Document dGEQXg82BvzN6yE9V7mX67Z6

- 37 N. I. NISSEN Jsi! A. SOGBORG OHLSEX - (Submitted for publicstion September 95, I%%.) . _.--- -_ .- c_- -.-_ -- . - IY'Eile eflhroblasts (i. e., imxzdture, nucleoted erphrocrte3) a;e s e e ~n~ ~ t Seqiientlp in the blood of newborn chilt'lteu and infants, notrually 3s dias even after mild infectious disease.,, their occurrcncc in adults in.re:Jtids !a+* numbers is nearly always a sign of disfunction of erythropoiesis, D reactioc to a - --- ---.serious toxic attack on the erganism, or evidence of a reparati7e or corrpezsatory ._- measure on t5e part of the organism. -_._L__-. - ..~., .a ERYTII It031 TELQ.5IP. a--4 Eveu in the absence of any sharp Lurderlinr, the Inorbid coridiiiunj Kith incrpuscrd occurrence of crythroblasts in the Llood stream may rough!? be dixideJ -- into two main groups accordinc t o whether the erythroll.ist p r o ~ l u c t i xb~e mafilly intramedullary or estr~uredull~iryA. thorough studv and ticfinition c i these con- . times also-the terminal &.age .in pol;;r.$hPmia vera. - In 1917-1926 Giovnnni Di Guplielmo \vas the first t o try t o e1ucids:e the clinical .- - - - - --. r._ .-7T-- -. . +L-e+.--*-- . :-* .->::.-:-.=.-- * - -..- . .s .3 2 t u e.+ -a..J. -*.::.a f ;:.-:-G<z:I I. .... . -.- .a . . .-I- ., ... ? - - ....: . _- .- . '. , !? P .. - _ .- eI_n 1_940 -.,and ca&& 3!oeschlig published a critical to.-fhe-condusiotnhat onlF review 5 cases of the cases conformed reported up t o to the criteria that time set up by .'* Di Guglielmo, namely: besides the t.wo cases reported by Guglielmo, 3 cases reported-by.b z a r c o , Binedet.ti &.Paradim.Later, 2 cases were descrihed hr Luck t- a& bF Israels, In addition, Heilmeyer and Schouer, and Liidin have reported a-' s having a more chronic course. Whether the disease map br c l a s i f i d under .- one or other form will depend me think on t5e maturing tendency in the pro!if- eratiug erythropoietic twue. In sdAtion to the acute *pure9 erq.ah?:nycIoii cases of so-called fi true wythmiP1ikemw have been &scribed by Gc;LrIrso anti other Italian kraiatologiits ~ z &do hp orhers e. g., Blackburn 3nJ. L3jth3. Uor-Pch- l i , and Lii&in.. In these cases the boce narroz prwents a c o m W proiik2- - of both the eythruoyoietic and lzukopolrtic s y s t e m lea&nq to erpthobl3;tojis as well 08 myelollrruto~is.TL condition shoilrl uot be mistaken far s y n , p ! . ~ ~ r r j : ._ erythro2cuEemia in which the e r - n b b l w t o s u .is mablp. d u e t o . r - e i n p B s y - extr3rnedullary production of red has been suppressed or ichibitect blood by th eceliel3ukboeptouies teict hteissIuzlee.dTuIhLorycoen+ch!ugspivoii u6i i6-- dence of true erythro1eul;~miaL c!aimrd t o Le the much hi;her er!~b,roh!~j-i: percentage in the bone marrow than in the b ! d -~?=nl~z+- z?zz applies to eymptomatic erythroleukemia. -:?e :??$site -. - : Guglielmo considered erytbomFelosb analogocs to l e u k o ~ i -~ sometkir.- Papperheirn bad been lookin.; for sj eai!p 2s LL :?! 1. .'.,; :.. .. -. - hGaudglsieulcmcoeemdeedntiionnpedr otdh aa tc iEqllesrumchaaan ia hi3 type. . .s t u & c ~on tTaP<fPmh!* ehjn1-m )a**'*nrlz X . ~ : , , j U a u ~ , , u ~ y . ~. ~ , uvJLc,.JLI> .L'du. seldom, for which reason it h3.9 been d a c r h u ouly exceptionaiiy in in' e :en.b o o b and this may perhaps be one of the rc35ons why the diamojiq is aot m j d e frequently.' In this connection it will be appropriate to refer'-to Handhct! der Inneren JIedizin (Btrgmann and Starhetin) in which Hcilmeyer recognizw er:-tb$- .myelosis as a malignant lesion. - -. tisto the differential diagnosis, hemolnic anemia h3s to be taken into.considera- tion and before the introduction of liver thenpy also.pemicious anemia. Perhaps c u e s of crytbornpelosis may have been includcd among the T a p e clinical pictures aa Juksch-Hayem's anemia. leukemia. d e u k e n k hemorrbaecs Fronck, and others. Like leukosis. malignmt erphromyelosis is also taken to be a neoplastic lesion, the eliciting factor of which has remaiud obscure to the above-mentioned authors. So it is of considerable interest that in bcnzene (benzol) poisoning it has been possible t o demonstrate pronounced h-yperplasiaof the-erJtiP . ropoietic myelosis system with clinical features (Xallory, Gall and Bricklep). corresponding to those oi - . ..-. - .--acu.te--er)zhro--- - -.- --_.. 2- . - Such a case has been admitted to the 3Iedical Department E of Frederiksberg hospital, Copenhagen, apparently the f i t case of this kind dexribd in Denmark. .. . .. .. .. .. _. Case Petotd. - .. -- The patient wmi a gas-worker 60 ~earsold age, 8 sib, all well. (Rec. So. 753151). Parents d i d oi old. - The patient had always felt rciiuntil Dccemkr 1950. wben he started to feel cobhntly . tired, lost appetite, lost weight. and k a m e readily clrspnoeic. and 3150 d17zy. On admission 1 @ / t 51 he was very pale and sliohtly cyanotic. So definite abnom3litp could be demonstrated on examination of the heart and lungs, no enlargement oi the liver, spleen or lymph nodes. SO petcchia~seen. 4 1 ? a- ' I.U3L1lEBL-kZhSFf3':.'Il!?uysayosllc&araPr.mrspt.wocs1>w.tierion!s'a3ae~*prarp,?nporuAyzkbwotbuhnpai4dulpioupuoi*njh1lOlhyobmht.e!tl9iiolecyo1ll.imlr~sl-syertcscrceb.Imy-tymv.tcyseem..etsO.ultycy.e.bi..lec.c.es.e9.n.o.s.io.-l...ol.c.a:*.~J..co..:f.....yc.y.p.Jcs...rpt..t..day...aldm...t.I..t.tlc.....~h...a.rC..r:.....u....e........U.....b.-..w........i......w.....h-........C...:i.....C.......tS...........e....U.r.....-..............Sr.............p....................t.............e...................m...............................n..............................w....................e..............r................e..........................f......o................u...i.................n..................d....................:.......................................................................-............................................................................................................................................................'........:.....I.iI1!iiji!. .-.3.5.0. 212.25 3.25 0 13.YS 06 7-75 7; 2.25 7; .0o ... 47.25 76 0 0.25 yo 5.50 76 60 I I: ,fX3 tnI f I '.I L wi4m I . .-.- ._ I 61 .. . Fig. 4. The tempemturn curre nnd trrstmcnt. EKTTLII:OSITfLOSIS. 63 yari.;on of thi3 trpc of b9ne imrrow with the m:trrow foticd in mrr:aloblastic anerua with 3 k w IlemogloPiti percentner, the httcr a130 found t a ~ T C P Wn~u increase in the nurnher of c e l ! ~but the hypprpl;L:.id ; n ~ o l v c +t.l)th 7 itr r:l**p.tlul*lwttcernhopoies& and the myeiocytic system. In thz pre*ent u s e , hosever, the crythropoiptic 5YStetIA inadz t p neirly the cntire marrow. In hrrnolcic m e m w too, the myioc5ic.iE;LS c a d s i t i n e a iciatively greater p r t of tke total - u i.: rvident. froin the cell count. In our case t5e ancmi:, persi.ited in spite of trmitrnsnt with Heps('i 3Ico., ritamh B : I and terofoh. X firrther5J bloc4 trwsfudians welt! given with on@ trsnsitorr cifect. -The temperature was slightly r8leratp.d throughout the course of the disease as S L 0 U - c in Fiz. 4. ;isziticrticu as Dipenicllhn Leo and Bcrcomysin End uo par5cdar effect. X rep'a..-cmcnttransLian was p!snnetl Llit a cor~sider:tblaa;cmvution of the patient's cor-d:ion now occurred in the form of severe heniorrhwic di:rtheRis, and before the --re,r.;acrrztrittrpnsfuusion could tie carried ou'. t.he jdipnt. d i d kiter ahout. thre- months &E-* . - .- .. A i h p - j . Auong the autopsy findinqs BhouldLe mentimed in particular that the spleen & r h c i i40 G , %as deep red acd very scft. T h liver was considerallr eular~eied.There was no enlargement of Ipmp!~node;. "he brcarrhzic diathesis w3s found in m3nnp orpns. The hone marrow was red and h p e r - .pI-ls:ic;-Ziiertucopyshowed the enormous hyperplasia of the boue mnrrow ahead! obsemed, w i t h marked prepondcrance of the proliferating emhroblastic tissue. Further, _ _the splenic pulp sbowed a very pronounced byperpkutic pruliferati~~~rythropuiesis., ~ Tbe liver showed moderate erythropoiesia. Thespleen, liver and lymph nodes showed also a d numben of myeloblasts and mydo- cFes cx$iining the occurrence of these cell-types in the peripheral blood. The ckzical diagnosis was,thus verified by the autopsy findings. .- -\ik.#h- -3. &--. 3r. .. .. .. L;E e e r u p .. for thc kind permission to use the material. .... 1 Fig. 5. Puraytbroblut x l.OO0. 5430613. I c t a mcd. Seandinav. ro1.C U I ' . Fig. 7. Paraq-tbroblasr in atypical mitosis x 1,030. ti5 ..I . . -_ -. .. 66 67 - .- .- -,. - .. Fig. 11. Hernrtopoietic infiltmtion in liver x 400. -.- . - . Fii. 1% Hem.topaictic i n f i i o a in rpknic tirsue x 400. - - ', - .. -.-. ERTTII R O N FELOSI F. 69 '. . Rersj~itulntionof the Syiiiptoais. 1. Severe propw-sive anemia. 2. C r ~ ! ~ o h 1 3 s t .p,rcsent in t lie peripheral hlood. 3. .X>p-r??a.-ticpro1i:zrAiive erythropoiesis with sliF!it tc!o?lency to maiuration In tho borie m ~ i r o w ,and 3130 in the spleen, l i w r oud 1;;mph nodes. 4. Contkuouu elevation of the t.emperature. 5. Izdopmi3. 6. Propp;sir> I c.tisuluc~ccpo!iirr. - 4. T;rrombocyt.oprnia. 8. ICtEi:tS indes s1igSrl.c hcrra..cd. - Et i d o g - , P:ithogenesis nrid 1)isctrssion. OE p t i e n t had been employed at the Eastern Gasworks, Copenhagen from :a I 4i, from '/, 4i--'l,l, 48, froin Ai4+, 48 and from 1J/4-','B 48; at VsIiJr Gasworks from rs/B-2/,o 49 and finally, from **j, 49 to the onset of fitness 51. For about six months before the onuet of his ill.nes.s- he had been. . - . worLing at the benzene (benzol) plant -thoughnot in it -occupied with trans- 1 . p3tinp >tar acidw from the plant to a pool. This \vaa done by inems of a nlrgon with a t i u k holding about two hundred litres. The angon was hauled by a motor truck 2x3 at the pool two men tipped the tad-,st.andingon the wagon, and emptied it rapidly. l'histransport took about one hour, twice a dry. Vnder certain weather conditions the patient was grcatly inconvenienced by the fumes from tbe *tar acido, with imitation of the nose and throat and coughing spells. He had often t o rear rubher clothes t,o avoid corrosion of the skin. Sometimes he felt ill during tlis work. The *tar acid, \s3s a b p o d u c t of Lenzene (benzol), for which 92 ?& sulphuric acid was use& it was said to consist of sulphonated, unsaturated hydrocarbons, aulphuric acid and presumably sulphurous acid. Its benzeae @ea- 201) content was assumed to be about 1 %. The development ofintense heat when the *tar acido was poured into the pool rnust be taken into cooPidmtioa In the paat !20 years c h i d obrcrv;rtionr and experimental resesrch h.rs now . f i i p esdablisbed that benzene (bepzol) and ita deritrtiwa can'rrot only * produce tfre clhaical pictam of aplastic anemia bat Jso act UJ g=nio k i t a n t on the bone m w urd produce not only mvemible Ienkemoid -. conditions but r k o irreversible r e a m of leukemia, e,rytkoleukk rad -probably lllost infrequently an attack'upon the qthmpoietic t h e doM, rssulting in e@uomyelosis. For information 03 this matter, lee W.-C. Hueper: - j2k%- ..*. - *%. * -&**&. - .. I. -. x;&:&-><-:* **--..:Lz-+r'*-w-<-A- .--4y- :r$.-.:,$ -,.q-j;+G*is* .L;s. ---ar;& .t;:--= --..-.-e .. . , .Ys...+*.-:s:.&, .r.- GTZ- --. 1 _. . --c.- - . . .-.*y%%mZ+D> . . w-?-?.--=- . .. = - - a e - . . . :-3;: .+gag7zTg>y*-a ! , , -. ; w * . L z # u w r - - - 3 L - _.I..-.-:-:--<:2- ~s-cs-~.lsr-.r-*,).-~.-&c-&:I*---.d--z.e.w%.-..-Mg- 4?*. 's1-4!W. s? I i , .1 . . . 1. .. . ., t. . . i 'I * * ..! .*.' . . 1. N. I. X I S L Y ASD A. WESORG O K E E S . anemia have been iuterpreted enoneouilp 3 3 oecmurilp dependent upon 3plari.l of the bone marrow: #thatsuch 3 picture in the periphprill LIooll doe3 not, Eowver. ~ecesssrilyindicate an aplastic m 3 m w ha3 been recognizeil by numerous observers in recent years. Blumer, Tto3pson. Richttrr and Edsail, Rhodes and tion of an n p l ~ ~ c i c marrow is uot always wirrariteci i a h r siich csnditiocs. In fact relativeiy f5w cases cited by these authors showed any diminution of borie marrow activit?, whereas the majority exhibited m x k d medullary hyperplasia. o Nallwy, Gall and Brickley further repvrt 19 c s e s of henzenz (benzol) poisoning, with a fatal course in 1-1which were examined and foilowed closely. Of thc.:e patients C ahowc*l *.:la cliniml picture u3uaUy described with 1r7lasi3of the bono -.- --.mamw. wherrm 6 prrsnted 3 picbse ezxrly correqondmg t s tfLlt of acuto -1 - - - - - I . - : W U ~ U c~.LJuu-, --.I VUG ,A,,,,hwl..dc I y y I b~@.tloiC! !euke?=i3 s d one iymphoqenous - -*lcru1r.;urro* . .- . "----"-I Z i e s Siiihi-s I-"3.--i--....z . snd -A0Ef.x:er L z i ~ sr d~ ih i emphasize as 3 signiiicnnt pokt duiation of expoiure to t t e actidn or hmrsnr! {oenxnij cha sensiiix-ky&v ut &e giveit individual t o this action must he highly wnrirhle j7v-t. R- the s e m i t i d y to the toxic effect ol othcr cctmpmds t h o b e e rnzrmw !e- 9. a E & h ~ , ~ na,rid me&$ tluournciU. rurthemore, Hunter who observetl89 individuals expcwd to benzene (beutol; fumes has pointed out that it may take some lenj$h of time Lefore the first symptoms of poisoniq aunifest themsel.ies. FiEallp the hypothesis was advanced by Xallory, Call anil Brickley that pro:- nostically the hyperplastic reaction of the marrow is the more favourable form, aUowing continuous exposure of the individual to the benzene (benzol) fumes for many yeam whereas the aplastic form is far more serious unless the patient is removed from contact with the tosic agent. The hyperplastic reaction m a r conceivably represent au overcompensation of the bone marrow as a means of defence against the toxic agent. Somethig analogous is w u m d to 3ppIy to chronic radium intoxication (Martland). A a d i n g to r e m : researcII, the polymwphbus patholop'c-anatm~icupl 'clure of ben- m e ( b e n d )poiaoniq has io be looked upon ar an cstoblishd fod, a d thw it eonnot bq - -ezduded thnt benzene (benzol) tqcther witla i d i r i d w l hypetsntir~vene.w mwt haw played o d e i n the &eZqwrmt ot acuk qthromjelosir in mi p t i e r ~ . n e possibility of benzene intoxication being the causa of the illness was not admitted by the insurance board. .. . Snmnrr,r. .L. .. A brief survey of erythxoblastmk i3 given together Kith the report of 8 case of acute erythromyelosis (morbus Di Guglielmo) that appeared in A gasworker employed in the benzene (benzol) plant. n e t o ~ ceffect of benzene (beruol) on the bone marrow k discnssed, with particular e q h a s i a on the point that hyperplastic reactioa of the erythropoietic system has to be looked upon as more frequent than usually assumed, 'and sometimes leading to erythromyelosis. . ..- .. .. -.. . . ._. . ... I .. .. -. . .- . - ..