noble-mengert-fish or nmf operation

noble-mengert-fish or nmf operation : THE American gynecological society ; the American association of obstetricians, gynecologists, and abdominal surgeons ; new York obstetrical society ; obstetrical

noble-mengert-fish or nmf operation | Full text of “Daily Colonist (1961-02-03)”

AMERICAN JOURNAL

OF

OBSTETRICS AND
GYNECOLOGY


Fred L. Adair
Brooke M. anspach
James R. Blobs
L tJCIUS E. BURCH
Walter W. Chipman.
YVillard B. Cooke
Harry S. Crossen
Thomas S. Cullen
Arthur H. Curtis
YVilliam C. Danforth
Walter T. dannreutiier
Carl H. Davib


Advisory Editorial board

Robert L. Dickinson
PALMER Findley
C. Frederic Fluhmann
Robert T. Frank
WILLIAM p. healy
F. C. IRVINO
Jennings C. Litzenberg
JAMES C. Masson
HARVEY B. Matthews
JAMES R. McCord
Norman F. Miller


Emil Novak
Everett D. Plass
IsiDOR C. Rubin
Otto H. Schwarz
Paul Titus
Herbert F. Traut
Norris W. Vaux
George Gray Ward
Benjamin P. Watson
Philip F. Williams
Karl M. Wilson


Official Organ

THE American gynecological society ; the American association of obstetricians,
gynecologists, and abdominal surgeons ; new York obstetrical society ; obstetrical

society op PHILADELPHIA ; BROOKLYN GYNECOLOGICAL SOCIETY ; ST. LOUIS GYNECOLOGICAL

society ; new Orleans gynecological and obstetrical society ; Baltimore obstetrical
AND gynecological SOCIETY; CHICAGO GYNECOLOGICAL SOCIETY; CINCINNATI OBSTETRIC
SOCIETY ; CENTRAL ASSOCIATION OF OBSTETRICIANS AND GYNECOLOGISTS ; AMERICAN BOARD
OP OBSTETRICS And GYNECOLOGY ; WASHINGTON GYNECOLOGICAL SOCIETY ; PITTSBURGH
OBSTETRICAL AND GYNECOLOGICAL SOCIETY ; OBSTETRICAL SOCIETY OF BOSTON ; LOUISVILLE
obstetrical AND GYNECOLOGICAL SOCIETY ; SOUTH ATLANTIC ASSOCIATION OF OBSTETRICIANS
AND GYNECOLOGISTS ; SEATTLE GYNECOLOGICAL SOCIETY ; SOCIETY OF OBSTETRICIANS AND
GYNECOLOGISTS OF CANADA ; ALABAMA ASSOCIATION OF OBSTETRICIANS AND GYNECOLOGISTS ;

Akron obstetrical and gynecological society ; Kansas city obstetrical and

GYNECOLOGICAL SOCIETY ; CENTRAL NEW YORK ASSOCIATION OF GYNECOLOGISTS AND
obstetricians; new jersey obstetrical and gynecological society.


EDITOR

GEORGE W. KOSMAK
ASSOCIATE EDITORS

HOWARD C. TAYLOR, JR. . . . WILLIAM J. DIECKMANN


VOLUME 56
JULY-DECEMBE^l, 1948


ST. LOUIS

THE C. V. MOSBY COMPANY
1948


Copyright, 1948, by The C. V. Mosby Compaky
(AU Rights Reserved)


Printed tn Uie
United States of America


The C.


Press oj

V. ifoehy Compart}/
St. Tjouis




American Journal
Obstetrics and Gynecology


VoL. 56


July, 194S


No. 1


Transactions of the Central Association
of Obstetricians and Qynecologists. Annual Meeting Held
October 23 to 25, 1947, at Louisville, Kentucky


THE EFFECTIVENESS OF VARIOUS DIURETIC AGENTS IN CAUSING
SODIUM EXCRETION IN PREGNANT WOMEN-

Willis E. Brown, M.D., and J. T. Bradbury, Sc.D., Iowa City, Iowa

(From the Department of Obstetrics and Gynceology, State University of Iowa)

T oxemia of late pregnancy remains tlie one large cause of maternal
morbidity and mortality for which there is no adequate etiologic explanation.
Many students doubt that it is a single disease entity and differential classifica-
tions have been offered to explain the variety of clinical manifestations. In
spite of the extended investigative efforts that have been expended on this syn-
drome, it still remains a therapeutic enigma, our ministrations being quite
empirical.

Edema is one of the most common signs of toxemia, and yet it is not dear
whether the accumulation of ‘fluid represents a disorder of water or sodium or
protein metabolism. Earlier workers focused attention on water metabolism
and treated such patients by manipulations of water intake. Limited investiga-
tions in this direction have been complicated by the difficulties in obtaining
proper control. During the past two decades the concept that edema may be due
to a disorder of sodium metabolism has gained i^opularity to the extent that the
clinical management of toxemias of pregnancy now generally includes a reduc-
tion in sodium intake (sodium chloride and sodium bicarbonate) .

*Read before Central Association of Obstetricians and Gynecologists on Oct. 23, 1947. at
Louisville, Ky.


Note: The Editors accept no responsibility for the views and statements of author.s
as published in their “Original Communications.”

1


2


BEOWN AND BEADBUEY-


Am. J. Obsu k Gjmcc.

July. 194S


– Because of tlie interest in sodium and in the factors involved in augmenting
its excretion, a series of studies was undertaken to investigate tiie effects of so-
called diuretic agents on the fluid and sodium excretion in women with noi-mal
and toxemic pregnancies.

Water balance studies require a long-time control of intake and output, in-
eluding the insensible lo.ss of water through respiration and perspiration. Be-
cause of these difficulties, several investigators have attempted to study sodium
balance. In general, the methods of sodium analysis have been too cumbersome
for routine laboratory determinations. Consequently, more work has been done
on chloride balance studies on the assumption that there is a definite relation
])etween chloride and .sodium. This is obviously incorrect since not all the
chloride in the urine and food is sodium chloride. In addition, attempts have
been made to investigate the effect of ammonium chloride, whei’e the excess
chlorides make chloride estimations entirely unreliable as an index of sodium
excretion. A simplified method of .sodium estimation developed in this labora-
tory made it possible to study the effect of various diuretics on sodium output.

Observations were made on pregnant patients given high and low sodium
diets. Hourly fractional or total twenty-four-hour urine specimens were ob-
tained and determinations made of the sodium concentration in the urine. From
these data, information regarding the mobilization and excretion of sodium have
been obtained which may have some direct application in the clinical manage-
ment of edema of pregnancy.

Methods and Materials

Sodium Method . — There are two basic methods for measuring the sodium
content of biologic materials. The physical method makes use of a flame
])hotometer.^ The substance to be measured is di.ssolved and burned at a con-
stant volume rate. The intensity of the .sodium flame is measured and computed
as grams of sodium. While this method has many advantages, the operation of
the flame photometer is such a highly technical procedure that its use is not
satisfactory for most laboratory teehniciaiis.

The chemical method involves the precipitation of sodium by uvanyl zinc
acetate.- The quantity of sodium in the precipitate can be determined by
gravimetric or colorimetric procedurc.s.

The sodium detci’minations in this study -were made by a colorimctilc tech-
nique based on the original gravimetric method. When the triple salt, uranyl
zinc sodium acetate is precipitated, the reagent solution lo.scs color in proportion
to the amount of uranyl ions lost from solution. The loss of color is measured
by an eloctrojihotometcr and its sodium ecjuivalent is determined from a
standard reference eurve.^ In this report all values for .sodium are expre.ssed in
terms of sodium chloride; the convci-sion to sodium can be obtained by multiply-
ing all figures by 0.4.

Patient Control . — The patients used in this .study were hospitalized in the
obstetric wards. Their diet.s were prejmred by the Department of Nutrition
and the caloric valiu’.s and sodium content.s calculated from tables. The.sc diets
have been varied from low values of 1 to l.o Om. of sodium chloride (0,4 to O.fi
Gm. sodium) per twenty-four hours to nonnal values of 4 to 6 Gm. per twenty-
four liouiK; higher intakes of 10 to 15 Gin. were achieved by giving the ])aticnts
additional salt.



Y, SODIUM- EXCKUTION IN PREGNANT WOIifEN q

Tlie patients were housed in a si^ecial ward and their water intake recorded
daily. The studies wore continued over periods of sevei’al weeks. Each patient
was given a controlled sodium intake for a minimum of three and usually five
days prior to establishment of a treatment schedule. The experimental schedules
were generally arranged to correspond to the usual clinical therapeutic plans
employed in the hospital. Observations . were made, on normal and toxemic
pregnant patients and on a few nonpregnant women in the childbearing age.

Urine was collected daily as a twenty-four-hour specimen and the sodium
content of each was determined. The average values for Ihe specimens tlnce
days prior to, and three days following treatment were used as coni.rols and com-
pared with the urine volume and sodium value obtained on the day of the test.



Key to figures ;

1 . Pretreatment control (1 day or average of 3 days)

2. Day of treatment

3 . Post-treatment control (1 day or average of 3 days)

The figures illustrating the text are constructed in the same way as this sample grapli.

Materials Studio . — The following substances were selected and studied for
their effect on the excretion of water and sodium.

1. Water (by mouth) given in quantities of 2,000 to 6,000 c.c. daily. A few
patients received this amount of water in two to four hours.

2. Dextrose (intravenously) ; given as 5 per cent, 10 per cent, 25 per cent
and 50 per cent solutions in amounts varying from 400 to 4,000 c.c. de-
pending upon the concentration.

3. Aminophylline (intramuscularly); given in doses ranging from 120 mg.
to 150 mg. daily- (1 gr. b.i.d. to 7^/^ gr. t.i.d.).

4. Mercurial diuretics (Salyrgan (100 mg./c.c.), Salyrgan-theophylline
(mercurial 100 mg./c.c. ])lus theophylline 50 mg./c.c.) and jMei’cuhydrin
(mercurial 88 mg./c.c. plus theophylline 48 mg./c.c.) given intravenously
in doses ranging from 2 to 4 c.c..

5. Ammonium chloride (by mouth and intravenously) ; given in amonnt.s
yarying from 8 to 16 Gm. per 24 hours,



4


BKOWIv AND BKADBUKY


Am. J. 01)51 , & Gyjicr.

July. I’l^S


6. Urea (b.y moutli) ; given in amounts of 60 Gm. per 24 hours (20 6m. in
SO c.c. of water t.i.d.).

All of these substances have some effect on sodium and/or water excretion.
The effect varies with the diuretic but each agent follows a fairly consistent
pattern.

Data

Effect of Dietarij Sodium on Urhianj Sodium Excretion . — ^When patients
entered the hospital having been on an unregulated diet, it was found that their
sodium excretion usually raiiged from 8 to 10 Gm. per twenty-four houns. “WTien
placed on bed rest and given a general hospital diet, their urinary sodium con-
tent dropped slightly during a three- to five-day interval and stabilized at 6 to 8
Gm. per twenty-four hours.

The effect of changes in the level of sodium intake was observed in one
patient who was given 10 Gm. of salt daily in addition to her diet. It is apparent
in F’ig. 1 that there was a lag of three to five days before the sodium excretion
i-eached the level of intake after the extra salt was given and again after it was
discontinued. This exemplifies the need for maintaining a knonm sodium intake
to evaluate the significance of changes in sodium excretion.

Effect of Forcing Flui/I.^ on Vrbuirij Sodium . — It is customary in this clinic
for all patients presenting evidence of toxemia of late pregnancy to be given a
low salt diet and to receive fluids up to 4,000 c.c. daily. To check the effect of
this schedule, noi-mal pregnant women Avere placed on a similar regimen. In
some patients, 6,000 c.c. of Avater AA’ere giA’en orally in tAvo to three houi*s to see
if any augmentation in sodium excretion could be obtained. The effect of such
fluid intake on sodium and urine excretion Avas noted and those data are illus-
ti’ated in Fig. 2. It is apparent that u7-inan’ output can be increased bj^ aug-
mented fluid intake, but the excretion of sodium Avas decreased during the day
of forced fluids. Xot only AA-as the concentration of sodium per liter of urine
reduced, but the tAventy-iour-hour .sodium output Avas also dimini.shed. It made
little difference Avhether the fluid Avas giA’cn in Iavo to three hoiirs or oA’er the
tAventy-four-hour period. These findings are in accord Avith earlier reporis that
chloride excietion may be reduced by forcing fluids.

To check this effect 2,000 to 4,000 c.c. of fluids AA’cre given by vein. In thc.se
])atients, theic Avas also a slight decrease in urinary sodium concentration but
the greatly increased urine A’olume produced a slight increa.se in the total sodium
excreted in tAventy-four liour.s. Fig. 3. There is a difference in the amount of
sodium excreted Avlicther the fluids are giA’en by moutii or by vein.

The Effect of Inirnvuwns Dextrose em Sfjdinm Excretion. — To determine
whether this apjmrenl advantage of intravenous fluid in increasing sodium
excietion Avas due to the dextro.se or to the fluirl. studii’s Avere undertaken to
measure these factors. Two hundred grams of de.xtrose were given intravenously
in 4.000 c.c. (J) per cent ). in 2.000 c.c. (10 jier cent ). in ^’00 c.c. (2-“j ]»er cent), or
in 400 c.c. (uO per cent) (as rapidl.A’ as clinically feasible). The proce.ss Avas
then rCA’crsed and the volume in.iecled was held constant : the jiatients Avere giA’en
400 c.c. of eacli solution. per cent. 10 per cent. 2.o per cent, or aO per cent
dextrose. The ex]icrimenlal day was measured from the on.sct of the infusion,
usually from 8 a.m. to 8 a.m.

The twenty-four-hour urinary excretions olitaincd under these condition.s
are recordeil in Figs. 3 and 4. When 200 Gm, of dextrose Avere giA’cn as 400 c.c.
of a oO per f-eiit .solution, there Avas usually a retention of .sodium during the



Volume 56 SODIUM EXCEETION IN PEEGNANT WOMEN

iNumbcr I


1000


NaClIO GM/DAY



Pig. 1. — Graphic representation of tlie daily excretion of urine and sodium u-hen the salt in the
diet (3.8 Gm.) yas augmented by g-iving an additional 10 Gm. a day for five days.



Fig. 2. — Gi’aphic repi’esentation of the excretion of urine and sodium when fluids were given bj’
mouth, 6,000 c.c. for one day, and 4,000 c.c. for three successive days.



6


5000


3000


1000


9000


TOOO


5C00


3000


1000



I’iK. V..—r,r

V’* r* ri 1

for ahr’iit
I ‘lt



Volume S6
Number I


SODIUM EXCRETIOlSr lET PEEGNANT WOMEN


7


twenty -four iiours. As tlic volume of fluid was iurreased and llie eoueeul ration
of dextrose decreased, there Avas a i)i‘oj»ressive l)ut. sli^lit increase in the tweut}’-
four-hour sodium excretion so tlmt- the 200 (hn. of dextrose given as 4,000 e.c.
of a, 5 per cent solution produced a definite and consistent increase in sodium
output. AVhen the volume, of injected dextrose was constant, thei’c was no


sooo


2000


1000


5000


JOOO


1000




Fig. 4. — Graphic representation of the excretion of urine and sodium yj’sn
given 400 e.c. of glucose (dextrose) solutions intravenously. The iriterval between
in these three patients varied from flve to seven days. There is demonsnr
urine or sodium output oven though the dose of dextrose varied from -0 to -uu u


patients were
the injections
ible effect on


s


IJHOWX AND


A;-i. J.O> rr,-.-.
J-.’r. f’-r-


cliange in niinary on?pui as the fonc/’ni ration of doxtros^,- variod

from 5 to 50 por rent. Thus it mak».’.s no diffoi-onr-o %vl!frthc-r 20 or 200 Orn, of
doxtrose is added to the 400 o.e. infusion ^vijon tlie total tv/enty-foTir-hour urinan,’
volume or sodium is eonsidei’ed. .Sirn-e any dinretie effeft of a crystalioid is
transitory, similar hourly fractional studies of sodiTirn excretion v.-cre under-
taken to ascertain v.-hetlier an initial divircnc effect had !>een missed in the total
tventy-fotjr-hour sample. Eix’ht hundred cubic centimeters seemed the maximal
atnounl that could siifely be intioduccd into tlie blood stream v.dthin tvo hours.
The patieitts’. sf-hcdulc.s were arniiiucd to provide unne samples at two-hour
intervals from S A.^i. to § n.:i- Inlyinsr urethnil eat.heters were employed to
in.sure that the bladder was cmjilied at the end of eacii two-hour inteiwal. The
overaight sr>ecimens were pooler]. Unne .samples vrere obtained in this manner
for three successive days. Eight bundled cubif- centimeters of 5 per cent or 25
jjer cent dextrr^se vrere given inti-avcnously on th.c .second da.y. (Fig. 5.) In
each instance, there ws.s a marked increase in urine during the period of in-
fusion but in neither case did the urine output egual the amount of fluid in-
jected. In the two-hour fi-ietions. the sodium foment and concentration ’vere
decrea.sed. but the twenty-four-hour output of sodium ^vas not altered by either
solution. The addition of dextrose to intivivenous fluids does not seem to aug-
ment the dinretie efier-t of the water which carries it when measured by urine
volume. This is found in both fiaetional and poohA twenty-four-hour specimens.

The administi*ation of >00 c.c. of 25 per cent dextrose was followed by ^
diminished urine and .sodium excretion 5;. The oliguric phase which

follows the administretion of a h>T)ertonic solution has been shown to be due to
the relea.se of the antidiuretie hoirnone from t.he posterior pituitary/ This anti-
diuretic effect of ht-penonic solutions detracts from their use as diuretic agents.

The E^eci of Aminoplv;)lline on Hodhim ExerrAion. — -Vrninophylline has not
been extemsuvely -used in the trwitment of edema of pregnancy, and %‘er:.’ few
data are anmilable regarding its effect on sodiiun excretion. ^lost reports deal
with the effect of arninophyliinc in conjunction vrith other diuretic agents and
the effects are measured in terras of total nrinary volume or of the decrease in
weight or edemarous patients. To study the effect of amtnophylline alone a-s
well as in conjunction with other agents, it vras first given separately. A series
of patients was given arninophylline intramuscularly in doses ranging from 1
grain b.i.d. to 7h<2 grains t.i.d. 1 120-1.500 mg. daily The smaller doses of
aminophyllinc had no measurable effect on the patient, the urinars* v’olume, or on
sodium excretion. When patients were given 7(4 grains t.i.d. intramuscularly,
vomiting occuired frequently. It hs apparent that \’omiting associated vrith
arninophylline administration is central in origin. Despite this loss of sodium
intake due to the vomitus. there was a marked increase in urinary sodium.
This increase in urinarev sodium was obtained primarily b;*’ an increa-se in .sodium
concentration in the urine. Xo evidence is a’.-ailable from these studies to ex-
plain the mechanism of the increase in sodium concent ration in the urine
(Fig. 6).

The Eueef of Iferc^iriols on i^odium Exerefion. — Saljugan was obtained
without theophylline and injected intravenously into a series of patients at
seven or eight o’clock in the moraincr in dose.s rancring from 2 to 4 e.c. (2W to
400 rrm.). This merenirial caused a marked increase in urinarx’ sodiiun and
volume. This increase in S’^diurn is due largely to an increased concentration
in the urine (Ficr. 7). The degree of increased sodium excretion varies with
the dosase of mercurial administered. A dose of 2 c.c. was frequently ineffective



Volume 5(5
Number 1


SODIUM. EXCJU-JTIOX IX PEEGXANT \YOMEN


9


in increasing tlie nrinaiy volnme or total sodinin excretion while 3 or 4 c.c. was
consistently effective.

On the clay lollowing lliis marked output of sodium, there was a transient
retention of sodium as manifested by a sharji drop in urinary sodium per twentv-
four hours.





Fig-. 5. — Graphic representation o£ the excretion of urine and sodium for two-hour inter-
vals during the day when 5 per cent or 25 per cent glucose (dextrose) was giv’en intravenously.
The arrows indicate the duration of the infusion, about two liours. Tlie overnight specirnens
were pooled and the two-hour average output is plotted over the wide bar in the base line.
The total output for the twenty-four hours is also plotted as a two-liour aver.age. The Mercu-
hydrin is included for contrast. Each 3-column group represents the same two-hour interval
in the day on three successive days. The plus signs indicate glycosuria.


30


HnoWX AND HHADDUKY


Am. j, Oi> t, cc Oyt’Ci’.

July, IV4K

The Effcci of Mercurial Theophylline Compounds on Sodium. Excreiion . —
When tlieo])hyliiiie is added 1o ilie mercurial eomjjoiiiid (Salyrgaii-lheophylline
or IMercuhydrin ) an effect similar to that obtained with mcmirials alone is
observed. These data ai-e reeoj’dcd in Figs. 5 and 8. A considerable increase
in urinary sodium excretion is obtained through tiie mechanism of increased
sodium concentration and increased urinary volume.

The effect of Mercuhydrin appeaj-s within an ])our and increases over a
]ieriod of seven to eight houi-s (Fig. b). In this case the amount of sodium
excreted in the fourth two-hour interval exc(.‘cded the total exci-etion of the
preceding control day. On the basis of these observations it ai^pears that the
mei’curial eojupounds are most elective in mobiliy.ijig sodium.


AMINOPHYLLINE


3000

1

1

1





2000



–



—

1000

1


1

–

]| 111

■IT


1


Ill

llgl HI

Trr


7.5 GR. T.l. D. IM.


Pig, 5 , — Graphic representation of the excretion of urine ami so’lium v/Iien aminopliylline (T–!
grains t.i.<l. – 1,500 mg.) %va.s given intramuscularly.


The addition of theophylline to the mercurial agents does not increase
their diuretic effect. It was noted that there was no vomiting in this .series.
Small non-nau.seating dose.s of aminopliylline wei’c shovai to be ineffecti%’e in
mobilizing sodium. In all probability the lack of any additive effect obtained
by tliis combination is due to the veiw small amount of the xanthine in the
mercurial diuretics. (100 mg. to 200 mg.)


The Effect of Ammonium Chloride on Sodium Excretion . — Ammonium
chloride lias been the standard diuretic agent used in this r-Iinic during tiie riasl
rears. It has been customary io give 8.0 Cm. daily in divided dose.s, and to
continue it for four days. The effect of this regimen on mobilizing and excreting
sodium and water was studied. In addition, some patients were given 12 and
16 Gm. of ammonium chloride daily, botli orally and intravenou.sly. The patients
were on a standard diet eontahiing 7-0 Gm. of sodium chloride a day. Eight
<‘-rams of ammonium chloiide caused a slight increase in sodium excretion, while
19 0 Gm daily pioduced a significant increase in both urinary volume and
-odium excretion per twenty-four houis. Tlie .sodium concentration, however,





Volume S6
Number 1


SODIU]\[ EXCBE’J’IOK IN PREGNANT WOMEN


11


iV Oa/^/yon kV//Aou/ ‘TAco/^Ay/Z/m



Fig. 7. — Grai)hic representation of the excretion of urine and sodium wlien saiyrgan nas nd

ministered in doses of 2 and 4 c.c. (ml).



jTip:. g. — Grapliic rcprc.«entation of the excretion
or salvrgan-tlieopliylline \va.« given in riose.s of 1. ana
llioopliylline 100-200 mg.).


r urine and .sodium wlien mcrculiydrin
c.c. (ml) (morcuri:il 200-400 mg. with



22


?.J{OWN AND mrAlJl’.ITHV


Afii. J. Of? }, S, Gviitr.

‘ july, IVIB

was not inci’eased; Die iiKO’casod sodium ouJpnt was due lo j7iej’easod urii)a 7 -y
volume. Sixteen g7-ams of ji7nmo7iii7m eh]o7-7dc hjid a 7 i 777consistenl efl’cet pi’ob-
ably l)eeiA\ise of 777te7-,fci’i7if? Yomitin»:. Ai)i)a7-e77tly <]ie7-e is 7io ine7-easc in sodimn
exe7’etion ovci- that due to tlie 12 Gm. dose, suggesting that that Jimount 7 -ei)re-
senls a77 oi7li77ial dose. It l)eemne ap])am7t thal lho mjixi 7 iinl efl’cet was ol)tai 7 ied
witbi?) 1we7i1y-fou7- to foTly-eiglit l70U7-s Jind lliat eo7)ti7iued l7-eatment had no





Tj.:™ 9 Grapliic representation of tlie excretion of urine and sodium wlicn 8 Gm. of am-

monium cliloride and given for tliree days (upper row of three patients) and given for two
day.s (lower row).


effect on uilnary .sodium excretion oi- ui-inai-y volume. A deei-ea.se in sodium
exc 7 -etio’n oecuri’ed in .some patients dui-ing tlie continued administi’ation of
ammonium chloride (Figs. 9 and 10).

A^Tien the dietaiy sodium was decreased to 2.0 Gm. per twenty-four houi-s,
ammonium chloride had no effect on ui-inaiy .sodium output Appai-ently there
must he a fair supply of available .sodium for its inei-eased excretion to he ob-
tained with’ ammonium chloi-ide. ^ , , . , , r? i

Tt has been ,sugge.sted that the ammonium chloride produces its etteci
u tUn foPowin” mechani.sms; The ammonium ion is comliincd with
Sif dioxide in the liver to produce urea. The urea is a neutral substance



Volume SC)
Is’ umber I


soDIu:^^ excketiojSt in pregnant woaeen


13


and is pxereted as sucli. Tiic negative chloride ions ]n-oduce a state of acidosis
which is reduced l)y a reaction of the excess cliloride ions witli the sodium
bicarbonate buffer to form sodium cliloride and carbon dioxide. Sodium chloride
is excreted in the urine and carries with it an increased volume of water; the
carbon dioxide is eliminated through the lungs and further reduces the aeido.sis.



Fig. 10. — Graphic representation of the excretion of urine and sodium when 12 oi IG Gm. of

ammonium chloride was given for two days.


The validity of this theory was te.sted by measuring urinary sodium,
chloride, ammonia, urine volume, and blood carbon dioxide combining power.
The results are tabulated in FigT 11. This concept seems to be basically correct
for there was an increased urinary sodium and urea associated with the increased
urinaiy volume. There was also an inei’ease in chloride more than could he
accounted for by the increased urinary sodium. The absence of an increase in
urinary ammonia, indicates that little if any aminoniiini chloride is excreted.
The excess chlorides found in the urine were in combination with some unde-
termined cation. In .these patients the increase in sodium excretion wa.s asso-
ciated with a drop in carbon dioxide combining power, ivliich indicates a loss ot
buffer sodium salts.



14


HHOWN ANIJ IJKADJUJKV


Am. J, Olrt. f. Oyiicc.

July, IV tK


III a prior .study olj.sorvutioii.s on wci*?!!! loss ,’ind olianges in Idood oarijon
dioxide coml)iiiiii}i: power were reeordod durinj^ liie ini ravenous iipi’cction of
anunoniinn ehloridc.


AMMONIUM CHLORIDE



Ammonium eliloride was prepared as chemically pure crystals and auto-
flaved in ampules. It was determined tliat from 0.5 to 1 per cent ammonium
in 5 ner cent dextrose would not produce hemolysis in vitro and wa.s
n cntisfaetoiw .solution for intravenous injection. When 10 to 15 6m. of am-
chloride were injected into patients, vomiting occasionally occurred.
SnSd iniection seemed to favor vomiting. This suggests that the vomiting asso-
ciated with ammonium chloride administi’ation may be cential in oiigin.


Volume S6
Number 1


SODim[ EXCRETION IN PREGNANT WOMEN


15


^ It. was observed tbat effective mobilization of edema occurred over a short
period of time and Avas associated with a considerable decrease in the blood
carbon dioxide _ combining power. (Fig. 12.) Prompt Aveight loss can be in-
duced by the intravenous injection of ammonium chloride and the resulting
acidosis.

It thus api)ears that ammonium chloride administration can increase
urinary sodium excretion, that this increase is of short duration, and maj^ not
be maintained even AAuth the continued administration of the drug. The in-
crease’ in sodium excretion is effected by an increase in urinary Amlume rather
than by increased sodium concentration. TAvelve grams of ammonium chloride
seems to be a satisfactory daily dose.



The Effect of Urea on Sodium Excretion . — It has been suggested that urea
is a diuretic agent that operates by increasing urinary volume. In order to
determine the effect of urea, patients Avere giAmn 60 Gm. of urea daily. The
data from these studies are recorded in Pig. 13. Tliere is a questionable transi-
tory increase in urinary volume, AAdiieh may be due to the considerable Amlume
of fluid necessary to ingest the urea. There AAms no increase in ui’inary .sodium
and no alteration in sodium concentration in the urine.

Sodium, and Water Excretion in Toxemic Pregnancies. —It is apparent
from the aboA^e data that certain agents are more effective in the mobilization
and excretion of sodium than ai’c otliers. Since these studies Avere carried out on


JJKOWX A.\D JiI{A])J?UKV


Auk J. Ofr.i, ^ Gyucr.

1918


310J Jiicil ])i il, ■\Vi’is of iiilorc.st 1o dclcrniiiie wiieliier a .siinilar
iiicclimiisiii “was ojici’filivd in psiliftiits with toxemia ot’ ]atc jp’fifrnaiicv. Three
patients witli moderately sevei-e toxemia were studied with roj^ard to both sodium
and UJ inary cxeretioJi. Jliey wo’c ])laecd on the nsiial routine of low sodium
diet., ]i])cral fluids by 7uoulh, 8.0 Om. of ammonium ehloride daily, and bed re.st.
Alter stabilization on this sehedulc, they were given inti-avenous dextrose; there
was a slight inei-ease in urinary volume but- no increase in a twenty-four-hour
.sodiuin l^^o cii])!^ (‘ODtiTncloi’s of i\lG)*c*nIiy(lriTi ’vvcrc Jhcjj f^ivon <i 7 id

it produced both a ma7-hed diui-etie and .sodium excretion effect. This suggc.sts
that, toxemic piiticnt.s I’csjjond similai’ly to Jioj’mal jji’cgjjajit womcji a.s re^’ards
the dextrose and mercurial diuretics. °



i;i. — Gj’apliic represen t.’ition of tlie e.xcrelion of urine anil .soilium for tliree nonpresnanl
subjects receiving GO Gin. of urea on two successive days.


The patients reported under the section on intravenous ammonium chloride
(Fig. 12) all had toxemia and showed a very satisfactory weight loss indirectly
indicating loss of water and sodium. Three eclamptic patients who had pro-
gressed to the point of marked oliguria (10 c.e. per hour or less) or complete
anuria were given varying concentrations of glucose by vein without effect.
Seven and one-half grain.s of aminophylline were given intramuscularly and in
two of the three patients urinary flow was establi.shed within a few hours. These
urines contained high concentrations of .sodium. This suggests that anuric and
oliguric patients may respond to aminophylline in a similar manner to normal


pregnant women.

Sufficient studies have not been made on toxemic women to indicate the
effectivene.ss of these agents in the clinical management of the disease. These
notations are included because they suggest that the mechanism of sodium
excretion is of a similar nature in normal and toxemic pregnancies.

An attempt was made to test the .suggestions that morphine might have
nn antidiuretic effect. Twenty patients were given variable amounts of 5 per
PMit dextrose intravenou.slv at a comslant rate each day. On alternate days they
rpre “•iven 10 to 15 mg. of morphine at the onset of the infusion. Jfany but
all of these patients shmved a sodium and water retention for three or four



Volume S6
Number 1


.S0DIU:M: EXCEETION in PEEGNANT WOitEN


17


lioui’s. K lliese oliscrvalioiis ai-e confirinecl, they .suggest tliat the large doses of
morphine commonly used in tlie control of eclampsia may conti-ibnte to an
oliguria or anuria.

Discussion

From the experiment al data, it becomes a])parenl that sodium excre-
tion is a complex process and that a variety of factors modify its mobilization.
Prom the standjioint of clinical management of toxemic patients, no evidence
is presented as to the relative value of increasing urinary volume or urinary
sodium excretion. The.se studies do not offer any evidence on the basic ab-
normality productive of edema, namely, whether it is a disorder of .sodium or
water metaboli.s]n. The effect of diuretic agents on twenty-foiu’-hour urinary
volume and .sodium excretion is relatively .transitory. Except in the case o1
ammonium chloride, no attempt has been made to introduce these agents con-
tinuomsly. As far as the mercurials were concci-ncd, this Avas avoided both bo-
cau.se of concern about potential renal damage to the Avomen and because of
.statements in the literature that the effect Avould last for seA’eral days. The
data obtained in the.se ox]Aerimcnts suggest that the effect on sodium excretion
is relatiA’ely transitory, lasting about tAventy-four hours. In the case of am-
monium chloride even the continued admini.stration of the drug is not attended
by maintenance of increased urine or sodium excretion.

In practically cA’cry case folloAA’ing cxcessiA’c .sodium mobilization, theic
AA’as a transit oiy (probably compensatory) retention of sodium apparently to
permit a restoration of sodium balance. Sodium retention Avas especially maihed
the day after the use of mercurials or large doses of aminophyllinc. It is in-
teresting to note that Avith hypertonic glucose there is a tramsitory increase in
urine Amlume apparent only Avhen hourly fractionated studies aaui-c run. Hoaa-
ever, even during the diuretic phase the amount of fluid eliminated is not as
great as that injected and then a pcidod of oliguria and decreased sodium excie
tion folloAVs Avithin tAvo hours.

It became apparent that tlie so-called diuretic agents have been acia IooscIa
defined. When one introduces 1,000 c.c. of fluid into the blood stieam anc
recovers 800 c.c. of urine, it becomes a que.stioii as to Avliether or not the fluid
represents a diuretic. Hourly’’ urine collections shoAV an appaient ineiea.se in
urinary Aulunie over and aboAU the control period. If this inciease in uinie
output is less than the normal excretion plus the inclement intio uce 33
it becomes a matter of opinion as to AAdiether the inciease in uiine is a s ’
filtration phenomenon produced 133 ^ the fluid introduced, 01 aa let lei 1 lepiese
a diuretic effect. Since the total output is less than the total intake (^’^l^ether
measured on an hourW oi’ ^ tA\’ent3’-four-hour basis) t lese s u les si^
that hypertonic solutions of crystalloids introduced into the blood stveam arc
ineffective as diuretics. HoAvever, b3′ contrast, the intioc uetion o o .
mercurial diuretic Avill cause a marked increase in niinai3 V ,

fluid Aulume of the injected material becomes negligible. t a\o



18


BKOWN AND BKADBUKY


/wri. J, OU f. A G’/DCf.

hh\ vn%


llie latter ty])e of agent might be riglil fully eallecl a diuretic. This group in-
clude, s the mercurial and xanHiine comj)ound.s. It is of interest in this corinee-
lion to comsider the effect of intrarnu.scular a7nino]>hyllino in large do.sos. Despite
a decreased intake of fluid and sodium induced by vomiting, there may be in-
crease in urinary volume. Thus it becomes a])parent that aminophylline is a
diuretic agent in that it can mobilize and excrete finid and sodium even in Die
face of decreased intake.

It is of interest to note that some pi-ejiarations which are jKjpular as
diiD’ctics such as urea and dexlro.^e wci’e .shown to he ineffective in that they
did not increa.se urine outi)Ut.

There .seems to be a slight iiKU’case in uihie volume and sodium e.xerction
induced by adequate amounts of ammonium cliloride. It is of interest to note
that this effect of ammonium chloride is almost entirely eliminated by the sharp
reduction in dietary sodium. Exjdanation of this phenomenon is not apparent.
It Avould appear that the efl’ccl of the .shift in the acid )>ase balance, which
neee.ssitates the mo])ilization of sodium and other buffer- salts, takes place only
in the presence of available sodium. Moreovei-, the continued administration
of ammonium chloride over the second and third day, aftei- an increased sodium
excretion has been obtained, is i-elatively ineffective.

The increase in urinai-y volume associated with amnionium chloride admin-
istration is difficult to evaluate. The patients who i-eceived the 12 and 16 grams
of ammonium chloride became thii’.sty and inge.sted a larger volume of water.
The increase of urinary output, thei’cfore, may simply represent a function of
the increased ingestion of fluid rather than any direct diuretic effect of am-
monium chloride.

When one sti^dies the effects of these diuretic agents on sodium excretion,
their action tends to fall into three general categories. In the first place in-
creased urinary sodium output can bo induced in patients by giving fluid by vein.
While this effect is .slight, it is appai-ent Avhen hypotoj}ic .solutioii.s are given in a
relatively .short pei’iod of time. The increa.sed ui-inaiy sodium excretion i.s
obtained with a decreased sodium concentration in an increased output. This
type of effect we have called a “wash out” mechanism. It appeal’s that the
increased urinary sodium is obtained by the direct effect of an augmented
urinary volume produced by the increa.sed fluid intake.

A second meehani.s’m of increased sodium excretion is produced by a change
in acid base balance. Ammonium chloride is the best example of this type. An
increase in urinary sodium can be obtained if one produces a rather rapid and
sudden shift toward the acid .side. Apparently this change mobilizes .sodium to
compensate for a relative acidosis, and thus an increa.sed amount of sodium is
excreted by the kidneys.* This increased .sodium excretion is brought about by




Volume S6
Number 1


SODITJ]\r EXCKIiTION IX PIIEGNAXT WOIMEN


19


an increase in urinary volninc bui witboiii change in sodium concentration.
Tins is in contrast to Ihe decreased sodinni concentration found in jiatients
descril)ed under the “wash-ont” process discn.sscd above.

The third mechanism by which sodinni excretion may be increased is
through some change in renal function. Mercurial and xanthine diuretics pro-
duce this type of effect. They cause a moderate increase in urinary volume
and the most marked increase in total urinary sodium of any of the agents
studied. This effect can be obtained with either the mercurials or aminophylline
but, from the pharmacological point of view, there seems to be little advantage
in combining the two as in the commercial compounds. Because of the small
amounts of aminophylline in the pharmaceutical preparations, it is impossible
to judge the additive eifcct produced by the combination. It would be of
interest to learn whether an inci-eascd amount of aminophylline together with
a mercurial diuretic would cause an augmented effect.

While the studies which are available on toxemic patients are too few to be
of any clinical value, it is of interest that apparently the toxemic patient handles
water and sodium in a manner similar to the normal pregnant woman and will
respond in a similar fashion to diuretic agents. The evidence available suggests
thht the mercurials and xanthines are worthy of clinical trial in the management
of toxemic patients.

The clinical management of toxemic patients generally includes a liberal
use of sedatives, such as morphine. If the observations of the antidiuretic effect
of morphine are confirmed, its use in patients with oliguria may need to be
. restricted.

As yet there is no good explanation why the toxemic patients who excrete
large volumes of urine and are losing weight have a better prognosis than those
patients who do not respond. Nevertheless, there is general clinical agreement
that such is the ease. It would appear, therefore, that, on the basis of these
experimental observations, toxemic patients might be improved by the clinical
trial of some of these preparations. In all probability, tlie edema is not the
cause of toxemia of pregnancy but is merely a symi^tom of an underhung
biochemical derangement which has not yet been identified.

Conclusions

1. Diuretic agents vary in tlieir ability to increase tlie excretion of water
and/or sodium.

2. Diuretic agents increase sodium excretion by three mechanisms: (a) by
a “wash-out” process induced bj’’ increased fluids given intravenously; (b)
bj^ the production of an acidosis; (c) by a change in renal function which in-
creases the concentration of sodium in the urine.

3. Hypertonic dextrose solutions do not increase sodium or water excretion.

I. Induced increases in sodium excretion are transitoiy (tAventy-four to

forty-eight hours) .

5. Apijarently toxemic and normal pregnant Avomen respond similarl}’’ to
diuretic agents.



20


HI{()W>\ ANT) JTliATTHUHV


Am. J. 0^*J. & Gyncc.

J«b’. lV4g


Wo arc iinlelitod io T^onna T^la<!La(‘lilaii, TioUy Joaii Ilaridcty, and Eiloa(! PoteiHon for flic
dietary iir.uiagoinenl. and for tlio f:odium detorniiiiations on flic jiationfs nned in fliin studv.


Addendum

Since ,siil)niill,in»’ lliis nninnsciipt foi- publication, we have given hypertonic
dextrose intravenously at a Jiioi-e rapid rate in foui- instances. Noi-mal women
were given SOO c.c. of 25 per cent dextrose at. a J’ate of 0.25 c.c. per kg. (appi’oxi-
ifiately 16 c.c.) per minute. lJuring the 1‘orty-hve to fifty minutes of the in-
fusion, the output of urine increased when tlie blood .sugai* concentration ex-
ceeded 500 mg. ])er cent and the urine .sugar concentration was ovei- 1 per cent.
lIowevcT’, the nierease in UJ’ine flow ovci- that of the control interval Avas !c.ss
than 16 c.c. per minute so that not all of the infused fluid was recovered. In
only one fifteen-minute intej-val, in one jratient, did the ineioase in urine flow
equal or exceed the 16 c.c. i)er minute increment which was given as 25 per cent
dextro.se. Tn two instances the urine out]>ut decrea.sed during the la.st fifteen
minutes of the infusion. Immediately after the discontinuance of the inti-ave-
nous dextrose, the urine flow diminished i-a])idly as the blood .sugar levels
dropped.

The abrupt decrease in urine flow aftei- the administration of hyi)ertonic
solution Avas discontinued, and its decrease during the infusion in Iavo instanec.s,
suggested that tlie increased osmotic pre.ssure of the blood may have caused the
liberation of antidiuretic honnonc from the poslei-ioi- ])ituitary. This rc.sponse
of the neurohypoi)hysis Avould tend to defeat the purpose of the hypertonic
intravenous fluid.”’ ” Even tliough the urine output Avas increased dui’ing the
rapid infusion of dextrose, in owv experience, this increment of urine Avas not
apparent in a total tAventy-four-honr urine volume and was less than the amount
of extra fluid administered.


References

1. Davis, A. K., and Overman, R. K.: I’ederalion’’Proe. Part 11, 6: 04, lfi4 7.

2. Barber, H. H., and Kohltoff, I. !M.; .T. Am. Cliem. Hoe. 50: 1025, 1028.

Bradbury, J. T.: .T. Lab. & Clin, :^red. 31: P257, 194G.

4. Cliamljers, G. H., ^relville, E. A’., Hare, R. S., and liarc, I\.: Am. .J, I’livsioi. 144: 311,

]045.

5. Carter and Rotjbins: .J. Clin. Endocrinot. 7: 75.3, 1047.
f). Verney: Proc. Roy. Hoe. London s.B. 135: 25, 1047.


Discussion

DR. FRANK E. AVHITACRE, ATeinptii.s, Teiin.— Drs. Brown and Bradlmry have
brougiit out so many faetors in this timely report that any one of them could be the subject
of debate among the phy.siologists, patliologi.sts, and elinieian.s. In reviewing this extensive
piece of work, water balance is of sj)eeiul interest.

Dextrose, from this rejiort, is no better as a diuretic than water. It would be helpful to
Itnow more accurately the speed of administration of hypertonic dextrose solution, as it is well
known that this has considerable effect uj)on the volume of urine retumed, and, to e.vpeef •’*
diuretic effect, the renal thre.shold mu.st be exceeded. Home of the water is retained with
‘ducose as the glucose is rapidly absorbed from the blood. Any procedure which attempt-^
to increase sodium excretion will be followed by a ])eriod of sodium retention until the bfd-
nnee i.s restored. Sodium and water are presumably retained in the body by .some extra renal
mechanism. One can reduce water and sodium temporarily, but after the diuretic procedure
is stopped, both are retained as before. Hodium and water retained in edema fluid are inac-
cessible to the kidney unle.ss some diuretic agent is used. AVater e.xcrction reflects primary
reciprocal changes in tubular reabsorption of water. Daily variations in water excretion are
believed to be due to changes in facultative water rcab.“orption through the antidiuretic



Volume
Xumber 1


SODIU:\r EXCRF/riON in pregnant womeet


21


hormone mceluuiism. It is possilile that Ihis mochiinism is involved in the disturhanves of oiir
toxemic patients. The amount of sodium and chloride reahsorhed varies inversely with the
A. D. H. concentration, hut the amount of water reabsorbed varies directly.

The combination of ammonium chloride and dextrose seems to be innocuous treatment
and caused considerable weight loss through the excretion of water and salt. However, if
used for very long, acidosis could result due to depletion of alkali reserve.

The effect of mercurial diuretics is that they block the tubular absorption of sodium
and chloride. They have been considered to be ideal diuretics and widely used, and the sug-
gestion of the authors that they be given a try in toxemic patients must be carefully con-
sidered. There is evidence that the mercurials can cause necrosis of the convoluted tubules
leading to irreparable damage. Sprunt has reported that in 741 autopsies, nine had received
mercurial diuretics and of these, three showed necrosis of the tubular epithelium. He could
not correlate tho amount given with the extent of the renal damage (Arcli. Int. Med. 46: 494,
Sept. 1930). It seems reasonable to conclude that where contraindications, such as fever,
tuberculosis, or chronic ncpliritis are present or, if there is evidence of kidnej” damage, the
mercurial diuretics should not be used. –

Tho effects of the various diuretic agents mentioned .‘••hould not be left without empha-
sizing another factor. Generalized angiospasm in the toxemic p.atient could be expected to
reduce renal blood flow, and the effect of diuretic agents is enhanced by relieving by various
commonly applied means the spasticity of the arterioles.

It is a good thing for someone to bring into ciuestion our establi.shed ideas on what a
diuretic really is, and it is questionable that a substance can be considered as a diuretic wlien
the amount of fluid .given to the patient so far exceeds the amount returned in the urine.

DR. LESTER. ODELL, Chicago. — During tho past six months atothe Chicago Lying-in
Hospital tho effect of the various diuretics has been reinvestigated. Our efforts have been
.directed toward urine sodium and tho volume of urine excreted. Employing the diuretic
agents recommended by Dr. Brown, we found more .sodium excreted and a greater urinary
volume following hypertonic glucose. We feel that the urinary volume is the best single prog-
nostic guide we have in eclampsia. We have advocated the use of intravenous hypertonic glu-
cose in maintaining an adequate urinary volume, and recommend 1,000 ml. of 20 per cent
glucose every eight hours. If such concentrations are unsuccessful, use 750 ml. of 30 per cent
or 400 ml. of 50 per cent glucose solutions. Hypertonic glucose is the best thing available
at present for maintaining the adequate urine A’olume so necessary for recovery of the eclamp-
tic patient.

I would like to ask Dr. Brown two questions; First, how many severe toxemias of preg-
nancy have been treated by mercurial diuretics alone? And bj” the term “diuretic” I mean
to include hypertonic glucose solution.s. Secondly, in using mercurial diuretics clinically, how
can one be sure that no renal disease exists? In short, how will one differentiate between
severe preeclampsia and nephritis prior to the use of mercury?

DR. BROWN (Closing). — We wish to point out that this report was designed to make
available basic information about the action of these diuretic agents in excreting sodium.
We have presented no evidence that sodium or water retention has necessarily anything to
do wdth the outcome of toxemia of pregnancy. It is generally agreed that if an increased
mdnary volume is obtained, these patients are improved. The.^e observations offer mechanisms
by which increased urinary sodium and volume can be accomplished. It is yet to be proved
that these changes have a beneficial clinical effect.

The question of what constitutes a diuretic has to be considered. According to our
interpretation, if one administers 1,000 c.c. of solution to a patient and recovers only 500
to 800 c.c. in the urine, that agent is not a diuretic. I do not disagree that the patients at
tho Chicago Lying-In Hospital are improved, but I do question that intravenous hypertonic
glucose solution is a diuretic agent.

In answer to Dr. Whitacre’s question, I would like to show three .slides. The first slide
demonstrates the similar effect produced by giving 6,000 c.c. of water in three hours and in



22


linOWK AKD


Ain. J. 01) I* 5: Gyiior.

ms


twoiiiy-.rour liour.s 2). Tlio i^i’cojhI hI’uIo compurcs llio eil’cct of ‘nilravenouf’ ^lueo.«f;

(isotonic niul Iiypcrlonic) ^iven in two iiours (Fi*^. ~>) and over six Iionrs (Fiji. ‘i’lic rate
of ndiniiiisiriition in (liesc experiments lind no ;ipp:iroiit etreid. oji (lie (wonly-fonr-liour nrinary
volume or .sodium oulimt.

From (licso studic.s it is njipiirenl. flint, sodium and water exinefion can lie manipulated
independently of eitcli otlier. Increased urine volume may be obtained with both liigh and low
concentration of .sodium. Likewise, tbe amount of sodium in the urine can be increased with
minimal increase in urine volumes.

In-presenting this material, we hope others will be encouraged to try these agents in
the clinical management of toxemia so that we may come to learn their true value. IVc now
have a method for studying both sodium an<l water excretion independently of each other.



MESONEPHRIC REMNANTS IN THE CERVIX*

John W. Huffman, M.D., Chicago, III.

(From the Deparlment of Ohsieirics and Gynecoloyy, Norihwesicrn University Medical School)

I T IS well known that certain portions of the mesonephros may persist near
the ovary and in the broad ligament and the vagina of the adult human
female. That fetal remnants of mesonepiiric origin maj* persist in the uterine
cervix is less commonly realized. From time to time reports have appeared in
the European literature commenting on the development of tumors arising from
mesonephric residues in the cervix. MeyeF’® has presented factual data estali-
lishing the embryonic source of such neoplasms as being from the cervical portion
of the mesonephric duct.

With the exception of Wolfe’s ease reports several years ago,^ the American
literature has contained no reference to this unique and unusual problem. It
should be a matter of interest shared in common by the clinician, the gynecologic
Jiistopathologist, and the embryologist. This is particularly true when it is
realized that mesonephric remnants in the cervix may cause confusion in the
histologic study of surgically excised tissues and that they may give rise to
bizarre tumors which can be either benign ‘or malignant. Because of ‘the
paucity and the relative inaccessibility of available information on the subject,
it has seemed worth while to make this presentation an attempt to portraj’’ in
definitive fashion the embryology, the histology, and the microscopic pathologj’’
of mesonephric remnants in th.e uterine cervix. In order to accomplish this the
literature has been reviewed, serially sectioned tissues have been studied, and
sections tyom 1,192 surgically excised cervices in the gynecologic laboratory at
Northwestern University Medical School (comprising tissues from Passavant
i\Iemorial and Wesley Memorial Hospitals) have been examined.

In the development of the female urogenital system it will be recalled that
the first primitive organ is the pronephros and that as a result of fusion of the
pronephric tubules a pair of collecting ducts develop. After the degeneration
of the pronephros the two excretory ducts persist as the mesonephric (wolffian)
ducts into which the mesonephric tubules empty (Fig. 1). These ducts extend
caudally along each side of the celomic cavity to empty into the ventrolateral
])ortions of the cloaca. The paired paramesonephric (mullerian) ducts extend
first lateral and then medial to the mesonephric ducts. As the mesonephric
and paramesoneiihric ducts increase in size, a fold of peritoneum (the urogenital
fold) groAvs about them. . The caudal portions of these two lateral urogenital
folds fu.se transvei’.sely in the lower abdomen to form a medially placed genital
cord. In the center of this genital cord arc the two jiaramesoneplu’ic ducts

‘Read by invitation, before tlie Central Association of Obstetricians and Gynecologists. Oct.
25, 1947, Louisville, ICy.


23



24


lIUFFiAIAK


Am. j. Oi>M. Gynci.

July. WS


(imilionnii) ];ilcr fuse 1o iovm fJie vicroviv/mti] eaTuil. SoiuewJial lateral

to the parauiosoueplii’ic duels hut si ill ivitliiu tlic frenital cord are the paired
lucsoucphric duels.


P]‘om tlio 4 to tlic 55 nuu. slaj’e oJ! enil)]-yonie devclopinoiit llie nies’onephric
duels oinply iulo Ihe cloaca aJid laler Die uro/^euila) sinus. I)urinf>- Diis period
they lie in Die geuitnl cord parallel and lateral to the paramesoucphric ducts and
arc intact throughout their lengths (Pig. 2). Shortly after the 55 inin. .stage,
however, the openings in the urogenital sinus close and degeneration of the
mesonephric ducts begins (J<hg. 3). This degenoi-ation continues throughout the
remaindei’ of embryonic life and in mo.st individuals only a few ve.stiges of the
mesonephric tissues persist: in the adult degenerated portions may1)e found
near the ovary, in the me.sosaljnnx, and in the biwul ligament, (iccasionally
persistent portions of the mesoneiihric ducts become dilated in the anterolateral
or lateral vaginal walls to form the familiar Oarlnci’’s duct cy.st.s.



‘While the .sequence of events in the development and degeneratioji of the
mcsonepln-ic ti.ssucs as .just dc.seribed applies to the ma.iority of individuals.
Meyer has demonstrated that certain interesting exceptions may occur. Meyer-’
ha,s shown that an ampullar dilated portion of the mesonephric duct is tre-
quently observed as a rather wide circidar enlargement of the duct lumen in the
fetus as early as the second month. In older embryos the mesonephric duet is
occasionally found as a narrow cylindrical tube pcneti’ating from the para-
metrium into the middle of the lateral uterine wall. Prom this point of entrance
the duct proceeds in a downward direction in the uterine wall (Pig. 4)_. As it
enters the lowennost eoi’pus and cervix the narrow e.vlindrical lumen dilates to
form a distended ampulla located in the middle muscle layers of the lateral
cervical walls. At the end of the fifth month of fetal life the ampulla forms a
cleftlike eamty which has, in cross section, .slight bends and curves and the
beginnings of a few rather large diverticula (Pig. 5).

° When the mesoncphi-ie duct pensists in the cervix (in ap])roximately 20 per
pfmt of the fetuses hlcyer’’’ examined), it reaches its full development at the
seventh or ei’dith month of fetal life. At this time the am])ulla lies chiefly m
the lower part of the smpravaginal portion of the cervix and in the upper portion



Volume 56
Number 1


]\tESONEPHRIC REMNANTS IN CERVIX


25


of the portio vag’iiialis. Tlie dilated ampulla extends downward from the upper
cervix as an elongated dorsovenli’al slit lying in the middle muscle layers of
the lateral cervical walls. From the portio vaginalis the duet turns and runs
laterally in a diagonal upward direction until it passes over into the vagina.



Fig. 2. — Diagram. Prior to their degeneration tlie inesoneplu’ic ducts extend along each
side of the uterovaginal canal (which was formed by the fusion of the paramesonephric ducts,
A. Mesonephric ainpuliae tubular diverticula develop in some (20 per cent according to
Meyer) fetal uteri, B.



. . .Eig. 3. — Diagram. Degeneration of the mesonephric duct begins during the later stages
or tetal development. This degeneration may be complete or remnants may be left m tne a a-
gmal wall, the cervix, the uterine wall, or the broad ligament or near the ovary.


At the point where the ampulla turns laterally in the cervix it sends more or
less deep branches into the substance of the cervix. These branches may form
extensive coiled or snarled twisted canaliculi or tubules tvliich extend into the
anterior and posterior portions of the cervix. After the duct passes over into the
vagina, it again becomes narrower and assumes a cylindrical tubular form as it
extends downward along the anterolateral vaginal wall to terminate near the
hymen.

In the fetus a muscular tunic lies about the mesonephric duct eephalad to
the ampulla (Fig. 6). This tunic consists of a -broad inner longitudinal and a



20


jrUFFJfAX


Aij». J, OIfj.

I7t8


lliiii ciivnilar Ijiycr, Aloj)<r the (‘onrso of Dio OiK-Oed at/rjnilla iha muscular

limic hmmics rolulivuiy indislincl. Jn liu- .same fasliiou a stroma of .s/uudJeliko
(.’Oils IS touiul about, jjuj duel, above llie ampulla (Fj*r. 0, A) ; there is little or uo
stroma atioiit tlie caiialieuli wjneii braneb nfi’ into Die lower cervix.

serial seelious of fetal uteri stained wilb a lrie})romc slain
{iilillioau) A was- iioled that the stromal and mijseular eon.stituenj.s of the
mesouejdirie duet tend to jiersisi after deoeneralion of the epithelial eleinerifs
A.s a rftsuU of this observation it. wa.s po.ssible to folloiv the (h’/ener.Ajn^
mcsonejilu ie duct in the uterine wall lor some distance above the ampulla.



Fig. 4. — In the older embryo (7 inontli.s) the middle portion of tlie rne.’–onephric duct may
pe;’.si.st in the uterine wall. In thi.s photonilcroKr.aph the me.sonephric duct .above the .auipull.’t
is 55een as a curved canal lined by columnar cpitlielium and .“iirrounded by a .‘^tronia of spindle-
like cells. It ha.s a distinct muscular tunic. The oervicjil gland.s .arc on the left.


The epithelium lining the duct cephalad to the ampulla con.si.sts of a single
layer of cj’lindrieal cells witJi oblong, almost rod-shaped nuclei (Fig. 6, B). The
cells are highe.sl in tlie dilated ampullar portion, while in the tubular ramifica-
tion.s the height of the epitheium is le.ss and is proportional to tlie size of the
tubular lumen. In the narrowest twisted tubules the epithelium is low
evlindrieal or cuboidal. In this cuhoidal epithelium the nuclei tend to he
.spherical or ovoid. In tlie .smallest tubules the cells of the cpillielial lining often
appear fused.

After renewing the literaluro witJi the published case reports and stnd.ving
the material available in this laboratory, it appears that remnants of mesonephric
origin may be found in the adult eenix either as persistent fetal structures or as
new “Towths arising from fetal residues. Tho.se remnant.s which are not neo-
nlastie may occur in .several different forms. They may be seen as occasional
imotl isolated tubules or eanaliculi (Fig. 7. A) cither in the middle portion of
cervical wall or near the mucosa in the region of the internal os. These
isolated tubules are distinguished from the cermcal glands (Fig. 7, B) by their



Volume 56
Number 1


MESONEPHEIG EEMNAISTTS IlST CERVIX


27



1 ’’’■ — ^^Vhen the mesonephric duct persists in tlie cervix of older embryos it forms a

clefthke ampulla which has, in cross section, slight bends and curves and the beginnings of a
few diverticula. Occasional tubules branch off from it. (Photomicrograph of a cross section
through the ceiwix of a 7-montli fetus).



A. B.

Fig. G. — In the fetus tlie mcsonepliric duct cephalad to tlic ampulla has a disUnct mus-
cular coat, yl. The epithelium lining the duct lumen is made up of columnar cells with oblong
almost rod-shaped nuclei. A stroma of .spindlelikc cells lies between the epithelium and the
muscular tunic, B,


28


IIUKnfAX


A})}. J, A’ Gyiicc,
July. 19^8


dislinclivc low cuboidnl epill.oiio) Jijiini? juul l).y their* failnre to take a muci-
eaiimiic Kfniii, Oil on those .seaMeml tuhnles lyiiifr in close proximity to the
j^hinds oi the iifenno rsthmii.s so rcsenihle the hitler as to make rlUTcvcntiution
between thenr diffieu t itioro deeply within the cervical nrrrscnlatS*rclosel?
appioximatcd cystic dilations ol several ampullar tubules with occasional smaller
tnbu es about tliem may be /mind (Fi- 8). These Jiave, a-ain, a typical non-
becI•eloI^ low columnar cjnthclnim. I )i ft eren tint ion between those ampullar
tubules and cervical glands is le.ss difficult than is the differentiation between
isthmic glands and isolated mesonejihric amjnillar tubules near the mucosa.



Fig. 7. — Occa.slonal i.sol.itcd mcf-onoijltric .ampullar tubule.’!, A, may be found in tlie cer-
vix. The.so tubule.s are di-stinBui.sIied from cervical gland.”, J). by their low cuboida! epithelium
which is coinpo.sed of cell.s with large di.s: ■ ■ ■ nuclei and by their lack of .secretory

activity. The cells of the nie.«onephric ■ • . • ; do not take a mucicarmine .sUiin,

while tho.se of the cervical glands stain vividly with iriuticarmine.


The cells which line the tubule.s lying within the cervical musculature are similar
to the cells of the fetal structures described abot’C: there is a .single layer of low
euboidal epithelium (Fig. 9) wliich lias a clear tramshicent cytoplasm with a
spherical to egg-shaped dark-staining large nucleus. Wlien stained with iron
hemotox.vlin the nuclei stand out from iJie clear cytoplasmic background in a
characteristic fashion. i\Iucicarminc staining show.s little or no .secretory
aetivikr, although occasionally a iiinki.sli mass will he found within a tubular
hunen.* This is in .sharp di.slinction to the epithelium of cervical glands of com-
parable size where the tall columnar epithelium contains long rod-shaped nuclei
occupying but a .small portion of the cell. The rieline.s.s of secretory activity
in the epithelium of the cervical .glands is well presented by the vividness witli
which the cells take a mucicarmine stain.

Elongated narrow clefts with surrounding small tubules (Figs. 10 and 11)
Ivimr in the middle muscle layers of the cervix are most characteristic of all of
the fetal reinnaut.s of tlie me.soneplirie ampulla in the adult cervix. These arc
counterpai’is of the .spurs which the ampulla .sent dmniward into the ceivix m



V’olumc 56
Number I


]\rES02sErHEIC RE:M]S’AXTS IX CERVIX


29



.. Fig. S.— Remnants of the mesonepliric duct in the adult cervix often occur as cystic dila-
tions of the ampullar tubules with smaller tubules about them. This photomicrograph is from
p”® ^de of a serially sectioned cervix which contained bilateral mesonephric remnants. (See



Fig. 9. — The mesonephric ampullar tubules in the cervix are
cuboidal epithelium whose cells have clear translucent cytoplasm
large dark-staining nuclei.


lined by a single layer of low
and spherical or ovoid-shaped



JIUFFAfAN


Am. J, OI..I, &• Oriica
July, 19(8


.’50



Fip, 10 — A longitudinal section tiirouf^h a cervix to show a mesonephric remnant in tlic
inid-corvical wall. In this instance tliere is a persistence of a narrow cicftlike large tuhulo
wliich is surrounded by numerous small canaliculi. (See Fig, 11,)



urrouiK^ing’ them. (Sec Fif?- 10.)



Volume S6
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MESONEPHRIC REMNANTS IN CERVIX


31


]ate fetal life. Tlie lining epitlieliinn of these eleftlilce siriictiires i-esemblcs that
of the tnbnlcs except that Ihe .columnar epithelium is often higher and the
nuclei of the colls making up the epithelium tend to bo more rod shaped.

Usually the persistent* mosone])hric remnants are found in only one wall of
the cervix. However, in one serially sectioned cervix included in this report,
bilateral cervical remnants were discovered (Pig. 12). In this specimen it was
possible to follow the mesonephric duct structures from the vicinity of the
internal os to the lower portion of the portio vaginalis. The tubules lay in the
musculature of the middle portion of each lateral cervical wall. They cor-
responded in position and in vStructure to the fetal mesonephric ducts observed
in seriall}’- sectioned embryonic uteri.






Fig”. 12. — Cross section through the two liaivcs of a serially .sectioned arfult
ooxetl areas contain bilateral persistent mesonephric tUict tissue \vhich lias the same iiisioio^jc
structure as found in the fetus. (Sec Fig^. S.)


There is consideinlile variation in Ihe reported incidence of pei’sistent
mesonephric dnets in the cervix. In a series of fifty-four adult uteri ex.amined
specifically for mcsonc]>hrie remnants, IMeyer found ])ortions of the duct m
twelve specimens. Rieder’ noted .similar rests in 20 jier cent of the .specimous
he studied. IMaudaclP reported mesonephric rests in 40 per cent of the utoi i
from all newborn and oldci* cliildi’cn he examined. Fischer, ** on the other hanf .
found a mesoueplirie duct, in hut one adult uterus ot fifty which lie m.sjiccfcf .



32


II IJFFMAX


Am. J, Oh*i, Gjncr.

July. 1948

‘riicrc were five noniicoiilnslic, inesoncj)hrio duet renuianls in 1lie 1,192 specimens
exiiiniiK^d in lliis !a))orafo]’\’. In a scries of 1,413 eej’vie(;s (jxaniincd by Wolfe,
“only one eonlaincfl noi-inal vemnanls of t.’arliKn-’s duel.” It ivould appear
lliat tliG earlier workers held a iinaniiniiy of o])inion as lo the presence of
inosonephric residues in the adult cervix but that they disagreed notably as to
the frequency of such remains. They were in agreement in stating that the.sc
residues were lo)’ the most pail coin])ai’a!)le in struetui’e with the mesonephric
tissue.s found in the fetus near tei-m. 9’hat neither Wolfe nor T found me.so-
nejdirie tissues in the cervix with a frojjuejicy comj)arable with that of ]\Ieyer
and others niay be due to the fact that our specimens were from .surgical patho-
logic material and that we had access to but onc! or two blocks cut. from each
cervix. Jt is quite pi-ol)able tiiat our iiicidence would moi’c closely approximate
IMeycr’s if we had serial sections fi-om each of the cervices iu our series. In
addition in the series repoited here, all specimens difficult to differentiate (par-
tieularly wliei’c there wei’e questionable tubules near the islhmie glands) were
discarded.

It is necessary to differentiate between a simj^le I’cmnant of a fetal slimeture
in the adult and a ncoplnsm arising from .such a tissue. IMeyer'” makes this dis-
tinetion particularly evident in discu.ssing the persistence of mesonejdiric cervical
remnants when he ])oint.s out the difference between the factoi’s leading .to the
])revention of the normal disappearance of fetal tissue (phylogenetic autonomy)
and those factors leading to tumor formation (pathologic cellular autonomy).

Three types of neo])lasms of mc.sonej)hi-ie duct oi’igiji may be expected
to develo}) in the uterus — cysts, adenomatous prolii’erations of varying degree,
and adcnocai-cinoma.s.

A eystadenoma develojnng from rests of wolffian duct origin in the cer\nx
is reported bj^ Dworr.ak.” irenkcl’- described a “hypertrophia portionis
cystica’’ which he stated was a cystic transformation of cervical rests arising
from the wolffian duct, .Stubler,’-* Kustcr,” Arx,”’ (Jombert,’® Knauer,*^ Gudim-
Lewkowitseh,’’’ Klein,’” von Kecklinghausen,”” and others liavc also reported
cysts of the uterus which presumably were of mesonephric duet origin. Critical
review of inost of these case reports, however, makes it difficult to determine
whether or not the neoplasms actually originated in the cervix or whether they
developed in the lateral uterine wall.

Criteria have been c.stablished for the diagnosis of uterine cysts of meso-
nei)hric origin by Meyer, Dworzak, and Klein. They state that for such cysts to
be topographically correct they should lie in the longitudinal axis of the uterus,
they should have a serpentine or coj-k.screw course, and they should be lined by
columnar epithelium characteristic of the lining of mesonephric structure.s;
there may, in addition, be a scattering of .surrounding muscle and stroma whicli
resemble.s that surrounding the fetal me.so7jep})ric duet above the ampulla. One
specimen in the 1,192 examined in this laboratory showed cy.stie cavitations m
the lateral uter-ine wall beginning below the level of the internal os and extend-
in” uprvard in the mvometrium to a point approximately midway between the
internal os and the fundus (Fig. 13). The serpentine course of the cy.stie cita-
tions in the ixterine wall and the low cuboidal epithelium lining the ey.stic cavities
sim^ested that this was a cystic mesonephric duct remnant.

‘^Sfever mentions that occasional isolated mesonephric ampullar tubules
evstic He .states that while tho.se cy.stie clianges are oceasionaliy
the’ fetus thev are much more common in the adult. Rarely are the
‘T !■ i tl ^2 5 mn. in Jwmolor. Differentiation between these e, -.sis end
T 1 ,. Xel Mated ev.sls of the eervieal alands is not always ea.s.v Jtaed

eySsin?o’™>’ in

of the cervix.



Volume 56
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IMESONEPHRIC REMNANTS IN CERVIX


33



^ Fig. 13, — Pliotomicrograph througli the uterine wall showing a cystic cavitation wh^h,
beginning helow the level of the internal os, extended for a distance of 2 cm. cephalad. The
irregular course of the cavitation and the low cuboidal epithelium which lined it suggested that
tins was a cystic mesonephric duct remnant.











IIUFFMAK-


P>4.


Am. J, 01)1, fc Gyncr.

Jvly, 1948


Af1(mo]n;itoiis Jiypoi-jjlnsi.’j of ijjesoJKipJn’ic diud ronmnnU in iha coirix oc-
eiii-.s .’IS a coiifiloiiiorale mass ol’ closely packed small tubules oi* caualiciili -which
may bo found oil her near Ihe ee?’vical mucosa or, more often, in the middle
layers of Iho coi*vic*al louseulatiii’e 14), Tlicso tKleiioinalous proliferations
rarely become tumoi-s of appreciable si/x‘ and are most often discovered in the
course of histologic examination of cervical tissues T’cmoved eitlier for biopsy or
at the tiine of amputation of an nnheallby cm-vix. The tubules or eanaliculi
usually lie in groups iji the interstices of Die cervical musculature. There may
be, however, occasional isolated masse^s of closely packed tubules near the endo-
cervical mucosa. Mieroscoj)ically the tubules ai’(; small aud are j’ound or ovoid in
sba])e. 1.be.y may vary iu diametei* from capillary siae to macroscopic

cysts, a dislinguisbiug cliaracleifslic which I have seen lias been the tendency
foj’ most of the tubules to be apjiroximalely Die name diameter. When larger
tubules arc present they may show oul])OUclnngs and diverticula. There is little
or no musculature almut the luliiiles and .scajity or no filroma. When stroma
is present, as descril)cd by llust,*’ it is of a spindle or l onnd cell character similar
to that seen about the duct above the ampulla. Ka7e]y a long narrow ductlike
cleft will be discovoi’od in the jnidst of an adoiomatons jmolifci’ation; .such a
duetlike remnant may be the I’cmains of tiic ainpullar cleft seen in the fetus.

The tubules (Fig. lo) which com))rise these adenomatous hyperpla.slic
formations are lined by a single layer of cylindrical epithelium. The cells are
low cuboidal in type and the individual cells cojitain a tJ’au.slucent pale cyto-
plasm. with a large round or cfjffec bean-shaj)ed juieleus which fills much of the
cell body.

The nuclei are ridi in ehrotnaiin and stain intensively. An occasional
tubule will show some secretory activity as evidenced by a mucicai’mine staining
of its contained seci’ction; for the most i)art, however, the tubular lumina are
empt.y and the cells do not take a mucieai’minc .stain.

Meyer, Klein, and O’bumin described cervical adenomas of mesonephric
origin many years ago. l^fore receiitly, Kust, Kockstroh, Reeb, and Wolfe have
repoj’ted similar ones. In each of these repoj’ts the findings are essentially
as de.scribed here both as to oi-igin and .stJ’ucturc of the neoplasm. In none was
the diagnosis made pjfor to histo])atliologic examination of the excised li-ssues.

There were four cervices -0111011 contained adenornatou.s Jiyperplasias of
mesonephric duct origin among the 1,192 specimens examined in this laboratory.

In one of these tlie majoj- portion of the post ctoI ate ral cervical wall was in-
filtrated by innumerable minute twisted tubule.s having the typical histologic
picture just do, scribed; the otbei’ tln-ec contained areas in which there were
compact ma.sses of eanaliculi having a topographic location and microscopic
appearance compatible Avitb a diagno.si.s of adenornatou.s hyperplasia of mc.so-
nephric ampullar tubules.

Adenocarcinomas may develop from mesonephric duct remnants in the
cervix Gro.ssly the tumor ha.s u.sually been found (in those cases reporter] where
the neoplasm had not as yet involved tlic entire cervix) in the anterolateral or
vosterolateral midcorvical walls. The growth is a gi-ay-white or biwvmrsh
friable area Mliich can be differentialcd from the remamder of the cer^x.
Microseonieallv the tumor eonsi.sts almo.sl entirely of raa.s.ses of glandbke tubules
Uicb’ ar-e packed closely togelber. These tubule,s sliow an unorganised arrange-

endure of varviug .sixes, many having distended lumrna while the lumma of
Srs a« nallwcd or oMitcralcd by 11, a many lave, a o£ ce lla forming .tl,c
?nbular wall In some areas epithelial probfei-ations or paprJla^^ extrusion.s
tubular tubular lumina. The cells and tubule.s be in the fibromu.scular

SSti™ cervix and tend to invade between tl,e mnaele bundles.



Volume 56
Number I


MESONEPHRIC -REMNANTS IN CERVIX


35


The epitheliiiin lining the tnl)nles is hi- and innlti-striated throughout and is
marked by nnnsiial irregularity in the height of the cells and the position of the
nuclei. The cell nuclei are for the most part large lightly staining and contain
an increased number of mitoses. Muciearmine staining shoAvs no evidence of
any apprecialDle amount of mucus in the cells, but in many places the lumina
Imve a thin mucuslike layer on the epitlielial surface ; this layer takes a light
pinkish stain with muciearmine.



Eig. 15. — The tubules making- up an adenomatous hyperplasia of mesonephric duct rem-
nants in the cervix are often found in closely packed masses. They are lined by a single layer
o j cylindrical or cuboidal nonsecretory epithelium, the cells of -which have a pale cytoplasm
ana large round or ovoid well-staining nuclei. (See Fig. 14).


• The first report of a carcinoma of tlie ampulla of the mesonephric duct was
made by Meyer in 1903.^’^ The same author reported a second case in 1907.^^
In the first instance the nature of the tumor ivas recognized by the fact that the
upper part of the mesonephric canal was still intact and that the adenomat()us
glandular proliferation arising from it gradually merged into a destructive
neoplasm of the cervix and portio which had the characteristics of the tumors
described. The second ease was histologically similar to the first. DanneeP^
also describes an adenocarcinoma of the cervix which Avas assumed to have
deA^eloped from mesonephric duct remnants because of its position and structure.
This opinion was concurred in by Meyer Avho saAV sections of the neoplasm.
Wagner, in 1929-* and Roekstroh, in 1935^® reported similar tumors.

One adenocarcinoma of the cervix haAung an architectural pattern suggest-
ing origin from a mesonephric remnant Aims among the 1,192 specimens examined
for this presentation. The tumor, discovered in routine sections, invaded but
a small portion of the posterolateral Avail of the cerAux at the leAnl of the internal
os. It consisted of strands and masses of glandlike tubules (Fig. 16) exteiiding
into the substance of the’cerAux and invading the loAver eoi’pus. The lining of
the tubules is composed of -cuboidal and Ioav columnar cells of irregular height
haAung large pale-staining nuclei. There are numerous mitoses. _ In many places
the configuration of the tribular structure is lost. The neoplasm iiiA^ades betAveen


30


HUFFMAN


■Am, J, Ol?*!!, & Gj’ftcc,
July, 1948


Ihc iiiisdo iibci’s ol 1.])e itvsix. 3’hc a.ssiiiiijjlioii Ihnl this wircii)onia developed
lio m rests oX mesonephric; chiei ois-in (insofar as sueli a diagnosis can be inade
1 the absence oJ typical nonnal mcsonepliric tissue) is iiased on the position
o the tumor and its arclntoctural pattern. It slunvs no similarity to tlfe s .a
malignancies arising from mucous glands. It has striking similarity in
anoe to the case dc.seribed by i\levcr in Avhicji an adenocarcinoma could be identi-
fied a.s ai ising iiom a .still intact mesonepliric remnant.



Kijr. 16. — Ailcnocarcinoma of inosoncpUric duct oriRin in tlio cervix con.si.sts of ina-s-ses
of Klandlikc tubulc.s which are clo.sely packed. These lubiile.s have n disorganized arrangement,
arc of varying sizes, and their liimina may be obliterated by many layers of cells.


Discussion

A fetal remnant ivliich is homologous 11-1111 a portion of the male genitals
and wliich, instead of degenerating in a normal fashion, per.si.st.s in the adult
female should logically be diminutive in size and embiyonic in character. The
exact homology of the me.sonephrie ampulla in the female has not been demon-
strated. The hypothesis has been advanced tliat it is liomologoiis with either
the ampulla of tlie vas deferens or the .seminal vesicle. If this contention is
accepted it would he assumed that tissues resembling the fetal mesonephric
structures would he found. Furthermore it would not be anticipated that the
development of the embryonic stimetures would progress beyond a late stage in
female embryonic development. Rather, ina.smuoh as the remnants disappear



Volume 56
Number I


isrESONEPHEIC EEMNANTS IN CEEVIX


ill most individuals, tliose which do occasionally remain, unless undergoing nco-
])]astic changes, would tend to be small- in size and poor]}’ developed.

It is not within the scope of this presentation to attempt to explain why fetal
remnants of the mesonephros i^ersist in some women and not in others. i\Ieyer
has attempted an explanation of the phenomenon on the basis of the prevention
of the normal disappearance of fetal parts by a particular stimulus located
either in the vicinity of the fetal stmeture or else within the cells of the struc-
ture itself; this hypothe.sis is gone into in -considerable length in his monograph
entitled TJeher cpiilielialc Gclnldc im Myomeirium einscMicsslich dcs Gdriner-
sclicn Ganges jiublished in 1899. That remnants of the mesonephric duct do
persist in the fetal cervix has been well demonstrated by j\Ieyer, IMaudach, and
Rieder. Stud}’ of serially seetioned fetal uteri reaffirm their observations. The
definitive evidence in support of their efforts would be wax model reconstructions
])repared from serial sections of the fetal and adult cervices containing
mesonephric remnants ; .such a project is at present under Avay in this laboratory.

A number of case reports have appeared during the past half century
giving histologic descriptions of tumors similar to those first described by
i\royer. There are now a sufficient number of these to warrant the acceptance of
mesonephric duct renuiants in the cervix as a histopathologic entity. In order to
facilitate further investigation a table of publi-shed case reports is included here-
with (Table I).

TaiujK I. PL’DrasiiKi) Cass Eecorts of Mesonephric Dcct Ee.m.vants in

THE Adult Human Cervix



38


nuPFaiAisr


Am. J, OIjst. & Gyncc.

July. ‘1948


In. tiie classification oi’ mesonephric remnants in tlic cervix differentiation
s loiild be made between nondefjcneratcd .fetal .struetni’os (occasional tubule.s,
poi tions of ])cisistcnt duels, and seallercd canaliciili) and new growths arising
from such stimclurcs (cysls, adenomatous i)rolifern tions, and adenocarcinomas).


In 1,192 cervices thoA’c were five speeimens in which mesonephric remnants
^ycrc found, one cyst oi. the eorvicocorporeal uterine wall presumably of
mesonephric origin, four adenomatous })rol iterations of. mesonephric ampullar
tubules, aud one adenocarcinoma of the cervix which architecturally and
topographically was of mcsoncplulc origin. Detailed case repo’ls have not
been included because they arc similar in all respects to the general description
of cacii entity ineindod in tlic text.


The diagnosis of a remnant of mesone])hric tissue or a tumor arising from
such a remnant will rarely be made grossly. The diagnosis is obviously a histo-
pathologic one. It will be made foi* the most part during the eouise of histologic
study of “routine’’ sections. If Inil one block of tissiie is taken through the
lower posterior lip of the cervix, as is customarily do)m in examining cervices
which are not suspected of harboring a malignancy, these interesting le.sions
will frequently he missed. It is quite probable that j\Ieyer’.s statement that 20
per cent of all cervices have mesonephric remnants in them is more nearly correct
than the incidence of approximately 1 per cent that I am reporting.


The identification of typical mesonephric duet remnants in the cervix is
not difficult. The location of the tnbnlcs in the midporlion of the lateral cervical
wall is characteristic. Characteristic also arc the small rounded canaliculi lined
by nonsecretory occasionally ciliated low eohimnar or cnboidal cells with their
translucent cytoplasm and large, round, clearly staining nuclei.


Summary and Conclusions

This presentation is an attempt to portray the embryology, the histology,
and the microscopic pathology of mesonephric remnants in the uterine cervix.
In order to accomplish this the literature has been reviewed, .serially sectioned
tissues have been studied, and sections from 1,192 surgically excised cervices have
been examined.

The presence of an ampulla of the mesonephric duct in the fetal cerAux has
been demonstrated by Meyer and others. Study of serially sectioned fetal uteri
confirms their observations. Remnants of these fetal elements may persist in the
adult cervix either as nondegenerated structures or as neoplasms arising from
sucli residues. These remnants will ordinarily be discovered during study
of routine sections of the ceiAux. The characteristic histologic appearance of
mesonephric remnants in the cervix is that of small tubules or canaliculi lined
by a typical low columnar nonsecretory epithelium consisting of euboidal ecus
containing a translucent pale cytoplasm aud large well-staining ovoid or luund
nuclei. These tubules can be differentiated from cerncal glands. The hism
pathologic appearance of neoplasms arising from these remnants is gne

detail.



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Five cases of mesonephric remnants in the cervix and five neoplasms arising
from mesonephric remnants in the cervix are added to the literature.

There is now sufficient evidence to warrant acceptance of mesonephric duct
remnants in the cervix as a histopathologic entity.


References

1. Meyer, E. : Ztsclir. f. Geburtsli. u. Gynak. 42: 526, 1900.

2. Meyer, E. : Die patliologische Aiiat,. d. Gebarrautter, Handbuch der spez. path. Anat. u.

Histol., vol. 7, xJtu’t 1, Henke u. Lubarsch. Berlin, J. Springer, 1924, p. 43.

3. Meyei’, E. : Handb. d. Gyniilc., vol. G, i)art 1, AV. Stoeckel, Miinchen, J. E. Bergman, 1926,

p. 651.

4. AVolfe, S. A.: Air. J. Obst. Ss Gynec. 39: 312, 1940.

5. Meyer, E.: Arch. f. mikr. Anat. u. Entwges. 73: 751, 1909.

6. Meyer, E.: Ztschr. f. Geburtsh. u. G.ynak. 58: 527, 1906.

7. Eieder, C.: Virchows Arch. 96: 100, 18S4.

8. Maudach, F. y. : Virchows Arch. 156 : 94, 1899.

9. Fischer (quoted by Mej^er) : Ztschr. f. Geburtsh. u. Gyniik. 37: 327, 1897.

10. Meyer, E. : Ueber epitheliale Gebilde im Mjmmetrium des fotalen und kindlichen

IJterus einschliesslich des Gartnerschen Ganges, Berlin, 1899, S. Karger.

11. Dworzak, H.: Arch. f. Gyniik. 157: 162, 1934.

12. Henkel, M.: Arch. f. Gjmiik. 113: 427, 1920.

13. Stabler, H.; Zentralbl. f. Gyniik. 47: 1068, 1923.

14. Kuster, F.: Ztschr. f. Geburtsh. u. Gyniik. 80: 666, 1918.

15. Arx, W, V.: Ztschr. f. Geburtsh. u. Gjmak. 79: 52, 1917.

16. Combert, S.: Inaug. Diss., Abs. Zentralbl. f. Gyniik. 44: 1271, 1920.

17. Knauer, E.: Zentralbl. f. Gyniik. 19: 498, 1895.

18. Gudim-Lewkowitsch, D.: Abs. Zenti’albl. f. Gyniik. 38: 1048, 1914.

19. Klein, G.; Virchows Arch. 154: 189, 1898.

20. V. Eecklinghausen (quoted by Dworzak) : Die Adenonijmme und Cystadenome der

Uterus und Tubenwandung, ihre Abkunft von Eesten des -Wolffschen Korpers,
Hirschwald, Berlin, 1896.

21. Meyer, E.; Virchows Arch. 174: 270, 1903.

22. Meyer, E.: Ztschr. f. Geburtsh. u. Gyn’ak. 59: 234, 1907.

23. Danneel, H. : Arch. f. Gyniik. 159: 395, 1935.

24. Wagner, G.: Zentralbl. f. Gynak. 53: 1336, 1929.

25. Eockstroh, H.: Ztschr. f. Geburtsh. u. Gyniik. 112: 95, 1935.

26. Eeeb, M.: Gynec. et obst. 36: 401, 1937.

27. Eust, W.: Arch. f. Gyniik. 162: 350, 1936.

28. Thunin, L.: Arch. f. Gynak. 61: 15, 1900.

29. Froboese, H.: Gesell. f. Gyniik., Berlin 12: 4, 1934.

Discussion

HAEOLD L. GAINEY, M.D., Kansas City, Mo. — Mesonephric duct remnants in the
adult female are a phylogenetic anomaly. The cranial end is normally encountered in the
mesovarium and the lateral third of the mesosalpinx forming the epoophoron. Caudad in the
vagina, it again appears in the more familiar foi-m of Gartner’s duct cysts. That wolffian
duct remnants persist in the cervix “is less commonly recognized” as stated by the author
and readily accepted by our own experience and with V’olfe’s report of one in 1,413 cases.
Wolfe’s explanation for his low incidence and my inability in several large pathology de-
partments to find one case is that in routine sections of the cervix the area likely to be af-
fected is not studied.

Dr. Huffman in this excellent presentation has made a definite contribution to American
gynecologic literature. His review of the literature and presentation of the results of studies
resulting from serially sectioning 1,192 surgically excised cervices are given. Five cases
of mesonephric remnants in the cervix and five neoplasms (one malignant) arising from
mesonephric remnants in cervix are added to the literature.

This paper should arouse interest in more extensive studies of the uterine cervix, and
with the increase in complete hysterectomy, opportunities for such studies will be more frequent.

The morphologic and the cytologic characteristics have been clearly demonstrated and
described. Outlined are such details as the presence of a muscular tunic with a stroma of



40


HTJPFilAX


Am. J. Obst. & Gyncc.

July, 1948


i^piiullolikc cells above llic anumlla aiu’l tlieir absence or prcscuec in sniull uinounts below
11)0 ampulla. ‘J’lio eluii’.acler of liie epifhelial o/emeals vtiryht}^ from a .‘•ingle layer of
cyliiiilricjtl cells with oblong roil-.’^liiijied mmlei lo low ciibf)i<]iil witli ovoill nuclei, will) fsiiliiie
to tiiko nmciea.rminc sljiin, while, the gliimlular stnicliircs of fhc ccrvi.x ilo, aids in iilenf ificiition
and differenliaiion of 11ie.se struct nre.s.

Tlio anatomic and psitliologic .signilicancc of this pre.sentation can be readily accepted.
The clinical significance may be even greater than would be .suggc.stcd by the low incidence
of occurrence, 1 jier cent. Further studies of malignant tumor.s of the cervix, p:irticularly
adenocarcinoma,’ might ])0ssibly reveal a higher percentage having origin from this source.
A Tcccntly studied, yet lo be reported, rnespdermal mixed tumor of the uterus, when reviewed
in the light of thi.s jmper, contained some highly suggestive tubular .structures.

I would like to ask Dr. Huffman his reaction to thi.s thought.

Dll. HUFFMAN (Closing). — I wish to thank Dr, Gainey for his di.scu.^.sion and wi.’-h
T might have summarized the material I prei^ented as adequately as he has done. Dr. Gainey’s
description of !i mixed tumor of the uterus containing tubular elements strongly sugge,sts
that it originated from a persistent mesonephric duct remnant. Undoubtedly mesonephric
remnant.s in the uterus arc frequently missed in the study of “routine” sections. The
rarity with which multiple sections arc taken from supposedly normal tissues surely must
rc.sult in many similar omission.s of other equally intere.sting 7)athologic entities.



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Fig. 3 A. — Schematic illustration to show extent of potential visceral distortion when pro-
lapse of vagina is complete. Kinking of urethra interferes with bladder function. Perineal
body and rectovaginal septum are intact. Rectum is not involved in posterior vaginal wall
hernia (enterocele). ’



— Schematic illustration to show intimate connection bet\\een an terio
Wadder as compared with that which exists between posterior vaginal vail an j
pelvic viscera.



44.


FJ.E’J’OHE]]’


Am. J. ft Cyncc.

July, IviK


cntoi-ocdc 3 A niid 4). It i.s jnij)OJ-Unit to diffcTejitjalc between j-cefocele

tiiicl ciileioccio beCcUiso e.ovi’oelion oi lliese dciecls i7ivo]ve.s two enlij’eU’ dift’ereiit
operative proeeduro.s. JlioJi eo]po])orijieorr]iap]iy is required for the former,
wJnic coiu])lete oblileration o(. the cul-dc-sae, from above, may lie iicce.vsaiw in
the latter (Figs. 7 and 8). Botli procedures may have to be employed if the
two conditions coexist.

4. Tlie rectum and vagina are less intimately coniiccled than the bladder
is 1o the anterior vaginal wall because the cellular ti.ssue of the rectovaginal
septum is flexible and lax, in oitler io adapt ilself to llie rectal movements in-
volved in the act of defecation.


According to Demarost* the rectal supjiorls are stiunger than tho.se of the
bladder lieeausc the ])uliorcetal fibers of the levator ani arc intimately connected
with the rectum. IJenee di.splaeement of the postei-ior wall of the vagina and
rectum has less significance, clinically, than the dowinvard movement of the
bladder with the anterior vaginal wall (Figs. 3A and 3B).

When looking. at the condition from al)ovc afica- the abdomen is opened, the
vagina is inverted and the walls descend toward the cervical .stump or toward
the vaginal cicatrix which is ijresent if the patient has had a complete hysterec-
tomy. A funnel-shaped arrangement is t.hus ejicounteicd with the cei-vical
stump or vaginal cicatrix being in the most dependent position, eompaj’able to
the small end of a funnel (Fig. ]). Tlic peritoneum de.scends into the vaginal
funnel covering the bladder ; thcii, after leaving the bladder, it extends on to
the posterior Avail of the vagina and is reflected u])ward on to the anterior wall
of the rectum and sigmoid. Bccau.se the uterus has been removed, the cul-de-sac
of Douglas may be elongated. This ]>redi.spo.ses to the development of an
entCJ-’oeele. It ma.y or may not be a.s.soeiated .with rectocele, since the latter i.s
dependcjit to a very great extent upon the funetiojial effieioncy and anatomical
integrity of the perineal body and rectovaginal septum (Fig. 4).

Complete obliteration of the eul-de-.sac .should be dojie ii7 the.se patients if
the best ultimate result is to be obtained (Figs. 7 and S).


Commentary

Berkely and Bonney^= said, “The possibility of curing a case of pinlap.se
in which the entire uterus has been removed, without narrowing the vagina to a
degree which prevents sex relations, is practically nonexistent. ’ ‘

Palsey- reported a successful cure of ])rolap.se of the urethra and bladder
in a 15 – 3 mar-old girl by anchoring the anterior wall of the bladder to the perios-
teum of the pubic bone, as described by Hepburn.® In this case the defect was
primarilj^ urethral.

PhaneuF stated, “Subtotal colpeetomy (LePort operation) is useful in
older women with total prolapse or invci-sion of the vagina following hysterec-
tomy. The one disadvantage, namely, clo.sure of the vagina, makes it applicable
onh’ to those Avomen Avhose age make .sexual relations unimportant.” He re-
unrted a series of tAventv-six cases of subtotal colpeetomy and six cases of total
c^obmetomA^ but he did not say at Avhat age sexual relations become unimportant
in wnmeii We believe that colpeetomy is unnecessary at any age if the condi-
tion of the patient Avill pennit her to be sub.iected to an abdominal operation.

E, ihn analysis of 730 operations for uterovaginal prolapse Avhieh he has
in tne ancn.>.V& UJ. lu i “mhn nr



micraftefiisi’^^^^^^ for correction of a large^posterior



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vaginal ‘wall liernia. “In noilhcr ease was furtliei- correction necessary.” He
goes on to say that “adequate repair of the pelvic floor is essential in all eases
unless the perineum is intact and gives good support,” and, “Subtotal or total
eolpectomy are the only operations from which satisfactory results ma}^ be
expected.”

We would like to submit the “rectus suspension principle of crossed-
suspender support” as a dependable surgical procedure in the treatment of
complete prolapse of the vagina and bladder following hysterectomy for patienls
in whom an abdominal operation is not contraindicated.



^ Pig. 4.— First patient, fifteen months after operation. Shows relationship of en^
to rectum, perineal body, and vaginal introitus. Ventral vaeinal her-

marited stretching of posterior vaginal wall, causing elongation of cul-Ae-sac and paginal
niation. Normal relationship of bladder and urethra to symph>sis is maintained, i er
body and rectovaginal septum arc intact.


Rectus Suspension Principle of Crossed-Suspender Support

‘ The ability of the vaginal walls to stretcli when subjected to strain, tension,
or pressure is well known. When ventral fixation of the vagina is employ ed as
the only means of correcting bladder prolapse, the ability of this museulai tulio
to maintain permanently the bladder in normal position behind the sympli}sis
is subject to question. If the vesicovaginal connective tissue septum is intae ,
ill good condition, and can be included in the ventral fixation sutuies, the piOj,
iiosis is better than if the fascia is tliin, atrophic, torn, and separated.