Table of Contents, Quarterly Report, Contract 48, October 1947 - January 1948 (Partial)

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. Lethol 3:ffects on Lice of 180 liev Deuterons fran t h e r x rth erik per hi ents Concerning the Biological Effects A dni nist rat Ion Hemtologicnl S ff ect s of Totai Bsdy 1rrr;dIct ion Metabolism and Z fi ect s of Atdio-Icdire ( I from Exterz-1 a d Xnferncl Sourc BEST COPY AVAILABLE

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UNIVERSITY OF CM FOR NIR MEDICAL SCHOOL This pm j oct,str r tod on OSD subcontract totha Univorsity of Chic-40, hcs co2tinusd t o ths prcsont aidie now part of tho Univorsity of Calif osa i a program for tho Atomic Enmgy CommiRnion. wow puhlinhod intho CH ra ports from tho Univorsity of Cflicceo. No scion tif i cr a port hcs proviously bsan mea2 through tho Radiation Lcborntory ncd hcnc- t h o prsnont progross r3port i 6 somouhot gonaml i n nctur2, th dc t to npt boiw t o bring tho roodsrs up t o dato on what Futuro prograss roport s will bo smovihat Doctor Lon-Bdsr has bscr. cortinounly i n chnrgc of t h o program lcborntory tsc.h ici cn up t o Octobor 1947. 133s Jing has baon roplncod by Kiss m.2 Poulson who h r s bccn with Dcctor Low-Baor sinco Soptombcr hom to logic zl problems haw bsoii discussod with diff Jr on t homntologists, Mxy otha doctors mC tochniclans cidod in this work in so for Doctor Mill x star to6 tho sccocd s oct ion for tha study of radioiodine i n 1946, bsczuss of th apr nio us work with iodin2 at thil .Ur;ivorsity of C...lifornic Abdiccl School by Doctors Scloy, E:n i l t o n ?ad otho rs,cnd tiic knoijlodgo gciusZ praviously on rndictioii off oct s by Bogdaoff took on thor csp on sibi lit is of scjcrstnry t o 48-C.

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Tho objoctiva of this projoct has boon to in vos tl gc to tho offs ct of thora p zu tic dc so ~of ionizing rn diz t ions on ths blood Glmonts of humn subjocts. P?.tionts soloctod for this study wors thoso whoso disaaso roquirod th cm psu tic ir rcd in t ion of tho on tiro 80 tr oct ad to obsorvo th a off oct s on thoir blood pic tura. avant6 w d is not r;lportzd hum. pot on ti cls of 100 LT, 200 kv &id 1000 k7 worn uscd for a x torn al rc diction cnd radiocctiva phosphorus vics ussd as 2 sourco of in torn rl ir rc dio tion. From thJ inczption of tho projoct in Octobor 1042 t o Juno 1946 twontyTwo p z tion ts wora tr mts d with dcily Gosos of 5 r; 5patio nts with 10 r dosos; 17 pat is nts with 20 rd03 ~ 3 ; 2 pztiolits with 15 r dosos; 1 pct i cz t with 30 rmd1pct isnt with 50 r dci ly dosas. (skin), 300 r baing tho most frquuont totA. tho coi : t x of th;: body vmiod from =pproximr.tJly 60 r to approx imt ely Tho patio nts Bora soloctod for troctmsnt With rcdiationf3 a d Tho totcl body cxposiiros vzridd biltvmoii 100 r rnd 390 r Tha ccl cul c tad dosc i n Studios ltncludod cht;rrminctions of homoglobin, rod blood coll count, white blood call count, pl st clot count, diffomntit..l count, irrospoctivo of si%: of th.2 doss a d of physic21 f z ctor s of trsctmont. Such dccrcoscs vmrc followsd by rccovcry during t h o post-trc?.tnmt poriod. kr lso d fluctuation in t0tx.l vrhito blood colls 2nd noutrophils counts Woro obsorvod froquzrhly dur iw th s troctmcnt psriod, but thsso isi ths numbor of po.lymorphonuclc?r cJls of n sign if iczn t numbor of 60 days nf=or conclusion of tmctmnt. A l o f t shiPt of tho polymorphonUClOW n su troph l los was obsorvod in ths nino pot is nts in whom this Qs 0. gOnOrjl pat torn of fluctuation during tr cet non t ?ad in tho oarly PntiJntS Who had boon t m a t o d with 1000 kV gOnJr2tOd X-rays, mound 1i;tnocytos showad ncrkocl l ability vahich In thc, latcr post-troctmont pcriod tho monocytc

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Tho orythrocyto count cnd homoElob,in occasion ? n y shmod n significant docroaso during th3 courss of tmetrnant. by rccovory t o pro-irrodintion 1Jvi11s i n tho ocrly post-troatmant 250 days rftor conclusion of trcntmsnt, thsro occurod a tJnlporary docronsc in orythrocyto cow.t, nccompenicd by n riss i n homoglobin. Tho pic turan t this timo was ono of rmcrocytic hyperchromic anomia. This vfns fol lom d prothrombin tima (nino pot i ants), sodimontation rrts, hzmatrocrit and From July 1946 t o Dccmbor 31, 1947, 31 pn tion ts v101'o th2 pori & Octobor 1942 t o Jw.0 1946. Thrss p z ti ants wora tract zd with drlily doscs of 20 r (sbifi); ths two otiims rzczivcd dfily dosos of doses of PA' vcr is d from 3.5 to8ml lli cur ~ i s agivon i n visokly f rnc t ions. dl rscoivzd totd dosos of 300 r(s kin). Tho tot21 1942 t o 1946, 4 showod mr kad ly highar hac rj lob in lzvzln (cpproximctsly plus3 porcont) during this lat a post-oxposur; pariod 38 conpzrod with pro - ir rc dlc tion lcvols. Fivo of thaso pc.tisxts showod nnrkodly othsr signific'wt ch.z?sos wro obcsrvod in my of tho gins p?.tisnts. and with no ciir:nga i n mcthod o r tilchniquc. pcriod, oxcapt for ci vzry tm xi to ryd2crxss of l*pphoc-ytzs shortly No sign if icc nt homztological chmgas hnva boon notod i n followed forn long znough tim top z rn it com.ccts on th z c ffcc ts of thore diz tion so rtha hcnn!ztologicnl condition. The moot consist mt off oct s shows by th.: fourtJori pct i ants troD t mp or cry doprassioii of tho plc to lat count, r. t mp or cry dscrooso i n prothrmbir, tmo,md tmPOr2rYd a vc tion of sodimontation mto. Fluctuctions i n crythrocyto Count homoglobin veluas, u.d into t nl whito blood count cnd CutWDous honorrhagcs, o r toxloncy t o blzoding wcro not obsorvod i n olly of tho potionts,, Sovcn of tho fourtoon potion ts rac_oivsd gold thorcpy prior to t root nmt with $2, an^ following F 2 trontmont. n o

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temporary deprossion of tho platelet count occured in all of the patients, however, so thrt it cannot be attributed t o gold therapy. In August 1947 the he m to logic dl project was enlarged fur thor to include patients treated with radio-iodine. So for, 10 additional patients treated with radio-iodine are being studied. obsorvotion period for pat lon ts added tothe study from that time on is too bri of to permit any evaluation at this the. From July 1946 t o December 1947, 553 hematologicol examinations wore mnde in the study. All exeninntion8 included complote blood count with o q thro cyto moasuroment and lob ation index. In addition, approx ht ely 100 prothrohbin, cho lest arol, hematocrit, and sodimontntion dotorminations were made. exanlnntions wero dono on the patients. Besides those laboratory studies, newly acquired items of oquipmont hevo beisn cal ibm tod and standardized. were mado on all patio nts includod in tho study. Charts and graphs The purpose of tho study of 1''' In patio nts has boon primnrily t o dotarmine hc rn ful off oct a of 1131, c cu to ly and over a long period of time in humus. I n order t o know tho amount of om sur o of tho pntirtnt to th a rod la tion from tho radio-iodine, it is ln port mt to study moans of dotermining upteko of thein tho thyroid with tho thyroid intact in the patio nt,mdto study Urinary oxcrotion of 1131 from pot i ents has boen measured i n most CQSCM I n which thyroid uptako atu dies wore made in order t o dotermino what portion of t h e iodine could be accounted for by thyroid uptakkai and urinary ox cm tion by our methods, what errors thoro wore in tho mothods, and what fraction of the administored 11.91 wcs lost by othcir routes of excretion or wns s to rod in other sites in tho body. Choice of Subjocta. A row young doctors on tho house stzf'f of the Univorslty of Cnlifornin H03pita1, fully cognizcnt of the dcngers, voluntoorod t o soma cs normc.3, controls. studied whose thyroid function was noml, but who Wore to hovo oporctions on tho glcnd for nodulos. This pexmittod study of t h e nomly functioning eland 09 wall aa of the cbnormnl nodules. A number of patio nts woro choson for study whose primcry diaense was The ndministrntion of ro lc ti vol y largo doses of Pft o thosa pn tion ts,wa warranted as a troatmont of their diseaso. This was ap nrt icu ln rly valuablo group boccuso of thc into rest of the pntiont in h in s alf and his disease and because of tho interest of As e rios of patio nts were

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the clinic im in closo lcborctory and clinic clf oll m - up. lest group of subjoc1;s vore tnose in which carcinomn of t h o thyroid was w sp oct xl or provod. of tis suo studies vm:o mydo. of vary lcrgcr rlosos of 1-31 wc.8 w xm n tod. In this group d80, tho cdministrotion In th z nods, no do to mink. In subjacts nit3 nodules intho thyroid or with hygercc t iv it y of tho thyroid, his to rios VKIIY: tzkan u d physiccl oxminations count, a-ini, ox min z tio as, blood cho lost or ol, bas21 wtc b of ic rzto, cnd protoin bound io ii ne in $he serum. In th s sub j oct s with hyportions ossmticl1.y duplic Aod ths pro lim in xy aork-up. me2suss ti;,- mount of 11'' ir tho. rmcvoe spccinicn for con pais on I n thd sub j oct sTi th ccacor, rout in o his to rios,p ky sic tl urinizy ozcrot ion macsursnisnt 3 woro cx rio d out. Doscs of 11'1 Administorad. t o b3 cporutsd upon for nodillas, :: doso of 250 pc IP3l was givm In th on owl a cnd in at i ents who NCrc I n subjocts with hyperthyroidism, from 250 pc t o 4000 pc by ki&Jrcountor for i t s 1131 contctnt. iiocsuromonts of thyroid UPtilkC Were n-dc ct cbout noon -nd 4 Pti of tho s r m dzy, norning, noon lc to aft x noon of t!,; following dny, ai3inth3 morning of tho third dzy. Lhoro possiblo, a not hsr mansurornont cno wook letar wcs SP0ChOns, a d in most of tho casos i n four 1 2 hour samplos. contcnt wm dotdrmiricd i n thoso. Tho iodind was cdTho doso iics c - re fully nconurcd in Thd bot t lo cootrinin; tho doso t o bo given wcs choc!:cd

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1131contont of tho thyroid rvns ncdo just prior to surgory. ronovod at opor-tion uos t&on from th.2 oporating room, moasurod on t h o countor cnd woighcd. Xicroscoplc soctions woro obtninod. To dutcrmino th:, uptckc of 1131 i n th2 thyroid, it w2s first nsc.;sszry t o nako csot of standards t o bo usod as subst it nts bot t los. Etch wcs fills d with cn cquoous solution of I13f of known ohoson baczuuso thz solution In oach was nbout th:, s m vroight 2s ?. sembling th3LJC ~ in si zo, 53 c n bolow th of aca of c Gzigzr comt or nnd tho numbctr of counts por minuto from oach was rocordob, I s thon graphod 2 s counts p r minuto against uc I1'l. A = dim stmdord w;?s u ~ c d2s o constant sourco of ganx rilys for Cilocki.n& Inch thick ?ad cn insicio dirmstar of 2 1/4 incnx. Thd cm n tar iiindow vies 7 cm from thd mouth of thc! cylindor which poifitad at tho p-.tiant o r spacinsn. Tho mouth of tha l o a 3 cylinrlor wcs covorodwith t lccd fil tor 118 inch thick. chossn i n oruor that 'th3 uncortairity dua t o thic: unknom Copt9 of, tho thyroid i n tho nsck would ba roducod ton mlnimum. Ilsl ViloIlld bo canplot o l y nbsorbod. would introduc2 an orror cggcin bocauso of ths unknovin dopth mds i zo of tho thyroid. cdaition, sinca t h a moitrrts of ioGino t o b,: mccsurxl cro l?.r&:~, If this wcr3 not absortsd, it X shcllowly locntsd thin thyroicl would cbsorb lass urine, ths ebovc considorctions of dlst ~ m c sa d fil tr z tion do not ZpplY sinco th Jur in s s po cim n and thr: stc?r,d:d::rd cro put into ids ntico l is sncli, c short a is t mcs cnd thin fil t cr wurc us3d. o qui im nt,c stmdcrd vihosc count i a n&rly thrt of tho thyroid is on cn x-ray tubc stand, was novcc? o v x tha thyrcid. counts por ninuto vias rGcord2d in this position. Tha countsr wcs

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than movcd ovx tho thigh and tho counting rct a in this position and shapo of tho nocb: and contcins bond, m s c l z .?n3 blood cs doss counti,ng x t o ovcr tho nock if t h o thyrold wora not prossnt. Tho nunibor or counts por mlnuto duo totho thyroid l o nccoptad os tho dirforonco bctwoon thOS0 from tho nock cnd thoso from t h 3 thigh. Rosults of 1Bcsurm~1~.In gcnoral, thc t kv roid t & o s up tho c irc ul ct - ing iodine vow rcpidly. Tha mount of iodino i n thcl thyroid rocehcs 2mhun in lass th m 24 hours, r.nd in soma ccscs with inc vory row hours. I n gsnor.d, tho thyroid r stains most of tha iodind it s;?lscts from tha blood strom. Thoro is scino ovidsnca t o ,mggcst th?.t tha rctc of uptrlro of 1131 in tho thyroid is c function of thyroid acCivity. Bocnuuno mcking thosa mocsuronmts is so tim s consuming, wc at first apynront nocl, thct mora offort is nmdod i n studying th s oz rly pmt of th: uytcko CUNO. 35 PJrCOnt o f t h a administorad IlS1. Tho pcrcont upt&k3 of 1lh in dosas aro givzn, 0.g. first tr z cor thoii lcrgcr doss. I n goiiorcl, tho porccnt upt&o of io dinu i;S tlis thyroid is c fairly dir3ct funtion of tho thyroid z ct iv it y. hzvc oxtrcnoly low u:pt?kcs ?ad sub j oct s with hyporthyroidism hnvo high UptakCS. HoViOVJr, in spitz of this gancrolixntioc, no sin&lc test such IS cs tim tod thjrroid sizs, B.M.R., prot-in-bouncl iodine i n tha blood, blood cho lost cro l or m y conbinction of th J …