1948 3: 91-102 BERTEL VON BONSDORFF LIGHT OF RECENT INVESTIGATIONS PERNICIOUS ANEMIA CAUSED BY DIPHYLLOBOTHRIUM LATUM, IN THE http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#repub_requests Information about reproducing this article in parts or in its entirety may be found online at: http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#reprints Information about ordering reprints may be found online at: http://bloodjournal.hematologylibrary.org/site/subscriptions/index.xhtml Information about subscriptions and ASH membership may be found online at: Copyright 2011 by The American Society of Hematology; all rights reserved. 20036. the American Society of Hematology, 2021 L St, NW, Suite 900, Washington DC Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by For personal use only. by guest on August 12, 2011. bloodjournal.hematologylibrary.org From
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BERTEL VON BONSDORFFLIGHT OF RECENT INVESTIGATIONSPERNICIOUS ANEMIA CAUSED BY DIPHYLLOBOTHRIUM LATUM, IN THE
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http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#reprintsInformation about ordering reprints may be found online at:
http://bloodjournal.hematologylibrary.org/site/subscriptions/index.xhtmlInformation about subscriptions and ASH membership may be found online at:
Copyright 2011 by The American Society of Hematology; all rights reserved.20036.the American Society of Hematology, 2021 L St, NW, Suite 900, Washington DCBlood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by
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92 . D IPH Y L L O B O T H R IUM L A T UM A N D A N E M IA
G . T #{ 24 6} tte rm an ( 1944 ) says tha t h e has en coun tered cases o f m ild m ac rocy tic an e-
m ia in tapew orm carrie rs tha t d id no t re spo nd to live r trea tm en t b u t show ed good
rem issio n a fter a w o rm cu re . H e assum es th a t th e p a thog en etic m echan ism fo r th is
fo rm of an em ia is d iffe ren t from tha t fo r th e tru e pe rn ic ious tapew o rm anem ia ,
w h ich d oes respond to liv er the rapy .
O n the o the r h an d , the re hav e been num erous repo rts in F in land of case s o f hy po-
chrom ic an em ia in tapew orm carriers w hich w ere no t cu red b y expe lling the w orm .
O n th is po in t, con flic ting in fo rm a tion is still foun d in the lite ratu re .
Th e q uestion w hich is o f sp ecia l in tere st fo r re search is : w hy do so few w orm
carrie rs have p ern ic iou s anem ia? O r fo rm ula ted in g rea ter de tail : w ha t are th e
fac to rs w hich lead to th e rise o f w orm anem ia and w hy are these fac to rs ac tive in
on ly a sm all num ber of cases?
H ithe rto , the se q uestions have n o t been sa tisfacto rily answ ered . Th e d iscussio n
of them and the tapew o rm anem ia prob lem as a w ho le has b een reported in d eta il
by B irke land ( 1931 ) .
T he presen t kn ow led ge of the genesis o f pe rn ic ious anem ia sug gests th at in som ew ay the w orm in te rfe red w ith the pro duc tion o r absorp tion o f th e an tianem ic fac -
to r o r w ith the produc tion o f th e com ponen ts inv o lved in its fo rm atio n . T h is
tho ug h t w as firs t ex p res sed b y S a ltzm an ( 1935) . O n the basis o f sim ilar reason ing
the pern ic io us anem ia in con nec tion w ith sp rue , v en tricu la r les ions, in tes tina l re -
sec tion s, e tc., can , a s is w e ll kn ow n , be exp lain ed .
A n investig atio n is h e re repo rted ca rr ied ou t on these line s w ith the o b jec t o f
e x pl a i n i n g t h e p a t h o g e n e s i s o f c a s e s o f p e r n i c i o u s a n e mi a , mo s t o fhem due to
tapew orm in fe sta tion . T he tes ts have been go in g on sin ce937.
1 . T H E IN T R I N S I C FA C T O R
a ) The course of rem ission after rem oval of the w orm .f the w orm is ex pe lled in the
u s ua l wa y (w ith 3 -4 .5 Gm . Ex tractio n filic is ) from hosp ita l p atien ts o n an un -
re str icted d iet, a b lood rem issio n beg ins sho rtly a fte rw ard s and co n tinu es un til the
b lood p ic tu re has becom e no rm al. In a g ro up of 7 cases, it w as obse rved th a t the
re ticu locy tos is began on the fo urth to the s ix th day afte r the w o rm w as expe lled in
6 of the pa tien ts and in case , no t un til th e e leven th day . Th e re ticu locy te m ax i-
m um was reached in th e firs t 6 cases m en tioned be tw een the seven th and the ten th
day afte r the w o rm cu re , and in the sev en th case on the th irteen th day . Th e m axi-
m um re ticu locy te va lues varied b e tw een 7 .4 an d 2.3 pe r cen t. In th ese case s, ex -
am ina tio n of th e b lood befo re E x trac tum filic is w as g iven show ed tha t the e ry th ro -
cy tes w ere b etw een ii a n d i.i m illion per cu . mm . of b lood .
A pparen tly , a fte r the w o rn i cu re , th e reticu lo cy tosis gene rally se ts in a few d ay s
la te r th an afte r a stro ng in itia l live r trea tm en t. T he m axim um fo r re ticu locy te
va lu es is on the average som ew hat low er than in cases o f pern ic iou s an em ia treated
w ith liv er , bu t on th e o the r hand , th e re ticu locy te c ris is la sts lo nge r . T he in crease
o f t h e e r y t h r o c y t e s i s g e n e r a l l y a b o u t ioo ,ooo pe r d ay , w h ich is ju st a s g rea t a s
wi t h a d e q u a t e l i v e r t he r a p y .
It ha s been fo und by m eans o f a ste rna l pun c tu re th at w ith in 48 hours a fte r the
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94 D IPH Y L L O B O T H R IUM L A T UM A N D A N E M I A
fam ilie s m any cases o ccur o f bo th cryp to gene tic anem ia and p ern ic io us anem ia due
to w orm . T he cause of th is has b een con sidered a spec ial‘cons titu tion al d ispos i-
t ion ’ ‘ fo r th is type of anem ia . It m ay be tha t th is‘d ispos i t ion ’ ‘ con sists in a de-
fic ien t p rod uc tio n o f in trinsic facto r .
2.. T H E E x T R IN sI C FA C T O R
a) Clinica l observa tions . Experience in F in land show s th at w o rm carrie rs can
have p ern iciou s anem ia even thou gh the ir food con ta ins a su f fic ien t am oun t o f p ro -
tein o f d iffe ren t k inds . A pparen tly , lack ofex trins ic fac to r is no t essen tia l fo r the
occurrence o f pern ic ious tapew orm anem ia (in con tras t to som e other cond itions
such as , fo r ex am ple, th e nu tritiona l trop ica l pe rn ic ious anem ia). H ow ever, ce r-
tam fac ts do support the id ea tha t a re lativ e de ficiency in ex tr in sic fac to r
can con tr ib u te to th e r ise o f the d isease . G . T #{246}tte rm an fou nd in h is m ate rial a
h igh er frequen cy of pern ic ious tapew orm anem ia in942 . th an in 1943 . In th e
fo rm er year the food s itu ation in our coun try w as particu la rly se riou s; the re w s a
spec ia l lack of p ro te ins. Th e nex t y ear the situa tion had im p roved con siderab ly .
My ow n expe rience ag rees w ith th at o f T#{246}tte rm an’s . In som e cases o f w orm ane -
m ia , I have seen a sligh t re ticu lo cy tosis and ev en a cer ta in im provem ent o f the
ery th rocy te coun t during the adm in istra tion of m ea t. T h is w as the case w ith
so ld ie rs w ho cam e for trea tm en t d irec tly from the fron t. C ram er1911) observed
pern ic ious tap ew orm anem ia a t the sam e tim e in 3 s iste rs w ho , by reason of som e
m enta l pecu liar ity , lived like herm its and fed them se lves w ith an ex trem ely in -
sufficient d ie t .
b) The course o f remission a fter remova l o f the worm in the a bsence o f extrins ic fac tor.
It is log ica l to assum e th at the re w ill be no rem iss ion af te r th e w orm is exp elled if
the p a tien t, shortly befo re and afte r th e w orm cure , h as taken food co n ta in in g n o
ex trins ic fac to r. T he correc tness o f th is reaso n ing has been sh ow n in a se ries o f
tw elve tests. W hen the p atien ts w ere adm itted to the hosp ita l they w ere p laced
on a bas ic d ie t as f ree f rom ex trins ic fac to r as possib le . A fte r som e days , th ey w ereg iv en a w orm cu re . V ery ins ign ifican t s ig ns of b lood regenera tion , o r no ne a t a ll,
w ere o bserv ed even af te r tw e lv e to fifteen d ay s. O n the con tra ry , th e b loo d p ic tu re
o f t e n becam e p rogressive ly m o re abnorm al. A soon a s substan ce s know n or be-
liev ed to co n tain ex trinsic fac to r w ere ad ded to the d ie t, a m arked re ticu lo cy to sis
began and the b loo d p ic tu re im prov ed rap id ly . It has been p rovedha t th is is
tru e w hen m eat, m ilk , H amm arsten ’s case in , pep ton , b rew er’s yeast and concen-
tra ted yeast ex trac t and , to a lesse r d egree , so y bean pro tein w ere ad ded to the d ie t.
T h ese observa tion s con firm Cas tle ’s theory tha t b o th in trinsic and ex tr in sic fac to r
a re necessa ry .
T he m ethod fu rn ishes a m eans of tes tin g subs tan ces fo r the ir co n ten t o f ex trin sic
fac to r .
One practical conclusion is that, after worm cure, patients with worm anemia
m ust be g iven a d ie t rich in pro te ins if a rap id rem issio n is to be expec ted .
3. T H E IN T E R A C T IO N B E T W E E N T H E I N T R IN S IC A N D E X T R I N S IC FA C T O R S
Castle ’s test has no t been prev ious ly carried ou t on pa tien ts w ith pern ic ious tape-
w orm anem ia , ye t th is experim en t is o f g rea t im por tance . It is co nce iv ab le tha t
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: O n t h e r em iss ion a f t er r em ov a l o f t h e w orm in p e r n ic iou s ta p ew orm an em ia in p r esen c e an d a b -
s e n c e o f e x t r i ns i c f a c t o r i n t h e f o o d . Ac t a me d . s c a n d . i i 6 , 7 7 ,943.
: ‘ ‘C as t le’s t e st ’ ‘ in p ern icious ta pew o rm anem ia . A cta m ed . scan d . S uppl. 19 6 , 456 , 594 7 .
D oe s fe ed ing o f D iph yllo bo thrium la tum inf luence the in tera ctio n be tw een th e in tr ins ic and th e
ex trins ic fa ctors of C astle? A cta m ed. scan d . In p re ss .
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I n p r ess .
- :T he s ite o f in fes ta t ion w ith fish tap ew orm de term in ed by m eans of in test ina l in tuba tion . A cta
me d . s c a n d . I n p r e s s .
-: Folic acid in the trea tm en t of p ern ic ious tap ewo rm , anem ia. A c ta m ed . scand . In p re ss.
C R A M E R , A .: T ro is cas sim u ltan #{233} s d ’an #{233}m ie pern ic ieu se bo trio c# {2 33}ph alique ch ez tro is soeu rs. B ull . e t
m#{233}m.S o c . Me d d . h o p . d e Pa r i s 4 6 . ’ 5 4 7 5 ,192.2..
E H RS TR #{2 46 }M , R O BE R T: Z u r K en n t n is d er D a rm p a r as it en in F in n la n d . A c ta m ed . scan d . 64 .’.9, 192. 6 .
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H E L A N D E R , E. V .: U be r d ie M agensekre tio n be i B oth rioc eph alu str#{228 }gern . A cta m ed .cand. Supp. 1945.
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an aem ia . A cta m ed . scand . S upp .78: 582 . , 1936.
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R U N E B E R G , J . W : De u t s c h . Ar c h . f. k Im . M ed. 41. ’ 304, 1887 .
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me d . s e a n d . S u p p . 7 .’ 2 .6 8 , 192.4.
-: O m den p :rn ici# {2 46 }sa an em in i lev erte rap ins be lysning . F in ska L#{228 }k .s# {228} llsk . H dl . 77 ? 5 89 ,
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S E P P A , T. : Du o d e c i m 43 . 101 , 192 .7 .
TALLQv I S T , T. W .: Zu r Pa tho gen ese der pe rn iz i#{246} sen A n#{228}m ie , m it besond ere r B er#{252 }cks ich tigu ng d er B oth -
rioc eph alu san #{228}m ie. Z tschr . f. k Im . M ed .6i: 42 . 7 , 1907.
T A Y L O R , F . H. L. , CAST L E , W B. , H E I N L E , R. W , A N D A DA M S , M A. : J. C lin . In ve sti ga tio n I7.’ 1938.
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s c a n d . ii8.’ 42.2. , 5944 .
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