Document eme5yEn0Y9LzwLzBpxjQYxBgp

Intraperitonaal Ruction* otund by Dusts Preliminary Report* I PLAINTIFF'S | EXHIBIT IWtt '3HO. \9 021 and OSS* is s Mtai of orientation a to tbs ultimate tissue reactions of two given dusts, oto>*rs* sdmm& and 021, "stnoephsric dust?- s short preliminary experiment was carried out, uslag as controls co lanp-black, s known inert substance sod *slilea saoks* QS8, s activs OZM. IsaliaiaJUL* Aqueous suspensions of such of those four dusts wore prepared so that one cubic centimeter contained SO as* of dust* en--e- ln Innl Only two guinea pigs were used in the preliminary experiment* After rendering the fields as sterile as possible by thawing the fur, washing with soap and water, and disinfesting with alcohol, fifty ag* of each substance to be tested were injected subcutaneously in saeh . abdominal quarter of the animal* Stations ef the ensuing Issloas(g*w* ware aade et the end of ferty*olght end of adaety*stx hours* 4 2S)i; One of the anlasle, whose peritoneal carlty was InaitTssl wily penetrated when the carbon lnoeulationa were node, was allowed to live and serred es s control in the longer experiment* Xntraperltoneal injections were used in the second, larger;series of pigs, following exactly the technique described by Uller et al* The only planned control in this group was the *silica atoke". Its known irritating properties were used as a basis of comparison with Si gj the unknowns G20 and 021 t=4- On September 29, 1289* three pigs were Injected Intrsperltoncally with 2 co* of s 109 suspension of 020; three mere were injected with a (cg, similar quantity of Otl, while the last three received OSS* . Considern-^gj bis difficulty was s. ugiey. - y> . . -2 j :.Tie or the dust particles caused clogging of the piaton in the syrin s=2 barrel. If the Injections were made quickly, however, approximately all of the .2 gms. could be introduced* The original plan of killing the animals so as to observe tissue ^r"- reactions at monthly intervals could not be carried out because of them died prematurely. One pig, which was injected with 020, died O=e0lb i shortly before the end of the second month, but was not replaced* Two others, Inoculated with 021 and G22 respectively, died after five weeks. Two freshly Inoculated animals were substituted, but they, too, died exactly at the end of two months. Thus, the progression m of lesions at one, two, and three months intervals could be observed only in the animals injected with enamel. Fortunately, the 1 with the accidental peritoneal injection of carbon, lived for over four months and offered an opportunity for studyix^ intraper1tonaal carbon nodules and subcutaneous silica nodules of four months duration* The Subcutaneous Lesions. As was to be expected, the most intense reaction was produced by the silica* At the end of 48 hours there was considerable he^ orrhage and necrosis with slight fibroblastic proliferation* 7ery little phagocytosis of dust bad occurred as yet* Hinety-six hours later, an occasional silica-bearing phagocyte was seen, and there was energetic fibroblastic activity not only Immediately surrounding the Injected dust, but st some distance from It* Hemorrhage, edema, and a number of acute Inflammatory cells were still present. An acute inflammatory exudate, but no actual areas of necrosis, surrounded the injected enamel at the end of forty-eight hours. The sections made at the end of ninety-six hours were unsatisfactory* -3 A moderate Inflammatory reaction was provoked by the atmospheri dust in forty-eight hours. An occasional fibroblast was noted. At the end of ninety-six hours, a few phagocytes and fibroblasts were present. jjpjj Forty-eight hours after injection, both acute and chronic in- 0 0 fdamnatory cells and about an equal number of dust-filled phagocytes were seen around the lamp-black deposits. Fibroblasts were surprising^ numerous. Although comparatively little carbon was seen in the sectifea-'i Th<OJ at the end of ninety-six hours, there was a moderately marked inflaaa- tory reaction with a large number of fibroblasts. It was difficult to tell whether this response was provoked by the carbon or whether ljS^, was a distant reaction due to atmospheric dust, which was injected at the opposite lower quadrant of the abdomen. The Intraoeritoneal Lesions. Gross Description. Macroscopically, the nodules produced by Q20-, 081, and G22 did not show marked variations in appearance, except for the fact that m due to enamel could be distinguished by their characteristic bluishgray color. Several features were common to all: intra-abdominal transportation of the dust, far from the original site of injection, evidently occurred rapidly; at the end of the first month the surfacJWi of practically every organ was studded with nodules. They varied in M size from that of a millet-seed to that of a small llma-be&n, and h&< a tendency to remain discrete, although a number of conglomerate fo: were seen at the end of the second month, The anterior visceral C peritoneum seemed to be the site of predilection, with the mesentery next frequently involved. The omentum was generally rolled up some CS\ where in the upper abdomen; dense bands of adhesions matted together many of the organs. Is mentioned above, superficial nodules war# found on most of tht abdominal visceral the diaphragm, liver, gall bladder, stomach, spleen. Intestines, testes* lone, however, were noted on the kidneys. Microscopic Appearance * O0 The Silica Modules. iss) it the end of the first month, the nodule consisted of a centreing necrotic plug, surrounded hr a tone of chronic inflammatory calls j0> and a sharply circumscribing fibrous capsule, attempted organisation aas shown by a number of new blood vessels seen most frequently perl* pherslly; fibroblasts were numerous. Since it was difficult to recognise the injected dust in the stained sections, the extent of phagocytosis could not ba judged. On# month later, organization was much more advanced. The cellular zone around the central area of necrosis was broader, the ompsule firmer, and a generous network of new blood vessels penetrated the greater pert of the nodule* The four-months old subcutaneous nodule was completely organised* Becrosis had disappeared and was replaced by anmerous foreign body sl giant calls and new fibrous tissue. In sharp contrast, the carbon (peritoneal) aodul* of the same age showed no cellular reaction what* ever. Most of the carbon was contained within large foreign body ,n giant cells, but there was no attempt at organization* Tht gflWl In the month-old nodule, the enamel was seen as a more or loss C=^ amorphous, slightly refractHe, greenish-bluish material interspersed ' with large, irregular, dark-blue, granular clumps* The center of the nodule was composed of this dust and eellular dsbris. Towards tbs periphery, however, large pteagoeytaa, and a ' <; *. '-VS. new blood vessel* were noted. Connective tissue proliferation not merged and only about a sixth to a third of the distance from the periphery wae organised. Little change occurred in the nodule at the end of almoet two months. A few collagenous fibrils ware seen, but vascular!satloa s i oo was not marked. rJ^ Section through a three-months nodule showed that aost of the QO dust had been pbagocytosed. Almost the entire nodule w vascularIsed , j^jgj but the total amount of fibrosis was slight. The Atmospheric Pust_Modules* After one month, faintly luminous particles of a yellowish-green! cast were seen both intrs- end ertra-cellularly. A chronic Infl I--t reaction with marked fibroblastic proliferation surrounded the central coagulum. Indeed, there teemed to be more collagen in some of these nodules than in those caused by either silica or enamel* Oddly enough, another month did not offset groat changes in the nodule. The center wae still Isrgely necrotic end only at the its erne periphery was there s narrow cellular seat. Quite a little fibrosis surrounded this zone, however, and extended for some distance from the lesion. ' Unfortunately, both the original and substituted enlaal died at the end of two months, so that three months old lesions caused by atmospheric dust could not be studied. The alcroscoplc appearance of the nodulee produced by the abowe & mi ?s) named dusts was very similar to the subcutaneous nodules described c=* by E. H. Kettle*. ' V* Cs=3 1. An Atteapt nda to eetlaata the relative htrafulaes* of too oo dusts, 080 (enaael) and 08X (ataospherlo dost) , by the XUler aethod of latraperltoneel Injection, using o dost, 088 (*silice aaoke") as control. .2 Widespread intra-abdoainal noduloo were produood by oil tbroo ggj & saaples. 2. It was lapossible to separate thoso staples Into injurious and Innocuous dusts by the appaaranca of the gross lesions alone. 4. The activity of each dust vas judged by the speed with which It was sngulfed by phagocytes and the ensuing cellular response with particular eaphasls on its capacity to excite fibrous tissue proliferation. A. The aost active excitant of fibrosis was the dust GSS* B. Q1 provoked less fibrous tissue reaction then 088, but perhaps, a trifle aore than 080* Approved // i Submitted -c< J.W.Miller, R.R. Sayers, Wa.P. Xent Response of Peritoneal Tissue to Dusts Introduced as Foreign Bodies. 1934, CIII, Ho. 18, 907. E.H. Kettle - The Interstitial Reactions Caused by Various Dusts and their Influence on Tuberculous Infections. J. Path. & Beet., 1932, XXXV, 393. in"t C=* $-&-l^ Po 9* 8-36-1065 088 Silica 8voka 1 Thera alight latearatlaa at the alt# of several laxga aodulas wt tot one larf irregular ova at tb# level of tb# v^fcHSao# iUMi, to W _ tb# result of several coaliteed aaiaUf, they --n ojiraij ai sub nioif~V to pea-sised, tad distributed all tnr tb# abdoatal ilt|i l#rg# eaa^^ vaa found Just ond#r the loft eoatal border; they vara found oa tb# oMBtSagH' tba surface of the intestines* tha liver, diaphragm, aplsea, mesentery perl-reael fat tissue and teetta. A few vara aaa& oa tba posterior ab- r--~ dolnal vail. ^ S-36-1229 Silica Smoke* 2 Booths tba peritoneum vaa adbaraot to almost all tha ahdoaloal viscera* tha oaaatua vaa partially tucked under tha spleen* A dans# hand of adbaal matted tafathar tba splaao and stomach; tha gall bladder aas attached to tha syphold* there vara uaroos variously fixed and shaped nodules, diffusely scattered all over tba anterior abdominal vail, tha surface of tha spleen and liver, tha mesentery, tha fat tissue surroadlng tba kl and a fav avail ones oa tba posterior abdominal vail*