Certain laboratory findings and interpretations in eclampsia

430

AMERICAN

JOURNAL

OF

OBSTETRICS

AND

GYNECOLOGT

4. Because of the peculiar sensitivity of the fetal respiratory system to depression by anesthetics, the factor of anesthesia must be regarded as an important one in the pathogenesis of respiratory failure at birth. REFERENCES (1 ) Snyder, F. P., N. E., u7kd Blumenfeld: Rosenfeld, N. : Am. F. : J. Pharmacol. & F. (‘.: Surg. Gynec. Am. J. Physiol. 121:

CER.TAIK

and

Rosenfeld, N.: J. A. R4. A. 108: 1946, 1937. (2) Bonar! Surg. Gynec. Obst. 66: 179, 1938. (3) Snyder, F. P., arid J. Physiol. 119: 153, 1937. (4) Rosenfeld, M., and Snyder, F. Exper. Therap. 57: 139, 1936. (5) Clifford, S. H., and Irvviny, Obst. 65: 23, 1937. (6) Eosenfelrl, 34., znd Snyder, F. F.: 242, 193%

LABORATORY IN LEON

(Prom

the Department .

c.

C~HESLEY,

FINDIKQS AND ECLAMPSIA PH.D.,

of Bioch,emistry,

JERSEY Margaret

INTERPRETATIONS

CITY, Hague

N. Maternity

J. Hospital)

N CONSIDERING laboratory tests in eclampsia, au incomplete conception of any of several factors may lead to erroneous conclusions. In interpretation, at least three questions must be borne in mind. First, what do we expect of the test; second, what are the vitiating or modifying factors which may complicate the final result; and third, what do the results mean? I can make HO pretense of bringing a complete conception to the interpretation of biochemical observations. However it is not out of place to present the results of some tests in a fairly large series of eclamptic patients and to attempt to explain some of these results. Several writers have concluded that renal function tests are of no value in toxemia of pregnancy, either because the tests have no value in predicting the later development of toxemia, or because the). give normal results in toxemia. It is apparently assumed that the toxemia is either a manifestation of, or is caused by, renal deficiency. In a very recent paper, McPhaill writes, “It is believed that toxemia will not develop if no impairment of renal function exists.” This, probably unfortunat,ely, is widely believed. Many writers, however, do not accept renal insufficiency or deficiency as a cause of toxemia of pregnancy. Too much is expected of the function tests if it is thought that they may serve to predict toxemia. As for factors modifying the tests, one might again cite the renal function measurements. The restriction of salt, commonly practiced in the treatment of toxemia, will at once reduce by nearly one-fourth the significant figures in the attainable specific gravity.” Or again, a tendency to oliguria is common in toxemia; in oliguria the glomerular filtration is a,pparently reduced,3 and therefore most, if not all, excretion tests are modified. For instance, in oliguria the calcula,tjon of standard urea. clearances gives grossly erroneous results.43 5 Yet there

I

CHESLEY

:

LABORATWY

TESTS

IN

ECLAMPSIA

43 1

are several papers in which low urea clearances, calculated from low urine volumes, are reported and considered as valid and typical findings in eclampsia. What do the results of the test mean ! In eclampsia many, though not all, investigators report that the blood uric acid is elevated. dome believe that this means renal retention, others that it means failure of the liver to destroy its cluota of uric acid. In many eclamptics the blood nonprotein nitrogen may also rise. Some interpret this as evidence of an underlying and causative renal impairment ; ot,hers think that it is causecl by renal damage secondary to the toxemia. Since in oliguria glomerular filtration is diniinishetl ,:< the rise in nonprotein uitrogen might be attributecl to this factor which may be wholl- inclependent of any renal lesion. primary or sec~onclary.

The present study is based upon 90 cases of eclampsia occurring from Jan, 1, 1934 to date. With very few exceptions, renal fun&on tests were done on each patient. Blood chemistry values were obtained in patients in a postabsorptive state. except when urea clearances were done. TTric acid of the blood was determined by Folin’s last ruetlrodjG in the Folirr-7Vrr tiltrate. Nonprotein nitro(lsn of the blood was determined by 1Vong’s method.’ Protein&a was detected by the sulfosalicylic acid method. If positive. quantitytive measurement was made by the procedure of MaeKay. Urinary qnecific gracity was determined by means of a Westphal balance.7 In the earlier cases a calibrated hydrometer was used. All readings were corrected for protein content of the urine and were discarded if sugar was present. * Volhard’s urine concentration teds was used. The patient was given no food or fluid for seventeen hours after a 5 P.M. supper. IJrine specimens were collected at 3, 9, and 10 A.M. the following morning. The specific gravit,?; was corrected for protein content,, and disregarded whenever melituria was encountered. Urea cleayances were calculated by Van Slyke ‘P conventional formulas.7 No results are reported in the statistics for c31caram~cs calculated from volumes of less than 25 ml. per hour. PheltoZszcIpholte~hthalein excretion was measured at 13, ZO, 60, and 120 minutes after the intravenous injection of 1 ml. of the dye. RESULTS

AND

DIS(‘C3BIOS

Blood liric B&X.--Stander and Cadden,% 10 as well as others, have reported that in eclampsia the blood uric acid is increased; concomitantly there is little or no increase, or only a later increase, in the other nitrogenous metabolites of the blood. High blood levels of uric acid are also found when the nonprotein nitrogen rises because of renal impairment. This suggests that absolute values for the blootl uric acid may not have as much significance, in toxemia of pregnancy, as would the ratio of uric acid to some other substance or group of substances. Accordingl> a study has been made of the ratio between the blood uric acid and the nonprotein Since different -methods for either uric acid or nonprotein nitrogen tlo nitrogen. not give identical values, it must be remembered that the absolute values of the Furthermore, uril, ratios reported here would change n-it11 change in methods. acicl itself varies more than any other nitrogenous constituent of the blood (Folinr 1j Both absolute values and ratios of uric acid to nonprotein nitrogen may therefore be expected to show considerable variation. The relation of the blood uric acid to the nonprotein nitrogen was analyzed in :! (B) in 69 convalescent eclamptic control series: (A) In 60 normal patients at term; (C) in 152 blood chemistries on 2% patients patients, seven to ten days post partum:

432

AMERICAN

JOURNAL

OF

OBSTETRICS

AND

GYNE~COLCGY

with renal impairment as shown by lowered urea clearanres and often by nitrogenous retention. In the first 2 series, the blood uGc acid showed no definite relation to the nonprotein nitrogen, except that in most cases the uric2 acid was less than II per cent of the nonprotein nitrogen. The low coefficients of correlation, given in Table I, merely emphasize the variability of the blood uric acid levels. The higher, and significant, correlation coefficient in the patients with renal impairment indicates that the level of blood nonprotein nitrogen should be considered when assessing the blood uric acid level, especially if the nonprotein nitrogen is somewhat elevated. Again, in this series, the ratio is usually less than 11 per cent. The statistical data are summarized in Txhle 1. ‘I’lw frrqurnc.y d istrihutions of tlw ratios are shown in E’ig. 1.

Fig. L-The frequency distribution of uric acid/nonprotein the blood of eclamptic and control patients. Note that eclamptic characteristically above 10 per cent, while patients in the three ratios usually less than 10 per cent.

nitrogen patients control

ratios in show ratios series show

Roughly then, we might take the normal proportion of uric acid to nonprotein nitrogen as about one-tenth. Accepting 10 per cent as the normal uric acid nonprotein nitrogen ratio, a blood uric acid of 4.0 mg. per cent would be of more serious import in a pre-eclamptic patient whose nonprotein nitrogen was 20 than in one whose nonprotein nitrogen was 40 mg. per cent. It is suggested that this ratio is of more In the present series significance than the absolute level of the blood uric acid. 13 of 73 eclamptic patients had blood uric acids of less than 4.0 mg. per cent on the day of convulsion, but, only 4 had uric acid/nonprotein nitrogen ratios of less TABLE

Normal Renovered eclamptics Renal impairment *152 blood

I.

RELATION

j chemistries.

OF THE BLOOD NITROGEW IN

URIC

ACID TO THE CONTROL SERIES

BLOOD

NONPROTEIN

CHESLEY:

LABORATORY

TESTS

IN

430

ECLAMPSIA

10 per cent. In Fig. 1, it may be readily seen that the uric acid/nonprotein nitrogen ratio is characteristically above 10 per cent in eclampsia. In passing, it might be worth while to note that about half of the nonconvulsive toxemia patients observed have had elevated uric acid/nonprotein nitrogen ratios (mean 0.109, u = 0.034). It is before the outbreak of convulsions, of course! that laboratory tests of possible premonitory significance are of the most value. 17%~~ Specific Gravity.-Alving and Van Slyken found that about one-fourth of the significant specific gravity of the urine was given by chloride, and that another one-fourth was attributable to urea. Chloride and urea excretion vary directly with the dietary intake of chlorides and protein, respectively. Since salt is very often, and protein sometimes, restricted in the treatment of toxemia, one might expect the urinary specific gravity in toxemia to fall short of levels otherwise attainable. IdOW urinary specific gravities, in eclamptic patients who have been under such dietary restrictions, cannot be interpreted as evidence of renal impairment. Furthermore the presence of edema makes effective restriction of water all hut impossible. I;101 even if water is not taken by mouth during a roncentrat,ion test, the urine may .qtill be diluted hy the discharge of edema fluid. In the present series of eclamptic patients, more than half failed to att,ain a speeifie gravity of 1.023 or higher as shown in Table II. To emphasize the diet,ary facto] in this test, it is interesting to note that in the 33 patients on whom the c*oncentrat,ion test was done ante par&m, all who failed to roncentrate to 1.023 or higher, had had prenatal care. Of those giving a “normal ” urinary specific gravity, half had no prenatal care. In a few eclamptic patients and in many nonconvulsive toxemias, we have observed that the attainable specific gravity is highest at the time when the patient is admitted to the hospital. Under treatment, with the restriction of salt, the urinary specific gravities seen in the concentration tests, and in the . morning urines, progressively decrease. In brief, then, low urinary specific gravities in eclampsia mean little or nothing so far as the measurement of renal function, or of prognosis, is concerned. Orea iV/Nonprotein Nitrogen Ratio.-The nonprotein nitrogen of the blood is made up of many substances, some of which, chiefly urea, are excreted by the kidney, and some of which are not excreted. If there should be an impairment in the kidney’s excretory function, the fraction of the blood nonprotein nitrogen which would be affected would be first and chiefly the urea nitrogen. Since the “normal ” blood nonprotein nitrogen varies considerably, the ratio of urea nitrogen to nonprotein nitrogen would be a more sensitive indicator of the disturbed renal function than would the absolute level of either. Mosenthal and Hiller,le who advanced than

RlQV.21,

FI‘X('TI0.U

TEST

Urinary specific gravity Ante vartzlm Puerperium Urea N/nonprotein nitrogen Ante partwm Puerperium Two-hour excretion of phenolsulphonephthalein Ante partzlm Puerperium Urea clearance Ante pa.rtzlm Puerperium 1 year or more post parturn *IJpper

limit

of

---2zz: PERCENTAGE OF CASES IX

normal.

3i

8”

/ 1.022

“5

0.0057 0.005li

58

0.088 Ii.087

18 “9

8.20 8.75

10 64 41

9ti.7 96.8 97.1

1 19.i / 15 .3 , 17.4

1.023

/

!

60 Ix

70 70 70

//

1

46

56 I ! I

76 85 98 93

434

AMERICAN

JOUR.NAL

OF

OBSTETRICS

AND

OYNECOLOQY

this concept, suggested a ratio of 0.45 as the upper limit of normal, Many writers have reported a diminution of this ratio in pregnancy. In Table II are summarized the urea nitrogen/nonprotein nitrogen ratios found in the present series of eclamptic patients. Assuming an upper normal of 0.40 in pregnancy and 0.45 post parturn, it is seen that many eclamptics fall outside of the normal limit. Perhaps this can be explained by the tendency to oliguria, or at, least by the diminished urine volume output. The excretion of urea is essentially independent of the urine volume when the output exceeds 2 ml. per minute (2,880 ml. per twenty-four hours); at all lovver volumes, the urea excretion diminishes as the volume falls. (These familiar facts are the basis for the calculation of maxinml and standard urea clearances.) When the urine volume is 0.5 ml. per minute i 720 ml. per twenty-four hours), the excretion of urea is half what it wouhl be at a volun~ of 2 ml. per minut,e (2,880 ml. per twenty-four hours), The urea which is not excreted must, of course, he retained; this retention is physiologic and not dependent upon a renal deficiency. The retention of urea then increases the urea nitrogen/nonprotein nitrogen ratio in the blood, perhaps driving it above the arbitrarily chosen ” nnrmal” of 0.45. It. is probable that the urea nitrogen~‘nonprotrin nitrogen is of little value in eclampsia, and that high v:~lues often \v~~ultl he misleading if interpreted to mean renal impairment,. PhrnoZszllphollrphthaleila.-iMan?of the eclamptics, as Table II demonstrates, seemed to excrete subnormal amounts of phenolsulphonephthalein. According to Stander13 ureternl dilatation, found in about 85 per cent of pregnant patients, may become so extr,eme as to increase the volume capacity of the ureter to as much as 60 ml., twice the average volume output of urine per kidney per hour. While the kidney may excrete normal amounts of the dye, there will be a long lag before the excreted dye reaches the bladder. An un,te-pa&m factor which magnifies the apparent reduction in dye excretion is the usual low volume of urine. If it were not, for diffusion and peristalsis in the ureters, the entire two-hour excretion of dve might he retained within the ureters in many cases. With the post-partzcm diuresis, the stagnant urine in the ureters is swept out more rapidly than ante pa&urn, thus accounting for the larger proportion of patients showing apparently normal excretions after delivery. We have discarded this test as worthless in thr toxemias of pregnancy. D’~cc Clearance.-There is some disagreement as t,o the effect? if any, of normal pregnancy upon the urea clearance. Some writers, as Nice,14 report that the clearance progressively increases as pregnancy progresses. Others, as Gantarow and Ricchiuti,la In a previous paper16 I have restate that the clearance progressively decreases. viewed the literature am1 found that In 183 normal cases, published by 9 authors, the The range was 28 to 266 per cent. However, urea calearance averaged 101 per cent. the range is given hy extreme values which represent, single determinations. If perhaps half a dozen of the 188 cases be thrown out as too high or too low, the range would hecorne the familiar oue seeu out of pregnancy. Dieckmann,r; for instance, reports his own clearance as varying from 15 to 170 per cent; my own range agrees closely with this. We conclude, therefore, that the urea clearance is unchanged in normal pregshould be checked to denanc\*. Here, as nut of pregnaucy, a low clearance termine whether the low value is a normal variation or a constantly depressed level. As Table II shows, the urea clearance in eclampsia is usually normal. Only 3 ants-parturn and 2 post-parturn patients (total 3 patients) of the 72 eclamptic patients who had urea clearances, showed plearrnces of less than 70 per cent. A onerevealed persistent hypertension, and four-year follow-up of 2 of these patients The third proteinuria, and constsntly low urea clearances and specific gravity. patient had an acute pyelonephritisa ryith her eclampsia, and within a year had returned slowly to a normal renal functfOlia1 level as indicated by the urea clearance. Forty-one eclamptic patients have been followed up for periods ranging from one Only 3 of these had subnormal clearances at to five years after the eclampaia. Two of the 3 were the patients mentioned above, the last, or any, observation.

CHESLEY

who third

:

LABORATORY

TESTS

had persistent hypertension, proteinuria and patient’s clearance, in a single determination,

IN

ECL&MPSIA

4%

diminished renal function. The was 68 per cent (abnormal?).

I am not in agreement with several statements made in certain publications dealing with the urea clearance in pregnancy for reason’s to be described. The mechanism of urea excretion, as shown in detail by ChasiH18 as well as by other writers with different methods, is as follows. The glomeruli of the ideal normal adult filter from the plasma a fluid volume averaging 122 ml. per minute. This ultrafiltrate is essentially identical in composition with protein-free plasma. It is remarkably constant in volume, whatever may be the final urine volume above :I critical limit (see below). If all of the urea thus filtered mere found in the final urine, the plasma urea clearance would be identical with the glomerular filtration, i.e., 122 ml. per minute. There is, however, an immediate and obligatory reabsorption of about 40 per cent of the filtered urea; if no more be reabsorbed. the plarmn clearance of urea would then be about 73 ml. per minutlrarancc ( I‘\*,jFZ : follows :L l”~\v”r (‘ul’\(’ the equation for which averages UV/B where U = whole blood Therefore volume below as a standard urine volume

urine urea urea. the actual Y ml. per of reference, set at 1 ml.

concentration,

= V =

-

54 \! V, volume

of urine

per

minute,

ant1 Ii< :

urea clearance, IX/B, is different at e:lch and every urine, minute. In order to get a consfmt which might be t:rktln as 100 per cent, the equation is jugglrtl, ant1 the st:ln(lsrll per minute, getting the form: Standard

Li Clearance

”

=

1: \‘-? B

The result of this calculation gives n-hat the patient’s urea clearance would be it’ the urine rolume were 1 ml. per minute. It does not give the acstual clearance which is always UV/B. When the urine volume output falls to 0.35 ml. per minute. th(h urine is apparently maximally concentrated, and any further decrease in volume must be related to a parallel reversible decrease in glomerular filtration.:< Several investigators have reported low urea clearances in eelampsia; some hart> mentioned the fact that the clearances were donr with low urine volumes.173 19 This accounts for the low clearances. For instancbe, in one eclamptic patient of the prraent series, an ante-pa&m urea clearance was done with the following result: The hout’5. average minute volumes of urine were 0.18-, 9 0.241, 1.3, and 1.86 in ruccessive The calculated standard clearances were 34, 42, 81, and 83 per rent,. The first two are in error though it has been c>ustonlary to calculate standard urea clearances hs mentioned above, recent norkb. ,/ from any urine volume belolv 2 ml. per minute. has shown that the assumption on which standard clearances arc calculated does not obtain when the urine volume falls below 0.35 ml. per minute7 and that such ~a.lcuI:ltion gives results far lower than they actually should be. In the present series, all recorded clearances were calculated from urine volumes of more than 0.5 ml. pcl minute. Low clearances, such as are reported in the literature, could be caleulatrtl in many cases where the volume output of urine in the first hour or two of the t& However the recorded clearances were obtained by continuing was below 25 ml. the test over a longer period until the volume of urine passed was satiafWtory. The statement has been made that the~urea c1earanc.e in normal and in toxemic pregnancy is decreased because of the diminished urine volume.1; SO far ~LS the HoTever, in these cases, standard actual clearance is concerned, this is true. clearances have Ibeen calculated, and the cause assigned for low standard clearT,olume is less than 0.35 ml. p(‘~ ances cannot be accepted (unless the urine minute, in which case standard rlearances must not Ir? c:lll:u1Rt?li).

436

AMERICAN

JOURNAL

OF

OBSTETRI(‘S

AND

UYNECOLOQY

It will be seen that in the equations for maximal and standard urea clearances Therefore errors i,n the determinhon of blood urea the blood urea is the divisor. will raise or lower the calculated clearance. Actual variations in the blood urea will not have this effect upon the clearance. The higher the blood urea, the more urea is filtered; of the filtered urea a constant proportion is reabsorbed (with correction for urine volume, discussed above). The clearance is essentially independent of the blood level of urea. Therefore the statement that edema affects the urea clearance by diluting the urea of the blood (which is in equilibrium in all of body water) cannot be accepted. Nor can another investigator’s statement20 be accepted that the urea clearance varies with the binding or release of urea by the ‘(tissues” (unless the i ( tissues ’ ’ are limited to the renal tubular epithelium) 111 some cases of edema, there may be an oligemia (hemoconcentration) of In such cases thesufficiently marked degree to diminish the renal blood flow. glomerular filtration would probably be lowered, and extrarenally caused diminution In many xuc~h cases, the concomitant oliguria in the urea rlearanee would result. would point to the fallacy of calculating thr standard urea clearance.

An analysis of some laboratory findings in 90 eases of eclampsia is presented. In the interpretation of laboratory tests, certain modifying factors must be borne in mind. Some of these test,s and their modifying factors include the following. Blood Uric B&d.-The absolute level is often elevated in eclampsia. More generally, the ratio of uric acid to nonprotein nitrogen is increased. The upper normal ra,tio, by methods used here, is about 10 per cent. Tirir&apy Specific Gravity.-The attainable concentration of the urine is markedly reduced, not by eclampsia usually, but by the prophylaxis and treatment of the disease. 7Jrea’ N/Nonprotein Nitroge?z.-This ratio varies with the urine volAs a measure ume output and tends to decrease in normal pregnancy. of renal function, it is nonspecific and. in toxemia. especially, is unreliable. Phenolsulpho~~ephthalein.-In eclampsia and in pregnancy generally ureteral dilatation may be so marked that in spite of a normal renal The dye may excretion of dye, the test seems to give subnormal results. be excreted, but stagnating in the ureters, is not available for analysis. Urea Clearance.-In my opinion, the urea cleara,nce is unaffected in pregnancy and is normal in eclampsia, unless there is a concomitant renal disease. Urea. clearances, if calculated as standard clearances, a,re grossly erroneous when the urine volume output falls below about 0.35 The calculated standard clearance, as well as the maximl. per minute. mal clearance, is independent of the urine volume output (above 0.35 It is also independent of the blood urea and of factors ml./min.). influencing the blood urea, such as tissue binding or tissue release of urea. When marked hemoconcentration occurs, the clearance may be low because of this extrarenal factor. I am services typescript.

indebted practically

to Drs. S. A. Cosgrove, all of these patients

J. F. Norton, were drawn,

and for

E. G. Waters, reading and

from criticizing

whose the

RUSSELL

ROACH :

AXD

13. WEI,(!HII

INFECTIONS

-M

REFERENCES (1) McPhail, F. L.: J. A. M. A. 111: 1894, 1938. (2) Alving, A. S., and Van Slyke, D. D. : J. Clin. Investigation 13: 969, 1934. (3) Chesley, L. C.: Ibid. 17: 591, 1938. (4) ChesZey, L. C.: Ibid. 16: 653, 1937. (5) Chesley, L. C.: Ibid. 17: 119, 1938. (6) Folin, 0.: J. Biol. Chem. 101: 111, 1933. (7) Peters, J. PI, and Van Slyke, D. D.: Quantitative Clinical Chemistry. Vol. II. Methods, Baltimore. 1932, Williams and Wilkins, pp. 527, 564, 682. (8) Fishberg, A. M. : Hypertension and Nephritis, ed. 3, Philadelphia, 1934, Lea and Febiger. (9) Stander, H. J., and Cadden, J. F.: AX J. OBST. & GYNEC. 28: 856, 1934. (10) Zdem: Ibid. 37: 37, 1939. (11) Folin, 0.: Physiol. Rev. 2: 460, 1922. (12) Mosenthal, H. O., and Hiller, A. : J. Urol. 1: 75, 1917. (13) Stander, H. J.: Williams Obstetrics, ed. 7, New York, 1936, Appleton-Century, p. 686. (14) Nice, M.: J. Clin. Investigation 14: 575, 1935. (15) Cantarow, A., and Ricchizlti, G.: Arch. Int. Med. 52: 637, 1933. (16) Chesley, L. C.: Surg. Gynec. Obst. 67: 481, 1938. (17) Dieckmanla,W. J.: AM. J. OBST. & GYNEC. 29: 472, 1935. (18) Ctiis, H.: Cited in Smith, H. W.: The Physiology of the Kidney, New York, 1938, Oxford University Press. (19) 11: 1119, 1932. (20) Thomm. Hwrwitz, D., and Ohler, W. R. : J. Clin. Investigation W. -d., Allen, E. D., Bnzter, C. P., n,nt7 Frerlnnrl, Jf. E.: r\nr. d. 0~s~. & GYNEI‘. 30: fit%,

193.i.

B. WELCH11 WITH

A REVIEW

OF THE LITERATURE

1'. B. RUSSELL, JR., (From

the

Depnrtmen,t

INFECTIONS

ND.,

of

IN PREGNANC1’# AND A REPORT OF SEVENTEES

ASD $1. J. Ro.\cE-I,

Obstetrics, th,P .7ohn

M.D.,

University of Tenuessr~ G&on Hospitrrl)

MEMPHIS, Metli~n7

CARES TENN.

Collegr~

nut7

N 1928, Toombs and Michaelson’ recalled at,tention t,o the problem of B. w&!&ii infections in the puerperal state. Since then, a number of notable papers have appeared upon this subject. in American and foreign literature. We propose to review this literature with particular reference to dia,gnosis and treatment, and to present a series of 17 eases occurring in our clinic. I

REVIEW OF LITERATrRE The sources from which one may contract a B. ,welchii infection are manifold. Usually, this organism is found in the intestinal tract of herbivorous animals, though almost any animals, and even man, may be carriers. There are many such cases reB. aerogenes oapmlatus, B. phlegported. The synonyms for this organism are: monis emphysematosae, B. perfriagens, and B. welchii. The latter term will be used throughout this paper. The nature of this infection must be diagnosed or strongly suspected, before or very shortly after the onset of its symptoms and physical signs, in order that treatment may be instituted if it is to be effective. In 1930, Wrigley2 promulgated certain postulates and, with a few observations concerning his first postulate, we will propeed, in the light of subsequent research, to modify all of these: Wrigley was unable to find the B. wetchii in the contents of the cervical canal in early labor, nor could he find it in the lochia when the pregnancy, labor, and puerperium had been normal. Fall@ found the B. welchii organism in the vagina in 5.5 per cent of the 270 cases examined prenatally in 1933, while Byssher in 1938 found five positive cultures in 222 prenatal eases examined, and one positive culture in 42 eases examined on admission to the labor room. These postulates are as follows: &last Be Intro&oed Into the Uterus From Withont. Postulate 1. The Organism or, in rare cases, the organism already present in the vagina or cervix must be carried *Read cologists,

at the annual meeting of the Central Association Minneapolis, Minn., October 6 to 8, 1938.

of Obstetricians

and Gyne-