the hospital, she had been fed at the breast, but had been given supplementary feedings of a proprietary food and milk for a short time. She had always vomited more or less after the feedings and had recently been losing weight. Her weight on entering the hospital June 5, 1913, was 3.10 kilograms. The physical examination showed her to be a poorly developed, poorly nourished, and emaciated infant, with almost no subcutaneous fat. All of the peripheral lymph glands were slightly enlarged and there was a slight rosary. The other organs were normal. She was given a diet of modi- fied milk during her stay of 6 weeks in the hospital; on her discharge she weighed 3.20 kilograms. The hospital diagnosis was “regulation of feeding.”’ Since the average weight at 4 months is 6.25 kilograms and the expected weight would be essentially the same, she was about 3 kilograms under weight when discharged from the hospital. Subject, E. L. Male; born January 19, 1913, of syphilitic parents; birth- weight unknown. This infant was breast-fed for 1 month, then fed on modified milk, but was not satisfied with the food and did not gain in weight. He entered the hospital on May 15, 1913, at the age of 4months. When examined he was found to be a rather small, fairly nourished infant, that lay quietly in the nurse’s lap. He could not hold his head up. The skin was lax, with small amounts of sub- cutaneous fat. The physical examination was normal except that the edge of the spleen was felt just below the costal margin. The Wassermann test of the blood on May 20 was negative. He was fed with modified milk supplying approximately 120 calories per kilogram of body-weight. The temperature was normal. He had a chronic otitis media which required paracentesis five times while he was in the hospital. Any digestive disturbance during his stay was probably secondary to the infectedears. His weight on entering the hos- 76 GASEOUS METABOLISM OF INFANTS. pital was 4.15 kilograms; on June 1, 4.48 kilograms; June 12, 4.48 kilograms; and on June 18, 4.68 kilograms. Since the average weight for 4 months is 6.25 kilograms, he was about 1.75 kilograms under weight. Subject, R.L. Male; born at full term Aug. 14, 1912; birth-weight, 2.27 kg. He entered the hospital on February 24, 1913, and an operation was per- formed for hare lip and cleft palate on March 12. The temperature became elevated after the operation and on the 16th a typical measles rash appeared. The temperature dropped to normal on March 22, He was discharged from the hospital on March 27. On April 5 he again entered the hospital with a high fever, a right upper lobar pneumonia, and infected ears. The tempera- ture dropped to normal on April 19 and remained there until April 26, when he had pneumonia for a second time, which continued 8 days. On May 6 a double paracentesis was again necessary and from that time on there was no elevation of temperature. He was a large, well-developed, and well-nourished infant, with normal digestion. On April 15 he weighed 7.60 kilograms, while on May 16 he weighed 7.30 kilograms. At the age of 8 months, therefore, his weight was 0.47 kilogram less than the average for that age; on May 16, when he was 9 months old, he had lost weight and was about 1 kilogram below the average weight. On the other hand, as he was 1 kilogram or more under weight at birth, he was a little over the weight which would be expected with normal development. Subject, D. M. Male; born April 24, 1912; birth-weight, 3.00 kilograms. This infant was prematurely born at 83 months. He was breast-fed for the first 5 weeks and subsequently fed on various modifications of milk, malted milk, and condensed milk. During November, 1912, he gained practically no weight and had frequent colds and pertussis. On February 24 he was brought to the Out-Patient Department of the hospital with a double otitis media. Later he had chicken pox. He entered the hospital when he was 11 months old (March 25, 1913). At that time he was found to be a fairly developed and nourished infant, with a small amount of subcutaneous fat and soft muscles. He was unable to sit up without support, the back showing a marked curve of weakness. The head was square, with a flat top and promi- nent parietal eminences. There was a slight rosary, but no enlargement of the epiphyses. The physical examination was otherwise normal. Despite the infected ear, the temperature did not rise higher than 37.78° C. (100° F.) during his stay in the hospital. He was given milk modified to suit his diges- tion, with a fuel value of about 140 calories per kilogram of body-weight. During the first few days he did not take the food from the bottle well, but after he had become accustomed to his surroundings, he gained in both weight and appearance, the gain in his general condition being much more than the weight indicated. When he entered the hospital, he weighed 5.20 kilograms; this weight fell to 5.10 kilograms on March 29, after which there was a gain until he was discharged in April, when he weighed 5.23 kilograms. He was about 4 kilograms below the average weight for his age, and about 3.6 kilo- grams below what he would have weighed had he gained in the usual manner. Subject, F. M. Male; born September 13, 1912; birth-weight unknown. His past history was unknown. When he entered the hospital on January 16, 1913, he had congenital syphilis, with a positive Wassermann reaction. The general physical examination was normal except that he was under weight, weighing only 4 kilograms, while the average weight for an infant of this age (4 months) is 6.25 kilograms. His temperature and digestion were normal. STATISTICS OF OBSERVATIONS. 77 Subject, J. M. Male; born July 28, 1912; birth-weight not known. For the first two weeks after birth he was breast-fed; subsequently he was given whole milk diluted with water, which seemed to agree with him. Then he had diarrhea and was fed condensed milk. When 5 months old he was brought to the Out-Patient Department of the Massachusetts General Hospital, as he was constipated and not gaining. His weight on January 9 was 5.20 kilograms, or 1.60 kilograms below the average weight for this age (5 months). He was given milk suitably modified and gained weight slowly, his stools show- ing good digestion. About this time he had several colds. On March 6 he developed an acute otitis media which necessitated opening both ear drums; the discharge from the ears persisted up to the date of his entrance to the hospital ward on March 27, 1913 (at the age of 8 months). At this time he was found to be fairly well-developed and nourished, with a moderate amount of subcutaneous fat. The head was somewhat square and there was a slight rosary. There was a purulent discharge from both ears. All the peripheral glands, including the epitrochleas, were easily palpable, being the size of small shot. The physical examination was otherwise normal. Although the dis- charge from the ears continued, the ear infection caused no elevation of tem- perature after April 1 and no other symptoms. He was given milk modified to suit his digestion, with a fuel value of about 140 calories per kilogram of body-weight. His digestion wasnormal. At the time he entered the hospital, his weight was 5.50 kilograms; when he was discharged it was 5.63 kilograms, these weights being about 2.5 kilograms below the average for his age (8 months). Subject, M.M. Female; born January 21,1913; birth-weight, 3.18 kilograms. She was fed on modified milk and did well until several days before coming to the hospital, when she began to vomit after feeding and to have diarrhea. Her mother gave her one-half ounce of castor oil and changed her diet to barley water. The infant entered the hospital on May 28, 1913. The physical examination showed her to be well-developed, strong, and bright, with a good amount of subcutaneous fat. The skin was a little loose, indicating a recent loss of flesh, but otherwise the examination was normal. The temperature, which was elevated on the day of admission, soon dropped to normal. She was given weak mixtures of modified milk which contained about half as much food as she required to gain weight. Her weight remained stationary at 5.35 kilograms. This was about 1.15 kilograms lighter than the average weight for an infant of her age (43 months) and about 1 kilogram lighter than she would have been had she developed consistently from birth. The diagnosis was acute gastro-intestinal indigestion. Subject, E. N. Female; born November 17, 1912; birth-weight not known. Previous to coming to the hospital she had been fed on various pro- prietary foods, separately or in combination. She cried considerably and was hungry. She did not vomit and her stools were soft, green, and foul. When she entered the hospital on May 19, 1913, she was found to be a well-developed and fairly well-nourished infant, with a strong cry. The subcutaneous fat wasin small amounts; the skin was lax and the muscles flabby, but the grasp was strong and she was able to hold her head up. The rest of the physical examination was normal. She cried very little while in the hospital, but “ate, laughed, and slept.” Her weight on entering was 5.40 kilograms and on her discharge on June 2, 1913, it was 5.26 kilograms. She was 2 kilograms below the average weight for an infant of her age (6 months), but was other- wise normal in all respects. Her case was considered to be one requiring a regulation of feeding, her condition being due to improper feeding, with prob- ably too much carbohydrate. No permanent injury had been done, as her 78 GASEOUS METABOLISM OF INFANTS. digestion quickly became normal when she was given milk properly modified, with a fuel value of about 140 calories per kilogram of body-weight. Subject, L. O. Male; born September 5, 1912; birth-weight, 3.75 kilograms. This infant had always been fed with the bottle on mixtures of various proprietary foods, with little or no cow’s milk. He lost weight on this diet and had never regained his birth-weight. When he entered the hospital at the age of 43 months (January 29, 1913), the physical examination showed that he was a small, rather emaciated infant with a pinched face and practically no subcutaneous.fat. The musculature was slightly flabby and he was unable to hold up his head. The cry was fairly strong and he seemed bright. The physical examination was otherwise normal. His weight on entering the hos- pital was 2.93 kilograms and it continued about the same until approximately February 15, when he began to gain slowly. On March 10 he weighed 3.32 kilograms. After that date his temperature was elevated and it was dis- covered on March 14 that he had measles. During the period when his meta- bolism was being determined, his temperature in the wards varied between 36.1° C. (97° F.) and 36.7° C. (98° F.), being subnormal in the morning and usually reaching 36.7° C. (98° F.) in the afternoon. On March 12, the tem- perature became elevated with the prodromal symptoms of measles. He was a very much under-weight and under-nourished infant, with an indigestion which was presumably due in the first place to too much sugar in the diet and secondly to too much fat. There was no difficulty in digesting protein in relatively large amounts. His diet during his stay in the hospital was cow’s milk modified to suit his digestion, and on this he gained slowly and consistently in weight until he had measles. The stools were at first loose, watery, and acid, but after the food was regulated they became firm, solid, and alkaline. He weighed less than his birth-weight when he should have weighed almost double his birth-weight; taking into account the subnormal temperature, general appearance, and history, he might be considered a case of infantile atrophy. Subject, J. P. Male; born prematurely at 7 months April 11, 1913; birth- weight, 2.05 kilograms. He was never breast-fed, but was given condensed milk, or modified milk with a proprietary food; hehad neverthrived onthis diet. He entered the Float- ing Hospital August 14, 1913; his physical examination wasnegative at this time, except for emaciation. He gained in weight up to 4 kilograms, but then had indigestion, and was given a formula containing malt soup, which resulted in a gain in weight up to 4.54 kilograms. On September 12, 1913, he entered the Massachusetts General Hospital and was found on physical examination to be moderately emaciated, with an indigestion due to too large a proportion of fat in the diet. He was put on a diet of modified milk, regulated to his digestion, and on September 28 began to gain rapidly. On October 25, he weighed 5 kilograms and on November 8, 5.5 kilograms. He was happy and smiling, well covered with fat, and his physical examination was normal. He was, however, approximately 2 kilograms under weight, as the average weight for his age (7 months) is 7.7 kilograms. Since he weighed 1.35 kg. less than the average at birth, he would have weighed 6.4 kg. if he had gained nor- mally. On this basis, he weighed 0.9 kg. less than he should have weighed. Subject, W. P. Male; born August 23, 1912; birth-weight, 2.73 kilograms. His history previous to his coming to the hospital was unimportant, save that his food contained practically no fat, he was very constipated, and not gaining in weight. On January 24, 1913 (age, 5 months), he entered the hospital ward to have his metabolism determined. At that time he was an STATISTICS OF OBSERVATIONS. 79 undersized and rather poorly nourished infant, with but a small amount of subcutaneous fat. He noticed objects, and held up his head, but could not sit up without support. His physical examination was normal except that there was a slight rosary. While in the hospital he kicked and laughed a good part of the day while awake, slept 6 hours during the day and all night except when fed at 10 p. m., 2 a. m., and 6 a. m., and was considered a particularly happy infant. He made slow but consistent gains without symptoms. His food was modified milk and his digestion was normal. When he entered the hospital, his weight was 4.14 kilograms and on February 2 (9 days later), 4.39 kilograms. When discharged from the hospital, he was about 1 kilogram below the weight he would have been if he had doubled his birth-weight in 5 months and 2.5 kilograms below the average weight for a baby of his age. Subject, D.Q. Male;born at full term on Aug. 2, 1913; birth-weight, 2.5 kg. He was breast-fed for the first 2 months, and subsequently on modified milk. When on the latter food, he had diarrhea in December, but when the formula was modified the digestion became perfect. He entered the hospital on December 22, 1913, at the age of 44 months, for the purpose of having his metabolism determined. He was then reported as gaining rapidly. He was well-developed and nourished, with firm muscles, and a well-developed layer of subcutaneous fat. Both the physical examination and the temperature were normal. He was under weight, as he weighed only 5.2 kilograms and the average weight for this age is 6.5 kilograms. His birth-weight was, however, 0.9 kilogram less than the average infant at birth and if he had gained normally he would have weighed approximately 5.6 kilograms. He was, therefore, 0.4 kilogram below what he should have weighed. Subject, H. R. Male; born January 12, 1913; birth-weight, 2.95 kilograms. His father was unknown; his mother was treated for syphilis by two injec- tions of salvarsan during pregnancy. During the first seven weeks he was breast-fed; subsequently he was fed both breast and modified milk on which he did well. He entered the hospital April 11, 1913, to have his metabolism determined; at that time he was well-developed and well-nourished with a moderate amount of subcutaneous fat and strong muscles. The physical examination was normal except for an enlarged spleen which could be felt 3 cm. below the edge of the ribs; this was believed to indicate syphilis. His temperature was normal. At birth he weighed 0.45 kilogram less than the average infant; when he entered the hospital he weighed 4.50 kilograms or about 1 kilogram less than the average infant of the same age (3 months). His digestion was normal and except for the first few days, he gained weight consistently during his stay in the hospital, that is, after his food was strength- ened from 100 to 120 calories per kilogram of body-weight. Subject, K. R. Male; born December 6, 1912; birth-weight, 4.55 kilograms. Previous to his coming to the hospital, he had always been fed on modified milk, but did not do well. He entered the hospital on April 2, 1913, at the age of 4 months. On physical examination he was found to be poorly devel- oped, poorly nourished, and almost emaciated. He had a thin, pinched face, no subcutaneous fat, and the skin was rather loose. The muscles were small and fairly firm. He cried considerably and held his breath for periods as long as 45 seconds, during which he became distinctly blue, but there was no suggestion of a crow or of laryngismus stridulus. The physical examination was otherwise normal. The urine was also normal except that on one exami- nation it showed a possible trace of albumen. This, however, was probably of no significance, as there were no other pathological signs. He was fed on a 80 GASEOUS METABOLISM OF INFANTS. mixture of cow’s milk, relatively low in fat, which gave him about 120 calories per kilogram of body-weight. During his stay in the ward his digestion was apparently normal. His temperature was normal or subnormal. He was an undersized infant, whose digestion had been upset by over-feeding with fat. When he entered the hospital, his weight was 3.07 kilograms, which was less than his birth-weight. If he had developed in the ordinary way, he would have weighed about twice as much, the average weight for an infant of his age being 6.25 kilograms. When discharged from the hospital, he weighed 3.19 kilograms. His case was considered to be one of infantile atrophy. Subject, A. S. Male; born at full term Dec. 26, 1912; birth-weight, 3.75 kg. His history was unimportant, as he had always been breast-fed. When he entered the hospital on March 26, 1913, he was well developed and well nourished, with a normal amount of subcutaneous fat and firm muscles. He appeared strong and bright and held his head up without support. The physical examination was normal. During his stay in the hospital he was fed both breast and modified milk; his digestion was normal. It was neces- sary to puncture his ear drums on March 29 to relieve an acute otitis media, after which the temperature, which had previously been moderately elevated, dropped to normal. His weight remained stationary in the week he was under observation. He was a normal breast-fed infant, weighing approximately 6 kg. or about 0.5 kg. above the average weight for his age (3 months). Subject, E. S. Female; born of healthy parents on October 13, 1912 (pre- sumably premature at about 7 months); birth-weight, 1.93 kilograms. She was breast-fed for 3 months but did not gain. She was then put on a diet of malted milk and later on a proprietary food, both of these being mixed with milk. While she did not vomit, she spit up her food occasionally, and had two brown stools a day which irritated the buttocks. When she entered the hospital on March 19, 1913, she had not gained weight recently. On physical examination she was found to be a poorly developed, thin infant, with an anxious expression. There was no subcutaneous fat, and the muscles were flabby. She appeared quiet but bright, and had a strong cry. The skin showed a dull redness, with macular papular eruption on the chin, joints, and buttocks. ‘The physical examination was otherwise normal. She was fed on milk modified to her digestion, with a fuel value of about 140 calories per kilogram of body-weight; while under observation, her digestion was good. This infant was much under the average weight and also under the weight which she would have been had she gained consistently. With a history of prematurity and a birth-weight of 1.93 kilograms, it would be expected that at the age of 5 months (her age while in the hospital) she would weigh approxi- mately 5.35 kilograms, whereas her average weight for this time was about 3 kilograms. The average weight for an infant of 5 months is 6.82 kilograms. She was, therefore, considerably under weight. Furthermore, the tempera- ture during her entire stay was subnormal. She was accordingly considered to be a case of infantile atrophy. Subject, E. H.S. Male; born at full term Aug. 28, 1913; birth-weight, 3.18 kg. He had always been fed on modifications of cow’s milk or on condensed milk, but did not thrive on any of the diets used. He had had symptoms of indigestion ever since birth and had lost weight, weighing when he entered the hospital on October 27, 1913, at the age of 2 months, only 2.4 kilograms. He was a poorly developed and nourished infant, with the expression of an old man. The face wrinkled when he cried, and the skin hung in folds on his arms and legs. The fontanelles and eyes were sunken; the skin was dry; STATISTICS OF OBSERVATIONS. 81 the hands and feet were cold. The physical examination was otherwise normal and the Wassermann reaction was negative. During a part of his stay in the hospital, it was impossible to give him the usual number of calories in his food, as, for instance, on November 24, when he received only 90 calories per kilo- gram of body-weight; the temperature at this time was subnormal, being 36.1° C. to 36.7° C. (97° F. to 98° F.). On November 13 and 21, when he received about 130 calories and 145 calories respectively, the temperature was normal. When he was discharged on December 27, 1913, he weighed 3.05 kilograms. His case was diagnosed as infantile atrophy. He weighed when 2 months old 0.8 kilogram less than at birth. His digestion was very weak. Subject, G. S. Male; born December 1, 1912; birth-weight, 3.64 kilograms. Since his birth he had been fed on various home modifications of milk, barley water, lime water, and milk sugar. He seemed hungry, cried consider- ably, and did not gain in weight. When he entered the hospital February 12, 1913, he was found on physical examination to be a well-developed but poorly nourished infant, with a small amount of subcutaneous fat. He appeared bright and active and had a strong cry. His weight was the same as at birth, whereas at his age (24 months) it should have been 1.5 kilograms more. He was given milk modified to his digestion, with a fuel value of about 100 calories per kilogram of body-weight. Digestion not remarkable. His temperature remained normal. He was considered to be a case of regulation of feeding. Subject, J. S. Male; born December 28, 1912; birth-weight, 5 kilograms. For the first 6 weeks he was breast-fed; subsequently he was given a modi- fication of cow’s milk, but vomited after each feeding, cried most of the time, and was very constipated and hungry. He entered the hospital on June 3, 1913, at the age of 5 months. On examination he was found to be a small, emaciated infant, with the facies of old age. There was no subcutaneous fat and the skin hung in folds. The muscles were strong but firm. There was a slight rosary, but the physical examination was otherwise normal. He was given modified milk, with a fuel value of approximately 120 to 140 calories per kilogram of body-weight. The temperature was normal during his stay in the hospital. He was an atrophic infant with no definite signs of indiges- tion. His weight on entering the hospital was 4.08 kilograms and on his discharge 4.53 kilograms. This was less than his birth-weight and only half what he should have weighed at his age. Subject, P. S. Male; born December 23, 1912; birth-weight unknown. He had never been a well infant. On September 20, 1913, he had acute bronchitis. He entered the hospital on November 19, 1913, and had broncho- pneumonia on November 21. Later he had otitis media. In the week pre- ceding the determination of his metabolism, his temperature had been normal and he had gained in weight, although previous to that time he had lost considerable weight. His digestion was also good, and his physical examina- tion was normal. His weight on December 18 was 7 kilograms, this being about 2 kilograms under weight, as the average weight for an infant of his age (12 months) is 9.5 kilograms. Subject, H. T. Male; born October 25, 1912; birth-weight unknown. This infant was breast-fed from birth and had always been healthy. He was brought to the hospital for weaning and taken into the ward on April 15, 1913, to have his metabolism determined. The physical examination was normal, showing that he was a strong, well-developed and well-nourished infant, with a large amount of subcutaneous fat. During his stay in the hos- 82 GASEOUS METABOLISM OF INFANTS. pital he received both breast milk and modified milk. His digestion and temperature were normal. He weighed about 2 kilograms more than the average infant of the same age (53 months), his weight remaining stationary at 9.28 kilograms while he was in the hospital. Subject, J. V. Female; born prematurely at 8 months on October 10, 1912, of a syphilitic mother; birth-weight, 1.45 kilograms. She lost weight until at the end of the first week she weighed only 1.30 kilograms. For the first 4 weeks she was fed on human milk; she was then discharged from the Boston Lying-in Hospital to the Massachusetts General Hospital, which she entered on December 18, 1912. At this time she was a moderately nourished, poorly developed infant, about 45 cm. long. She cried lustily and took her food with a Breck feeder without help. A diagnosis of congenital syphilis was made by the skin department of the hospital before she entered the Children’s Ward. From December 25 onward, she was given inunctions of mercury, one-half strength, until her discharge from the hospital. On December 15, two days after her entrance, the temperature became elevated and remained so until the 20th, when it was found that she had an acute otitis media. After paracentesis, the temperature dropped to normal and remained there for several weeks. On March 11, the temperature again became elevated and 2 days later it was found that the infant had measles. The temperature remained elevated 7 days. She was allowed out of quaran- tine on March 27. On March 31 she again had acute otitis media, which was relieved by paracentesis. The ears continued to discharge until April 10; two days later paracentesis was once more necessary and there were symptoms of adenoid obstruction. On April 17, the adenoids were removed under ether, thus relieving the obstruction. After this the infant ate, acted, and looked better. On April 20 it was noted that there was marked craniotabes, a moderate rosary, a liver which could be felt 4 cm. below the edge of the ribs, and a spleen 3 cm. below the ribs. The ears stopped discharging shortly after the adenoids were removed and the general condition was much improved. On May 12, the record was made that she “laughed out loud.” She was fed on increasing strengths of modified milk. Her digestion was weak during most of her stay in the hospital. The weights recorded were as follows: October 10, 1912 (birth-weight), 1.45 kilograms; December 14, 1.84 kilograms; January 1, 1913, 1.84 kilograms; January 15, 1.92 kilograms; February 1, 2.05 kilograms; February 15, 2.22 kilograms; March 1, 2.50 kilo- grams; March 15, 2.70 kilograms; April 1, 3.10 kilograms; April 15, 3.00 kilograms, this being double her birth-weight; May 1, 3.10 kilograms; May 12, 3.33 kilograms. Although she doubled her birth-weight at 6 months, she weighed less than half the average weight of infants of the same age. Subject, P. W. Male; born September 8, 1912; birth-weight unknown. His family and past history were unimportant. He entered the surgical department of the hospital on March 26, 1913, because of acute retention of urine due to a horse hair tied tightly around the base of the penis. This was quickly relieved by removing the cause. His physical examination was normal. He was a healthy, well-developed infant, who acted normal in every way. During his stay the infant was given modified milk and digested it well. His food contained only about 85 calories per kilogram of body-weight, his weight remaining stationary at 7.10 kilograms. Since his birth-weight is unknown, it is impossible to calculate what his weight should have been for his age on that basis, but this weight is approximately the same as the average for his age. His temperature was normal and he could be considered a normal infant of average development. STATISTICS OF OBSERVATIONS. 83 CLINICAL STATUS OF INFANTS. Table 22 summarizes the clinical status of each infant studied, and gives the age of the infant during the metabolism observations. TaBLe 22.—Clinical status of infants studied. Age during Name metabolism Clinical status. observation. F, B. 53 months. | Convalescent stage infantile atrophy. M.A. 9 months. | Under weight, splenic tumor, with anemia. J.B. 5 months. | Congenital syphilis, convalescent stage, infantile atrophy. Ty B, 4 months. | Under weight. L. R. B. |4-44 months. | Normal infant. 14 months. | Slightly under weight. 4 months. | Normal infant or slightly under weight. 4-5 months. | Convalescent stage, infantile atrophy. 2-3 weeks. Normal infant. 4} months. | Under weight or slightly under expected weight. 3 months. | Normal infant. 10 months. | Normal infant. 17 months. | Much under weight; rachitis, recovering from broncho-pneumonia. 7 months. | Under weight. 34-4 months. | Under weight. 4 months. | Under weight, otitis media. 64-9 months. | Approximately normal; later, under weight. 11 months. | Much under-weight, rachitis. 4-5 months. | Under weight, congenital syphilis. 8 months. | Under weight, otitis media, rachitis. 43 months. | Under weight following an acute indigestion. 64 months. | Under weight. 5-6 months. | Infantile atrophy. 64-7 months. | Under weight, gaining weight rapidly. 5-53 months. | Under weight. 44 months. | Under weight. 3 months. | Under weight (slightly). 4 months. | Infantile atrophy. 3 months. | Normal infant, weighing more than the average. 5 months. | Infantile atrophy. 24-4 months. | Infantile atrophy. 24 months. | Under weight. 5-6 months. | Infantile atrophy ? (temperature not subnormal). 12 months. | Under weight. 54 months. | Normal infant, weighing more than average. 33-9 months. | Prematurity; congenital syphilis; infantile atrophy in subnormal temperature, and convalescent stage. 7 months. | Normal infant. PH PAMO SSMS SOD a> aE P EDS Pua DDoyvoZzZeee errr Anayhyvaa & Gas PORE ae TEENS CEE a TES SUE Ne MB sty4o 4 supe * RESULTS OF OBSERVATIONS ON THE GASEOUS EXCHANGE. ‘With an investigation extending over so many months and dealing with so many subjects as were used in this research, it is obviously impracticable to present protocols for each observation. On the other hand, as the carbon-dioxide production, oxygen consumption, pulse- rate, and muscular activity were accurately recorded in each experi- mental period, it seemed desirable to present the data in permanent form. This is done in table 23. Accordingly, the carbon-dioxide production per hour, respiratory quotient, average pulse-rate, and the estimated activity are given for 84. GASEOUS METABOLISM OF INFANTS, all of the observations and one line of the table is assigned for each experimental period. The arrangement by subjects is arbitrarily alpha- betical, the observations with each infant being recorded in chrono- logical order. Additional information is given as to the sex, age, and body-weight without clothing for the infants included in the study. While the carbon-dioxide production has been calculated on an hour basis, the actual length of the periods is also given, and the carbon- dioxide production for the individual periods may be readily calculated. No period is included which was less than 10 minutes in length. The results for the preliminary period of nearly all of the observations are given, usually appearing in the first line of the data, but as these are not used either in securing the average minimum metabolism,? or in com- puting the respiratory quotient, the experimental periods are bracketed to indicate this. No time is given for the observations, as the experi- ments were almost without exception carried out in the afternoon. The relation between the times of the observation and of the last feeding is recorded in the footnotes of the table; when this is not indicated, the feeding was invariably within 3 hours of the time when the infant was placed in the apparatus. Usually the preliminary period ended about 1 to 13 hours after feeding. A key to the designa- tions of the relative activity is placed at the head of the table. A full explanation of this method of estimating the activity may be found on p. 186. TaBLE 23.—Results of observations on the gaseous exchange of infants. [I, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Date Geil aa ees Length of feos Respiratory | Average | Relative aves WE clothi period. | produced | quotient. | pulse-rate.| activity. BBs per hour.! 1913. | M.A., male, 9 mos. mins. gm. Nov. 12 | 5.70 kilos.......... 203 5.71 asec 117 Vv 30 4.66 103 III 30 5.04 0.81 103 Til 30 4.64 . 101 Ilr 42 5.01 104 IV Nov. 14 | 5.63 kilos......... 71 5.97 suns 125 VI 30 4.68 105 II 30 4.96 0.79 101 III 22 5.65 113 VI Nov. 17 | 5.80 kilos......... 25} 6.45 ayasiten 118 IV 30 5.90 114 WI 30 5.96 0.88 116 IV 23 5.66 110 IV 22 5.29 110 Ill 1Calculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. STATISTICS OF OBSERVATIONS. 85 TaBLe 23.—Results of observations on the gaseous exchange of infants—Continued. (I, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon Date. oe ai ree t Length of | dioxide | Respiratory | Average | Relative clothing period. | produced | quotient. |pulse-rate.| activity. per hour.1 1913. M. A. (cont.). mins. gm. Nov. 17?| 5.73 kilos.......... 35 5.45 sie 123 VI 35 4.87 } 0.80 { 103 II 30 5.00 ‘i 108 Ill Nov. 18?| 5.50 kilos.......... 26 5.28 seesita 125 VI 29 4.86 116 Vv 30 5.30 > 0.78 118 IV 25 5.69 134 VI Nov. 18*| 5.48 kilos......... 17 4.73 117 IV 27 4.64 110 III 30 5.00 > 0.73 3 114 III 34 5.49 118 Vv F. B., male, 5} mos. Apr. 23 | 4.75 kilos.......... 10 7.38 127 IV 30 5.44 112 II 20 7.68 122 Ill 30 5.42 > 0.87 4 112 Il 80 5.74 117 II 29 5.50 107 II Apr 245 | 4.83 kilos.......... 11 7.47 dastnles 123 IV 28 5.19 112 II 29 5.15 117 Ill 22 4.80 r «60.85 107 I 23 5.22 114 I 30 6.74 138 VI Apr. 25 | 4.75 kilos........... 14 6.69 aah 118 III 20 5.58 111 II 30 6.14 116 Ill 18 5.30 r 6890.86 107 III 20 6.27 113 IV 254 §.11 J 101 II Apr. 29 | 5.15 kilos........... 14 5.91 sion 126 II 23 5.79 119 I 25 6.07 121 III 24 5.88 r 0.88 4 114 III 22 6.41 116 IV 25 5.38 108 II J. B., male, & mos. Mar. 15 | 3.23 kilos.......... 11 3.71 aides 109 II 41 3.95 113 IV 27 3.76 | 0.94 103 II 21 2.94 94 Il 15 4.08 acciees 102? Il 1\Calculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. “Last feeding was about 6 hours previous to these observations. 3Last feeding was about 20 hours previous to these observations. Sterile water was substi- tuted for food at subsequent times of feeding. 4Last feeding was about 25 hours before these observations. Sterile water was given in place of food at subsequent times of feeding. 5Last feeding was about 7 hours previous to these observations. Sterile water was substi- tuted for food at subsequent times of feeding. 86 GASEOUS METABOLISM OF INFANTS. TABLE 23.—Results of observations on the gaseous exchange of infants—Continued. [I, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon Date. ae cd Length of | dioxide | Respiratory | Average Relative clothing period. | produced | quotient. |pulse-rate.| activity. . per hour.! 1913, J. B. (cont.). mins. gm. Mar. 17 | 3.23 kilos.......... 12 5.35 96 II 30 3.88 97 II 21 4.14 0.96 106 IV 264 3.35 7 87 I 204 4.10 ake IV L. B., female, 4 mos. Feb. 1] 4.06 kilos.......... 12 5.85 135 Vv 30 3.80 127 II 30 4.14 133 I 30 3.84 0.84 123 I 30 3.90 122 I 30 3.84 120 III Hes. 3 lies saiauietdenas de 10 6.00 ses 139 IV 30 4.00 127 II 37 5.04 0.91 133 Vv 18 4.33 125 IV Feb. 4 | 4.04 kilos........... 30 4,24 121 IV 17 4.76 127 Vv 17 5.96 130 VI Feb. 5 | 4.01 kilos........... 13 4.94 135 Vv 30 4.08 121 Il 27 5.40 0.92 138 Vv 19 5.34 136 VI 14 5.61 ‘ 127 Vv 30 4.22 119 II 30 4.04 0.95 121 III 30 4,12 117 III L.R.B.,female,4mos. Nov. 1 | 6.08 kilos........... 17 6.28 ee ake Vv 27 4.64 bes Ill 55 6.08 0.80 ad. VI 30 4.30 rare III Nov. 3 | 6.05 kilos........... 30 4.62 \ 0.85 { oe, II 50 6.14 $64 VI Nov. 3? | 5.93 kilos,..........- 23 6.68 oe39 137 VI 23 4.36 106 III 26 4.18 0.77 113 IV 30 4.20 107 I Nov. 4° | 6.95 kilos........... 29 4.12 102 II 30 4.52 0.73 110 II 29 4.14 103 III Nov. 44 | 5.95 kilos........... 51 5.96 aes ake vI 29 4,39 \ 0.74 { Reh Il 35 5.54 f 124 VI 1Calculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. 2Last feeding was about 4% hours before these observations, sterile water being given in place of food at the next time of feeding. 3Last feeding’was about 193 hours before these observations. Sterile water was substituted for food at subsequent times of feeding. ‘Last feeding was about 24 hours before these observations. Sterile water was given in place of food at subsequent times of feeding. STATISTICS OF OBSERVATIONS. 87 TaBLE 23.—Results of observations on the gaseous exchange of infants—Continued. (I, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VIL, Very active, most or all of the time.] Carbon Date. coo t Length of | dioxide | Respiratory | Average | Relative clothing period. produced quotient. |pulse-rate.| activity. : per hour.! 1913. |Z. R.B.(cont.),44mos.| mins gm. Nov. 5 | 6.00 kilos........... 28 6.43 126 VI 30 4.70 105 Ill 22 5.73 0.83 119 Vv 30 4.70 ; 106 II 22 4.96 110 Ill A. C., female, 14 mos. Mar. 19 | 3.00 kilos........... 10 3.48 188 IV 30 2.20 120 I af 2.49 0.84 129 III 294 2.24 ‘i 119 II 303 2.81 132 IV Mar. 20 | 3.02 kilos........... 26 3.35 142 Ill 30 2.40 131 II 24 2.53 0.93 128 II 274 2.23 120 II Mar. 24 | 2.95 kilos........... 32 2.94 139 Ill 30 2.48 131 I 30 2.84 141 Ill 27 2.64 Oa88 132 I 25 3.02 1386 IIt 1914. M,C. aoe sh mos. Jan. 6.05 kilos. ee 163 6.23 119 VI 25 4,42 99 II 26 4.78 109 II 37 4.52 Dees 107 II 20 6.09 124 VI Jan. 2 | 6.20 kilos........... 29 5.54 121 Vv 23 5.22 102 II 23 4.67 0.88 102 III 30 5.98 122 VI Jan. 8 | 6.25 kilos........... 243 6.56 124 VI 26 4.82 99 II 22 5.84 | 0.85 | 107 Vv 31 5.18 103 II Jan. 5 | 6.08 kilos........... 434 6.30 areas 136 VI 25 4.75 0.90 121 IV A. D., female, 4 mos. Apr. 28 | 2.65 kilos isseySrielio.o, 22,02 46 4.43 wages 128 Vv 84 3.94 0.83 126 Vv May 8 | 2.95 kilos........... 20 3.27 112 IIT 23 3.34 121 I 24 3.00 110 I 22 2095 0.89 106 II 30 2.86 106 tI 20 2.76 99 II 20 4.71 146 VI 1Calculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. 2Last feeding was about 7 hours previous to these observations. tuted for food at subsequent times of feeding. Sterile water was substi- 88 GASEOUS METABOLISM OF INFANTS. TABLE 23.—Results of observations on the gaseous exchange of infants—Continued. {I, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon Date. at par Length of| dioxide | Respiratory | Average | Relative clothing. period. | produced | quotient. | pulse-rate.| activity. . per hour.! 1913. | A.D. (cont.), 43 mos. mins. gm. May 12 | 3.01 kilos........... 14 4.54 127 I 30 4.20 131 III 32 4.18 131 II 30 3.56 O88 116 I 33 3.71 123 II May 15? | 3.20 kilos........... 21 5.14 143 Vv 30 3.80 124 III 29 3.37 0.94 111 II 19 3.98 . 123 IV 28 5.74 154 VI May 19? | 3.23 kilos........... 14 3.13 115 I 30 3.10 120 II 25 3.02 113 I 31 3.12 0.77 117 Ill 23 2.66 104 I 30 8.74 128 Vv A. D. (cont.), & mos. May 24 | 3.43 kilos,.......... 31 5.83 137 Vv 24 4,28 118 III 30 4.30 0.92 127 II 26 3.60 ‘ 113 I 30 3.92 124 Ill M. D., male, 2 weeks. Mar. 8 | 4.08 kilos........... 19 3.95 Sos biys 150 IV 30 3.14 \ 0.86 { 136 IV 30 4.64 i 152 Vv Mar. 10 | 3.97 kilos........... 17 3.67 145 IV 21 3.00 144 Ill 30 2.92 140 Ill 30 3.00 0.80 140 Ill 30 2.86 135 II 25 2.74 131 Ill Mar. 11 | 4.00 kilos........... 30 2.90 133 IV 30 2.66 129 I 30 2.88 0.84 123 II 30 2.60 121 II 20 3.99 137 IV M. D. (cont.), 3 weeks. Mar, 14 | 4.00 kilos........... 22 3.08 128 IV 37 3.47 0.83 132 Vv 24 4.15 149 VI 1Calculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. 2Last feeding was about 3 hours before these observations, sterile water being given in place of food at the time of feeding preceding these observations. ’Last feeding was about 21 hours previous to these observations. tuted at subsequent times of feeding. Sterile water was substi- STATISTICS OF OBSERVATIONS. 89 TABLE 23.—Results of observations on the gaseous exchange of infants—Continued. (I, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon Date Buh . ne Length of | dioxide | Respiratory | Average | Relative . us iod duced tient Ise-rat tivit clothing: period. | produce L quotient. |pulse-rate.| activity. per hour. 1913. R. E., male, 44 mos. mins. gm. Dec. 4 | 5.10 kilos........... 41 6.64 129 VI 24 4.55 114 IV 23 4.70 0.83 118 II 21 6.14 137 Vv Dec. 4? | 5.03 kilos........... 463 5.89 141 VI 22 4.45 121 III 32 4,22 0.82 115 IIl 29 4.04 117 IV Dec. 5° | 5.00 kilos....... sue 163 4,22 106 Ill 30 3.92 109 II 24 4.08 0.74 115 II 30 3.90 114 II 30 5.18 137 Vv Dec. 64 | 4.95 kilos........... 15 4.36 Be 119 III 29 3.68 \ 0.72 { 119 III 111 6.46 : 141 VI Dec. 9/| 5.03 kilos........ aye 19 5.94 133 Vv 31 4.63 114 Ill 33 4.36 0.74 115 II 31 5.54 131 VI Dec. 12 | 5.00 kilos........... 73 7.61 ieee 140 VI 26 4.32 0.99 113 IV E. F., male, 8 mos. Dec. 2 | 7.05 kilos........... 183 8.98 Jabs 146 VI 31 4.20 \ 0.81 { 109 II 26 8.45 : 140 VI Dee. 3 | 7.08 kilos........... 324 9.32 edited 140 VI 25 4.70 } 0.89 { 113 Ill 24 8.78 : 137 VI E. G., male, 10 mos. Nov. 26 | 9.48 kilos....... wuiea 153 6.77 ee 112 II 31 6.70 119 Vv 23 6.63 115 IV 23 5.97 0.72 111 II 30 6.78 120 II 30 8.44 133 VI Nov. 27 | 9.45 kilos........... 47k 7.71 eee 116 VI 32 6.36 \ 0.76 { 109 Il 194 6.74 : 115 IV 1Calculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. 2Last feeding was about 6 hours before these observations. for food at subsequent times of feeding. : 3Last feeding was about 18% hours previous to these observations. in place of food at subsequent times of feeding. 4Last feeding was about 24 hours before these observations. for food at subsequent times of feeding. Sterile water was substituted Sterile water was given Sterile water was substituted 90 GASEOUS METABOLISM OF INFANTS. TaBLE 23.—Results of observations on the gaseous exchange of infants—Continued. [I, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon Date. oon eS, Length of | dioxide Respiratory Average Relative clothing period. | produced | quotient. | pulse-rate.| activity. 7 per hour. 1913. E. G. (cont.) mins. gm. Nov. 27? | 9.45 kilos........... 18 6.77 eeshees 105 I 30 5.76 98 I 28 6.11 0.71 104 II 30 5.94 100 IV Nov. 283 | 9.18 kilos........... 173 6.58 111 III 25 6.70 115 Vv 26 6.81 0.72 113 IV 30 5.94 , 108 II 25 7.87 137 VI Nov. 28! | 9.20 kilos........... 34 7.13 115 Vv al 6.46 112 IV 32 6.11 0.70 110 Til 21 6.03 112 IV 26 7.75 126 VI E. K., male, 17 mos. Dec. 16 | 8.03 kilos..... Saas 72 7.84 gas 116 Vv 29 6.70 \ 0.30 { 105 II 29 6.83 ; 105 II F. K., male, 7 mos. May 2 | 5.68 kilos........... 22 7.45 138 VI 16 6.34 121 IV 22 5.40 0.84 109 I 30 5.96 116 III 30 7.58 141 Vv May 3°! 5.68 kilos........... 13 6.69 129 Vv 20 5.13 109 I 27 5.62 0.78 122 II 20 8.94 168 VI May 5° 5.70 kilos..........- 14 7.24 128 Vv 23 5.30 108 III 32 5.64 0.84 118 III 24 5.30 : 111 II 20 6.78 136 Vv May 6 | 5.70 kilos........... 19 7.39 7 136 VI 20 5.73 112 II 20 5.82 112 II 23 6.37 0.89 119 IV 21 5.71 109 \IT 30 5.98 119 Tit 1Calculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. 2Last feeding was about 5} hours before these observations. Sterile water was given in place of food at subsequent times of feeding. 3Last feeding was about 19} hours previous to these observations. Sterile water was substi- tuted in place of food at subsequent times of feeding. ‘Last feeding was about 244 hours before these observations. Sterile water was given in place of food at subsequent times of feeding. 5Last feeding was about 3 hours previous to these observations, sterile water being substi- tuted for food at the next time of feeding. ‘Last feeding was about 6 hours previous to these observations. Sterile water was given in place of food at subsequent times of feeding. STATISTICS OF OBSERVATIONS. 91 TasLe 23.—Results of observations on the gaseous exchange of infants—Continued. [I, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon Date. ae Length of | dioxide | Respiratory | Average | Relative clothing period. | produced | quotient. |pulse-rate.| activity. per hour.! 1913. F. K. (cont.) mins. gm. May 7?! 5.75 kilos........... 14 7.11 anes 133 Vv 23 5.03 103 II 19 5.49 0.78 113 III 82 8.06 160 VI May 93) 5.72 kilos........... 18 7.60 seas 138 VI 18 5.30 113 III 21 4.89 0.77 105 II 20 7.20 159 VI A. L., female ,3} mos. June 14 | 3.10 kilos........... 21 5.11 Para 136? VI June 16 | 3.10 kilos........... 60 4.82 acsers 127 VI 15 4.28 \ 0.89 { 110 I 23 4.77 : 138 Vv June 20 | 3.14 kilos........... 82 6.18 saitines 145 VI 82 6.69 uss 157 VI June 234; 3.13 kilos........... 20 5.37 ee 142 VI 44 6.52 ees 161 VI June 244] 3.20 kilos........... 14 4,11 eae 119 IV 21 3.00 \ 0.88 { 112 II 24 4.45 , 133 VI A. L. (cont.), 4 mos. June 28 | 3.15 kilos........... 42 4.73 ees 118 Vv 17 3.42 \ 0.81 { 101 II 22 5,21 : 125 VI 36 5.17 Seuss 137 VI E. L., male, 4 mos. May 17 | 4.15 kilos.......... 12 6.75 ate 136 III 23 4.28 126 II 24 4.98 134 Til 30 4.32 0.83 127 I 30 4.90 130 III 29 4.39 132 Ill May 20 | 4.25 kilog........... - 25 6.07 Eyer 149 IV 49 6.39 0.92 158 VI May 215| 4.30 kilos........... 13 4,48 Sei 128 I 47 6.87 0.93 159 VI R. L., male, 6} mos. Mar. 3 | 8.10 kilos.......... 30 6.20 112 II 30 6.54 0.87 117 II 30 6.84 . 121 III 30 6.66 126 II 1Calculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. 2Last feeding was about 9 hours previous to these observations. Sterile water was substituted for food at subsequent times of feeding. 3Last feeding was about 21 hours previous to these observations. Sterile water was substi- tuted for food at subsequent times of feeding. 4On June 23 and 24 the last feeding was about 3 hours previous to the observations, sterile water being given in place of food at the next time of feeding. 5Last feeding was about 3 hours previous to these observations. Sterile water being given in the place of food at the next time of feeding. 92 GASEOUS METABOLISM OF INFANTS. TaBLE 23.—Results of observations on the gaseous exchange of infants—Continued. (I, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon Date. Sone ees Length of | dioxide Respiratory Average Relative clothing. period. | produced | quotient. | pulse-rate.| activity. 5 per hour.! 1913. R.L. (cont.) mins. gm. Mar. 4 | 8.09 kilos.......... 22 9.38 138 Vv 30 7.62 129 IV 30 6.84 0.87 128 Ill 30 8.06 : 137 Vv 30 7.20 130 III Mar. 7 | 7.97 kilos........... 61 8.28 141 VI R. L. (cont.), 83 mos. Apr. 26 | 7.68 kilos.......... 25 8.18 ee 138 Ill 20 7.65 137 II 30 7.64 0.88 137 Il 26 7.75 149 IV May 9 | 7.25 kilos .......... 20 8.46 Seas 125 Vv 21 6.89 0.89 119 IV May 10 |} 7.18 kilos......... ‘ 32 7.31 bg iay 115 Vv 26 5.91 0.81 105 II May 13 | 7.25 kilos........... 40 8.30 : 131 VI May 14°] 7.25 kilos.......... 15 7.96 119 IV 20 6.78 110 II 22 6.74 114 Ill 22 7.06 0.86 3 107 IV 30 6.90 107 Ill 18 7.50 114 IV May 16*| 7.30 kilos........... 23 6.99 125 Vv 20 5.64 110 II 30 6.40 114 Ill 26 5.93 0.74 110 Ill 29 6.14 113 Ill 28 5.66 111 IV D. M., male, 11 mos. Mar. 26 | 5.21 kilos.......... 32 7.13 ieee 151 VI 46 6.53 138 Vv 22 5.43 0.89 123 III 30 7.66 147 VI Mar. 27 | 5.28 kilos..... eae 55 9.39 ‘ 176 VI Mar. 31 | 5.15 kilos........... 15 8.48 161 Vv 30 6.26 140 Ill 30 6.04 132 III 15 5.48 0.84 121 Ill 26 5.77 ’ 127 IV 30 5.24 115 II 17 5.75 120 III 1Calculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. 2Last feeding was about 3 hours previous to these observations, sterile water being given in place of food at the next time of feeding. ‘Last feeding was about 21 hours previous to these observations. stituted for food at subsequent times of feeding. Sterile water was sub- STATISTICS OF OBSERVATIONS. 93 TaBLE 23.—Results of observations on the gaseous exchange of infants—Continued. [I, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon Se: x, age, and Length of | dioxide | Respiratory | Average | Relative Date. weight without , : ivi clothing. period. | produced | quotient. |pulse-rate.| activity. per hour.) 1913. F. M., male, 4 mos. mins. gm. Jan. 22 | 3.57 kilos........... 36 7.37 sass 140 VI 26 4.75 127 IV 30 5.06 0.89 127 Vv 49 4.27 ‘ 118 III 30 4.48 116 Il Jan. 23 | 3.52 kilos........... 7 7.27 aioe 152 VI 30 4.02 119 II 30 4.46 0.86 123 II 30 4.00 116 I F. M. (cont.), & mos. Feb. 20 | 3.86 kilos........... 57 7.53 sribsene 147 VI 27 7.40 create 141 VI 30 4.86 0.83 { 119 Ill 30 4.70 ‘ 118 II J.M., male, 8 mos. Apr. 2 5.54 kilos.......... 30 6.82 121 II 23 7.25 122 II 24 7.63 0.87 125 IV 20 7.02 7 119 III 13 8.35 132 IV 25 6.94 115 Il Apr. 4 | 5.72 kilos........... 10 8.70 Seas 132 Vv 25 7.08 112 I 30 7.40 113 Ill 23 7,38 111 IV 18 6.70 0.89 102 II 30 7.34 112 IV 16 6.41 97 I 20 8.49 115 VI M.M., female, 4mos. June 2 | 5.43 kilos....... aece 20 5.91 Se 113 Vv 23 4.38 esciers 95 I 22 4.58 sucht 101 Til 24 6.18 Bales 118 VI June 3? 5.46 kilos........... 27 4.00 96 1 25 4.34 0.87 99 II 30 4.28 96 II June 5%} 5.55 kilos........... 28 4.84 sees 107 Vv 30 3.66 93 I 21 4.06 96 Tit 27 3.80 Oe 90 II oa 4.85 113 VI iCalculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. 2Last feeding was about 3 hours previous to these observations, sterile water being substituted for food at the next time of feeding. 3].ast feeding was about 9 hours previous to these observations. Sterile water was given in place of food at subsequent times of feeding. 94 GASEOUS METABOLISM OF INFANTS. TaBLE 23.—Results of observations on the gaseous exchange of infants—Continued. [I, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon Date. aoae ae Length of | dioxide | Respiratory | Average Relative clothing period. | produced quotient. | pulse-rate.| activity. i per hour.! 1913. M. M. (cont.). mins. gm. June 7?| 5.40 kilos........... 16 4.95 111 VI 28 3.62 98 I 19 4.52 104 IV 30 3.64 0.74 96 II 30 3.64 99 II 20 5.46 127 VI E. N., female, 6 mos. May 21 | 5.40 kilos........ eae 52 9.10 150 VI 19 7.36 134 VI 20 4.98 0.90 109 I 20 5.52 121 a May 22%} 5.40 kilos........... 23 5.48 119 II 28 5.40 117 I 20 5.49 0.92 112 I 32 5.42 115 I 20 6.99 139 Vv May 234| 5.41 kilos........... 72 7.83 152 VI 19 4.52 109 I 22 5.07 116 I 20 4.56 Ose 106 I 20 5.10 124 I May 26?! 5.25 kilos........... 15 6.16 126 IV 20 4.50 104 I 30 4,82 112 I 30 4.84 os 113 I 31 5.81 140 Vv May 284| 5.38 kilos........... 20 5.55 118 Ill 25 4.92 106 I 21 5.09 111 I 22 5.10 0.86 103 I 25 §.21 110 II 23 4.62 105 I May 29°| 5.45 kilos........... 14 5.79 124 Ill af 5.31 116 II 30 5.54 0.88 116 II 27 5.82 - 115 Ill 20 5.40 110 Ill E. N. (cont. ) ee mos. May 31?| 5.48 kilos.. 18 6.97 Saaade 117 III 25 5.33 104 I 24 5.65 114 II 23 5.19 is 103 I 20 6.78 i 130 Vv 1Calculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. 2Last feeding was about 21 hours before these observations. Sterile water was given in place of food at subsequent times of feeding. ’Last feeding was about 3 hours previous to these observations, sterile water being substi- tuted for food at the next time of feeding. 4Last feeding was about 9 hours previous to these observations. Sterile water was substi- tuted for food at subsequent times of feeding. ’Last feeding was about 4 hours before these observations, sterile water being given in place of food at the next time of feeding. STATISTICS OF OBSERVATIONS. 95 TABLE 23.—Results of observations on the gaseous exchange of infants—Continued. [I, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon Date. oe aac Length of | dioxide Respiratory Average Relative clothing. period. | produced | quotient. | pulse-rate.| activity. per hour.! 1913. L. O., male, & mos. mins. gm. Feb. 10 | 2.99 kilos........... 32 3.60 wha 106 III 30 3.88 sere 105 IV 30 3.98 heb 110 IV 30 3.92 Beee 109 IV Feb. 12 | 2.98 kilos........... 30 3.82 Bead 110 III 19 3.98 Bee 102 II 30 4.14 acne 109 IV 30 4.20 a ae 113 IV L. O. (cont.), 53 mos. Feb. 18 | 3.05 kilos........... 30 4.00 119 III 30 3.90 0.88 114 Til 30 4.08 i 121 Iv 30 3.86 115 IV Feb. 24 | 3.18 kilos........... 10 4.80 110 Vv 20 4.35 113 IV 22 3.63 99 II 30 4.12 0.87 111 TET 30 3.86 103 III 30 3.94 103 II Feb. 25 | 3.15 kilos........... 12 5.85 3 116 Vv 30 4.28 111 IV 30 4.22 107 II 30 3.84 r 0.90? 100 Til 30 4.04 104 Vv 30 4.18 111 IV Feb. 28 | 3.12 kilos........... 30 4.06 ( 112 III 30 4.06 103 II 30 3.90 0.95 102 II 25 4.20 125 VI 30 4.30 119 IV Mar. 1 | 3.15 kilos........... 11 4.42 J11 Iv 30 4.00 105 III 30 4.06 107 II 30 3.58 r 0.97 93 I 30 4.12 107 Vv 30 4.32 105 IV L.O. front ist 6 mos. Mar. 7 | 3.31 kilos.. : 10 5.52 es 121 VI 30 4.04 } 0.96 { 109 HI 22 4.25 . 115 Vv Mar. 12: | 3.38 KilGsin.cc.050 sa 5 30 4.30 123 II 20 4.74 129 Ill 30 4.52 0.89 130 Iv 23 4.62 | 122 HI 30 5.14 { 138 Vv 1Calculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. 2Determined for the time included in the first two and the last two periods. 96 GASEOUS METABOLISM OF INFANTS. TasBLe 23.—Results of observations on the gaseous exchange of infants—Continued. {I, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon Date. ae oe Length of | dioxide | Respiratory | Average | Relative clothing period. | produced | quotient. | pulse-rate.| activity. iB per hour.! 1913. J. P., male, 64 mos. mins. gm. Oct. 31 | 5.40 kilos........... 40 7.71 Sets 140 VI 30 5.84 desk II 30 6.40 III 29 5.52 poet i I 19 6.41 113 IV Nov. 6 | 5.60 kilos........... 25 6.72 114 IV 48 6.26 0.89 112 IV 33 6.45 110 Vv Nov. 7 | 5.65 kilos...... Bees 13 7.11 121 IV 30 6.48 102 I 30 6.14 0.91 103 II 35 6.29 z 107 IV 30 5.54 106 II Nov. 10 | 5.55 kilos........... 16} 6.91 115 Vv 30 6.40 105 IV 30 6.06 0.89 104 IV 30 6.18 . 107 III 30 6.16 106 IV Nov. 107} 5.40 kilos........... 88} 7.05 stat 126 VI 30 5.00 \ 0.86 { 102 Ill 30 5.52 F 108 Ill Nov. 113] 5.35 kilos........... 20 5.82 119 Vv 30 5.06 106 II 28 5.36 0.79 110 IV 20 5.55 108 IV J. P. (cont.), 7 mos. Nov. 114| 5.30 kilos........... 19% 5.63 129 Vv 35 5.34 112 Vv 32 6.06 0.73 117 vI 23 4.96 107 | IV W.P., male, & mos. Jan. 27 | 4.31 kilos........... 15 6.92 143 vI 30 6.26 134 Vv 30 5.16 0.88 120 IV 30 6.12 130 Vv Jan. 29 | 4.26 kilos........... 15 7.32 138 VI 16 5.81 122 VI 23 5.95 0.86 121 VI 274 4.41 99 Ill 124 5.76 115 VI 1Calculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. 2Last feeding was about 53 hours before these observations. Sterile water was substituted for food at subsequent times of feeding. Last feeding was about 19 hours previous to these observations. Sterile water was substi- tuted for food at subsequent times of feeding. 4Last feeding was about 24% hours before these observations. Sterile water was given in place of food at subsequent times of feeding. STATISTICS OF OBSERVATIONS. 97 TaBie 23.—Results of observations on the gaseous exchange of infants—Continued. {I, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon oye Rar boast vai Length of | dioxide | Respiratory | Average | Relative clothing. period. produced quotient. |pulse-rate.| activity. per hour.! 1913. W. P. (cont.). mins. gm. Jan. 30 | 4.28 kilos........... 26 5.58 117 VI 30 4.84 96 II 30 4.70 95 Til 30 4.46 0.92 94 III 30 4.60 | 97 II 19 4.89 109 IV Jan. 31 | 4.34 kilos........... 12 5.65 120 VI 30 4.46 95 I 30 4.78 102 ir 30 4.64 0.92 98 Ill 30 4.36 96 II 17 5.26 106 Vv W. P. (cont.), 5} mos. Feb. 11 | 4.57 kilos........... 36 7.02 135 VI D. Q., male, 44 mos. Dec, 22 | 5.20 kilos...... eae 30 8.93 save 142 VI 29 4.03 0.89 97 Ill Dec. 23 | 5.35 kilos........... 26 7.13 soaks 130 VI 30 4.48 106 I 30 4.54 0.81 102 II 30 4.06 98 II E. R., male, 3 mos Apr. 11 | 4.59 kilos........... 16 5.44 139 Vv 21 4.23 129 III 33 4.62 0.83 133 IV 57 4.38 _ 130 IV 17 4.16 126 Vv Apr. 12 | 4.49 kilos.......... 17 7.06 151 VI 21 4.26 124 IV 63 6.10 0.73 146 VI 23 4.80 . 131 Vv 24 3.58 122 II Apr. 14 | 4.49 kilos.......... 12 4.75 131 VI 27 4.11 119 Ill 31 4.32 124 IV 22 4.50 0.86 124 II 34 4.15 123 IV 20 4.14 119 I Apr. 15? | 4.49 kilos....... Sidiess 14 4.84 mae 120 VI 20 4.02 113 IV 26 3.72 110 Til 25 3.67 0.80 114 Ilr 26 3.90 . 110 Il 30 3.94 117 IV 21 3.37 106 II 1Calculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. 2Last feeding was about 3 hours previous to these observations, sterile water being given in place of food at the next time of feeding. 98 GASEOUS METABOLISM OF INFANTS. TaBLH 23.—Results of observations on the gaseous exchange of infants-—Continued. (I, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon Date oo marae Length of | dioxide | Respiratory | Average | Relative 7 period. | produced | quotient. | pulse-rate.| activity. clothing. eer kour! 1913. K. R., male, 4 mos. mins, gm. Apr. 5 | 3.14 kilos........... 78 4.51 asthe 5 116 VI 23 2.74 \ 0.83 { 91 II 40 5.33 . 140 VI Apr. 7 | 3.19 kilos........... 10 5.16 Mecivs, 116 Vv 30 3.20 107 I 30 3.44 108 Ill 27 3.31 0.88 108 II 30 3.44 115 III 26 3.14 106 II A. S., male, 3 mos. Mar. 28 | 6.04 kilos........... 11 9.00 yn 143 Vv 117 6.12 0.92 142? VI Mar. 29 | 6.10 kilos........... 37 8.51 sista eu VI Apr. 1 | 6.02kilos........... 16 4.73 ; 0.81 { 117 IV 234 4.19 . 113 II E. S., popes 5 mos. Mar. 21 | 2.95 kilos... , 17 4.98 126 VI 30 3.78 112 IV 30 3.36 0.94 | 115 r 30 3.30 . 107 III 30 3.82 114 Vv Mar. 22 | 3.00 kilos...... setvieane 13 4,29 99 Vv 26 3.25 101 III 20 4.11 = 114 IV 30 3.34 Bote 98 I 30 3.30 92 I Mar. 25 | 3.03 kilos........... 19 4.52 119 Vv 30 3.66 112 II 30 3.56 0.91 115 Ill 30 3.52 ‘ 110 Ill 30 3.34 100 Ill E.H.S. ye: fare mos. Nov. 13 | 2.85 kilos.. re 173 3.98 123 Vv 38 3.43 116 Vv 30 2.64 0.90 103 II 30 2.88 : 108 IV 33 3.38 121 VI Nov. 21 | 2.85 kilos........... 17 2.68 114 Ill 48 2.75 116 Vv 34 2.51 0.77 113 II 41 2.33 : 109 III 24 3.00 123 Vv E. HH. S.(cont.), 3mos. Dec. 1 | 2.88 kilos........... 40 2.93 Sete 83 Vv 32 2.61 78 II 25 3.12 91 IV 33 3.05 oe 89 IV 32 3.69 109 Vv 4ICalculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. STATISTICS OF OBSERVATIONS. 99 TaBLEe 23.—Results of observations on the gaseous exchange of infants—Continued. f1, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon Date. cae Fe t Length of | dioxide Respiratory Average Relative clothing period. produced quotient. |pulse-rate.} activity. per hour.! 1913. |E.H.S. pent eae mos.| mins. gm. Dec. 17 | 3.08 kilos.. : 17 3.60 Beis 122 III 24 2.93 113 Til 39 4.42 0.97 127 VI 31 3.25 113 II E. H.S. (cont.), 4mos. Dec. 29 | 3.15 kilos........... 18} 3.76 116 IV 24 3.68 112 III 24 3.20 103 i 30 3.38 O02 107 II 34 4.38 119 VI G. S., male, ee mos. Feb. 13 | 3.24 kilos... i 18 4,20 131 VI 23 3.16 122 III 22 4.36 » 0:95 4 134 VI 26 4.50 132 VI Bebe 14s ciccsasacsaahercewss 32 5.64 150 vi 12 3.85 129 Vv 203 3.04 122 Il 303 3.80 r+ 0.92 123 Vv 30 3.36 116 III 29 3.06 110 II Feb. 17 | 3.33 kilos........... 19 5.81 152 VI 26 3.42 124 IV 30 3.50 125 Ill 30 3.42 ~ 6.83 4 124 IV 30 3.26 121 III 30 3.02 117 II Feb. 19 | 3.33 kilos........... 30 3.48 125 IV 30 3.56 130 ii 30 3.50 > 0.88 123 III 30 3.32 121 III 30 3.24 118 IV J.8S., male, § mos. June 6 | 4.20 kilos........... 18 4.47 sane 99 IV 50 5.12 0.95 108 Vv 40 5.63 Sian atd 123 VI June 11 | 4.10 kilos........... 16 5.03 snes 107 Vv 20 4.77 ecsiec¥ 103 Vv 29 4.16 100 Il 30 4.44 0.95 105 Ill 30 5.84 123 VI J. S. (cont.). 54 mos. June 12 | 4.05 kilos........... 19 6.63 pane 122 VI 30 6.40 0.98 121 VI June 17 | 4.35 kilos........... 15 5.76 Anke 118 Vv 20 4.53 102 Ill 30 4.86 0.97 99 I 23 4.62 105 IV 1Calculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. 100 GASEOUS METABOLISM OF INFANTS. TaBLE 23.—Results of observations on the gaseous exchange of infants—Continued. {I, Very quiet, probably asleep; II, Slight movements, few in number, III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon D. Sex, age, and Length of | dioxide | Respiratory | Average | Relative ate. weight without : : Fes ‘ period. | produced quotient. | pulse-rate.| activity. clothing. 1 per hour. 1913. J. 8S. (cont.) mins. gm. June 182 | 4.40 kilos....... Bivies 15 6.16 112 Vv 23 4.23 95 II 30 4.58 105 I 22 4.72 111 IV 30 8.18 161 VI June 19?} 4.51 kilos........... 41 8.63 183 VI 15 5.40 ees 123 II 20 4.56 } 0.88 { 115 III 30 5.02 , 128 Il June 21° | 4.47 kilos........... 30 4.54 115 II 15 5.72 117 II 24 4.75 116 II June 24 | 4.50 kilos....... fhacsid 15 6.60 sats 132 Vv 27 6.38 0.95 a85 Vv June 26 | 4.55 kilos....... area 33 7.22 140 VI 23 5.63 115 I 25 6.10 0.96 129 Vv 27 6.22 122 IV J. S.(cont.), 6 mos. June 27 | 4.53 kilos......... aa 21 5.51 } 0.97 { 111 I 33 5.22 F 120 II P.S., male, 12 mos. Dec. 18 | 7.00 kilos..... Bitidesee 31 9.02 Suan 137 VI 19 7.29 114 IV 31 6.83 0.84 100 II 31 6.48 103 II Dec. 19 | 6.85 kilos........... 17 8.49 ete 118 Vv 30 6.24 101 II 30 6.98 100 II 23 6.16 0.84 95 II 20 8.91 124 vI Dec. 194 | 6.78 kilos..... Wea 43 6.81 whe 112 Vv 30 5.76 } 0.83 { 102 I 30 6.56 : 108 III Dec. 205 | 6.80 kilos........... 374 7.70 sates 128 VI 30 5.46 \ 0.71 { 98 Il 30 6.00 7 98 Il Dec. 208 | 6.58 kilos... ... Sea 21 6.68 suereve 109 Vv 30 5.20 ; 0.71 { 96 II 61 7.43 7 121 VI 1Calculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. 2Last feeding was about 3 hours previous to these observations, sterile water being given in place of food at the next time of feeding. 3On June 19 and June 21 last feeding was about 6 hours before the observations. Sterile water was substituted for food at subsequent times of feeding. 4Last feeding was about 5} hours before these observations. Sterile water was substituted for food at subsequent times of feeding. 5Last feeding was about 194 hours previous to these observations. Sterile water was given in place of food at subsequent times of feeding. ®Last feeding was about 243 hours previous to these observations. Sterile water was sub- stituted for food at subsequent times of feeding. STATISTICS OF OBSERVATIONS. 101 TaBip 23.—Results of observations on the gaseous exchange of infants—Continued. [I, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon Date. oe Length of | dioxide | Respiratory | Average | Relative slothing period. | produced | quotient. | pulse-rate.| activity. per hour. 1913. | H. T., male, 5} mos. mins. gm. Apr. 16 | 9.28 kilos........... 68 11.12 Sayeed 126 VI Apr. 17 | 9.33 kilos........... 10 5.82 eases 101 Il 26 6.55 \ 0.95 { 101 II 16 7.01 5 117 IV J.V., female, 34 mos Jan. 15 | 1.92 kilos........... 30 2.42 as 146 ? II 30 2.52 0.89 145? II ity 16 lov uendveaes< a xeemel an 14 3.47 en 136 II 30 1.44 \ 0.90 { 130 I 30 3.58 7 150 VI Pat. UF Nis eo na dear ve SES CRASS 16 2.89 ries 122 II 28 2.55 a aiece 129 IV 20 3.66 0.83 160 VI DAD 208 | erosrreveroucerata zoel dor doasStene va 36 3.55 eee 151 VI 30 2.26 \ 0.79 { 131 II 60 2.26 . 129 II Jan. 21 | 1.94 kilos....... Sonne 30 4.18 eens 156 VI DBD DEN 6 chests sacatets: tee oeeine-s 22 3.08 aie 121 Vv 65 2.78 } 0.38 { 132 Vv 224 2.80 : 132 Vv Jan 25 |icascuvereiw sone. s4 39 3.72 ee 145 VI 30 2.22 \ 0.85 { 126 III 30 3.04 : 143 ¥ J. V. (cont.), 4 mos JA 28 |. Scars ay Avinedenarczestoar arse 34 3.67 Bena 147? Vv 11 4.53 \ 0.94 { 160 VI 30 4.16 7 166 VI Feb. 11 | 2.10 kilos........... 20 3.18 sites 147 Vv 23 2.48 \ 0.94 { 138 IV 27 4.00 : 149 VI J. V. (cont.), 45 mos. Feb. 15 | 2.20 kilos....... Bante 30 2.74 he 141 II 30 2.86 ates 140 II 30 2.82 ah Sts 144 Ill 30 3.04 waits 137 IV 27 3.09 Brscetin 139 IV Feb. 26 | 2.45 kilos........... 18 4.07 er 143 Vv 66 3.65 142 Vv 30 3.60 0.91 139 ag 30 3.22 . 131 IV 30 3.36 130 II Feb. 27 | 2.45 kilos........... 28 3.96 aaa 143 VI 38 3.65 144 Vv 30 3.34 135 Ill 26 3.58 pee 141 Vv 30 3.28 136 III 1Calculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. 102 GASEOUS METABOLISM OF INFANTS. TABLE 23.—Results of observations on the gaseous exchange of infants—Continued. {I, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon Date a, Length of | dioxide | Respiratory | Average | Relative : ae thin period. | produced | quotient. |pulse-rate.| activity. g- per hour.! 1913. J. V.(cont.), & mos. mins. gm. Mar. 5 | 2.56 kilos........... 17 3.56 142 Il 35 3.67 147 IV 31 4.03 156 IV 31 4.35 0.92 152 IV 30 3.68 143 III 30 3.62 138 II Mar. 6 | 2.58 kilos.......... 16 4.43 147 IV 20 3.69 147 il 30 3.76 146 IV 30 3.68 0.94 140 III 30 3.76 7 137 III 30 3.24 131 i 20 3.81 133 IV J. V.(cont.), 5} mos. Mar. 13 } 2.73 kilos.......... 14 4.46 168 IV 25 3.91 156 Til 30 3.86 0.91 150 IV 30 3.76 146 It 30 3.58 141 II Mar. 27 | 2.98 kilos.......... 14 4.89 setae 144 Iv 30 3.90 \ 0.89 { 132 II 30 4.08 ; 134 Ill Mar. 29 | 3.08 kilos.......... 33 5.27 yan 148 VI 30 3.82 } 0.94 { 130 I 29 3.87 . 129 III J.V. (cont.), 6 mos Apr. 8 | 3.17 kilos.......... 45 4.18 145 Vv 25 3.62 132 II 20 4.17 0.82 134 IV 22 3.68 130 Ill 26 3.65 127 Il Apr. 9 | 3.17 kilos.......... 12 4.40 144 I 54 5.02 151 Vv 52 5.30 159 VI Apr. 10 | 3.17 kilos.......... 69 4.79 148 VI 22 3.74 \ 0.84 { 137 Ill 24 4.20 141 IV Apr. 17 | 2.89 kilos.......... 284 3.43 \ 0.79 {| 123 Vv 244 3.45 i 124 IV Apr. 18 | 2.98 kilos........ ree 10 3.60 130 I 22 3.27 123 II 18 3.63 128 Ill 24 3.53 0.82 126 IV 36 3.60 126 IV 29 3.39 128 IV 1Calculated from the weight{of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142, STATISTICS OF OBSERVATIONS. 103 TaBLE 23.—Results of observations on the gaseous exchange of infants—Continued. (I, Very quiet, probably asleep; II, Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon Date. ae sean Length of | dioxide Respiratory Average Relative clothing. period. | produced | quotient. | pulse-rate.| activity. per hour.! 1913. | J. V. (cont.),64 mos.| mins. gm. Apr. 21? | 2.98 kilos........... 52 4.26 ee 133 VI 26 3.55 123 III 33 3.91 132 Vv 28 3.15 0.79 126 III 21 3.26 122 III 21 3.43 123 Til Apr. 223 | 2.93 kilos........... 24 4.53 stage 136 Vv 36 4.25 140 VI 20 3.21 110 II 26 3.39 0.81 115 III 28 3.02 110 III 30 3.24 114 Ill Apr 30. | 3.13 kilos........... 29 4.86 sedis 147 Vv 20 3.78 } 0.85 { 127 III 40 4.76 “ 146 VI 12 6.50 aaitte 169 VI J. V.(cont.), 7 mos. May 14| 3.13 kilos.......... 40 3.81 0.78 130 Vv 10 3.96 wearers 135 IV 29 3.91 134 Vv 24 4.55 0.73 147 VI 30 4.84 154 VI J. V. (cont.), 73 mos. May 27 | 3.25 kilos........... 17 5.51 138 Vv 20 4.17 122 II 30 4.52 122 Ill 30 4.40 0.88 119 Ill 24 4.03 118 II 20 4.98 134 Vv June 4 | 3.30kilos........... 88 5.17 129 VI 15 5.80 149 VI J. V. (cont.), 8 mos. June 9 ! 3.50 kilos........... 40 5.79 145 VI 11 4.69 trator, 131 II 60 5.42 0.87 142 Vv June 10 | 3.35 kilos........... 48 5.80 149 VI 32 5.74 151 VI June 12 | 3.35 kilos........... 16 5.48 nfs 137 IV 19 4.58 } 0.94 { 129 II 30 5.86 ‘ 141 Vv June 13 | 3.38 kilos........... 15 5.92 eons 134 Vv 23 4.43 123 Ill 30 4.70 0.90 | 120 Ill 47 5.67 136 VI 1Calculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table. 31, p. 142. 2].ast feeding was about 3 hours previous to these observations, sterile water being substi- tuted for food at the next time of feeding. 3Last feeding was about 6 hours before these observations. Sterile water was given in place of food at subsequent times of feeding. 4Last feeding was about 21 hours previous to these observations. Sterile water was substi- tuted for food at subsequent times of feeding. 104 GASEOUS METABOLISM OF INFANTS. TaBie 23.—Results of observations on the gaseous exchange of infants—Continued. [{I, Very quiet, probably asleep; II. Slight movements, few in number; III, Some activity, but generally quiet; IV, Moderately active; V, Distinctly active; VI, Very active, most or all of the time.] Carbon Date. or a t Length of| dioxide Respiratory Average Relative clothing period. | produced quotient. | pulse-rate.| activity. : per hour.! 1913. J. V. (cont.), 83 mos. | mins. gm. June 25 | 3:40 kilésess oo ccccgs 17 5.29 kates 130 Vv 22 4.42 125 III 25 4.70 0.88 124 III 25 4.20 . 122 IV 30 5.62 140 VI June 30 | 3.39 kilos........... 17 5.15 eave 142 IV 26 4.59 135 IV 22 4.36 0.92 129 III 27 4.67 : 127 IV 26 4.68 125 IV P.W., male, 7 mos. April 1 | 7.11 kilos........... 21 7.69 ahaee 144 Vv 14 7.54 130 IV 10 2520 134 Vv 30 6.20 0.86 120 II 30 6.40 . 121 III 30 6.40 122 III 30 6.54 125 IV April 3 | 7.11 kilos........... 30 6.50 7 I 28 5.89 117 I 17 6.53 0.84 119 it 23 6.13 115 II 28 6.56 l 124 IV 1Calculated from the weight of carbon dioxide produced during the period. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 31, p. 142. While the data given in table 23 are made the basis of the discussion of our results in Part III of this publication, they may likewise be used for the discussion of many problems which have not been considered at this time. Furthermore, observations are still in progress in which supplementary evidence is rapidly being accumulated. Hence we wish it clearly understood that the data in table 23 are recorded here not only for present use, but for deferred discussion, in another place, of the many problems connected with the study of the metabolism of infants, such as the influence upon metabolism of crying, intense muscular activity, subnormal or febrile temperatures, and various distinctly pathological conditions. PART III. DISCUSSION OF RESULTS. In a recent study of the metabolism of diabetics in this laboratory, it was found that the experiments were much lessened in value because of the lack of suitable normal controls. This led us to believe that our best service to pediatrics would be to determine the normal metabolism of infants. Accordingly, while a few observations were made with dis- tinctly pathological cases, our data were secured for the most part with normal or under-weight infants. One important problem in such an investigation is the relationship between muscular repose and metabolism. The graphic registering de- vice for recording the muscular movements of the infant gave us an ex- ceptionally good opportunity to obtain data regarding this relationship, which was made an object of special study in this investigation. Furthermore there is a wide difference of opinion among physiologists as to whether or not during sleep there is a lowered metabolism, some writers maintaining that it is possible for a man to relax his muscles voluntarily so as to have a metabolism while awake as low as that during sleep, the sleep of itself having no influence upon the metabolism. With infants it is almost impossible to obtain periods of muscular repose while the infant is awake and it was recognized at once that only those periods when the infant was asleep could reasonably be looked upon as periods of complete muscular rest. It was hoped, however, that certain periods might throw light upon the effect of sleep upon metabolism. The influence upon metabolism of the ingestion of food also received some attention in this research as an increased metabolism following the ingestion of protein, fat, or carbohydrate has been noted in many observations made with adults. This increase in the metabolism has been variously ascribed to the mechanical work of digestion, to the so-called specific dynamic action of the foodstuffs, or, as is now the belief in this laboratory, to the stimulating effect of certain substances— the specific katabolic stimuli—absorbed from the food material through the alimentary tract, and there carried by the blood to the cells to stim- ulate them to greateractivity. Reasoning from the results obtained with adults, an infant receiving nutriment should have a greater metabolism than when he is without food; and it was hoped that experiments could be made with normal infants in which the influence of the ingestion of food could be more carefully studied. Difficulty was found at the outset in securing periods of quiet with infants under any con- ditions, but greater difficulty was had when the infants were not fed. Our experience, we admit, is very limited and we hope to profit by the suggestions of other observers, particularly Schlossmann and Mursch- hauser, in securing further aid in this important study. The data we have thus far obtained are somewhat fragmentary and by no means convincing; in fact, they hardly justify an extended discussion. 105 106 GASEOUS METABOLISM OF INFANTS. Our chief aim, therefore, was to study the metabolism of normal infants under conditions approximating the ideal, these infants to be selected, first, with varying ages; second, with varying weights; and third, of both sexes. That a sufficient number of observations could be made in one or two years to establish a standard for the normal metabolism of infants was hardly to be expected, but we at least hoped to make a good beginning, knowing that in subsequent years our data would be supplemented' and our findings from time to time revised. Perhaps the most important abstract problem which is met with in an investigation of this nature—a problem interesting alike to both physiologists and pediatricians—is the cause of the variations in the metabolism of the infant. For instance, is the metabolism proportional to the active mass of protoplasmic tissue? There is clearly a suggested relationship between the metabolism and the body-weight, but the metabolism per kilogram of body-weight is by no means an index of the mass of active protoplasmic tissue; nevertheless some relationship should exist. At present we are wholly unable to determine the total mass of the active protoplasmic tissue in an infant’s body. Unques- tionably much of the gain in weight of a growing infant is due to the storage of fat; it is likewise certain that the gain in weight due to the nitrogen retained may not all be due to the formation of active proto- plasmic tissue; thus the problem is doubly complicated. We may further ask “Is the metabolism proportional to the body- surface?” Such a stimulating suggestion has been made by Rubner, who computed in his earlier experiments the relationship between body- surface and heat-production, finding it to be relatively constant for prac- tically all species of warm-blooded animals, ranging in size from a horse toamouse. In round numbers Rubner finds this relationship to be not far from 1,000 large calories per square meter of body-surface per 24 hours. To throw light upon the important physiological problem of the relation- ship between the body area and the total metabolism was one of our main problems. PULSE-RATE. Very little attention has been paid to the normal pulse-rate of infants, so that only such general statements as the following from Holt? are found in the text books: “The pulse in early life is not only more frequent but it is very much more variable than in adults. The following is the average pulse-rate of healthy children during sleep or perfect quiet: 6 to 12 months, 105 to 115 per minute; 2 to 6 years, 90 to 105 per minute. 1As our page proof goes to press, we are informed that Hoobler and Murlin have very recently duplicated some of our experiments and although their observations include but two atrophic infants, they report that their findings are in full accord with ours. Their results were reported under the title ‘The energy metabolism of normal and marasmic children” at the fifty-eighth meeting of the Society for Experimental Biology and Medicine, in New York, April 15, 1914, and also at a meeting of the Inter-Urban Club, New York, April 17, 1914. 2Holt, Diseases of infancy and childhood, New York and London, 1911, p. 565. DISCUSSION OF RESULTS. 107 “The pulse is a little more frequent in females than in males. Muscular exercise or excessive excitement increases the pulse-rate from 20 to 50 beats. Very trivial causes disturb not only the frequency but the force of the pulse.” Some figures are given in a few observations by Townsend, which show that the pulse-rate of the crying baby is more rapid than that of the quiet baby, but no definite, continuous data have been reported other than the observations published by the writers in a previous paper.? An examination of the records thus far given in this report shows that it is of the greatest moment whether the infant is asleep or awake when the pulse observations are taken. It is probable that most of the records of pulse-rate previously reported by observers have been made when the infants were awake and possibly more or less restless. But little data are available, therefore, as to the minimum pulse-rate and the length of time required for the pulse to reach the minimum after muscu- lar activity. PRELIMINARY OBSERVATIONS. To secure more definite information on this subject, observations were made by one of us (F. B. T.) at the Boston Lying-in Hospital and the Directory for Wet Nurses at the Massachusetts Babies’ Hospital, in which a stethoscope was attached directly to the infant. Records could thus be taken by skilled nurses without disturbing the subject. From this extended series, a few typical pulse curves have been selected for reproduction here, including two previously published in the paper referred to. These give a fair index of the fluctuations which would normally be expected with infants of different ages and varying activity. The curve shown in figure 11 was obtained with S—ns at the age of 3 days, the records being taken practically every 5 minutes between 75 5™ p. m. and 6528" a.m. The maximum pulse-rate was 161 beats and the lowest observed value was 101 beats. When the curve is carefully examined, it will be seen that there was a general tendency for the pulse-rate to fall to a minimum of not far from 112 to 115, although the line is characterized by rapidly varying fluctuations. The second curve (see figure 12) was obtained 5 days later with the same infant, and shows the general irregularities of the first. The maximum record is even higher, 7. e., 174, while the minimum is 108. During the latter part of the night, the minimum count was not far from 115 beats for several minutes. A similar set of observations was made with Dow, 4 days old, cover- ing the same period of time as those with the first infant (see figure 13). The maximum pulse-rate with this infant was 165 and the minimum 1Rotch, Pediatrics, 5th ed., 1907, Philadelphia and London, p. 67. 2Benedict and Talbot, Am. Journ. Diseases of Children, 1912, 4, p.129. Since this was written the valuable article by Katzenberger, Zeitschr. f. Kinderheilk., 1913, 9, p. 167, entitled Puls und Bluidruck bei gesunden Kindern, has appeared. 108 GASEOUS METABOLISM OF INFANTS. 110. On one or two occasions the pulse-rate seemingly approximated a minimum of 112 to 118. With Weldon, 8 days old, the maximum was 161, and the minimum 111. Here again the curve, which is given in figure 14, is characterized by rapid and sudden fluctuations of considerable extent, although at times there is a tendency for the curve to reach a minimum of about 115. With Herbert W., 5 weeks old, the pulse records were obtained throughout the night for a period of 12 hours and are given in figure 15. The maximum record was 134 and the minimum 98. Several times during the night, the pulse-rate reached a minimum of about 100. Another 12-hour observation was obtained with Rita McL., 3 months old, giving a maximum pulse-rate of 140 and a minimum of 87 (see figure 16). A minimum average is shown at not far from 90. Paul, 3 months old, in the same period of time had a maximum pulse- rate of 154 and a minimum of 97, with an average minimum of approxi- mately 100. The curve is given in figure 17. Tremballe, 5 months old, gave a maximum of 147 and a minimum of 83. During the latter part of the night, the minimum records showed an average of not far from 90 (see figure 18). With Christine D., 7 months old, the maximum record was 139, while the minimum pulse-rate was 90, with the curve (figure 19) seeking an average minimum of 90 during the latter part of the night. While all the curves indicate a quick reaction to muscular activity of any kind, it would appear that the younger the infant, the greater these fluctuations were and the more sensitive the infant was to changes in muscular activity. The average minimum record for infants 8 days old or under was approximately 115, while infants of 3 months or over showed an average minimum of about 90. After nursing, the pulse-rate was always high, but would subsequently reach its normal level in about 30 minutes if the infant remained quiet. Although the difference was not very great, the curves as a general rule show that the older the infant, the more rapid was the return to the average pulse-rate after nursing. While the recent observations of Katzenberger! are of great impor- tance in supplementing our previous scant knowledge regarding the average pulse-rate of infants and hence make any extensive comparison of our data on different infants entirely unnecessary, we believe that our observations show for the first time the large variations in pulse- rate of afebrile infants during the night when extraneous muscular activity is presumably less than during the day. We may correctly infer that the fluctuations in the pulse-rate shown in these records are probably exceeded by variations during the day and, consequently, in the ordinary daily life of infants we have to deal with very wide fluctu- ations in pulse-rate. Comparative data for different infants, to be of value, should therefore be obtained at the minimum. Thiscan only be secured during deep sleep. Katzenberger, loc. cit. DISCUSSION OF RESULTS. 0d! oe! Ori 8 oll Kee Seed” changed tretcht, Sete fel and hands ar Gatch a me tre ee pare and legss Nol nursing ‘head and hands atte li Ror, “ng arms and legs s Moved right hand Quiet dais eae Moved head oe ve Quiet se. Syn. Sterile water given Moving about atest ‘Bout, Crying tag Asleep. ante o a Syutrming about, Seems hungry Movi earn Qu tee ro ae Moving arms Quiet a . Qu tee mo ving Ceres, Mover C41 ae ae ingens Ao both hands ulet Awake. aisles ncaa . ee oe Awake. Moved both Aands ee asteep: Qulet Awake. Hursing-auiet a m fursery jisked tet Awake. sing both Aands Aibete: Seis both hands ais wenn changed.Temp.9 Fic. 11. Pulse-rate curve for S——ns, July 1, 1911. Age, 3 days; weight, 4.3 kilograms. See, also, fig. 12. os| 091 Ooll 000! 006 8 “Wd00Z 00°21 002 W'V00' oo'e 00'9 00's oor 002 109 110 GASEOUS METABOLISM OF INFAN Ss Ss 8 oe! Ovl OI 3 8 fa bed, Asleep; Moving arms and legs Awake, Wiggting abou: Z we: oe wats Sing. aula ee “- oe Moving 4Aands ciee in case room. Asteex. Quiet coe oe ee “a Quiet o . or e Stretchin, ie OTN arms, ands Awake, Sierite water given Asteep. Qu ulet Awake, squirming around Movin erying. rere oUt, given Me Weckin wanes rg arms and legs aryiag as Moving about.Hungry SO dae Moving Seth arms Awake, Crying ue Marsing. Quiet in case room Asleep Awake. Moving about Asteep. uted A Ke. cryh: ae es ibs Asleep. Quiet te ° oe . se ee oe fin Moving Aead Be and Search , Qutae oS a Case roem Te vem ae f Cryt qulec Sroving arms and fest Kicking feet. Miccough ase “ mo: ULES vom legs ms and legs Asteep, Gute a u ee, ee ce ae a we “ a Aware. Stretch ing Fia. 12. Pulse-rate curve for S——ns, July 6, 1911. Age, 8 days; weight, 4.0 kilograms. See, also, fig. 11. ogi 008 Wd00Z Oot 0001 006 002I W001 KA oo'e 00'S 009 DISCUSSION OF RESULTS. 111 s 8 85 8 8 B ° oS °o o él Awake, Kap ste changed 8 sseee. , DS ory 0 Awak: Bigg ® gitodotee amnate « . grt é on a gn 78 aia REE Bi!’ ing arms and legs @ = oe Moved fingers of both hands o o rr a Moves both tegs and arms * ering as la hungry. Mo vingarms and lags sa Moving epee a Ahead and arms “ arms and legs wo ssi oe are Sone So re Yuh Gis aa ean ° Mave: ing Aead and ar. o Anees flexed. Moving arms Moving about. cryt ng bul not crytn. aes i jae Se 5 ‘ : wee phate Wekth. Evidently hungry 8 Coujtaags Moving about Sterle water given os ve Ag fands _ gdline left hand 8 bare ‘nes Sle eping, Ja jursersy Roiad RC ! z ee " > eghiha tare ene z a Moved hands nN Quiet Oo moved right arr © Qu aise both arms Serecening oe ue 7 w Awake. crying 2 . oe Seer Aungry S ee " suctite meting nese ec eryin. Squirming about - o o Aulake. autetn eS. ene ev ig Ran Wiand read w So s Rater e* to murserg o Sleeping oa Aan, o 2 seth Sfanged. Temp. 98 fo} ee au cet crying Fia. 13. Pulse-rate curve for Dow, July 1, 1911. Age, 4 days; weight, 2.5 kilograms. 112 GASEOUS METABOLISM OF INFANTS. 021 Oc! & 8 Oil dn bed. gsicer Aweke. Gate Marsing. Wiggting about Fussing, trying to nurse re CAaSC FOO. Mot Satisfied. Steriia water giver Squlrming aboi 4 s Yoved 17. or # ve eves Tang ere ot rright hand Qui Rte ning about Quiet Ty Moved arms Quiet oo Moved oth arms we wee . e eo oe Asleep. Quiet . oo “e o o oe crying. Hoving about eems Aungry ef oe Sterile water given. Jn case room, Moving aout Awake. aute Asicep : <3 Fig. 14. Pulse-rate curve for Weldon, July 6, 1911. Age, 8 days; weight, 3.0 kilograms. 09) ool 006 008 ‘Wd00z ool oo‘! 002 WV oo'e 00'S 009 DISCUSSION OF RESULTS. 113 oS 9S == tN gS = oO o o Oo IN Asleep. Quiet Oo - os oe oe v oe “ . . oO Awake, Moving about oO = oon Asleep. Quiet. . ee ” “ N . ae S Fic. 15. Pulse-rate curve for Herbert W., July 13, 1911. Age, 5 weeks; weight, 4.8 kilograms. 114 Awake, oe Asleep oe Co ‘an Sits 1ag GASEOUS METABOLISM OF INFANTS. Ss 8 8 6 021 O€! Moving arouna Quiet Moving Aead from side to side Qulee Stretching Quiet oe te oe ee Moving hands Quict o os. Fed € botdle Qulet se Moved arms Quiet we Moved Aands Quieé Mong: QePRE Ren changed oe Moved right hand arene: arms upward Restiess, Aunge: Me. Ars Lng EL Quiet = Stretching Gapin Moving right arm arms Hun gry Jn ‘bed.moving @bout et Moved head and arms Quist . Asleep. ‘ oo Qutet ny ve oe on o oe Fed. wlth Bote Awake, Mo ving about Sneezing Moving about Talking Fia. 16. Pulse-rate curve for Rita McL., July 14, 1911. Age, 3 months; weight, 6.6 kilograms. Ovi 00's O00v o0'e 002 WYOO! 002! 001 000! 006 ‘8 ‘Wd00z 009 DISCUSSION OF RESULTS. 115 wo 3 = BD = = — ee on ° sos S$ 8 & B& 8B J . v = Cryin aateee Asleep § 7 “ ° ” o Herd gee tere Qulet. Aslecp o o Ss ee ry ee — or 5 Moved hands: 8 Quiet Moving feet Quiet N = = nN oS oO ous arms ee wake. Kick 8 Cioing: icaing legs Sterile ater giren w Narsieg ee ee dn bed crying ee ord rs Turned on stomach Cc Crying 8 oe Awake. Moving about Asteer- Quiet . wn 2S o we or orging Yoided urine oe Sterile water given. Quiet oo of t a Oo N 9S Oo Fiqa. 17. Pulse-rate curve for Paul, July 12, 1911. Age, 3 months; weight, 5.5 kilograms. 116 GASEOUS METABOLISM OF INFANTS. o wo So = Nx) @ = S 6 8&6 6s 8 $8 8 Awake, Kicking ee Very active’ Crying. Moving about Awake. Moving about WMarsing. Qui Moved legs guickt Asteep. auret he ee a . a ee a te any a ae - ee «Moved an arr Quiet a e u Moved Aand and leg Quiet m7 w oe Pry o . vr oe ° " oe auvawe PSt0g gas “ crying Nursing. Quiet Moving legs Awake ee 7 te ee “e Mars! Awake, fn gitoving about moving oe sed Quiet moving left hand ee fends er and legs Zlrnirlg AE head Qui tet Fig. 18. Pulse-rate curve for Tremballe, July 12, 1911. Age, 5 months; weight, 5.7 kilograms. 0s! 00'9 00'S oo'V oo'e 002 WYOOl 002! o0'll 0001 006 ‘Wd00'? 002 DISCUSSION OF RESULTS. 117 oO s = N @ =~ Oo °o oS Oo o | Awake, Kicking 8 Siting up pingung v0 Qn back. vi, oul rg. BIKES. x =z Hurst . oe Dozing. Moving lefthand Asleep, Quite id 90 a “ a “ es ae “ . wo Awake, Rub, i oO ReeTiig ubbing eyes. Kicking 8 we Asleep. Quiet on “ es . Awake. Squirming about Oo oe Moved left hand S Kicklag Asien. auiee 8 a tee or a “ ee = oe c “ Q z = o Awake. Kish arms Mersing — Awake, Sitting up nN oving ands So or 5 ew ang about oO Awake: ee Upe our arms, ° avout “ 1 Sitting up : Crying. Lying onstomach ae ae {rar ee “ wow S o a - Awake, Quiet, Sterile water given = nN a Moving hands o ee arms Quiet “ OOE 00S ere: Quiet Aslea, . a S ae o Moving about, moulin. about Quiet SN Awake. suiting up oO " So Fie. 19. Pulse-rate curve for Christine D., July 13, 1911. Age, 7 months; weight, 7. 3 kilograms. 118 GASEOUS METABOLISM OF INFANTS. RECORDS OBTAINED DURING OBSERVATIONS WITH THE RESPIRATION APPARATUS. The observations just discussed were only preliminary in character and were necessarily liable to more or less error. We have, however, a large number of pulse records which were subsequently made while the infant was under constant conditions in the respiration chamber. These records were likewise obtained by the use of the stethoscope according to the method previously described.! It was frequently noted by the observer that the pulse-rate varied considerably during the minute of counting, particularly with very young infants. Thus, while the pulse-rate might be 20 beats in the first 10 seconds of the count, during the next 10 seconds it might fall to 18 beats, with similar variations throughout the whole minute. The pulse-rate was usually counted for one complete minute, but if the infant was crying it was counted for a half minute. At times when it was impossible to hear the pulse beat, the regular rhythm was counted by the observer and the count resumed by picking up the beats again when they became audible. Except during periods of crying, the pulse beats could be counted with a high degree of accuracy, but with the rapid pulse of severe crying slight errors unquestionably crept into the count. The arrhythmical pulse-rate of normal infants has recently been very extensively studied by Hecht.’ As already stated, we feel that the possibility for error in this method of taking the pulse records is too great and that some automatic form of recording the pulse-rate should be substituted. Every effort was made, however, to obtain pulse records as nearly exact as possible with this method, so that the pulse curves secured during the observations with the respiration chamber may very properly be carefully studied and relationships established with other records obtained at the same time. RELATIONSHIP BETWEEN PULSE-RATE AND MUSCULAR ACTIVITY. The simultaneous measurements of the pulse-rate by means of the stethoscope and of the muscular activity by the kymograph enable us to make sharp comparisons between these two factors. Such a com- parison is made in figures 20 and 21, in which the kymograph curves obtained with two subjects are compared with the curves for the records of the pulse-rate during the same period of time. The pulse and activity curves obtained for E. R. in the observation on April 12, 1913, are given in figure 20. The kymograph record shows that after a period of activity from 35 3™ p. m. to about 3" 16™ p. m. there was a short period of comparative quiet, 7. e., from 3" 16™ p. m. 41See p. 61. 2Hecht, Der Mechanismus der Herzaktion im Kindesalter, seine Physiologie und Pathologie, Ergebnisse d. inn. Med. u. Kinderheilkunde, 1913, 11, p. 324. DISCUSSION OF RESULTS. 119 * to 3" 36™ p. m., and that the last period from 507" p. m. to 5431™ p. m. was also sufficiently quiet to be characterized as activity IT. The remainder of the time the infant was quite active, so that experi- mental observations of the minimum metabolism were impossible. A close examination of the kymograph and pulse curves shows that there is a striking parallelism between them. Thus, from 3" 03” p. m.to about 35 16 p. m., the infant was restless, with a high pulse-rate, while between 35 16™ p. m. and 3" 36” p. m., the activity was at a minimum 310 330 350 410 430 450 510 530 1% Sof oes Sor $B i aoa i a0 saat“ - + ae ae Seo ar a ae = : 415 “ __ 4 oe 327 7 aap Wye aay id 350 LRH Rr rian bite babe ideon dp — sof = ae ues APRIL 12,1913 Fria. 20. Pulse-rate and kymograph curves for E. R., April 12, 1913. and the pulse-rate was low. About 3539" p. m. the pulse-rate again rose, the rise being accompanied by increased external activity. This reached a maximum about 4 o’clock and a period of decreasing activity followed until the infant became quiet at about 557" p.m. From that time until it waked up, just before the end of the observation, the infant was quiet with a minimum pulse-rate. Thus we see complete uniformity in both curves. A second set of curves, which was obtained with E. N. on May 23, 1913, is given in figure 21. These curves also show a general paral- lelism between the activity and the pulse-rate, with an apparently anomalous condition between 4" 25™ p. m. and 4"40™ p.m. At this time the pulse-rate was distinctly higher, while the kymograph record, 1For a discussion of the method adopted for designating the various degrees of muscular activity, see p. 130 and 136. 120 GASEOUS METABOLISM OF INFANTS. although not a perfectly smooth line, indicates no major movements. Another instance of fluctuating pulse-rate unaccompanied by changes in the kymograph record is seen in the period between 54 10™ p. m. and 5430" p.m. We thus have a general indication of uniformity between the pulse curve and the kymograph record, with a possibility of considerable fluctuation in the pulse-rate which is unaccompanied by external muscular activity. This feature will receive special con- sideration later. a2 aT oa f a 45) aa 8 azat Senne, Cree ee aan MAY 38 1913 Fia. 21. Pulse-rate and kymograph curves for E. N., May 238, 1913. An examination of the 193 kymograph records obtained in this series of experiments with infants shows the same general uniformity between the pulse-rate and the muscular activity as do the two specimen sets of observations given in figures 20 and 21. ‘There are, however, a sufficient number of well-defined instances of alterations in the pulse- rate, unaccompanied by changes in muscular activity, to justify the assumption that an increase in pulse-rate is not necessarily a result of extraneous activity. As further evidence of the uniformity between muscular activity and pulse-rate, particularly during periods of restlessness, we present in figures 22 to 37 comparisons of portions of kymograph and pulse-rate curves obtained with a number of subjects. This collection of kymo- DISCUSSION OF RESULTS. 121 graph curves is also of particular interest, since they are selected, for the greater part, to show the change from activity to repose, or the reverse. The bracketed portions of the kymograph curves correspond to the pulse curves. 170 .B. APRIL 24, 1913 442 446 450 454 458 S02 506 SIO) = (54 318-522 + ‘iis, ie a ae < the af eo : ih aes Cc 1=F %00, Fig. 22. Pulse-rate and kymograph curves for F. B., April 24, 1913. 14 : 2 F.K.MAY 3,1913 3.10 3.14 3.18 3.22 3.26 330 hese nena fh. Lie aiden pf Lee te ee Fia. 23. Pulse-rate and kymograph curves for F. K., May 3, 1913. 35 10™ p. m. to 34 30™ p. m. ¥ = . sap _| 332 F.K.MAY 3, 1913 | 342 346 350 354 358 402 406 410 414 418 422 426 aze a2 Bsa. 27 Ht Fra. 24. Pulse-rate and kymograph curves for F. K., May 3, 1913. 35 42™ p, m. to 44 26™ p. m. 339 122 GASEOUS METABOLISM OF INFANTS. E.L.MAY 20,1913 300 304 308 312 316 320 324 328 332 336 340 344 348 352 356 Es : t =) + ot my “fp ree + Ath tf | -spaniauanenies pelea} a Fie. 25. Pulse-rate and kymograph curves for E. L., May 20, 1913. E.L. MAY 21, 1913 394 308 3I2 316 320 324 328 332 336 340 344 348 352 356 + Leliait a a Ltd dls delete dhe mrt TIMMY + TOOT Pete epee Te bial +-thnhedirtiedebe-oufeliniieb-reehiirdb bead 3.00 CL af % Fia. 26. Pulse-rate and kymograph curves for E. L., May 21, 1913 322 D.M. MARCH 26, I9I3 404 408 4/i2 416 4200 424 48428 8432 6436 436 Al2 pte + I $4 + teh Fia. 27. Pulse-rate and kymograph curves for D. M., March 26, 1913 DISCUSSION OF RESULTS. 123 J.M. APRIL 2,1913 400 420 4.40 5,00 3.20. = 5.04 2 sof _J 5390 asa sass cates —t— ater 0 Og eh ng — ber ee Se ee + +. 4 ee, 4 ee eas “3 aaa a ie soe y ass i & “of a8 Fig. 28. Pulse-rate and kymograph curves for J. M., April 2, 1913. 130 M.M. JUNE 2,1 2520 «256 «6300 304 S082 36.320, 324 2B 332 s ys 333 thea). Hoste te bbb ies te +9 tpt F 2.30 4200 Fia, 29. Pulse-rate and kymograph curves for M. M., June 2, 1913. 130__+ M.M.JUNE 7, 1913 340 344 #346 352 356 400 404 408 41/2 416 420 a} i ais aap _J a 438 > tes adber Sas pve © + ase is sof A oe oe ey f- ae Por iL Fig. 30. Pulse-rateand kymograph curves for M. M., June 7, 1913. 35 40™ p. m. to 45 20 p.m. 140 M.M.JUNE 7, 1913 5.06 5.10 514 5.18 522 ~ 526 5.30 3.34 5.38 asa f- capt 437 Fia. 31. Pulse-rate and kymograph curves for M. M., June 7, 1913. 5° 8™ p. m. to 5 36™ p.m. 124 GASEOUS METABOLISM OF INFANTS. E.N. MAY 21,1913 32 5.16 3.20 524 5.28 532 536 540 S544 548 + 71 ; B37 saat | soz: at Fie. 32. Pulse-rate and kymograph curves for E. N., May 21, 1913. E.N. MAY 22,1913 ' 444 448 452 456 500 504 508 Sle 516 520 524 “5 , tT Pte Hr pt ene ptt ot sos] rc . ere E 522) az «of L 25. Fia. 33. Pulse-rate and kymograph curves for E. N., May 22, 1913. W. P. JAN. 31, 1913 ~ 323 327 33) 335 (339.3430 M7 351 355-359 © 7 a7 It es Pi ce a“ M4 ! he rey ers a Fia. 34. Pulse-rate and kymograph curves for W. P., January 31, 1913. DISCUSSION OF RESULTS. 125 i E.S. MARCH 22, 338 342 346 350 354 358 402 406 410 414 418 ud 358 «af ate 1 336 asf teoyyry 3% 1 Fic. 35. Pulse-rate and kymograph curves for E. S., March 22, 1913. .S.JUNE 18,1913 anc hewene Fic. 36. Pulse-rate and kymograph curves for J. 8., June 18, 1913. J.V. APRIL 22,1913 326 330 334 338 342 S46 350 354 358 402 406 4 oa 5 403 _J an #1sf aE 224 + oth “H H+ ie as 355 403 (3.40 T a7 : al ag + et ; Ta “L: 3.40, Fia. 37. Pulse-rate and kymograph curves for J. V., April 22, 1913. 126 GASEOUS METABOLISM OF INFANTS. EFFECT OF CHANGES IN ACTIVITY ON THE PULSE-RATE AT DIFFERENT AGES WITH THE SAME INFANT. The extreme sensitivity of the pulse-rate to major changes in muscu- lar activity has already been shown, but it is also important to note whether or not this sensitivity altered materially with increasing age. With one of the infants, J. V., we were able to make observations when she was 33 months old, with a body-weight of 1.9 kilograms, and again when she was 74 months old, with a body-weight of 3.3 kilograms. The curves obtained on January 25 and on May 27 are therefore compared in figure 38. (5S MINS. 118 118 14 Fic. 38. Pulse-rate curves with J. V. a. January 25, 1.9 kilograms, 3} months, awake and crying vigorously, restless, quiet (asleep). b. May 27, 3.3 kilograms, 7} months, moving and grumbling, then quiet. c. January 25, 1.9 kilograms, 3} months, quiet (asleep), moved, cried, restless, cried. d. May 27, 3.3 kilograms, 73 months, quiet, moving, moving and grumbling. In the period covered by the first curve (a) for January 25, 7.e., from 35 35™ p. m. to 4° p. m., the infant was at first awake and restless, then quieted down until she fell asleep. The pulse-rate fell from 168 to 130 per minute during this period. The second curve for this day (c) shows a change in the pulse-rate from 118 at 418™ p. m., when the infant was quietly sleeping, to 151 at 4" 36™ p. m., when she was awake, restless, and crying. In the first instance the fall in the pulse-rate of 38 beats required 25 minutes; in the second instance the rise in the pulse-rate of 33 beats took place in 18 minutes. On May 27, the records (curve b) show that the pulse-rate fell from 149 at 35 14™ p. m., when the child was moving, to a minimum of 118 at 35 36™ p. m., when it was quiet, or 31 beats in 22 minutes. The second record for this day (curve d) shows a rise in the pulse-rate when the infant woke up and cried from 114 at 5°06" p. m. to 147 at 5°22™ p.m., or an increase of 33 beats in 16 minutes. Comparisons of this kind are always complicated by the possible variation in the intensity of the activity, although in the instances selected the external activity seemed to be essentially the same under the various conditions. There was no evidence of greater sensitiveness in the later observations, but there was a distinct tendency for the minimum pulse-rate at the age of 73 months to be somewhat lower than at the age of 33 months. DISCUSSION OF RESULTS. 127 EFFECT OF CHANGES IN ACTIVITY ON THE PULSE-RATE WITH INFANTS OF THE SAME WEIGHT BUT DIFFERENT AGES. In order to compare the effect of changes in activity on the pulse- rate of infants of the same weight but of different ages, a number of pulse curves are given in figures 39 and 40, these being grouped ac- cording to weight. These curves, like those previously shown, indicate the rapid reaction of the pulse-rate with the change in activity, the reac- i swine a rg 145 GS. c d AC. AL. tg 101 8 108 131 160 e 135 f h AC. ES, 43 g KR 6 93 Fia. 39. Pulse-rate curves with infants of like weight but of different ages. a and b. G.S., February 19, 3.3 kilograms, 2} months, crying and moving, then quiet; E. S., March 22, 3.0 kilograms, 5 months, moved and cried, moving, then quiet. candd. A.C., March 19, 3.0 kilograms, 1} months, quiet, moved, cried lustily, crying, quiet; A. L., June 16, 3.1 kilograms, 3} months, quiet, then moving and crying. eand/f. A. C., March 19, 3.0 kilograms, 13 months, moved, cried lustily, crying, then quiet; E.S., March 21, 3.0 kilograms, 5 months, quiet, moved, moving and crying, then quiet. gandh. G.S., February 14, 3.2 kilograms, 23 months,moved and cried, restless,then quiet (asleep?)! K.R., April 5, 3.1 kilograms, 4 months, moving and crying lustily, moving and crying, then quiet. tandj. A.C., March 19, 3.0 kilograms, 1} months, quiet, moved, cried lustily, crying, quiet; L.O., February 28, 3.1 kilograms, 6 months, quiet, moved, moving and crying, moving a little. tion being at times so rapid that we may reasonably question the accu- racy of the record. The evidence given in these curves seems on the whole to indicate that the rapidity of the return to normal after crying and the increase when the infant waked up and cried are essentially the same with all of the infants, irrespective of age. This evidence does not agree with the results obtained in the earlier observations which were 128 GASEOUS METABOLISM OF INFANTS. made under less favorable circumstances. Obviously the curves given in figures 39 and 40 can not be directly compared with the long curves obtained in the hospital wards, since the former were secured under the absolutely uniform conditions obtaining in the respiration chamber and in relatively short experiments. a 160 '—s MiNS. M.D. b 142 FM. 9 15 100 138 160 d e M.M DM. ‘ f = ig 95 Né i) 109 Fia. 40. Pulse-rate curves with infants of like weight, but of different ages. a,b, andc. M. D., March 14, 4.0 kilograms, 3 weeks, quiet, then moved, crying and moving, quiet, moving, quiet, moving; F. M., January 22, 3.6 kilograms, 4 months, quiet, restless, restless and crying; J.S., June 11, 4.1 kilograms, 54 months, moving slightly, fairly quiet then moved, moving and crying. dande. M.M., June 7, 5. 4 kilograms, 43 months, quiet, moving, moving and grumbling, moving and crying; D. M., March 26, 5.2 kilograms, 11 months, quiet, moving and crying, moving, moving and crying. fandg. P. W., April 1, 7.1 kilograms, 7 months, moving and grumbling, then quiet; R. L., May 16, 7.3 kilograms, 9 months, moving, then quiet. EFFECT OF CHANGES IN ACTIVITY ON THE PULSE-RATE WITH INFANTS OF THE SAME AGE BUT WITH DIFFEERNT BODY-WEIGHTS. Though the undeveloped, atrophic infants have a different reaction of the pulse-rate to variations in muscular activity from those found with normal infants, some of our data may still be used to throw light upon the question of the differences in the reaction with different body- weights. Curves have been plotted showing the changes in the pulse- rate accompanying changes in body-activity from quiet to crying, or the reverse, with a number of infants of the same age but with different body-weight; these are given in figures 41 and 42. In only one of the comparisons is there a marked difference. The infants L. O. (curve e, figure 42) and J. 8., (curve f, figure 42), with body-weights of 3.3 kilograms and 4.6 kilograms respectively, when compared with P. W. (curve g, figure 42) with a body-weight of 7.1 kilograms, show apparently a greater rapidity in the return to the normal than does the heavier infant. Little can be inferred from the other comparisons. DISCUSSION OF RESULTS. 129 "5 MINS. c 138 d S ig b K.R. ee 129 116 4 90 100 f 135 MM. e 142 15 % Fig. 41. Pulse-rate curves with infants of like age but of different weights. aand b. E. R., April 14, 3 months, 4.5 kilograms, moving, then quiet, slight movements, quiet; A.S., April 1,3 months, 6.0 kilograms, moving and grumbling, alternately quiet and moving, then quiet. cand d. K. R., April 5, 4 months, 3.1 kilograms, quiet, moving and grumbling, moving and crying, moving and crying lustily; M. M., June 2, 44 months, 5.4 kilograms, quiet, moving and crying, moving and grumbling, moving and crying. eandf. F. M., January 22, 4 months, 3.6 kilograms, quiet, restless, restless and crying; M. M., June 7, 44 months, 5.4 kilograms, quiet, moving, moving and grumbling. es IS MINS a C ES. 131 d b LO 135 3 141 102 160 we e f Z JS. 4 LO. Na Pw “5 x 18 Fig. 42. Pulse-rate curves with infants of like age but of different weights. a and b._E. S., March 21, 5 months, 3.0 kilograms, quiet, then crying and coughing, crying, moving, crying; P. W., April 3, 7 months, 7.1 kilograms, quiet, then moved, crying and moving, quiet, crying. cand d. L. O., March 7, 6 months, 3.3 kilograms, quiet, then moved and turned over, moving: Pp. W., April 1, 7 months, 7.1 kilograms, quiet, moved, moving and grumbling. e,f, and g. L. O., March 12, 6 months, 3.3 kilograms, moving and grumbling, coughed, then quiet; J. S., June 26, 6 months, 4.6 kilograms, moving and crying, then became quiet; P. W., April 1, 7 months, 7.1 kilograms, moving and grumbling, then quiet. 130 GASEOUS METABOLISM OF INFANTS. RELATIONSHIPS OF THE MUSCULAR ACTIVITY, PULSE-RATE, AND METABOLISM. It has been a fundamental principle in all of our previous experi- menting, with both adults and animals, that only periods of complete muscular repose should be used for comparison in studying the metab- olism. The observations made with infants were also based upon this principle, the index used being the graphic records obtained with the mechanical registering device previously described. While for the major purposes of this publication, quiet periods were sought and the metabolism during periods of restlessness was only incidentally studied, we obviously unintentionally secured a large number of periods of more or less muscular activity. The relationships for the various muscular activities of the infant, the pulse-rate, and the total metabolism may therefore be readily discussed. To this end, a number of kymograph curves are reproduced in figures 43 to 48, showing the muscular activity of several infants. From a consideration of the mechanical principles of the swinging crib, it can be seen that the heaviest and strongest infants would produce the greatest amplitude of vibration of the crib, this vibration being, in turn, transmitted through the writing point of the tambour to the kymograph: While it would be useless to compare the muscular activity of two infants by comparing the excursions of the writing point on the kymograph, nevertheless a general impression of the activity and strength of an infant considered as a living mass of tissue may be obtained by an inspection of these curves. Accompanying the curves are tables giving the simultaneous records of the pulse-rate and the metabolism as computed on the basis of the total heat output per 24 hours. An estimate of the activity is also given in this table, using the basis of classification previously explained in table 23. For convenience in referring to these estimates, the key to the classification is given again here, being as follows: I. Very quiet, probably asleep. IV. Moderately active. II. Slight movements, few in number. V. Distinctly active. III. Some activity, but generally quiet. VI. Very active, most or all of the time. A comparison of the curves with this estimated activity will serve to illustrate the method of estimation used in previous tables. Observation with J. V., February 27, 1913. The kymograph curve given in figure 43 was obtained with J. V. on February 27,1913. This infant was very small and weak, weighing only 2.45 kilograms. She was restless throughout the observation and no period can be classified as activity I. Asis usual with many of the observations, the preliminary period, which began at 3" 6™ p. m., was characterized by considerable activity. At 35 34™ p. m. there was an ill-advised attempt to begin a new period, notwith- DISCUSSION OF RESULTS. 131 standing the fact that considerable muscular activity immediately preceded the beginning of the period. Up to 4" 12™ p. m., there was no approach to a condition of repose, but the period from 45 12™ p. m. to 4" 42™ p. m. was the quietest period of the observation. The activity about 4° 41™ p. m. was taken as indicating that the infant was waking up; as this would naturally be accom- panied by considerable activity, a new period was begun. In the last period, that from 55 8™ p. m. to 5" 38™ p. m., the curve is reasonably constant, the regularity of the line being broken by five or six movements. As a rule, per- fectly smooth lines could rarely be obtained with this infant. a3: asap 454 e Smet bpeeoh- aoa} 37 > 4+ > 530 eo - Wana ee asa 408 an — eer $$} ade + aoe 4 325 a sa) 34, 306 ia oe + wv. 325 , : FEB.27,1913 rr Ww wi MN Fia. 43. Kymograph curve for J. V., February 27, 1913. An examination of the estimated muscular activity given in table 24 shows that while it varied from III to VI, the estimates usually followed quite closely the total heat output. Thus, the two periods characterized as III represent 238 and 233 calories per 24 hours respectively, the two periods marked V correspond to 259 and 254 calories per 24 hours, and the preliminary period, which shows the most activity (VI), corresponds to 281 calories per 24 hours. The fluctuations in the pulse-rate are not very great in this particular observa- tion, the minimum being 135 and the maximum 144; in general they follow the muscular activity and the total heat-production. Taste 24.—Comparison of the pulse-rate, metabolism, and muscular activity in observation with J. V., February 27, 1913. Total heat- Period. production |Pulse-rate.| Activity. per 24 hours. cals. 35 06" p.m. to 35 34™ p.m.* 281 143 VI 3 34 4 12 259 144 Vv 4 12 4 42 238 135 iI 4 42 5 08 254 141 Vv 5 08 5 38 233 136 Ill *Preliminary period, A record of the sensitivity test is shown at the bottom of the kymograph curve, and the amplitude of the excursion and the regularity of the vibration vouch for the sensitiveness of the apparatus at that time. 132 GASEOUS METABOLISM OF INFANTS. Observation with J. V., April 22, 1913. Inasmuch as the longest series of experiments with any infant was that made with J. V., and this infant was very small and weak, a second curve is shown, which was obtained on April 22, 1913 (see figure 44). The body-weight at this time was 2.93 kilograms. But one period can be characterized as activity II, 7. e., that between 35 55" p.m. and 4" 15™p.m. The difficulties incidental - - } a ; ei + $a atet = aa5f + ' a + 4 JV. APRIL 22, I9I3 Fig. 44. Kymograph curve for J. V., April 22, 1913. to differentiating sharply between the several classifications of activity may here be pointed out, in that during the period from 4% 41™ p. m. to 5" 9" p.m., in which the activity is characterized as III, the heat-production was actually a little less than that in the period between 3 55™ p. m. and 4 15™ p. m., in which the activity was classified as II, while the pulse-rate was exactly the same (see table 25). On the other hand, in the preliminary and first periods, with the activity characterized as V and VI respectively, both the pulse- rate and the heat-production were considerably higher than in the other TaBLE 25,—Comparison of the pulse-rate, metabolism, and muscular activity in observation with J. V., April 22, 1913. Total heat- Period. production | Pulse-rate.| Activity. per 24 hours. cals. 2 55™ p.m. to 3 19™ p.m.* 329 136 Vv 3 19 3 55 310 140 VI 3 55 4 15 233 110 II 4 15 4 Al 247 115 III 4 41 5 09 218 110 III 5 09 5 39 235 114 III *Preliminary period. periods. Furthermore, in comparing these two periods with each other, we see that in the preliminary period when the activity was V and the pulse-rate 136, the heat-production was a little higher than that for the first experimental period, notwithstanding the fact that both the pulse-rate and the activity were higher in the latter period. Throughout this whole monograph, it is important to note that the use of data obtained in the preliminary periods may lead to error, since the amount of carbon dioxide residual in the chamber may be somewhat less at the end of the period than at the start and the temperature conditions may not be ideal; hence the determinations as a whole may be less accurate than those of the subsequent periods. Nevertheless, it is interesting to note in this curve the occasional lack of agreement between the muscular activity record, the pulse- rate, and the total heat-production. As a possible explanation of this, we may DISCUSSION OF RESULTS. 133 cite not only the opportunity for error in the determination of the gaseous exchange in a preliminary period, but the fact that the pulse-rates, particularly when the heart is beating rapidly, are difficult to count without photographic registration. Finally, there may always be a difference of opinion regarding the interpretation of the degree of activity shown by the curves. It is quite possible that the attempt to classify the activity under six heads is a refinement which the method will not warrant; unquestionably much less lack of agree- ment would be found if but four or even three classifications were used. Observation with A. L., June 28, 1918. The curve in figure 45 gives a record of the muscular activity during an observation made with A. L. This infant, who had at the time a body-weight of 3.15 kilograms, was evidently very active and much more vigorous than 1 alps, bee npeeerepe pe or — 09 3 s03 +h + peterpan tn fer pnt sae S ee on 03 é rr dpe — poem piney mf rote + th af efor 7 347 scefase «a spe tT ae a az $30 ar 3.08 = ee > + at er vis ” ° ae a ee anal ale + + Popp Sap Sea OP a Hen AL. JUNE 28,1913 Fia. 45. Kymograph curve for A. L., June 28, 1913. J. V., as may be seen by the frequency and the amplitude of the vibrations of the pointer on the kymograph. The activities ranged from II to VI, the quietest part of the curve being that between 3" 30™ p. m. and 3547" p. m., only two small movements near the end breaking the continuity of the line TaBLE 26.—Comparison of the pulse-rate, metabolism, and muscular activity in observation with A. L., June 28, 1913. Total heat- Period. production | Pulse-rate.|} Activity. per 24 hours. cals. 2b 48™ p.m. to 3 30™ p.m.* 343 118 Vv 3 30 3 47 247 101 II 3 47 4 09 379 125 VI 4 39 5 15 374 137 VI *Preliminary period. which otherwise would have been characterized asI. Much greater variations in the pulse-rate are to be found with this infant than with J. V., the records ranging from 101 to 137 per minute (see table 26). The minimum pulse-rate was obtained in the period from 35 30" p. m. to 3° 47™ p. m., with an activity of II and a heat-production of 247 calories per 24 hours. In the preliminary period, when the activity was V, the pulse-rate was 118 and the heat-production 343 calories per 24 hours; the last two periods also show a high pulse-rate and heat-production, with an activity of VI. Here again there is general uniformity between activity, pulse-rate, and total heat-production. Although 134. GASEOUS METABOLISM OF INFANTS. the body-weight of A. L. was but little more than that of J. V., the kymograph curve for the former showed a distinctly greater amplitude and more frequency of movement and the metabolism was also greater. This demonstrates in an interesting manner the fact that A. L. was a more vigorous infant than J. V. Observation with F. M., February 20, 1913. Another infant, F. M., with a body-weight of 3.86 kilograms, showed unusually persistent activity throughout practically the whole of the obser- vation on February 20, 1913 (see figure 46). The observation began at 34 18™ so sep te te as vce 300 ot i abot he—eabeipe- azz vr zat sas oan eepr repre * theta eI tr eee 45 azz aredibjwe- me Sturdy hes Tee ' —<— 4.00) FM. FEB. 20,19!I3 Fic. 46. Kymograph curve for F. M., February 20, 1913. p. m., but the activity continued throughout two lengthy periods, 7. e., until 4h 42™ py, m.; two reasonably quiet periods were subsequently obtained, with an activity of III and II respectively. As would be expected, the heat- production during the preliminary and first periods, when the activity was VI, was very large, being 535 calories per 24 hours in the preliminary period and 528 calories per 24 hours in the first experimental period (see table 27). In the period from 44 42™ p. m. to 54 12™ p. m., when the activity was III, the heat-production fell to 346 calories per 24 hours and the previous high pulse-rate of 141 and over dropped to 119. In the last period, that from TaBLE 27.—Comparison of the pulse-rate, metabolism, and muscular activity in observation with F. M., February 20, 19138. Total heat- Period. production | Pulse-rate.| Activity. per 24 hours. cals. 35 18™ p.m. to 42 15™ p.m.* 535 147 VI 4 15 4 42 528 141 VI 4 42 5 12 346 119 III 5 12 5 42 334 118 II *Preliminary period. 5» 12™ p. m. to 5" 42™ p. m., when the activity was slightly less and charac- terized as II, the pulse-rate fell but one point and the total heat-production was 334 calories per 24 hours. It will be seen that in this observation, also, the muscular activity, the pulse-rate, and the total katabolism follow almost parallel courses. Inasmuch as this infant was considerably heavier than either J. V. or A. L., the amplitude of the vibration of the pointer and the activity in general can not logically be used as indications of the body condition or strength of the infant except as showing that he should not in any sense be considered as weak. f 3.38 DISCUSSION OF RESULTS. 135 Observation with M. M., June 6, 1913. The kymograph curve for the infant M. M., obtained in the observation on June 5, 1913, has certain striking points, inasmuch as the minimum and maximum activity are very well shown (see figure 47). During the prelimi- + % ¥ Ane = ase) fos a + 420 «aif as sedi fg t+ 357 ao] 420 ‘ass aaop = as7 + aatuqert ies oe 4+ M.M. JUNE 5,1913 rr v Ws 7M Fic. 47. Kymograph curve for M. M., June 5, 1913. nary period from 3512™ p. m. to 3540™ p. m., the infant was somewhat restless, quieting down sufficiently about 3" 35™ p. m. to justify the beginning of a new period at 3°40" p.m. As a matter of fact, the infant was so quiet in the next period that the activity can be characterized as I (see table 28). TaBLE 28.—Comparison of the pulse-rate, metabolism, and muscular activity in observation with M. M., June 6, 1913. Total heat- Period. production | Pulse-rate.| Activity. per 24 hours. cals. 3. 12™ p.m. to 3 40™ p.m.* 365 107 Vv 3 40 4 10 276 93 I 4 10 4 31 “307 96 III 4 31 4 58 288 90 II 4 58 5 23 367 113 VI *Preliminary period. The activity in the last period, 7. e., that from 4" 58™ p. m. to 54 23™ p. m., was sufficiently great to be classified as VI. This curve shows clearly the futility of attempting to graduate by kymograph records the exact degree of the activity and the heat-production, for although the curve appears to indi- cate that the activity in the last period (from 44 58™ p. m. to 5" 23™ p. m.) was much greater than that in the preliminary period from 3" 12™ p. m. to 34 40™ p. m., the metabolism is very nearly the same and the pulse-rate is only 6 beats higher in the last period. This also justifies the statement previously made that the measurements obtained in preliminary periods are not sufficiently reliable to admit of extended discussion. The fact that no greater metabolism is shown in the last period than in the preliminary period, although the activity appears to be greater, should therefore be considered as a deduction based upon single measurements in two individual periods, either of which may be liable to error. Furthermore, when comparing the pulse-rates it should be stated that although the average pulse-rate in the preliminary period was 107, the individual counts ranged from 95 to 120, while the pulse-rates in the last period, although the average was 113, actually varied from 93 to 124. Discrepancies such as these serve again to emphasize 136 GASEOUS METABOLISM OF INFANTS. the fact that only periods of complete muscular repose can logically be used in discussing infant metabolism. In connection with the classification of the activity in the several periods, it is of interest to compare estimates made independently by two persons several weeks after the first estimate wasmade. Thisisdoneintable29. The TaBLE 29.—Comparison of original estimates of activity with later estimates made independently by two individuals. (Observation with M. M., June 5, 1913.) Estimates of activity. Period. Pulse-rate. Later. Original. |_———_—____- Reader A. | Reader B. 35 12™ p.m. to 3 40™ p.m.* 107 Vv Vv Vv 3 40 4 10 93 I I II 4 10 4 31 96 III III III 4 31 4 58 90 I I II 4 58 5 23 ig VI VI VI *Preliminary period, only disagreements after several weeks, during which time several hundred records had been examined, are found in the estimates for the second and fourth periods in distinguishing between classifications I and II. No attempt was made to classify the activities beyond V, any degree of activity beyond this being classed as VI. While one might say that the activity in the last period was two or three times that of the first period, since it is classified as VI, this conclusion is not justifiable, as is shown by the records of the pulse- rate and the metabolism in these two periods. Observation with F. K., May 2, 1913. Another infant, F. K., with a body-weight of 5.68 kilograms, showed activi- ties ranging from I to VI in the kymograph curve for May 2, 1913 (see figure 48). No curve previously given has shown a perfectly smooth line for an =m Nl pe , aie . YT m : aad ” : ae aso 1. ol | Ga ae 3e7 ape sso) 399 STRTTT Tt as cy i 3 re IT tt Pe a - EE ier MAY 2,1913 Fic. 48. Kymograph curve for F. K., May 2, 1913. entire period, but such a line was obtained in the second experimental period of this observation, 7. ¢., that from 3" 39™ p. m. to 4"1™ p.m. Incidentally this indicates how large an amount of experimental work must be done in order to secure a sufficient number of periods with minimum activity for comparison. Indeed, for the fundamental discussion of the comparative metabolism of infants, hardly one-third of our entire series of observations could be utilized. An interesting comparison of the total metabolism, the pulse-rate, and the records of the activity for this observation is given in table 30. A general uniformity is observed, although the preliminary period (from 3" 1™ p. m. to DISCUSSION OF RESULTS. 137 35 23™ p. m.) with an activity of VI has a heat-production and pulse-rate slightly less than the last period (that from 4" 31™ p. m. to 54 1™ p. m.) with an activity of V. This again illustrates the anomalies observed in comparisons with the results obtained in the preliminary period. TaBLEe 30.—Comparison of the pulse-rate, metabolism, and muscular activity in observation with F. K., May 2, 1913. Total heat- Period. production |Pulse-rate.| Activity. per 24 hours. cals. 35 01™ p.m. to 3% 23" p.m.* 526 138 VI 3 23 3 39 446 121 IV 3 39 4 01 382 109 I 4 01 4 31 420 116 III 4 31 5 01 535 141 Vv *Preliminary period. Additional comparisons of the muscular activity, the pulse-rate, and the metabolism may be made by reference to the kymograph curves given with the discussion of the relationship between the muscular activity and the pulse- rate.| The data regarding the pulse-rates and the metabolism will be found in table 23,? which gives the statistics for all of the observations. SIGNIFICANCE OF THE RELATIONSHIPS. From the preceding discussion the conclusion may be drawn that only periods of complete muscular repose may be used in comparing the results obtained with different individuals and with the same indi- viduals on different days. The total katabolism of the infant is the resultant of two factors: First, the metabolism due to the internal activity incidental to circulation and respiration and the general muscle tonus of the body, 7. e., maintenance metabolism; second, the meta- bolism due to the external muscular activity, which may vary from slight movements of the hand or fingers to violent movements inci- dental to severe crying. The internal muscular activity of the infant may also be affected by the ingestion of food and, as with adults, it may be affected by the general condition of the body, such as in disease or immediately follow- ing severe illness. For a short time after feeding, provided essentially the same kind and amount of food is given, it may be assumed that the metabolism due to internal muscular activity is fairly constant? with an infant. The effect of the ingestion of food upon the internal muscular activity of the infant is discussed elsewhere in this report,* but here we compare primarily the metabolism during complete muscu- lar repose and during various degrees of muscular activity. The external muscular movements are recorded with considerable fidelity upon the kymograph drum by means of the registering appa- ISee p. 118. See p. 84. 3Schlossmann, Deutsche med. Wochenschr. 1911, 37, p. 1635. 4See p. 145. 138 GASEOUS METABOLISM OF INFANTS. ratus described, but we have seen that this record does not give a comparative picture of the degree of activity of different infants. Consequently, for comparing the maintenance metabolism only periods in which the external muscular activity is eliminated should be used, since in the last analysis knowledge with regard to internal muscular activity is desired, uncomplicated by the increased metabolism due to external muscular activity. We believe that our evidence justifies us in asserting that we have two admirable indices for securing these ideal conditions of muscular repose for comparison, first, the graphic records obtained with the kymograph, and second, the pulse-rate. For comparing the metabolism of different infants, therefore, only those periods with records of complete muscular repose and with minimum pulse-rate can legitimately be employed. RELATIONSHIP BETWEEN PULSE-RATE AND METABOLISM. From the general pictures of the kymograph curves and the pulse curves, one may infer that the pulse-rate follows closely the muscular activity. Furthermore, since it has been shown that the relationship between the metabolism and the kymograph curves is comparatively constant, it is reasonable to expect that the pulse-rate will follow the metabolism. That this latter relationship is usually more nearly con- stant than the relationship between the metabolism and the record of the muscular activity is clearly indicated in a number of observations in which the kymograph record showed a complete absence of extrane- ous muscular activity, while the pulse records showed fluctuations. - An excellent illustration of this may be seen in the pulse and kymo- graph curves which were obtained in the observation of February 1, 1913, with the infant L. B. (see figure 49). Thus between 4 p. m. and PERIOD - II PERIOD - III PERIOD - IV COzperhr 414 gms CO2 per hr 384 gms. COz per hr 3,90 gms. 140. Pulse 133 Pulse 123 Pulse 122 oT AI | 120 rm LAN NY Vr 110) 355 415 435 455 515 ov ft + coo) ) ie aT Y aa woop ‘08 a5 af “a 345 oF oof 41s) Ihrem mmtpeetirney + asi LB 345 22 / FEB.1,/913 a w - : Fig. 49. Pulse-rate and kymograph curves for L. B., February 1, 1913. DISCUSSION OF RESULTS. 139 55 30™ p. m., one may assume that the activity was essentially of the grade I, 7. e., minimum. Nevertheless the pulse-rate is considerably higher in the period between 4 p. m. and 44 307 p. m. than in the two following periods, as is shown by the pulse curve and the figures for the pulse-rate per minute. As a matter of fact, the total metabolism is likewise higher in the first period as is evidenced by the carbon- dioxide output per hour which is given on the pulse curve. In this curve, therefore, which excludes the extraneous activity, we find the pulse-rate following very closely the total metabolism. While the -kymograph curve did not indicate muscular activity, nevertheless the pulse-rate gave evidence of an increased internal activity. A comparison of the records obtained for the muscular activity, the pulse-rate, and the metabolism in the observation with A. D. on May 19, 1913, gives further evidence on this important point (see figure 50). In the two periods from 3* 35” p. m. to 4 p. m. and from 4* 31” p. m. to 4" 54™ p. m., the muscular activity shown by the kymograph records would be classified as I. The pulse-rate in the first of these periods (period II) was 113 and in the second (period IV) 104. This variation in the pulse-rate is accompanied by a like variation in the carbon- dioxide production, which was 3.02 grams per hour in period II, and 2.66 grams per hour in period IV. Here again the pulse-rate is seen to be a closer index of the total katabolism than is the kymograph record. PERIOD - IV CO, per hr. 2.66 gms. 2 pulse 104° PERIOD - Il COp2 per hr. gms Pulse | 120 0 Se tite fit fi Fic. 50. Pulse-rate and kymograph curves for A. D., May 19, 1913. Two selected periods which were obtained with the infant J. M. in the observation of April 4, 1913, are compared in figure 51. These periods, both of which had an activity of I, also show the pulse-rate and the carbon dioxide output in harmony, the pulse-rate in period I being 112 as compared with 97 in period VI, with a carbon-dioxide production of 7.08 grams per hour and 6.41 grams per hour respectively. 100 . az a 1 es + Fe ponhe t-te ioe + as + nenyre ot aT a T aos ame 405 ace ae too —™~, 90 4 1 3:04 3.14 324 5JO 5.20 soe" rp f t sath 300 we suo), szel ra See 430 aso tet + me SS 300 ass wf tf ie see] 430. se b x t asef 405 3.18 azel na ae 230 a sof JM, APRIL 4,I9SI3 th W if Fia. 51. Pulse-rate and kymograph curves for J. M., April 4, 1913. With the infant E. N., three periods with an activity of I were secured in sequence on May 26, 1913 (see figure 52). The pulse-rate in the period I from 3" 21™ p. m. to 3" 41™ p. m. was 104 and the carbon- PERIOD - I PERIOD -IL PERIOD - IIL co, 50 0; 82 co. br. 4.84 2 Pe ulse 104 coaPRuisel2 2Pouise 13 322 342 402 422 442 eS get 4 Ay facemedles 442 dente} oy 308 cia aa] sas 354 <7 ae 530 aa 238 “hp “+ 3.06 T EN. pe ae MAY 26,1913 htt 1 i Fic. 52. Pulse-rate and kymograph curves for E. N., May 26, 1913. DISCUSSION OF RESULTS. 141 dioxide output per hour was 4.50 grams. In the next two periods, the pulse-rates were 112 and 113 respectively and the carbon-dioxide production 4.82 grams and 4.84 grams respectively, showing the usual harmony. This evidence of the relationship between the pulse-rate and the metabolism, taken in connection with the evidence presented in previous sections of this book, gives an entirely new significance to the pulse- rate, since it may be considered as a very fair index of the metabolism. In other words, an infant having a pulse-rate of 120 at one period of the day and of 150 at another period has unquestionably a greater metabolism in the second period. There is no evidence, however, that a difference in the pulse-rate of any two infants necessarily indicates a proportional difference in the metabolism, even though the infants be of the same weight and age, and the periods of observation of the same length. But it is safe to say that variations in the pulse-rate of an infant indicate a similar change in the metabolism. It is not to be inferred that we believe that the increase in metabolism noted with increased pulse-rate is due exclusively to the mere mechan- ical work of circulation, as this is far from our belief. We especially wish to emphasize the fact that we look upon pulse-rate as an index of muscle or general tonus in the body and not as referring solely to the work of the heart muscles. We may state, therefore, that. whatever increases the pulse-rate also increases the katabolism, so that when the pulse-rate is elevated by the muscular activity incidental to restlessness, playfulness, laughing, or crying, or pathologically as in fever, we have every evidence that the katabolism is likewise increased and a larger proportion of food material or body substance is being consumed. BASAL METABOLISM OF INFANTS STUDIED. In beginning this research upon infant metabolism, one of the funda- mental questions which presented itself to us with special force was as to what may be considered the normal basal metabolism of infants. Consequently we made it our aim to study as many infants as possible and to secure a sufficient number of periods of complete repose on a sufficient number of days to establish beyond reasonable doubt the basal metabolism of each infant. The infants secured for these obser- vations varied sufficiently in age, weight, height, and sex to permit a comparative study of the results as to the constancy or lack of con- stancy in the metabolism. 142 GASEOUS METABOLISM OF INFANTS. SELECTION OF DATA USED FOR COMPARISON. From the data obtained a table has been compiled which gives the average result of the periods with each infant in which the metab- olism was at a minimum (see table 31). The selection of the periods was based upon the records of the pulse-rate and the muscular activity, only such periods being used as showed a normally low pulse-rate and practically no muscular activity, 7. e., those characterized as I or II. The figures for the ages and weights are the average ages and weights for the experiments included in the table. The data are arranged according to the increasing weights of the infants. Since with one TaBLe 31.—Minimum metabolism of infants. Carbon- Body- Days in- [Period dioxide | Oxygen per é weight 3 YS iN- erlod’s| per sq. sq. meter, Subject. Sex. without Height. Age. | cluded in — waeter (Meeh) per clothing. average. | agec.| (Meeh) hour. per hour.! kilos. cm. mos. gm. gm. We WV cke aye & F 1.94 47 34 2 3 12.1 10.8 E.H.S M 2.96 51 34 5 8 11.6 9.6 Bie tna ked F 2.99 on 4 3 8 9.7 8.0 BS itanbonie F 2.99 ba 5 3 6 14.0 11.0 As Die ege F 3.16 56 4} 5 15 13.0 10.7 Ke Recetas M Bolt 56 4 2 4 12.1 10.2 Bes ike oes ya F 3.18 53 4 2 2 12.4 10.7 pe eee eee M 3.18 a8 6 rg 12 15.3 12.1 Jy Vier ee soe M 3.23 5 2 4 13.3 10.2 res ae Rs M 3.30 i 24 3 5 12.1 10.0 eV ce ean a r 3.38 53 8} 3 3 L6.7 13.4 Paws Sede M 3.65 es 44 3 5 15.4 13.0 M.D. 2caus M 3.99 wae 17 days 2 4 9.2 8.2 BiG TE oe cra ai F 4.04 sted 4 3 8 13.2 10.6 HS Gexevasoics M 4.15 59 4 1 2 14.0 12.3 WEP ye reutas M 4.31 oe 5 2 6 14.6 11.6 Vi Sokiene kgs M 4.41 63 5} 5 7 15.6 11.9 BR ose uwes M 4.49 55 3 3 5 12.0 11.0 We Dy oa heen M 4.87 60 54 4 13 15.7 13.1 Tee os kes M 5.04 60 4} 3 7 12.2 11.3 DM once es M 5.18 66 11 2 2 15.0 12.5 Di Qicescee M 5.28 62 43 2 4 11.9 1G BS Nesscicecies F 5.40 66 6 7 22 13.9 1D Dobe sie ee as M 5.45 63 7 4 7 15.3 13.0 M.M...... F 5.47 62 4} 3 ¥ 10.6 9.7 My secaetens M 5.63 62 8 2 6 18.2 15.1 M.LA....... M 5.67 68 9 4 9 12.9 11.7 Be Rey oie M ath 65 7 6 8 14.2 12.6 L. R.B.. F 5.99 64 4 4 11 11.3 10.4 AS. occas M 6.02 63? 3 1 1 10.6 9.5 IM Gicsiciices F 6.17 63 4 3 7 11.9 Pod PLS siieiiecos M 6.80 67 12 3 10 14.4 13.3 Bes press M 7.07 62 3 2 2 10.2 8.7 POW vccsaines M 7.11 64? - 2 5 14.2 12.2 Re Lose ance M 7.58 71 8} 5 8 13.9 12.2 Boe Mos ec teceeics M 8.03 73 iz 1 2 14.2 12.9 i: es eee M 9.33 75? 5} 1 1 12.4 9.5 Be Gi iesnineties M 9.37 74 10 3 5 11.4 11.4 1In accordance with the usage of Continental writers, we give these values, although we believe they are peculiarly liable to misunderstanding, and hence their use is unfortunate. 2The activity estimated for these two periods was II and III, respectively. : sl DISCUSSION OF RESULTS. 143 infant, J. V., the studies continued over a period of several months, the average minimum metabolism is given for periods secured at an early age, and again for periods obtained several months later. Various bases of comparison may be used, but in this table the infants have been compared on the basis of the energy transformation in 24 hours. In employing the data in table 31 for the discussion of the funda- mental questions considered, it is necessary to emphasize the fact that the amount of material and the method of its selection justify its use for a basis of comparison. The number of infants, 7. e., 37 in all, permits extended comparison and discussion. TasBLe 31—Continued. Heat produced. Per square meter per 24 hours. Average x Subject. Per 24 | Per kilo- rectal : eve hours. Od ke per Leica Lissauer Mech temperature. Sai ee See gang am | 18 We cals. cals. cals. cals. cals. °C. (OF) de Vide ost 164 85 984 1032 SSB ae cack eh tak di 129 E.. H. Si... 194 65 891 906 783 36 .8(98. 2) 109 Fe Oe 163 55 756 759 660 37 .2(98 .9) 126 HD Seescvesos 225 75 1036 1048 911 36.5(97.7) 107 Pe TO acs nis 229 72 1010 1026 895 36 .5(97.7) 114 BER ecsciesses 213 67 936 960 829 36 .6(97.8) 103 Ai Tisea ein 226 71 996 1020 876 36 .8(98.3) 107 Bie OP esate 260 82 1154 1172 1008 36.9(98.5) 106 Dio vise dvensaaite 223 69 978 996 854 36.1(97.0) 95 Re awa ttiey 216 65 931 946 818 36 .9(98 .4) 119 dhe Wagga a 297 88 1264 1280 1108 37 .3(99.1) 126 Be Mh ce eae 300 83 1219 1238 1064 37.1(98.8) 118 Me Dis sass 196 49 738 756 656 37 .0(98 .6) 127 da Biv eeres 272 | 67 1020 1041 901 36 .9(98.5) 124 Be lee pes es 306 74 1128 1152 995 37 .2(99.0) 127 We Peseun< 303 70 1076 1104 962 36 .8(98.2) 96 DD cna ie 319 72 1114 1152 997 36 .9(98.5) 111 Bs Rsv gsce 283 63 979 1013 873 37 .2(98 .9) 116 Pi ER eax. 5456 370 V7 1211 1257 1082 37 .2(98.9) 111 RB ceed 324 64 1035 1070 919 37 .1(98.7) 114 D.M...... 369 ah 1152 1188 1034 37 .3(99.1) 119 De Qisissce eas 305 57 930 972 846 37 .3(99.1) 101 BE Nes pee 353 66 1069 1117 962 37.1(98.7) 111 Ve Prsgiases 387 70 1152 1207 1039 36.8(98.3) 105 M.M..... 285 52 854 891 770 36 .8(98 . 2) 96 Je Misssnags 467 83 1368 1432 1239 37 .2(98.9) 112 Mi Abssecte 3 356 63 1037 1085 939 36 .9(98.5) 105 BIG, fad a8 381 67 1107 1158 1003 37.2(98.9) 109 Ge RB isc: 331 55 923 973 844 37.2(99.0) 106 AS vaio de 305 51 840 888 774 37.3(99.1) 113 Mis Gorecirs cd 333 54 912 967 837 37.1(98.8) 103 PS siisies. 5 3 453 66 1133 1219 1058 36.8(98.2) 100 nF ceusins 311 44 756 828 708 37.1(98.8) 111 Pe Weeeiss 439 62 1061 1147 998 37.1(98.8) 120 Re Litewa de 455 59 1038 1140 991 37.4(99.4) 115 HR AS eco aveses 497 62 1092 1212 1044 37.7(99.9) 105 Ty yacennes 420 45 816 O12 797 87 .2(98.9) 101 Be Geeciereve 479 51 922 1046 907 37.2(98.9) 106 See p. 22. 2During respiration periods. 144 GASEOUS METABOLISM OF INFANTS. Furthermore, the data are sufficiently extensive for each subject, as an examination of the table will show that, in all but two instances, at least two periods are used for securing the average value for each infant; in other words, the values were determined in duplicate. In many cases the number of periods for comparison greatly exceeded this; for example, in one instance 22 periods were available for averaging. The values for two infants, A. 8. and H. T., are each based upon only one period and unfortunately these two are among the relatively few infants not under weight. We believe, however, that the probable accuracy of these periods is supplemented by a careful examination of other periods with these infants in which the metabolism accompanying the varying degrees of restlessness and activity was measured. Under the circumstances we do not feel justified in excluding these values from the table, although it is to be noted that in all of the subsequent dis- cussion they may readily be omitted without in any way affecting the general inferences drawn from the research. Obviously no infant lives on a minimum metabolic plane throughout the entire 24 hours; indeed, but a small proportion of the total number of the experimental periods could be utilized for this important com- parative study. Nevertheless, since in but two instances was it neces- sary for us to rely upon the computation of the minimum metabolism of the infant from one experimental period, and in only one other instance were our data limited to those secured in two periods on one day, we believe that we have obtained a reasonably accurate estimate of the minimum metabolism of each infant, which justifies critical study and comparison. Minimum Extraneous Muscuuar AcTIvITY. In the previous discussion of basal metabolism,! we pointed out that this term is applied to the minimum metabolism of an infant, unaffected by extraneous muscular activity, and that it is probably best secured a number of hours after the last meal, when the infant is lying perfectly quiet, preferably asleep. It should here be emphasized that the dis- cussion of table 31 and the charts in figures 53 to 65 are based upon this minimum basal metabolism. As the investigation progressed, however, and the intimate relation- ship between pulse and muscular activity’ became apparent, we found ourselves compelled to utilize the pulse records intelligently as an important adjunct in determining the minimum metabolism. Any effort to quantify the kymograph curves which were other than straight lines was obviously very difficult, for a break in the straight line caused by a variation of the pointer over 11 mm. might signify one gross movement, while a number of very small breaks with a sum of 20 or 30 mm. need have no such definite mathematical relationship to the heat-production. On the other hand, when the pulse-rate was per- See p. 30. 2See p. 118. DISCUSSION OF RESULTS. 145 sistently low, even periods with kymograph records which were not obviously straight lines could logically be used. So extraordinarily sensitive was the tambour and suspended crib system that the slight fluctuation which would be characterized, for example, as activity II, if unaccompanied by an increase in the pulse-rate, showed almost invariably no effect upon the metabolism. In a relatively few instances a kymograph curve that might be classified as III or between II and III was likewise unaccompanied by an increase in the pulse-rate and corresponded to a low metabolism period. While in general, therefore, the results are drawn from periods of absolute repose as indicated by the kymograph records, we have felt perfectly justified in including periods with activity II and rarely III, if they were accompanied by low minimum pulse-rates and a low metabolism. Such a selection was especially fitting, inasmuch as the average minimum metabolism of each infant was sought and the data are nearly always drawn not from a single isolated period, but from many periods, usually obtained on a number of days. Occasionally an extraordinarily low value for the heat-production as computed indirectly was found for a single period. This low value was never included in the periods averaged for the minimum meta- bolism, as we believed it could be easily traced to an error in weighing the carbon-dioxide absorbers, or to some error in technique pertaining to the individual period. An examination of table 23 will show that these very low values were rare, being found possibly 4 or 5 times during the experimenting of a whole winter. It will be seen, therefore, that care was taken with every infant to secure the minimum value, knowing that ultimately several important comparisons would be made. All the information necessary for the use of investigators in making computations by any other method than those here suggested is given in table 23.1. The data in this statistical table can be used with con- fidence, although we have not thought it wise to reject arbitrarily the very low values found in isolated periods. We firmly believe, however, that these were due to some discrepancy which unavoidably crept into the technique and a, careful inspection of the data will show that they should not be employed in drawing average values. Minimum INFLUENCE OF Foon. In discussing our results, the criticism can be raised that one of the factors outlined in our definition of basal minimum metabolism was not as strictly observed in this study as could be desired, since the infants were rarely in the post-absorptive state, the observations being made for the most part from 1 to 14 hours after the ingestion of food. It has clearly been shown in experiments on men and animals that the ingestion of a mixed diet results in an increased metabolism. See p. 84. 146 GASEOUS METABOLISM OF INFANTS. When isolated nutrients are ingested, the greatest increase has been observed with protein. With fat there is relatively but little, if any, increase. With carbohydrates, while investigators differ as to the quantitative relationships, it has been observed with men in this labora- tory that cane sugar and levulose may stimulate the metabolism to a degree comparable with that resulting from the ingestion of an equivalent weight of protein. On the other hand, lactose—the chief carbohydrate in the diet of infants—has a minimum influence upon the metabolism. This criticism of our experiments has, therefore, considerable theo- retical importance, but practically we must consider the fact that the diet of the infant is of such a character as to produce a minimum amount of increase in the metabolism. With infants a large proportion of the protein ingested—some 60 per cent or more—may be stored in the body, and Rubner has shown that this storage does not affect the total metabolism. Since the protein ingested by the infant rarely exceeds 15 per cent of the total energy requirement of the body,! it can be seen that we may expect from this nutrient only the minimum influence upon the heat-production of infants. Fat has admittedly but a slight influence, while the predominating carbohydrate—milk sugar or lactose—has likewise only a minimum influence. On these grounds, therefore, one would conclude that the total nourishment of the infant consists of material which for the most part does not tend to stimulate the metabolism greatly. On the other hand, so keen an observer as Schlossmann’ states that the effect of the inges- tion of food probably persists for some 18 hours. Practically all of the investigators in metabolism have concluded that with adults, unless the diet is abnormally rich in protein, the metabolism reaches the basal line 12 hours after the last meal. In our studies while it was impracticable to secure the metabolism on all of the infants 18 hours after the last meal, an effort was made to find out the length of time required to obtain the minimum basal metabolism after feeding milk. To this end some five or six infants were studied 1, 24, 5, 9, 12, 18, and 21 hours after food. The difficulties in securing ideal periods of rest exactly coincident with definite periods of time after the ingestion of food are sufficiently obvious to need no special comment here; it is only necessary to state that our evidence is admittedly not so complete as we should like. A critical examina- tion of the data shows us, however, that on the whole the influence of milk feeding upon the metabolism of infants must be very slight. In certain instances the metabolism during quiet periods immediately after feeding is 5 to 10 per cent higher than 18 to 21 hours after, while in others the metabolism 21 hours afterward, even in periods of com- 1Rubner, Sitzber. K. Preuss. Akad. Wiss., 1911, 20, pp. 440-457. ?Schlossmann, Atrophie u. respiratorischer Stoffwechsel, Kassowitz Festschrift,Berlin, 1912, p. 318. DISCUSSION OF RESULTS. 147 plete muscular repose, was slightly greater than immediately after feeding. But the general picture derived from these observations indi- cates that the ingestion of milk played a very slight réle, if any, in affecting the heat-production of the infants studied. Recent observations in this laboratory during a 31-day fast showed that, as soon as food was completely withheld, the body storage of glycogen was rapidly drawn upon and a distinct acidosis appeared when it was exhausted. Our experience with diabetics and with normal individuals subsisting upon a carbohydrate-free diet! gives evidence that such an acidosis tends to increase the basal metabolism. Addi- tional light has been thrown upon this subject by Schlossmann and Murschhauser’ who have shown in a recent publication the influence of the withdrawal of food upon the excretion by infants of products of acidosis, particularly acetone, diacetic acid, and 6-oxybutyric acid. Even in the first 24 hours of fasting, definite evidence of the excretion of g-oxybutyric acid shows the beginning acidosis. Knowing, as we do, that acidosis strongly tends to increase the metabolism, one sees instantly that a point or a moment when the influence of the previously ingested food ceases and the influence of an oncoming, though slight, acidosis begins, is extremely difficult to foretell, with our present knowledge. It should not be overlooked, however, that Schlossmann and Murschhauser did not find an increased heat-production in these infants showing incipient acidosis although we are inclined to doubt the validity of drawing conclusions regarding so subtle a factor as aci- dosis from periods with such changes in the degree of repose. While, therefore, we recognize clearly that the presence of food in the alimentary tract of our infants has distinct theoretical objections, we believe that such influence, if it exist, can play no quantitative réle in the striking comparisons of the basal metabolism of different infants which are made in the subsequent pages. NORMALITY OF INFANTS STUDIED. In carrying out this study of infant metabolism, we found ourselves immediately confronted by the difficulty of determining what is the normal infant. An inspection of the data supplied by Holt,? Heubner,‘ Camerer,* Gundobin,’ and Sutils’ shows noticeable variations in the nor- mal weight of infants of different nationalities—variations that may easily amount in the earlier months to 5 or 8 per cent, even for a carefully selected, healthy, breast-fed infant. Our infants were usually bottle- fed and for the most part were under the normal weight. To show as 1Benedict and Joslin, Carnegie Inst. Wash. Pub. No. 176, 1912, p. 134. 23chlossmann and Murschhauser, Biociem. Ztschr., 1913, 56, p. 396. 3Holt, Diseases of infancy and childhood. New York and London, 6th ed., 1911. 4Heubner, Lehrbuch Kinderheilkunde, 3d ed., Leipsic, 1911, 1, p. 7. 5Camerer, Der Stoffwechsels des Kindes, Tubingen, 1896. 6Gundobin, Die Besonderheiten des Kindesalters, Berlin, 1912. 7Sutils, Guide pratique du pesage pendant les deux premiéres années, Paris, 1889. 148 GASEOUS METABOLISM OF INFANTS. clearly as possible the variations between the weights of the infants included in this study and the accepted normal weights of infants of similar ages, we give in table 32, first, the age; second, the weights of our infants at the time of observation; and third, the average weight for infants of the ages indicated, these averages being compiled from Taste 32.—Normal and expected body-weight of infants included in these observations. Body-weight| Normal Subject. Sex. Age. Height. without weight anected : weight. clothing. for age. mos. cms. kilos. kilos. kilos. Pe Va eee Female 34 47 1.94 5.90 3.95 E.H.S..... Male 33 51 2.96 5.90 5.68 As GC es acter Female 14 Bis 2.99 4.30 3.99 BoS. cnasane Female 5 ze 2.99 6.82 5.35 Bis Te 3:3. eee Female 43 56 3.16 6.50 5.46 Ko Resg cadens Male 4 56 3.17 6.25 7.40 ic deiatacioy acta Female 4 53 3.18 6.25 6.49 De O vis scics cies Male 6 3 3.18 7.27 7.62 VeBiaicawes Male 5 3.23 6.82 eae Ge Since sive Male 23 ee 3.30 5.16 5.40 die Vion a onee Female 83 53 3.38 8.28 6.33 BM es eppetnas Male 43 ee 3.65 6.50 igs My Di vecccas Male 17 days ous 3.99 3.60 acts Ts Br esseispasavs Female 4 es 4.04 6.25 6.71 i Mies es bacco Male 4 59 4.15 6.25 alate WP casas Male 5 ie 4.31 6.82 6.15 Dia She ceseniresncass Male 5} 63 4.41 7.10 8.70 E. 3 55 4.49 5.56 5.11 F. 54 60 4.87 7.10 8.24 R. 43 60 5.04 6.50 a:o7 Di, Me isg ses Male 11 66 5.18 9.20 8.80 DGius sexe y Male 43 62 5.28 6.50 5.60 EB. Ness sic ccs Female 6 66 5.40 7.27 stk FP ss essderse ses Male 7 63 5.45 7.73 6.38 M.M...... Female 43 62 5.47 6.50 6.28 Se Ms sieceee 5 Male 8 62 5.63 8.07 eae M. Male 9 68 5.67 8.49 8.84 F. Male 7 65 5.71 7.73 7.87 L. Female 4 64 5.99 6.25 6.93 A. Male 3 63 ? 6.02 5.56 6.91 M. Female 4 63 6.17 6.25 6.93 P. Male 12 67 6.80 9.55 wate E. Male 3: 62 7.07 5.56 6.38 P; Male 7 64? Pall. 7.73 aiayate R. Male 8} 71 7.58 8.28 7.15 E. Male 17 73 8.03 vane sinc H. Male 53 752? 9.33 7.10 sated Es Gisele ..| Male 10 74 9.37 8.75 8.98 1Calculated by adding to or subtracting from the normal weight for age the excess or deficiency in weight at birth, assuming normal birth-weight as 3.40 kilograms and that increase in weight after birth is the same as for normal development. Holt’s table for healthy, American, breast-fed infants. Even with normal infants there are great differences in the birth-weight; we have accordingly computed for this table the weight that would be expected for each of our subjects with a normal rate of growth, taking into consideration variations in birth-weight and using the curve for DISCUSSION OF RESULTS. 149 average weight of infants given by Holt.! (See table 33.) For example, if the infant weighed 0.5 kilogram more than the average weight at birth and we wished to know what it would have weighed at 5 months had it developed in the usual way, we added 0.5 kilogram to 6.82 kilograms (the average weight for this age as recorded by Holt) and considered 7.32 kilograms the weight that the infant would have weighed had it developed normally. The same procedure was followed if the infant was under weight. : TABLE 33.—Average weights of American It is clear that relatively few of age eens of infants (Holt). the infants included in our study can be considered of normal weight, that Age. | Weight. | Age. | Weight. is, the average weight of healthy ee i infants, as only 8 out of the 37 3.409 7.727 reported are equal to or exceed the wae Sets normal weight; one of the infants, 5.560 8.750 H. T., is considerably above the aa ee: normal weight. It is understood, 7.270 i then, that we are considering for the most part infants that are under weight. Certain of these were in the subnormal temperature stage of infantile atrophy; others were in the repair stage and with normal temperature. The term ‘‘infantile atrophy” is applied to an emaciated infant with such severe indigestion that it is unable to digest weak mixtures of cow’s milk, with no gain in weight, and with a subnormal body-tem- perature. The convalescent stage of infantile atrophy is that in which the same infant subsequently begins to digest its food and to gain weight, and has a normal temperature. Under-weight infants are those who are 0.5 kilogram or more below the average weight for their respective ages but whose digestion is not so severely deranged as those with infantile atrophy. This group includes all infants not classified as normal, or with infantile atrophy, or in the convalescent stage of infantile atrophy. RELATIONSHIP BETWEEN BODY-WEIGHT AND METABOLISM. One of the two factors commonly referred to as exercising a most pronounced influence upon the total metabolism is the body-weight. Charts have therefore been prepared in which comparisons have been made between the body-weights of our infants and the heat-production. 1We recognize that there is no absolutely definite normal weight that can be established for all infants. The charts of growth given by the various authorities are all very similar, their differ- ences being explained by the fact that they often represent infants of different nationalities or of different social and hygienic surroundings. Since the charts usually represent average and not normal infants, it is very difficult to apply the test of normal or abnormal weight to any given infant. Therefore, in comparing the infants used in this investigation, both the average and the estimated weights will be considered. Hereafter we shall use the term ‘‘normal weight” as meaning the average weight. The average weights of American infants are given in table 33, which is taken from Holt (loc. cit., p. 17), who made it up from the records of 100 healthy nursing infants and the incomplete weight charts of about 300 other infants. 150 GASEOUS METABOLISM OF INFANTS. COMPARISON OF THE BODY-WEIGHT OF INFANTS AND THE TOTAL HEAT-PRODUCTION IN 24 HOURS. A chart comparing the body-weight of our infants with their total heat-production in 24 hours is given in figure 53. In general one would expect that a large animal would give forth more heat than a small animal, and an inspection of this chart shows that for the most part those infants with the larger body-weight have a larger heat-production. On the other hand, it will be seen that the TOTAL HEAT PER 24 HOURS ACTUAL, WEIGHT HT EG I EK 76 3 RL 68 EF Pw PS C 60 " AS | RB . in (lek iS 52 mh Ee WN Je pe FB 44 ER, we? US -MD ; EL 3 FM GS = “1A JVavemos. KR: be) op AC] EHS 8D to Dl “UVavemos 165 195 225 255 285 3I5 345 375 405 485 465 495 Fic. 53. Chart showing actual body-weight of infants and total heat-production per 24 hours. values by no means lie in a straight line, possibly the most striking exception being J. M., with a body-weight of 5.6 kilograms and a heat- production of 467 calories. It is clear from this chart, therefore, that while in general the larger infants show the larger heat-production, this is by no means invariably the case, and a definite rule, based solely upon body-weight, can not here be established." It is obvious that the composition of the body must play a consider- able réle. Those tissues most active in the metabolic processes—the 1By selecting the “normal” infants, a straight line is approximated. Recently determined values on other infants of normal weight indicate considerable regularity in the curve. DISCUSSION OF RESULTS. 151 muscles and organs of circulation—must have a greater metabolism than the integument, hair, finger nails, etc.; thus, with a larger propor- tion of active protoplasmic tissue in a body, a greater heat-production would normally be expected. On the other hand, inert adipose tissue, even if it be present in large amounts, would not be expected to con- tribute materially to the heat-production. Hence it would be logical to assume that heavy, fat infants need not necessarily have a greater total heat-production than infants of the same weight having less fat. Unfortunately, in the discussions of infant metabolism presented here- tofore by the various writers, almost no consideration is given to the length' of the infant. An infant weighing 8 kilograms, 60 em. long, has obviously a larger proportion of fatty tissue than an infant of the same weight but 70 cm. long, and on the basis of body-weight alone we should normally expect that the longer, thinner baby, with the smaller amount of fat, would have the larger heat-production. As stated in the discussion of table 32 the infants included in our study were, for the most part, under weight. There would thus be a deficiency in fat, and possibly a deficiency in the active protoplasmic tissue, but all of the evidence points to the fact that a large part of , the discrepancy in weight must have been due to a deficiency in fat. In considering our infants, it should be borne in mind that the actual body-weight on these or similar charts does not give the slightest indication as to the probable chemical composition of the body, par- ticularly with regard to the proportion of fat or of active protoplasmic tissue. The great lack of uniformity in the total heat-production of 24 hours, when considered on the basis of body-weight, may, therefore, be considered as possibly explained by variations in the chemical com- position of the bodies of the different infants, 7. e., in the relative proportions of fat and active protoplasmic tissue. Accordingly the chart in figure 53 is chiefly of interest as indicating in this group of infants, as a whole, that there is no definite uniformity between body-weight and total heat-production for 24 hours in infants under uniform con- ditions as to muscular activity and general repose. HEAT-PRODUCTION PER KILOGRAM OF BODY-WEIGHT. A method commonly used for the comparison of individuals of different body-weights is to compute the metabolism on the basis of per kilogram of body-weight. Thus differences in total metabolism ascribable to body-weight alone are eliminated. Accordingly in the chart in figure 54 we have presented the heat-production per kilogram 4In this connection it should be noted that owing to the stimulating suggestions of Rubner, great emphasis has been laid upon the computed body-surface of infants and its relation to the total metabolism. Aside from the formula of Miwa and Stoeltzner (Zeitschr. f. Biol., 1898, 36, p. 314) for computing the body-surface of infants, all formulas, including those most extensively used at the present day, disregard completely the length of the infant in computing the body- surface, and the computation, therefore, rests upon a determination of the body-weight—the only measured value introduced into the formula. 152 GASEOUS METABOLISM OF INFANTS. of body-weight per 24 hours for all of our infants. An inspection of these points shows conclusively that there is no regularity in the values for the different infants. The heavy babies, H. T. and E. G., had a low energy transformation per kilogram of body-weight, but two very young infants, A. C. and M. D., had similarly low values, although in general the infants of the smallest body-weight have high values. HEAT PER KILOGRAM OF BODY-WEIGHT PER 24 HOURS ACTUAL WEIGHT oo HT EG 80 : EK] RL 70|_s PW: EF : PS MC 60) AS | LRB ‘ FKi MM: MA. ‘ UM ° N | JP 50) Oe ‘ s DM : FB 40 EB we 3 EL MD LB) FM 5 Rp) UB . 30) 6S KR “AL AD LO |JVeremos. AC EHS eS 20|_ : JVavemos. a5 50 55.60 65 70 75 80. 85 30 Fic. 54. Chart showing the actual body-weight of infants and the heat-production per kilogram of body-weight per 24 hours. Thus it is seen that in comparing the metabolism of different infants we have to deal with some factor or factors other than body-weight. Inasmuch as the state of nutrition is not indicated by the records of the body-weight at the time of the observation, it is obviously impos- sible to discuss the influence of this factor simultaneously with the total body-weight without further data. COMPARISON OF NORMAL BODY-WEIGHT AND TOTAL HEAT- PRODUCTION IN 24 HOURS. Since the infants were mostly under weight, a comparison between the metabolism as measured and the normal weight of infants at the same age is justifiable and may prove suggestive in interpreting the DISCUSSION OF RESULTS. 153 results. A chart has therefore been plotted (see figure 55) giving the total heat produced per 24 hours for the different infants and the average body-weight for a normal infant at the age when the metab- olism was observed. Here again no special uniformity is seen, although in general those infants with the largest body-weight have the largest heat-production. On the other hand, with infants ranging from 6.3 to 7.3 kilograms, many instances were found when both very low heat-production and high heat-production are noticed. wom TOTAL HEAT PER 24 HOURS “nnuos) i BS OM 2 MA EG JVe a aii le W2 MOS. bi RL JM S Kp Lo : N - (PW " JBIES we fis | rp i AD mt PQ) | eo . | FM, | REMC 60 J Varamos Kr pal 1B EL | URB EHS: ER’ AStee 6S 4 AC 3 D 165 195 225 255 285 3I5 345 375 405 435 465 Fig. 55. Chart showing the normal weights for the ages of the infants under observation and the total heat-production per 24 hours. COMPARISON OF NORMAL BODY-WEIGHT AND HEAT-PRODUCTION PER KILOGRAM OF ACTUAL BODY-WEIGHT. In an attempt to reduce one factor in the comparison to a common basis, the values for the heat produced have been computed on the basis of per kilogram of body-weight, using the average weight for normal infants of the same age (see figure 56). No greater uniformity is apparent here than in the preceding charts and evidently no corre- lation can be found between the computed normal body-weight and total heat-production either on the basis of the total heat per 24 hours or the heat per kilogram of body-weight. COMPARISON OF EXPECTED BODY-WEIGHT AND TOTAL HEAT-PRODUCTION IN 24 HOURS. The average body-weights of healthy infants used in the foregoing comparisons are based upon the assumption that the infant was of normal weight at birth. Since the birth-weights of many of our infants 154 GASEOUS METABOLISM OF INFANTS. HEAT PER KILOGRAM OF BODY-WEIGHT PER 24 HOURS NORMAL WEIGHT FOR AGE PS 9.0 DM: EG . MA R 8.0 RL UM J Vave Mos. FK, oP pw, ‘j : zol_hT EN J§ Lo MM J ; UB WP ES FB : MC. Da Re Uy AD FM. 60) LRB KR AL | FL SVavethos. EF AS EAS 24 ER gs 40) AC MD —as— S05 60 65 70 75 80 85 30 Fig. 56. Chart showing the normal weights for the ages of the infants under observation and the heat-production per kilogram of actual body-weight per 24 hours. HEAT PER 24 HOURS EXPECTED WEIGHT 10.0} 92) US mM EG 84) FB Fk KR 68 LRB vc RE AL LB JVeN iOS; e MM} Vp. EF Jp 60 1 AS aS gs |AD Da | RE ER* 44 §JVav2mos! AC- 36) 165 195 225 255 285 315 345 375 405 435 465 495 Fia. 57. Chart showing the expected weights for the infants under observation and the total heat-production per 24 hours. DISCUSSION OF RESULTS. 155 are known to us, we computed the expected weight of our infants as explained on p. 148, thus taking into account any variation from the normal in birth-weight but assuming normal growth. These weights, which are given in the last column of table 32, are compared with the total heat-production in the chart in figure 57. As in all the foregoing comparisons, no regularity is apparent. COMPARISON OF EXPECTED BODY-WEIGHT AND HEAT-PRODUCTION PER KILOGRAM OF ACTUAL BODY-WEIGHT. We have plotted in the chart in figure 58 the values for the heat-pro- duction per kilogram of actual body-weight for 24 hours for those of our infants whose birth-weight was obtainable. The same absence of any tendency toward regularity in the chart is seen as in the foregoing com- HEAT PER KILOGRAM OF BODY-WEIGHT PER 24 HOURS EXPECTED WEIGHT 10.0 9.0 2 7 EG . DM me Js 8. . Fk BO ‘ Lo sal KR MC’ ILRB RL LB JAL EF 5 JP. oJ Vaya mos. 60 MM wpe! AS ba EHS RE. *GS t ES 5a ERe a J Vave mos 40} AC 45 50 55 60 65 70 75 80 65 90 Fic. 58. Chart showing the expected weights for the infants under observation and the heat- production per kilogram of actual body-weight per 24 hours. parisons. We may therefore conclude that, aside from a slight tendency for the total metabolism to be larger with increasing weight, no regular relationship exists with infants between the total heat-production and the body-weight, regardless of whether the body-weight was actually found, computed from statistics of average values for normal infants, or was the expected body-weight based upon the birth-weight. This lack of correlation is likewise seen when the heat-production per kilo- gram of body-weight for 24 hours is computed on the various weight bases. It is clear, then, that some factor other than the body-weight influences the heat-production. 156 GASEOUS METABOLISM OF INFANTS. COMPARISON OF THE AGE AND HEAT-PRODUCTION PER KILOGRAM OF BODY-WEIGHT. Since an inspection of the data contained in table 31 appeared to show that the younger infants produced the least heat per 24 hours, it seemed desirable to study the influence of age upon the metabolism. A chart was prepared in which the heat per kilogram per 24 hours is compared with the age at the time of observation, this comparison being given in figure 59. Here again no correlation is indicated between the two factors, infants 43 months of age showing a heat-production per kilogram of body-weight ranging from 55 to 85 calories per kilo- gram per 24 hours. _ HEAT PER KILOGRAM OF BODY-WEIGHT PER 24 HOURS AGE Ekliz mos. PS Tl DM EG 9 MA : 2 ‘ JV RL iM i Fk JP Pw CEN 2 Lo} 5__Ht J§ FB e e es JB wP a ES 2 mM) MC | DQ RE UB AD). FM ire . KR OAL | CEL wy 3 EHS i EF AS eR 65 1 AC MD 45 50. 55 60. 65 707s 80 85 30 Fia. 59. Chart showing the age of infants and heat-production per kilogram of body- weight per 24 hours. From these data, therefore, it would appear that neither the weight nor the age shows a uniform relation to the total heat-production or to the heat-production per kilogram of body-weight. In this finding we are completely in accord with all other experimenters in metabolism, since the lack of relationship between body-weight and metabolism is invariably noted. This is particularly the case when two living bodies are compared which vary considerably in weight. With men, it is true, the metabolism per kilogram of body-weight is considered and commonly used as a reasonably accurate base-line for comparative purposes. Nevertheless the relationship is invariably disturbed when one of the individuals is very fat and the other under- DISCUSSION OF RESULTS. 157 nourished, so that although the use of the base-line of per kilogram of body-weight may be justified when comparing individuals of average weight and approximately constant body composition, 7. e., with no great differences in the proportion of body-fat and muscular tissue, yet when comparing bodies of widely varying body-weight and body-composition, this basis of comparison can not be considered reliable. RELATIONSHIP BETWEEN BODY-SURFACE AND METABOLISM. For many years writers in metabolism have been wont to emphasize the significance of the relationship supposed to exist between the metab- olism and the body-surface rather than that between the metabolism and the body-weight. The idea that there is an intimate relationship between body-surface and heat-production was first brought out by Bergmann! in 1847. The theory lay dormant for many years, but was finally resuscitated and put forth in a brilliant and highly stimu- lating manner by Rubner? in 1883, together with experimental evidence. Based fundamentally upon Newton’s law of cooling, it received great attention from practically all workers in physiology. Startling evidence was brought forward to demonstrate that the heat-production per square meter of body-surface was about 1,000 calories for practically all species of animals, and this lent further support to the hypothesis. In connection with our own researches we naturally expected to find a close relationship between body-surface and total metabolism, par- ticularly in view of the fact that recent observations from foreign laboratories appeared to confirm the validity of Rubner’s law. We were therefore greatly surprised on preparing our final figures to find this intimate relationship entirely disturbed. METHODS USED FOR MEASUREMENT OF BODY-SURFACE. In order to discuss intelligently the relationship between the metab- olism and body-surface, a critical examination of the various methods for determining the body-surface is essential. Using as a basis the relationship between the surface of similar solids which is expressed by the cube-root of the square of the weight, efforts have been made by a number of investigators to compute the body-surface of various animals and individuals from the body-weight. Meeh’ found that he could measure the body-surface of men by using the constant 12.312, which, when multiplied by the cube-root of the square of the body-weight in grams, gave the body-surface in square centimeters. Rubner and Heubner,* who first applied this formula to the study of the total metabolism of infants, rightly sub- 1Bergmann and Leuckart, Anatomisch-physiol. Uebersicht des Thierreichs. Stuttgart, 1852. p. 272. See also, Bergmann, Wirmedkonomie der Thiere. Gottingen, 1848, p. 9. 2Rubner, Zeitschr. f. Biol., 1883, 19, p. 545. 3Meeh. Zeitschr. f. Biol. 1879, 15, p. 425. 4Rubner and Heubner, Zeitschr. f. exp. Pathol. u. Therapie, 1904-1905, 1, p. 1. 158 GASEOUS METABOLISM OF INFANTS. stituted the value 11.9 which was determined by Meeh on the two well-nourished infants under 1 year that he measured. Recognizing the importance of considering the length of the body as well as the circumference of breast and abdomen, Miwa and Stoeltzner,! using Meeh’s measurements, proposed another formula, in which the length and circumference as well as weight should appear as factors. This formula has not been generally accepted by research workers. Actual measurements of the body-surface of cadavers have also been used in an attempt to find some mathematical formula expressing the relationship between body-weight and body-surface. Lissauer’® meas- ured 12 cadavers, 11 of which were under one year, and found that the constant 10.3 should be used in the Meeh formula instead of those previously proposed. It has been maintained by other writers that since many of Lissauer’s measurements were made upon thin, poorly nourished, and atrophic infants, they do not give standards for well- nourished infants. Sytscheff* measured 10 infants under one year of age, but computed no ratios. Howland,‘ employing Meeh’s and Lissauer’s measurements, has recently proposed still another method for computing the body-surface based upon a curve represented by the algebraic formula y=mx-+b. With these three methods in vogue for computing the body-surface, i. e., that of Rubner and Heubner using the Meeh formula with the constant 11.9; that of Lissauer using the constant 10.3; and that of Howland using the algebraic curve—it can be seen that, with the great weight laid by all experimenters in infant metabolism upon the relation- ship between body-surface and metabolism, it is incumbent upon us to present our results on the three separate bases, although the rela- tive values remain unaltered in all three cases. This is done in table 31,° the plotted values being given in figures 60,61, and 62. COMPARISON OF AGE AND HEAT-PRODUCTION PER SQUARE METER OF BODY-SURFACE. According to accepted ideas we should expect to find the heat-pro- duction per square meter approximately constant for all of our infants, 7. e., not far from 1,000 calories per square meter of body-surface. That this value is far from constant is seen clearly in table 31, but the variations are most strikingly shown if we compare them with the age of the infant, as is done in the charts in figures 60 to 62. In the chart in figure 60, the range in heat-production per square meter of body-surface (Meeh formula) per 24 hours is very wide, the lowest value being 656 calories for M. D., and the highest 1,239 calories 1Miwa and Stoeltzner, Zeitschr. f. Biol. 1898, 36, p. 314. 2Lissauer, Jahrb. f. Kinderheilk, 1902, 58, p. 392. . 3Sytscheff, Measure of volume and body-surface of children according to their ages. Disserta- tion, St. Petersburg, 1902. See, also Gundobin, loc. cit., p. 54. 4See p. 22 for further explanation of this method. 5See p. 143. DISCUSSION OF RESULTS. 159 for J. M. An inspection of the plot shows no average value, for even when we omit the extreme values for M. D., A. C., E. F., and J. M., the limits still remain 771 to 1,108. A larger number cluster around 875 calories, but there are too many scattering values to permit the use of 900 calories as an average value. If a line were drawn passing through the greatest number of points in this curve, it would indicate that there is a tendency for the older infants to have a higher heat- production, and yet, even with infants of the same age, wide variations are to be observed. This chart, therefore, leaves no doubt as to the lack of constancy in heat-production per unit of body-surface for the infants under observation in this research. HEAT PER SQUARE METER (MEEH) PER 24 HOURS AGE IN MONTHS 675 725 775 825 875 925 975 1025 1075 Il25 7S. Fic. 60. Chart showing age of infants and heat-production per square meter of body-surface (Meeh formula) per 24 hours. In the charts in figures 61 and 62, a comparison is made of the same two factors, using as a basis the Lissauer and Howland formulas respectively. The substitution by Lissauer of 10.3 for the constant 11.9 in the Meeh formula has not materially altered the picture as is shown by comparing the charts in figures 60 and 61. In the latter. the minimum value is 753 calories with M. D., and the maximum 1,432 calories with J. M., with a tendency for some of the points to collect about the value 1,025 calories. The plot in general can not be con- 160 GASEOUS METABOLISM OF INFANTS. sidered in any sense as indicating uniformity, although a slight general inclination is shown for older infants to have a higher heat-production on this basis. With Howland’s formula (see figure 62) the general picture presented is essentially the same. The lowest value on this basis is 739 calories with M. D., and the highest is 1,367 calories with J. M. The general tendency for the older infants to have a higher heat-production may again be inferred from an inspection of the chart in figure 62, though no definite regularity in the relationship between age and heat-production ean be seen. HEAT PER SQUARE METER (LISSAUER) PER 24 HOURS 825 875 925 975 Fic. 61. Chart showing age of infants and heat-production per square meter of body-surface (Lissauer formula) per 24 hours. It should be borne in mind that, according to the currently accepted views, the charts in figures 60, 61, and 62 should theoretically have been straight lines—that is, that the points should have grouped themselves more or less in a vertical manner. As a matter of fact, the grouping appears to be more horizontal than vertical, thus showing by a visual- ized method a complete absence of correlation in the heat-production per square meter of body-surface with infants of different ages. With such large variations it was highly improbable that further comparisons on this basis would lead to any explanation of the dis- crepancies. Nevertheless, so at variance are these results that we have deemed it necessary to make all possible computations and comparisons DISCUSSION OF RESULTS. 161 and to see if definite relationships can be established for the heat- production per square meter of body-surface and the age, weight, and length of the different infants. HEAT PER SQUARE METER (HOWLAND) PER 24 HOURS Age IH Fic. 62. Chart showing age of infants and heat-production per square meter of body-surface (Howland curve) per 24 hours. COMPARISON OF ACTUAL BODY-WEIGHT AND HEAT-PRODUCTION PER SQUARE METER OF BODY-SURFACE. In the charts in figures 63, 64, and 65, the heat-production per square meter of body-surface has been compared with the actual body-weight using the three formulas. In the chart on the Meeh formula given in figure 63, we should again expect according to current belief to find the values grouping themselves in a vertical line. On the contrary, the dispersion is even more marked than in the charts plotted on the basis of age, with a tendency, if any, toward a horizontal rather than a vertical alignment. The complete absence of correlation is here again strikingly shown, nor is the general picture of the relationship between actual body-weight and the heat-production per square meter of body-surface materially altered when the plots are made on the formula of Lissauer (figure 64) or on the formula of Howland (figure 65). It is again important at this point to recall the fact that the observa- tions made on these infants were all under constant conditions, namely, complete muscular repose and at approximately the same length of 162 GASEOUS METABOLISM OF INFANTS. HEAT PER SQUARE METER (MEEH) PER 24 HOURS ACTUAL, 80) EK, 70) Ee pW PS 60) AS i LRB ie “FKI yp JM 50 MM Da. RE| EN :DM | JS FB — zi WP* lee JB FM 7 30 : GS AR AL LAD Lo JVere Mos. AC EHS ES 20) UVare os} 675 725 775 825 875 925 975 1025 1075 125 175 1225 1275 Fia. 63. Chart showing actual body-weight of infants and heat-production per square meter of body-surface (Meeh formula) per 24 hours. HEAT PER SQUARE METER (LISSAUER) PER 24 HOURS _ ACTUAL WEIGHT 90 HT: EG ao EK RL 70 EF PW PS: 60 AS Me LRE MA | a aM 50 mia | DO, RE cil FK IDM up : | JS FB 40 ER} LB “WP cELI- MD & cM a0 > KR JB ALIAD LO- AC EHS ES 20 : V5 uimo 775 825 875 925 975 1025 loys N25 175 1225 i275 1325 1375 1425 1475 Fic. 64. Chart showing actual body-weight of infants and heat-production per square meter of body-surface_(Lissauer formula) per 24 hours. DISCUSSION OF RESULTS. 163 time after feeding. It is impossible, therefore, to explain these great discrepancies as being due to muscular activity, nor can they in any way be accounted for by the ingestion of food, since our experiments have shown that the food taken by these infants while under observa- tion had no material influence upon the metabolism. Finally, it should be noted that, in general, the observations were made at substantially the same time relations to the food ingestion. HEAT PER SQUARE METER (HOWLAND) PER 24 HOURS ACTUAL, 90) “HT EG 80) EK 70 EF RLIPw PS 60 AS Me LRB : . Mal. |FK WP 50 mM | Dd RE. | EN DM ae . we |. FB AO} ER | LB * |S EL m JB FM 30 [9S:-KR “FAL aD LO Mevanos AC EHS) ES 20 : JValvemos 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 Fia. 65. Chart showing actual body-weight of infants and heat-production per square meter of body-surface (Howland curve) per 24 hours. EFFECT ON METABOLISM OF POSSIBLE DISTURBANCE IN RELATIONSHIP BETWEEN BODY-SURFACE AND BODY-WEIGHT. It has frequently been the custom when discrepancies in the heat- production per square meter of body-surface are found with infants, and particularly with atrophic infants, to ascribe the variation to a disturbance of the relationship between body-surface and the body- weight from which it is computed. It is essential, therefore, at this point to discuss this possibility more in detail. The argument frequently raised is that disturbances in the relation- ship between body-weight and body-surface with under-weight infants precludes the use of any of the formulas now regularly used for the computing of body-surface, in that they give too small a value of body- surface for such infants. At the outset we wish to oppose this general thesis on the ground that in the most extensive and remarkably accu- rate series of measurements on infants with which we are familiar, namely, those of Lissauer, it is especially emphasized that 10 out of 12 164 GASEOUS METABOLISM OF INFANTS. of the infants were very much under weight. This will be seen by reference to table 34, which reproduces the weights of 11 of the infants measured by this investigator.! As Lissauer himself points out with regret, S—i was the only case which could be called normal, although S—r was practically of normal weight. All of the other cases were noticeably under weight, far more so than our infants as arule. Yet, in spite of this great deficiency in weight, the relationship between the body-weight and the measured body-surface was represented by the difference between the constant 10.3 used by Lissauer and 11.9, the constant of Meeh. In other words, this large variation in weight produced a maximum discrepancy of not over 15 per cent in the relationship between the body-surface as actually measured and the body-weight. TaBLE 34.—Body-weights of infants measured for body-surface by Lissauer. Average weight Name. Sex. Age. Body-weight. | for age obtained from Heubner. kilos. kilos. M—f..... M 33 mos. 3.27 6.2 H—r...... F 34 1.96 6.2 R—e...... F 33“ 3.37 6.3 S—e...... M 1 ne 2,22 4.008 S—r...... F 1 ie 3.83 4.008 M-r...... M 15 - 5.23 11.+ W-t...... M 17 days 1.73 a0 St....... M 22 ie 1.28 3.7 Poe ce. M 34 mos. 2.50 6.0 H—z..... M Ta 3.10 8.2 S-i...... M Be te 6.18 6.3 It is furthermore of interest to note, although this is probably a mere coincidence, that one infant, especially cited by Lissauer as a normal infant (S—i), gave a constant of 10.3. When one considers that the Meeh constant of 11.9 was based upon the measurements of but two infants less than a year old, it seems probable that the Lissauer formula is more nearly accurate and that the difference in the relation between body-weight and body-surface due to under weight is not appreciable. That the opposite is true, namely, that there is no disturbance in the relationsip between body-weight and body-surface when the infant is over weight, lacks, as yet, experimental evidence for confirmation or refutation. The possibility of the disturbance in the relationship between body- surface and body-weight in under-nourished infants has been provided for in the presentation of our data, in that the comparisons have been made upon the three bases of Meeh, Lissauer, and Howland. We 1Zissauer, loc. cit. DISCUSSION OF RESULTS. 165 frankly consider for our own work that the factor 10.3 which was most ' carefully determined by Lissauer is the one logically best adapted for use in computing the body-surface of the greater number of infants. We furthermore believe that Lissauer’s formula would, in general, more nearly fit the requirements of observations in clinics, where the larger number of infants are under weight. On the other hand, as we have already pointed out, it is distinctly questionable whether the methods of measurement! have even yet been sufficiently refined or are sufficiently numerous to give a reliable method for the computation of the body-surface from the body-weight. Tas eE 35.—Heat-production per square meter of body-surface (Meeh formula) for normal infants. Body-weight Heat per square Subject. without | Height. Age. Days. | Periods. | meter of body- clothing. surface (Meeh). kilos. cm. mos. days. cals. Mi) fisceted 3.99 ie ais 17 2 4 656 MC) icvsiase 6.17 63 4 3 7 837 L.R.B..... 5.99 64 4 4 11 844 E.G....... 9.37 74 10 3 5 907 Rein canae 7.58 ot 84 5 8 991 PW sccsereceies 7.11 64? 7 2 5 998 Although we believe that the lack of consistency exhibited by our infants in the heat-production per square meter of body-surface may not be ascribed to the fact that these infants were distinctly under the average weight, it is of special interest to select the relatively few infants who are of normal average weight and note the relationship between the heat-production and the body-surface. This has been done in table 35, in which the heat-production per square meter has been calculated for 6 of our normal infants of average weight. In no case were less than 4 periods used for averaging, and usually the average was drawn from a larger number of periods, the range being from 4 to 11 periods. Even with these selected infants, the variations in the heat-production per square meter of body-surface range from 656 to 998 calories. It is thus evident that the disturbance noted with our whole collection of infants in the relationship between the heat- production and the body-surface is also apparent with selected infants having a normal or approximately normal average weight. 1As an interesting evidence of our initial belief in the importance and significance of the measure- ment of body-surface and its relationship to metabolism, we should here state that extensive preparations were made by us for the measurement of the body-surface of a number of infants, and a method was developed for securing shadow photographs of infants in various positions, the areas of the shadows being measured by a planimeter. It was our hope to establish thereby some relationship with the body-surface as measured from the shadow photograph, and by actual measurements of cadavers, and the body-weight and length. It is needless to say that with our present views in regard to the significance of body-surface in its relation to metabolism, we have not felt justified in continuing such a series of measurements. 166 GASEOUS METABOLISM OF INFANTS. INFLUENCE OF VARIATIONS IN THE COMPOSITION OF THE BODY UPON TOTAL HEAT-PRODUCTION. Since a gross disturbance in the relationship existing between the body-weight and the body-surface as computed from the body-weight is highly improbable, whether the infant is atrcphic or well nourished, it is important to find out, if possible, if any relationship exists between the general composition of the body and the total heat-production. Our data aresufficiently extended to permit asomewhat incomplete discussion of this important phase of the comparisons. Heretofore, all workers in metabolism have considered only the relationship between body-weight and metabolism, or body-surface and metabolism. Since the body-surface is assumed to have a direct relationship to the body-weight, it can be seen that body-weight is the only fundamental factor which has thus far been seriously considered by investigators in comparing the metabolism of different infants. It is obvious that when two infants are of the same weight, the shorter one will have the larger proportion of fat. Furthermore, with two infants of the same length but of different weights, the heavier infant will have the larger proportion of fat. It can be seen, therefore, that an atrophic infant, weighing 4 kilograms and 65 cm. long, when compared toa well-nourished infant of the same weight and length, would have a smaller proportion of fat. Moreover,an atrophic infant, to have the same weight and length as a normal infant, must obviously be older, and we here find a new factor entering into the comparison of infants; as yet the element of age has received scant attention. Table 31 shows that in a number of instances infants with approximately the same body-weight and the same height differ greatly in age. Unfortunately our data are not so extensive as to enable us to compare infants with absolutely the same body-weight and height, but a number of compari- sons are justifiable and these have been included in table 36, which gives eight series of comparisons of the total heat produced, the heat- production per kilogram of body-weight, and the heat-production per square meter of body-surface for infants with the same body-weight and height but of different ages. The difficulties incidental to measuring exactly the length of infants make these measurements slightly proble- matical and there may be a variation of plusorminuslcm. We have, therefore, compared infants whose lengths do not vary more than 1 cm. The variations in weight are all within a few tenths of a kilogram. We note instantly several striking points in the data as presented. In each comparison the values for the younger infant are given first, and it will be seen that the older infant has invariably the larger total heat-production. The greatest difference is 182 calories in the com- parison of M. M. with J. M., the lowest difference being that of 16 calories between E. N. and D. M. Aside from this latter comparison, the increase in the heat-production for the older infants is very con- siderable. The heat-production per kilogram of body-weight and per DISCUSSION OF RESULTS. 167 square meter of body-surface also show this increase in the same general proportion, since the body-weights of the infants compared are essen- tially the same in all cases. TaBLE 36.—Comparison of heat-production of infants of like body-weight and height, but of different ages. Heat produced. ‘ Body- , Subject. Sex. i Height.| Age. ‘ Per square weight. Per 24 hours. oe he gan meter (Meeh) pel "| per 24 hours. kilos. cm. mos. cals. cals. cals. Bin Tiiccsdiactovin F 3.18 53 4 226 71 876 Dio Miccave F 3.38 53 8i 297 88 1108 BI AINY 3. ccdcoayee.tecd F 5.40 66 6 353 66 962 LE a Sees M 5.18 66 it 369 ah 1034 Mi Mise cca. d F 5.47 62 43, 285 52 770 VeM eciseersiae M 5.63 62 8 467 83 1239 Di Qyissieeauae M 5.28 62 43 305 57 846 Ji Pipes M 5.45 63 7 387 70 1039 M.M....... F 5.47 62 4} 285 52 770 BN xuicd ncn M 5.45 63 7 387 70 1039 DQ) oosacavusien M 5.28 62 4} 305 57 846 Dis Mies caeddincec M 5.63 62 8 467 83 1239 L.R.B...... F 5.99 64 4 331 55 844 Be i cased sacs M Biil 65 e 381 67 1003 Be Di cacicgee M 9.33 75? 54 420 45 797 Be Gas aaatens M 9.37 74 10 479 51 907 In the two series of comparisons in which the youngest infant is approximately 6 months old, namely, those comparing E. N. with D. M. and H. T. with E. G., the increase in the heat-production for the older infant is not so great. In the latter comparison, E. G. was of normal weight while H. T. was over weight, so that the excessive amount of fat actually lowered the total heat-production of the younger infant H. T. It is therefore clear that with the older infants, which were in most instances distinctly under weight, there was a deficiency in the fat with an accompanying increase in the proportion of active proto- plasmic tissue. While this method of comparing the metabolism of infants on the basis of weight, height, and age gives a clue to the prob- able preponderance of fat or active protoplasmic tissue, it is obvious that no quantitative relationship can be established on this basis. The striking comparison between M. M. and J. M. is particularly worthy of consideration, inasmuch as the value for M. M. is derived from observations on three days, and a total of seven satisfactory periods were available for averaging, while with J. M. the data were secured on two days with six periods for comparison. Here, with a difference of 33 months in the age, there was obviously a much greater proportion of active protoplasmic tissue with the older infant, J. M. That the active protoplasmic tissue determined to a very consider- able extent the total katabolism, not only with J. M., but with all of 168 GASEOUS METABOLISM OF INFANTS. the older under-nourished infants, is highly probable and we find ourselves thoroughly convinced that the metabolism is determined not by the body-surface but by the active mass of protoplasmic tissue. With normal infants of varying weights, it is quite probable that the active mass of protoplasmic tissue varies directly with the age. Since it has been shown that not only body-surface but more recently that the blood-volume, the size of the aorta, and the size of the trachea with several species of mammals bear a direct relationship to the cube root of the square of the body-weight,! it is not surprising that most experimenters have observed that with adults the metabolism is roughly proportional to the body-surface. If the blood-volume and the area of the trachea and the aorta are proportional to the cube root of the square of the body-weight, it is reasonable to suppose that the active mass of protoplasmic tissue may develop normally on this ratio. When there are marked variations fromthe average, as with excessive or with deficient adipose tissue, this relationship can not be expected to hold. If, therefore, it is maintained that the total metabolism is propor- tional to the body-surface, it should be stated that this is not due to the fact that there is a loss of heat from the body-surface and that Newton’s law of cooling determines the intensity of the metabolism, but that with normal individuals the body-surface, blood-volume, the area of the trachea and the aorta, and probably the active mass of protoplasmic tissue, are all in simple mathematical relation to the body-weight. Thus the apparent relationship which has previously been observed between the heat-output and the body-surface with normal or nearly normal individuals has an explanation in that with such individ- uals a simple relation exists between the body-surface, blood-volume, body-weight, and the mass of active protoplasmic tissue. In our series of observations we have attempted to eliminate com- pletely all muscular activity, to make the experiments under approxi- mately the same conditions as to nutriment, to select such a diet as was least stimulating to the katabolism, and to have our subject for the most part in deep sleep, thus eliminating psychic disturbances. With these conditions we hoped to obtain the fundamental minimum metabolism, upon which we might base our discussion. The basal metabolism as we have outlined above, can not in any wise be considered a direct function of the body-weight and the body- surface, and particularly has no relationship with body-surface on the basis of the law of cooling bodies. We believe that our evidence points strongly and conclusively to the fact that the active mass of protoplasmic tissue determines the fundamental metabolism. The absence as yet of a direct mathematical measure of the proportion of active protoplasmic tissue does not, we believe, in any wise affect the convincing nature of our evidence. 1Dreyer and Ray, Phil. Trans., 1909-1910, 201, ser. B, p. 133; Dreyer, Ray, and Walker, Proc. Roy. Soc., 1912-1913, 86, ser. B, pp. 39 and 56. rr BE ta a ESS ee ts Ae