BostaeO p. f^lotoer l:ibrarg CJLcxnJjuo "R^MJas^^'J ^°'..^ , Q^gi^jj^^k^^ J mM^j CORNELL UNIVERSITY. THE THE GIFT OF ROSWELL P. FLOWER FOR THE USE OF THE N. Y. STATE VETERINARY COLLEGE. 1897 Digitized by Microsoft® Cornell University Library RB 57.B24 A review of the pathology of superficial 3 1924 000 321 202 Date Due f^u 1 3 19R1 ~ ^ ft ..£ i%.h & \ ^ X J^S" dr f- ;, .><^ Library Bureau Cat. No. 1137 _ ' . ' . -^y,^ " . /"' ' i ' 1!a^^ 'J-.'-' '.i '-':r,\ ' ' Digitized by Microsoft® This book was digitized by Microsoft Corporation in cooperation witli Cornell University Libraries, 2007. You may use and print this copy in limited quantity for your personal purposes, but may not distribute or provide access to it (or modified or partial versions of it) for revenue-generating or other commercial purposes. Digitized by Microsoft® / r/p.' Digitized by Microsoft® 'M XI Cornell University Library The original of this book is in the Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924000321202 Digitized by Microsoft® Digitized by Microsoft® Digitized by Microsoft® Digitized by Microsoft® Digitized by Microsoft® Digitized by Microsoft® Digitized by Microsoft® Volume VII No. 3 -THE JOHNS HOPKINS HOSPITAL REPORTS REPORT IN PATHOLOGY CONTENTS. A Eeview of the Pathology of Superficial Burns, with a Contribution to our Knowledge of the Pathological Changes in the Organs in Cases of Eapidly Fatal Burns. By Chaelbs Eussell Baedeen, M. D. BALTIMORE Thb Johns Hopkins Pekss ' ' ' 1898 Tl Digitized by Microsoft® PRINTED BT BALTIMOKE, MD., U. S. A. 62^ Digitized by Microsoft® A KEVIEW OF THE PATHOLOGY OF SUPEKFIOIAL BUKNS, WITH A CONTKIBUTION TO OUR KNOWL- EDGE OF THE PATHOLOGICAL CHANGES IF THE ORGANS IN CASES OF RAPIDLY FATAL BURNS. By CHARLES RUSSELL BARDEEN, M. D. (From the Pathological Laboratory of the Johns Hopkins University and Hospital.) Inteoduction. The opportunity of studying tlie pathological effects produced iu a few hours in human beings superficially burned presented itself during the past year. Five children were brought to the Johns Hopkins Hospital who were so severely burned that they survived only a few hours. The autopsies upon the cases were made very soon after death, while the bodies were stiU warm, iand in one instance within an hour. Although death followed close upon the injury (occurring in one case after between three and four hours), the evidences of alterations in the internal organs were so striking that detailed study of the cases was undertaken. A review of the literature on the subject of the pathology of the body after bums has shown that while many articles have been written, few accurate post-mortem examinations have been made and recorded. The experimental work on the subject, though considerable iu amount, is also iu the main unsatisfactory. The objects of the following article are: 1. To give a brief history of the previous work, both from human autopsies and from experiments upon animals, dealing with the subject, together with a review of the various theories advanced as to the probable cause of death in such cases. 2. To formulate a summary of the chief lesions noted in the five cases studied, and to give a more detailed account of each of the cases. 3. To describe at greater length the lesions noted in the lym- phatic apparatus. 4. To deduce the probable physiological causes of death iu the oases studied. Digitized by Microsoft® 138 Charles Russell Bardeen. 5. To give a bibliography of the chief articles dealing with the anatomical and physiological changes due to superficial bums. I am deeply indebted to Dr. Simon Elexner, both for the oppor- tunity of making this special study and for invaluable aid in carry- ing it through. I also wish to express my thanks to Dr. L. F. Barker for much suggestive help, and to the members of the surgical staff of the Johns Hopkins Hospital for courtesy in supplying me with the hospital records of the cases. I. Review of the Litekattjee on the Pathology of Skin Bubits.' The causes of the severe constitutional symptoms following ex- tensive superficial burns have long been a matter of speculation and inquiry to the clinician and surgeon, as well as to the physiologist and pathologist. The constiLutional symptoms seem often much out of proportion to the severity of the lesion. It is commonly stated that a superficial burn extending over two-thirds of the body's surface will cause death, though the skin itself may be scarcely blistered. While this is not always the case,"" nevertheless well authenticated cases have been reported where superficial burns of slight apparent severity and involving but a hand and fore- arm have been followed by death.' Children seem to be especially susceptible. On the other hand, bums apparently much severer in quality, provided they be not too extensive, may be followed by but slight constitutional effects. A limb may be charred to the bone without severer bodily effects than those attributable to ^Most of the longer publications dealing with the changes produced in the body by burns contain more or less complete reviews of the history of the subject. Among the best of the more recent of these may be men- tioned the articles by Schjerning, Silbermann, Kijanitzin, and Boyer and Guinard. ' Proehlier in the Wurtemberger Corresp. for 1854; Heinecke in the Zeitschrift f. Chirurgie u. Geburtshilfe, 1868, and Busch in the Berl. klin. Wochenschrift, 1880, all report cases of superficial burns in children in- volving two-thirds of the body surface and followed by recovery. Abel in Friedreich's Blaetter, 1877, reports a ease of recovery where seven-eighths of the body surface was involved. (See Schjerning.) The antiseptic treat- ment now so generally employed has .undoubtedly added to the list of such recoveries. > = See Demme, Wiener med. Bliitt., vii. (1884), p. 1609, and xiii. (1890) p 198. Hsemoglobinuria was seen in these cases. ' Digitized by Microsoft® Pathology of Superficial Burns. 139 tlie loss of Hood. There seems to be something especially noxious in the merely superficial bum. The study of the internal pathological effects of burns dates back to the early part of this century. The first reported autop- sies I have been able to find are the five cases reported by William Cumin in 1823. In four of these death occurred within a few days of the bum, and the chief lesions noted were congestion of the various serous membranes, with here and there some serous exudate. Since then many autopsies have been reported, and at various times statistical summaries of autopsies and post-mortem pathological observations have been published.'' Chief among the lesions noted in the cases where death soon followed the bum is hypersemia of the organs of the thoracic and abdominal cavities and the cerebro-spinal canal. This hypersemia is not usually equally marked in all three regions, but is sometimes more intense in one than in another. Often enough, especially in cases of death occurring very soon after the bum, it is not found at all. Some- times it is accompanied by a serous or a bloody exudate. In cases which have survived for some days there may be well marked inflammation of the intestinal canal, the lungs, pleurse, kidneys and meninges. Of the more specific gross lesions noted, the best known is the duodenal ulcer, the first case of which was reported by Long in 1840. The following tables given by Schjerning may prove of interest in this connection. They are based on all the autopsy reports, some two hundred in number, which Schjerning was able to obtain, and show the ratio of the cases in which the Indicated lesion was found to the total number of cases reported where death after burning occurred within the time indi- cated in the column to the left of the tables. Table I. • ad 1 n si & i s <3S as g| 40.0^ 6.6 33.3 i v,a ;.< a p§ n (0 3 ■3) S 1 Death within 48 hours 60.0^ 30.6 49.0 53.7^ 23.7 36.5 30.0^ 30.9 38.3 1.5i 39.7 37.0 11.1^ 37.3 18.8 0.0^ 19.5 13.4 lt^7^ All cases including the above — 10.5 ' Of these the more important are the articles by Long, Erichsen, Holmes, Schjerning and Seliger. Among others are those of O'SuUivan, Litten, Cooper, Cuthburton, Greenwood, Halla, Hoffmann, Eokitansky and Jenner. Digitized by Microsoft® 140 Charles Bussell Bardeen. Table II. S 8i la tQ a Si §■3 tL o a Si Sa +3 g Sg s u5 Ui S 3 a g5 a S So § 3 H M° IZi S w« P< Death occurred 1-2 days after burn 60.0^ 53.7^ 30.0«g 7.5^ 40.0^ 11.1^ 0.0^ 4.5^ 3_7 larly poisonous. Kijanitzin concludes that the evil effects of gild- ing an animal are due partially to retention of products normally '■ Valentin reports a reduction of the CO2 eliminated to one-tenth of the normal amount and a decrease in the excretion of urea. ' See Kijanitzin, p. 449. ' Comptes rend., May 26, 1838. * Magendie, Kluge, Henle, Gerlach, Balbiani, Bernard, Breschet, Vernois, Valentin, Schiff, Bouley, Lange, Stokvis, Bonders, Colin, Laschkewitsch, Lomikowsky, SokolofC and others. ' Henle's Zeitschrift, xvii., pp. 35-105, 1863. Digitized by Microsoft® Pathology of Superficial Burns. 143 excreted, but more especially to the special biological conditions produced by tbe gilding. These special conditions tend to destroy the vitality of the regions covered or cause some injuiy to its cells, producing hypersemia, oedema, infiltration with leucocytes, the for- mation of triple phosphate crystals and certain absorbable poisons (ptomaines?) to which more especially the evil effects are due. Indeed Henle' long ago questioned whether a poison was really retained in the body by covering the skin, and suggested that some unknown substance was formed, or some substance in sweat or sebaceous glands was transformed into poisons and absorbed into the system in these cases. . Laschkewitsoh ^ attributed the main effects of gilding animals to loss of heat by radiation, and in this he was supported by Lomi- kowsky, Krieger and others. Their experiments showed clearly that death does not come on so quickly and at times may be warded off for some hours by keeping the surrounding temperature so high that the animal does not lose heat rapidly. Eventually, however, death does ensue in most animals whether they are sweaters or not and whether or not they are protected from heat radiation. It would therefore seem just to accept the idea of pathological tissue alteration with resulting formation of absorbable toxic sub- stances as the probable imderlying cause of death in these cases.' At any rate the light obtained from experimental studies on the gilding of animals does not tend to substantiate the view that the main harm done directly by superficial bums consists in the stop- ping of the excretory function of the skin in the burned area.* 1 Rath. Path, ii., 1846, p. 442. ' Archlv f. Anat. u. Phys. (1868), p. 61. ' In this connection it Is interesting to note that Senator found that, pro- vided radiation of heat were guarded against, no ill effects followed cover- ing the limbs, bacfe and abdomen of certain patients with coUodium, leav- ing free only the neck, face, genitals and anus. The patients he experi- mented on were rheumatics. Two were covered thus for a week and a third for three days (Virch. Arch., Ixx., p. 182). In his criticism of Sena- tor's previous work, however, Sokoloff (Vlrchow's Arch., Ixlv., 40, 1875) says no true varnish such as would stop the normal skin functions was used. Be that as It may, the belief has lately been gaining ground that man differs somewhat from the lower animals In the harm he receives from having his skin coated. * Oases like the one reported by L'AUnyaux d'Ormay (Gaz. mgd. de Paris, 1859, p. 29) are, however, Interesting; He noted that In the skin about the burned area in one of his patients there was a zone of Increased per- spiration. Digitized by Microsoft® 144 Charles Russell Bardeen. The main reason that this theory of the pathology of bums be- came so popular is due to the fact that Billroth, convinced by the work and conclusions of Edenhuizen, lent to it the great weight of his support. With respect to the loss of the heat-regulating function of the skin, we have seen that Laschkewitsch and. others attributed the bad effects of gilding animals to radiation of heat from the covered surface. A similar theory has been held concerning skin burns (Laschkewitsch, Talk and others). In animals it has been found that the temperature after a preliminary rise sinks below the normal in fatal cases of bums."^ The same thing has been observed clinically in man,''' though a high fever is common after 36-48 hours. Cold-blooded animals stand bums better than warm-blooded animals (Falk). The observed facts can be accounted for only on the supposition that there ensues either increased heat radiation or else decreased heat production, and that both factors play a part. I have already mentioned the fact that Yalentin found the excre- tion of- CO2 much decreased in burned animals. Laschkewitsch observed that burned animals lose more heat in a tub of water than do unburned animals. This loss of heat is due mainly to dilatation of the blood-vessels, which in part at least is independent of the central nervous system. On the other hand, Welti has shown that the animals die in spite of being protected against heat dissipation and that in these cases also the temperature is lowered. This has also been found to be true of patients in the hospital wards. Indeed it is probable that the lowering of the temperature of the body is the result rather than the cause of lowered tissue metabolism in fatal cases of bum. We have now considered the theories founded on the interference with the respiratory, the excretory and the heat-regulating func- tions of the skin. None are adequate to explain the severe consti- tutional symptoms produced by burns. Of the other two chief skin functions, the sensory and protective, but little need here be said. ' Markusfeld and Steinliaus find that In animals kept In the burning medium till death ensues there is a rise in temperature, measured per rectum, after removal from the external heat. ^ Horrocks reports, however (Lancet, 1891, p. 869), that immediately after a burn the temperature falls to 97° F., or even 95° F., but that at the end of 24-48 hours it rises again up to even 104°-106° F., and remains high till the 8th day. Digitized by Microsoft® Pathology of Superficial Burns. 145 In the old days before antisepsis came into general use the de- struction of tha protective powers of the skin opened up free portals of entry to bacterial invasion, and doubtless in the longer standing cases death has often been due to secondary bacterial infection through the skin. This danger may be considpred so much less- ened now that death occurring within the first 24-36 hours after the bum may scarcely be explained in this way. As regards the interference vsdth the sensory apparatus in the skin, Kuess ' is the only authority, so far as can be learned, who has attributed the severe symptoms to the destruction of the sen- sory end organs. His suggestion that the normal stimulus to the respiratory reflex is thus destroyed is noted here more as a curiosity than for other reasons. On the other hand, ideas relating to great over-excitation of the nervous system have played a prominent part ia the literature deal- ing with skia burns. To shock, vaso-motor reflexes and like phe- nomena, most authors have been content to refer those cases in which the anatomical lesions were slight or entirely escaped notice. This is especially apt to be the case where death occurs soon after the bum. Kemy, in 1835, suggested that the effects of the external irrita- tion are transmitted to the internal organs through the sympathetic system. The majority of the authors dealing with the subject, however, have preferred the use of the rather indeflnite term " shock," and to shock for a long time most writers were con- tent to ascribe what they could not attribute to the blood being driven in from the skin.' Falk (a) in 1870 gave good reasons for thinking pain no sufii- cient cause to which to attribute the symptoms following bums. Sonnenburg in 1877 performed an extensive series of experiments upon dogs and rabbits and found that if the animals' legs were scalded in hot water severe constitutional symptoms followed, ac- companied by vaso-dilatation ; but if the animal's spinal cord was previously cut no such bad effects were produced. He attributed death to nervous reflex exhaustion and consequent loss of vascular tonus. In quickly fatal burns he thought the overheated blood ' ^ Quoted by Boyer and Guinard. ' The idea of shock is prominent in the articles of the following authors: Dupuytren, Long, Vignier, Bonders, FoUin, Wilks, Sonnenburg, Schjern- ing, Hebra, Morton, Seydel, Roger and Boyer and Guinard. Digitized by Microsoft® 146 Charles Russell Bardeen. miglit paralyze tlie heart. Sonnenburg's conclusions have been severely criticised and probably with, justice. Talk had already shown that the cutaneous vaso-dilatation is largely due directly to the heat; Laschkewitsch had demonstrated that the loss of tem- perature is almost proportional to the area of skin thrown out of function, and Lesser (c) and Silbermann showed that Sonnenburg's experiments by no means justified him in his conclusions. His results were not only far from constant, but he did not lay suffi- cient stress on the different manner in which dogs and rabbits bear burns. Salvioli and Markusfeld and Steinhaus have pointed out that if the blood supply of a part be cut off and the nerves are left intact (as can be readily done in the case of the rabbit's ear), the burning of the isolated part produces , little constitutional disturb- ance. On the other hand, if the nerves are cut and the blood-ves- sels are left intact the same degree of burning will produce the severest sort of symptoms. Boyer and Guinard have recently studied this question experimentally. They describe after extreme burns, besides general weakness and rapid arrest of the main bodily functions, disturbances of the centres controlling the heart, the vas- cular system and the respiration. They find that immediately after the bum there is vaso-constriction combined with a rise of temper- ature, and that this is followed soon by a fall of temperature and a corresponding fall of blood pressure, in severe cases below the normal. They attribute this loss of vascular tonus to shock. To sum up we may say that the main effect of superficial burns on the nervous system through the nervous channels is to cause an exhaustion dilatation of the vascular system. But in most cases it is doubtful whether this is more than a minor symptom in the com- plex phenomena following skin bums.'' Hypersemia of the viscera is the lesion most commonly re- ported post-mortem in cases of skin bums. We naturally expect, therefore, the blood and the circulatory system to excite consider- able attention in the study of these cases. The reflex vaso-motor changes and the local effects of heat on the cutaneous vessels I have ^ Tschmarke, working under Sonnenburg's influence, has recently brougHt out a very elaborate article in support of the latter's theory that death occurring soon after burns is due mainly to a reflex lowering of vessel tonus. He brings forward, however,, no new proof of a convincing nature. Digitized by Microsoft® Pathology of Superficial Burns. 147 already spoken of. I have mentioned the fact that most of the older "writers spoke of the blood as being " driven in " by the action of the heat on the skin. Palk went to the other extreme, and start- ing from the established fact that the action of prolonged heat is to cause vaso-dilatation, he went so far as to suppose that the burned animal, as it were, bled into its own skin, which thus deprived the internal organs of blood and lowered the activity of the heart by taking away fluid for it to beat against. Falk, however, laid most stress on the loss of heat and on heart paralysis. Heart paralysis, by some considered a primary cause of death, has in these cases been ascribed to three causes : cooled blood (Ealk), overheated blood (Sonnenburg), and to poisonous substances in the blood (Boyer and Guinard). Talk's suggestion is scarcely a happy one; nor is it likely that the blood could often be overheated enough to injure greatly the internal organs. As for the third hypothesis the utmost that can be said of it is that it yet remains to be proved. Indeed Oatiano says that the exposed heart of a burned dog beats lustily and that the respiration stops before the heart. The first to lay much stress on the part played by the blood in skin burns was Baraduc in 1862. He thought that the blisters resulting from the burn extracted large amounts of serum from the blood; that the blood is thus thickened and the rapidity of the flow lessened, the " thick blood " then giving rise in places to throm- bosis. Maas, however, showed that the thickening of the blood per se causes very different symptoms from those seen in burn cases. Tappeiner studied carefully the blood of four patients and found a relative diminution in the amount of H2O (about 1 per cent) with an increase in the number of red blood corpuscles. He found likewise a loss of water from the muscles. Like Baraduc and Buhl ' he compared cases of skin burn to cholera. Hoch, who has studied the blood more recently in 16 fatal cases, found likewise that for the first 24-36 hours there is an increase in the specific gravity of the blood. He ascribes this to a functional loss on the part of the body of the power of keeping the blood at, a uniform specific gravity and not to the direct effects of the burn. This func- tion, Hoch thinks, may be due to injury to the red blood corpuscles, which, as Alex, Schmidt had shown, have the power of regulating ' Zeitsch. f. rat. Med., vi., p. 79, 1855. Digitized by Microsoft® 148 Charles Russell Bardeen. tlie amount of blood serum by cbanging their size. In any case the thickening of -the blood does not seem to be a lesion of great im- portance/ Max Scbultze published, in 1865, a masterly article on the effects of high temperature on the blood corpuscles." He found that at 52° C. the red corpiiscles become indentated at first slightly and then more deeply. This gives rise to budding out of spherical pro- cesses and to the formation of processes much like strings of pearls. Finally the corpuscles become split up into larger and smaller spheroid bodies. These spheroids at first contain coloring matter, but later this is given up to the surrounding fluids. This study of Schultze gave new impetus to several workers' on the complex problem of the pathology of skin bums. The first to study experimentally the effects of bums on the blood was Werthheim. From 1867-69 he performed quite a series of experiments, chiefly on dogs, in which he describes as taking place in the blood of the burned animals the changes experimentally produced by Schultze outside the body. He foimd, in addition, that the corpuscles show a tendency to run together. The patho- logical tissue alterations ascribed to this sudden destruction of red corpuscles consisted in parenchymatous changes in the kidney asso- ciated with the deposition of hse^moglobin or its derivatives in the epithelial cells of the tubules, thrombosis, collection of pigment in bone-marrow and spleen, and a few minor lesions including hy- persemia of the viscera. Werthheim ascribed death to the sudden loss of red blood corpuscles, and to the irritation in the kidneys caused by the elimination of the destroyed blood. Werthheim also mentioned a leucocytosis in these cases. Ponfick came to essen- tially the same conclusions from his own experiments, and held the main cause of death to be the anatomical loss of the red blood cor- puscles, while Werthheim laid more stress on the kidney complica- tions. Klebs showed that the red corpuscles die at 45° 0. and ' The appearance of the blood after burns has, however, excited some interest. Guensberg called it "tea-like," Ponfick likened it to " blue-berry juice," Baraduc to "syrup," Maschka to "wagon-gre£ise" (see Schjerning). ' Arch, f . micro. Anat., i., p. 1. ' The more important work on the blood has been done by the following investigators: Werthheim, Klebs, Litten, Ponfick, v. Lesser, Hoppe-Seyler, Trojanoff, Silbermann, Welti, Hoch, Boyer and Guinard, and Markusfeld and Steinbaus. Digitized by Microsoft® Pathology of Superficial Bv/rns. 149 break up at a liigher temperature. He considered, however, the circulatory disturbances of greater importance than the destruction of the corpuscles, v. Lesser carried on an extensive series of ex- periments in Cohnheim's laboratory which he published ia 1880. He ascribed death chiefly to loss of function on the part of the red corpuscles, i. e. to a dyspnoea due to extreme anaemia. He con- sidered the functional loss of the red corpuscles greater by far than the mere morphological changes revealed by the microscope would indicate. Substances, he says, which destroy the functions exer- cised by the red corpuscles produce effects similar to those of skin burns. Hence, too, thick-skinned animals like the dog stand burns better than thin-skinned animals like the rabbit, or adults better than children. However, as Silbermann has suggested, it is possi- ble that the corpuscles themselves also vary in resisting power. Hoppe-Seyler attacked v. Lessor's theory. In the first place he could not find that the erythrocytes were sufficiently altered morpho- logically or functionally to incline him to ascribe serious trouble to such alteration, nor did he observe so much free haemoglobin in the plasma as would be the case were the red corpuscles injured in great numbers. Maraghano ^ in 1887 described several very delicate methods for testing injured red blood corpuscles. Silbermann by the use of these methods found the damage to the blood after burns to be far greater than had thus far been demonstrated. Furthermore, Sil- bermann says that if the blood of a burned animal is injected into the body of an anaemic animal the latter will die from dyspnoea. To the same cause he attributes the death of a rabbit whose ear is kept in water heated up to 60° C.'' But it by no means follows that anaemia is the cause of death in these cases, for the necessary tissue oxidation may be carried on when even a far greater propor- tion of the red corpuscles are rendered valueless than it is ever likely is the case in superficial bums. In studying anaemia Kraus and Chovstek measured the oxygen absorbed by human beings and found that even in those cases in which the number of red corpus- cles was reduced to 1,000,000 per cmm. and the haemoglobin to 20 1 Berl. klin. Wochensch., 1887, No. 43. ' Markusfeld and Steinhaus have recently found that the blood of a rabbit whose ear Is kept in water heated to 50° C. shows red corpuscles budding into globules ^4 to % their natural size. Higher temperatures cause much corpuscular destruction. Digitized by Microsoft® 150 Charles Russell Bardeen. per cent no diminution occurred/ On tli© whole it seems improb- able that the body suffers very severely from the numerical loss of the erythrocytes in bums/ Hoch has described, in addition to the changes already men- tioned in the blood corpuscles, a greater tendency of the red cor- puscles to stain blue with eosin and methylene-blue stains. He also finds that in human beings the leucocytosis is chiefly of the poly- morphonuclear type. He found no increase in the eosinophiles. Thrombosis is supposed by many to play a great part in cases of burns. I have already mentioned that Klebs ascribed the cdnsti- tutional effects rather to circtilatory interference than to injured red blood corpuscles. The work of Eberth and Schiromelbusch ' on thrombosis gave new stimulus to the study of bums from this point of view." Welti, whose studies were made on dead human bodies, thought that death could be attributed to thrombosis caused mainly by the accumulation of blood platelets. Like Klebs he found stasis in the capillaries of the cortex, while fluid blood was found in the heart and large vessels. Welti found thrombi in the walls of the stomach and intestines, in the kidney, spleen and lungs, where extravasations of blood were likewise seen. He found the thrombi composed of platelets and altered red corpuscles. Silbermann has called atten- tion to the possibility that since Welti's studies were on post-mortem cases some time dead, he may not be justified in attributing the co- agulation of the blood in the capillaries to the effects of the biirns on the elements of this fluid.' Silbermann, whose own experiments ' Wiener klin. Wochensch., 1891, No. 33, quoted by Flexner, Fatty Degen- eration in Heart Muscle, J. H. H. Bulletin, Marcli 18, 1894. ^ In this connection it is interesting to learn that Salvioli found that those dogs stood burns well whose blood was repeatedly removed half at a time, defibrinated and returned. I may also refer here to what has been said elsewhere concerning the action of altered blood-serum in caus- ing thrombosis and consequent dyspnoea. ' Virchow's Archiv, ciii., 1886. * The chief contributors to the study of thrombosis in skin bums are the following: Avdakoff, Klebs, Foa and Pellacani, Welti, Silbermann, Salvioli, Boyer and Guinard, and Markusfeld and Steinhaus. ' Silbermann experimented by putting narcotized animals into boiling water so that they were scalded to the navel. Dogs stood this better than rabbits. He opened the thorax and abdominal cavity of the still living animal and always found a great amount of blood In the right heart, vena cava, portal vein and the other veins of the peritoneal cavity. The arteries were strangely empty. The following lesions were found: thrombi in a Digitized by Microsoft® Pathology of Superficial Burns. 151 seem to have been carefully performed, came to tlie f ollowiBg con- clusions: After bums tbe red blood corpuscles are in part altered in form and functional activity. The altered corpuscles, in conjunc- tion witb an increase in tbe number of platelets, cause thrombosis in various organs, especially in the lungs, kidneys, digestive tract, liver, brain and subcutaneous tissue. These thrombi arise intra vitam and cause venous congestion and arterial anaemia. The effects of the altered blood and altered circulation are to cause in the organs hsemorrhage, swelling and parenchymatous changes; thence also dyspncea, cyanosis, coma, weak pulse, cramps, anuria and lowered temperature. Children are especially susceptible owing to their thin skin, delicate blood corpuscles and small heart. Both Welti and Silbermann describe an increase in the number of platelets in the blood of the burned. Salvioli, who worked under Bizzozero, says that the platelets are decreased in the blood because they are used up in the formation of thrombi. He states that dogs whose blood has been repeatedly removed (half at a time), defibrin- ated and returned, stand burns much better than dogs with normal blood, and attributes this result to the removal of the platelets and consequent loss of capacity for thrombus formation. Salvioli studied the mesentery of various small animals inamersed in warm water (42°-45°-65° C.) and watched under the microscope the effects of the heightened temperature on the circulating blood. He describes the formation of thrombi composed of platelets which later became free and circulated as emboli. Death he ascribes to thrombosis, contracted arterioles and modified red corpuscles.^ IVEarkusfeld and Steinhaus have recently studied the pathologi- cal effects in animals burned immediately to death. They as- great majority of the branches of the pulmonary artery; bleeding in the' mucosa of the stomach, less often in the intestines; thrombi in the right, more rarely in the left heart, liver and cutaneous tissue. These thrombi, he says, were coagulation-thrombi and not embolic in origin, and were composed of platelets, shadows and fragmented red corpuscles. By in- geniously injecting eosin into the still living animal he found that the tissues in and about the thrombi took the stain differently from normal tissues. ^Wlassow (Ziegler's Beitr., xv., 1894, pp. 543-580), who has recently studied anew the subject of thrombosis, thinks the formation of the plate- lets due to destruction of erythrocytes. The platelet is, according to him, a body composed of colorless nucleo-albumin, lying normally in the centre of the corpuscle and released by the action of the blood plasma on an injured corpuscle. Digitized by Microsoft® 152 Charles Russell Bardeen. cribe death to altered corpuscles and to thrombosis. They put the ear of a rabbit into water heated to 56°-66° C. (as suggested by Klebs) and found death ensued only where free communication existed between the blood in the ear and the general circulation.' In conclusion it may be said that Schjeming gives but eight cases in his tables in which post-mortem thrombi were noted. The time between the burn and death iu these cases varied from 12 hours to 12 weeks. Before proceeding it may be well to here sum up the chief lesions believed to be produced in the blood by superficial bums. 1. The specific gravity is slightly raised. 2. The erythrocytes are in part injured: (a) Morphologically, where subjected to a heat of 52° C. they tend to fragment and the fragments eventually lose their haemoglobin. (6) Functionally, probably a temperature of over 45° C injures them without always changing them morphologically. 3. There is produced a hyperleucocytosis, chiefly polymorpho- nuclear in character. 4. There is probably an increase in the number of platelets. 5. Certain toixiues may be found in the plasma (see below). 6. It is possible also that the resistance of the blood to bacterial invasion is lessened (Kijanitzin). 7. There is said by some to be an increase in the "fibrin fer- ment " (Foa and others). The alterations in the blood thus give rise to the following effects: 1. The injured corpuscles become foreign bodies in the blood, of which the body must needs rid itself. The fragments are collected in cells of the spleen, bone marrow (Ponfick), and lymphatic glands (Trojanoff); the freed hgemoglobin is in large part eliminated through the kidneys (hsemoglobiuuria). * Foa and others have suggested that the burns cause an increase in the fibrin-ferments in the blood and that these give rise to toxic effects and to thrombosis. And indeed we have experimental proof that the rapid destruction of red blood corpuscles in the circulating blood may be fol- lowed by thrombosis of important blood-vessels and be the cause of sudden death. The injection of the blood-serum of an animal into the circulation of an animal of a different species is followed by extensive destruction of red blood corpuscles and often by a consequent thrombosis resulting in death. " Kijanitzin has called attention to the fact that the fixed tissues can stand for a short time a heat of from 70°-72° C. with no marked 111 effects. Digitized by Microsoft® Pathology of Superficial Burns. 153 2. Tlie functional loss of red blood corpuscles may give rise to dyspnoea, but it is improbable tbat to diminution in the number of corpuscles alone dyspnoea should be attributed in these cases. 3. The injured blood together with its increased number of blood platelets gives rise at times to thrombosis in capillaries and veins. The lungs are especially apt to be the seat of the thrombosis, and hence in part the dyspnoea and the venous congestion so often seen in the thoracic and abdominal cavities. Thrombi in the brain may produce special nervous symptoms. 4. The effects of poisons in the plasma will be considered below. The clinical symptoms seen after superficial bums in many ways resemble those of acuj;e poisoning. Apathy, sleeplessness, more rarely delirium, cramps, feeble pulse, irregular heart, cyanosis, albuminuria, diarrhoea and nausea, are not infrequently noted. It is the presence of these symptoms that has led many clinicians to believe that a condition of toxaemia exists. We have seen that the supposition of the poisonous action of products normally excreted by the skin could not be supported. We have likewise seen how probable it is that the gilding of an animal causes abnormal cell metabolism and the production of absorbable poisonous compounds. Similar theories are held as regards the effects of bums.' Avdakoff experimented on thirty animals and found follicular enteritis and changes in the muscles of the intestines to be the most marked and constant lesions after bums. He suspected the exist- ence of some poison but could not determine its nature. Blood transfused from a burned animal often caused the death of the second animal. Foa supposed the production of a fibrin-ferment which not only caused increased thrombosis but also had direct toxic effects. Oatiano on apparently purely theoretical grounds assumed the production in the burned area of hydrocyanic acid, its absorption and consequent evil effects. But there is no proof of the formation of this substance, nor does it when present produce in the body effects like those seen after burns. E. Fraenkel in 1889 published an account of a number of autopsies in which he had noted parenchymatous degeneration of the kidney and liver, and had found the spleen filled with fragmented red blood corpuscles. 1 The more important articles on this subject are as follows r Avdakoff, Foa,, Catiano, Trojanofif, Lustgarten, Kijanitzin, Relss, Boyer and Guinard, Markusfeld and Steinhaus, Spiegler, Ajello' and Parascandolo. Digitized by Microsoft® 154 Charles Bussell Bardeen. He attributed death to an unknown poison. Schjerning, Pflanze and others assumed that this poison might be the potassium salts set free by the destroyed blood/ Lustgarten supposed a poison similar in nature to muscarine produced in the burned area by bacteria. He tried with some success atropin as an antidote in several cases, a drug which had already been used by Hutchinson on empirical grounds.^ Kijanitzin, under the direction of Obolonsky of Kiew, experi- mented with a view of determining the chemical nature of these poisons. Dogs and rabbits were used. They were scalded in water (G0°-70° C.) or hot benzine. The blood was collected from the freshly killed animal and treated by the Stats-Otto and the Brieger method. The important viscera, after being chopped up, were treated in a similar manner. The urine was also carefully exam- ined. In all cases careful control experiments were carried on at the same time. Brieger had obtained from fibrin by means of peptic digestion a yellow amorphous highly toxic powder which he called pepto-toxin. Kijanitzin found that he could extract from the blood of a burned animal, four to five days after the bum, a similar toxin, while from the blood of a normal animal no such substance could be obtained. These ptomaines he also found in the tissues and sometimes in the urine. His ptomaine he considers a highly complex body with a chemically acid reaction, but with effects on the body like those of an alkaloid. It was found to vary somewhat in its nature. In the body it produces a fall in tempera- ture, weak heart, superficial breathing, vomiting, diarrhoea, sleepi- ness, apathy, etc. Section of the cord shows that the poison acts on the brain rather than on the cord. The ptomaine, he concludes, belongs to the group of " Leichen-Muscarines " and shows one of the early stages of proteid decomposition. It is due, he suspects, to altered metabolism combined possibly at times with bacterial action. Eeiss studied especially the toxic nature of the urine of patients suffering from burns. He found the urine usually toxic to ani- mals. From it he could get no definite abnormal substances by the ^ This idea had its origin in the fact that Kronecker (Deutsche med. Wochenschr., xix., 1882) had already shown the toxic nature of potassium salts. ^ Med. Times and Gaz., London, 1864. Digitized by Microsoft® Pathology of Superficial Burns. 155 ordinary methods of analysis, but he thought he was able by the sense of smell to detect pyridine or a pyridine-base compound. An alcoholic extract he found to have toxic effects. He observed similar toxic effects from an alcoholic extract of serum albumin, and hence concluded that the poisons of burns belong to the pyridine-chinoliae group. He even succeeded in isolating from the urine a substance which had many of the properties of pyridine. Beyer and Gruinard found that the toxicity of the urine of burned dogs varied greatly. Ajello and Parascandolo confirm the conclusions of Kijanitzin as to the existence of poisonous substances in the tissues after burns. They performed a number of experiments on animals, and have published an elaborate paper in which they claim that they have found poisonous substances in the burned area and also in the organs and blood removed from healthy animals and afterwards burned. The burned tissues they found poisonous when fed to healthy animals or when inoculated under the sMn. Death was supposed to result from the absorption of poisonous substances from the burned area. The work of these investigators, as they report it in their paper, is hardly so convincing as they seem to deem it. Pawlowsky found that if the animals are burned under aseptic precautions and the blood and organs after death are treated with like care the tissues are not poisonous to animals. Hence he re- jects the theory of a toxaemia. Boyer and Guinard, on the other hand, and E. Spiegler be- lieve that toxines play a predominating role in the pathology of skin burns. The exact nature of the toxines, they believe, can only be learned by the use of more delicate methods than those hitherto employed. Spiegler says that the poisons probably origi- nate in the burned area or are produced vsdthin the body owing to the action within it of substances absorbed from the sldn. He was unable to isolate, as Kijanitzin claims to have done, poisonous sub- stances from the organs in animals experimentally burned. In nine out of twelve eases he found pyridine compounds in the urine. In conclusion it may be said that while many facts point to the presence of toxines in the body after severe bums, the nature of these substances and the mode of their production are still obscure. The work of the chemists on the subject is very contradictory. But few, however, agree with Lustgarten in believing that the poisons are the result of bacterial activity at the surface of the body. Digitized by Microsoft® 156 Charles Russell Bardeen. Of tlie many varied ideas concerning tlie primary nature of tlie pathology of skin bums few are founded on sufficient clinical, ex- perimental or anatomical bases to entitle them to much considera- tion. We have mentioned the most important, viz. vaso-motor changes and shock; the alteration in the blood, especially in its relation to thrombosis; and toxaemia produced by the direct action of the heat or by an altered metabolism. To one or the other of these primary causes or to a combination of the three it is probable that most of the secondary lesions found in the body after death may be ascribed. We shall consider more at length in Part IV of this paper which of these factors seem to be chiefly concerned in our five cases. n. PaTHOLOGHOAL A]^^AT0MT OF OUE FlVE CaSES. We were exceedingly fortunate in having for study five cases which coincided in so many details. All were children (the young- est sixteen months, the oldest eight years); all had been very extensively burned; all died within a few hours of the accident (the earhest death taking place in less than four, the latest in nine and one-half hours). So nearly alike were the pathological lesions found ia each case that one description almost suffices for all. I shall therefore first give a general description of the post-mortem findings applicable to all the cases, and to this I shall add a more detailed account of each for the benefit of those who may be inter- ested in the more minute variations. The appearances as seen at the post-mortem table were as follows: External Appearance. Extensive superficial bums involved nearly the whole surface of the body. The bums varied consid- erably in degree, in places being so severe that the epithelium had peeled off. Oedema was very marked in the subcutaneous tissue, especially about the face and eyelids. In no ease was there char- ring, nor were there macroscopical evidences of bums below the (Edematous subcutaneous tissue. A few cutaneous ecchymoses were seen. The muscles appeared normal. The lymphatic glands of the groin and axilla were partially enlarged. Thorax. On opening the thoracic cavity the pleurge were found Digitized by Microsoft® Report of Cases. 157 normal, the lungs slightly congested and cedematous. The heart and pericardium appeared practically normal. The thymus was congested, the lymphatic glands were swollen and some were slightly congested. Abdominal Cavity. On opening the abdominal cavity no excess of fluid was encountered. The intestines were moderately dis- tended; the visceral peritoneum was slightly congested. The liver on section was pale and cloudy. The spleen was enlarged and soft, with rather prominent Malpighian bodies. The kidneys were pale, glomeruli not prominent, cortex cloudy. Adrenals and pancreas normal. Stomach and intestines showed marked swelling of the solitary and agminated follicles throughout. These enlarged lym- phatic patches were often- surrounded by a slightly hypersemic zone. The abdominal lymphatic glands were all greatly swollen and some were congested. The genital organs showed nothing important. Cerebral Cavity. Meninges not particularly congested. Brain negative. Cord not examined. Cultures for bacteria negative except for the micrococcus lanceo- latus in the lungs of one case. To sum up: The chief gross pathological changes noticed were cloudy swelling of the liver and kidney, softened and enlarged spleen, and above all swollen lymphatic glands and gastro-intestinal lymph follicles. The hypersemia of the thoracic and abdominal organs was moderate. Microscopic examination of fresh teased tissue was made in the case of the spleen, liver and kidney, and in addition the blood was examined in the fresh state. The most striking thing noticed in the last was a considerable fragmentation of the red corpuscles. Prozen sections of the kidney, liver, spleen and heart-muscle were examined. No abnormal fat was seen. The liver and kidneys showed cloudy swelling.. Many cells containing fragments of red blood corpuscles were seen in the spleen and some in the liver. Parts of the chief thoracic and abdominal viscera, and in one case of the brain, were taken for microscopic ' study. The chief microscopic changes noted were as follows : ^ Various hardening fluids were used; MuUer's fluid, alcohol, Zenker's fluid, formalin, Hermann's fluid, Flemming's solution, and others. Both paraffine and celloidin were used for embedding, and various staining methods were employed, such as hsematoxylin and eosin, safranlne, Benda's iron-haematoxylin, Weigert's flbrin stain, etc. Digitized by Microsoft® 158 Charles Russell Bardeen. The skin where much burned showed heat coagulation and the running together of the protoplasm of the tissue elements of the upper layers. The subcutaneous tissues of the burned region and lower layers of the corium were very oedematous. The smaller blood-vessels just under the epithelium were all iilled with destroyed blood and occluded by thrombi. The larger deeper vessels of the skin and subcutaneous tissue contained, on the other hand, few thrombi. In two cases the sweat glands showed protoplasmic and nuclear degeneration. The sikin of the scalp was affected Hke the skin of the surface generally. The blood showed considerable poikilocytosis, and there was a leucocytosis, chiefly polymorphonuclear, as well. Thrombi, except in the skin, were uncommon. The bone-marrow showed great reproductive activity in certain forms of cells, areas of degeneration, and a large number of cells containing fragments of red blood corpuscles. The lymphatic glands showed the focal areas of degeneration which are described in detail in Part III of this article. The tonsils showed the focal areas of degeneration seen in all the lymphatic tissue. The thymus showed some slight degenerative changes in focalized areas. The lung tissue showed in one instance, besides the congestion seen in that from all the cases, the early stages of a pneumonia. The heart muscle was quite normal. The liver showed parenchymatous swelling of the epithelium, with focal areas in which there was marked vaxuolization of the cell nucleus and some although slight nuclear fragmentation. 'So hyaline degeneration was seen. Capillary thrombosis was, how- ever, not very infrequent, and in several places karyokinesis was discerned in the capillary endothelium. A moderate congestion existed. The spleen tissue showed congestion and much fragmentation of red corpuscles, many of the fragments being contained in phago- cytic cells, many lying free. The Malpighian bodies showed focal degeneration. The chief lesion seen in the tissues from the stomach and intes- tines was that of swelling of the lymphatic tissue with focal degen- eration. There was also increased activity in the goblet cells of the mucosa. Digitized by Microsoft® Report of Gases. 159 Tlie kidneys stowed very marked parencliymatous swelling of tlie convoluted and ascending tubules, much nuclear fragmentation in these cells, hsemorrhage into the glomerular capsules and from the capillaries between the tubules; blood pigment in Henle's tubules, less marked in other regions. An occasional occluded thrombosed blood-vessel was found. The examinations of the sections from the brain revealed nothing of note. The same may be said of the adrenal and pancreas, thy- roid and thymus. To sum up: Of chief note microscopically were the focal degen- eratipns in the lymphatic tissues and liver, and the advanced paren- chynijatous degeneration of the kidneys. Wp now give an account of the five cases with the findings at autopsy as abstracted from the autopsy records of the Johns Hop- kins Hospital. Case I. The first case is that of a small bay, aged 5 years. He was brought to the hospital, March 28, 1895, covered with extensive bums. Death followed in less than four hours after the accident. The autopsy was performed by Dr. Flexner one hour after death. Anatomical diagnosis. Extensive superficial burn; cloudy swelling of viscera; great swelling of solitary and agmlnated follicles of the intestine; swelling of mesenteric glands; destruction of red blood corpuscles; acute splenic tumor. External appearance. Well nourished child. Exfoliation of skin and blebs over back, trunk, hands and upper extremities, legs and neck. Skin of abdomen intact, but of a bright pink color and so altered in con- sistence that thread used for closing the body readily breaks through. Thoracic cavity. Lungs congested and oedematous. No foci of consolida- tion made out; heart apparently normal. Abdominal cavity. No excess of fiuid, no abnormal adhesions, intestines moderately distended. Liver pale and somewhat cloudy. Spleen enlarged and softened; the Malpighian bodies do not seem increased in size. Kidneys pale, glomeruli pale, cortex cloudy. Mesenteric and colic lym- phatic glands swollen and congested. Beginning at the pylorus and ex- tending throughout the entire intestinal tract there Is marked increase in the size of the solitary and agminated follicles. Here and there above the valve the patches of Peyer form elevated plaques. The follicular tissue itself is pale and is surrounded by a zone of hyperaemia. Frozen sections. Heart muscle, granular. Liver, swelling of cells and increased granulation of protoplasm. Kidney, parenchymatous swelling; no fat. The teased splenic tissue showed many fragmented red blood corpuscles and cells containing erythrocytes. The tissues hardened and examined microscopically from this case were from the skin, lymphatic glands, liver, spleen, intestines Digitized by Microsoft® 160 Charles Russell Bardeen. and kidney. From the changes noted the following are abstracted as the more important: 8Jcin. (a) From an, area where the burn was especially severe. The epithelium has entirely disappeared, being burned or peeled off; the upper layer of the corium has been coagulated by the heat so that the various elements have run together and the cell nuclei have disappeared. The connective tissue has a glassy appearance and stains well in eosin. Lower down the corium is extensively (Edematous, a condition which is still more marked in the border- ing subcutaneous tissue. The epithelium of the hair follicles and sweat glands has an altered granular protoplasm, but the nuclei present nothing abnormal. The blood-vessels in the upper corium just under the coagulated area contain granular masses composed chiefly of fragmenting red corpuscles. In some of the larger vessels deeper down thrombi may be seen, but the majority of the larger cutaneous vessels contain, aside from the poikilocytosis and leucocy- tosis seen in all the blood-vessels of the body, apparently normal blood. The veins are much dilated. (b) From a burned area where the epithelium still remains. The outlines of the epithelial cells have in part disappeared owing to the fusion of the protoplasm; the nuclei, however, take the stain. The protoplasm of the epithelium of the sweat glands is granular, but the nuclei are intact. The connective tissue of the corium is not altered except for the extensive oedema. The blood-vessels show the same condition as in the previous specimen. Lymphatic Glands. Various glands from the thoracic and ab- dominal cavities were examined. Almost without exception they show oedematous swelling and focal changes in and about the " germinal centres." Fragmentation of the nuclei has not, how- ever, progressed far. JSFo karyokinesis is seen. In some of the bronchial and retroperitoneal glands there is venous congestion. 'No thrombosis is seen. Liver. The epithelial cells are swollen and more granular than normal; now and then groups of liver cells show vacuolization of protoplasm, and occasionally the nuclei are entirely absent or frag- mented. The veins and capillaries are much dilated; thrombi are seen here and there in the intralobular capillaries, and now and again fragments of red blood corpuscles can be made out. Spleen. Besides the congestion (the splenic pulp being engorged Digitized by Microsoft® Report of Cases. 161 witli blood) tlie veins contain many fragmented red blood cor- puscles partly included within cells and partly free. The most interesting observations, however, are met with in the Malpighian bodies, which show the changes mentioned in connection with the lymphatic glands. Thrombi are rarely seen. Intestines. The epithelium of the mucosa in the small intestine shows many karyokinetic figures and an increase in the number of goblet cells. The lymphatic tissue in the villi, solitary and agminated folKcles is much swollen. There is little actual fragmentation of nuclei. No karyokinetic figures are seen. Kidney. The pathological alterations in this organ are not ex- tensive, and are mainly connected with an increased granulation and swelling of the epithelium of the labyrinthine tubules. An occasional cell has lost its nucleus. The glomerular spaces are in some instances increased and contain a granular debris. In this fragments of erythrocytes may be found as well as in the tubules. Occasionally epithelial nuclei are fragmented. Case II. Boy aged 2. Burned, January 27, 1896, by accidental ignition of dress at fire grate. Death tools place at 4.30 p. m. (5 hours after the accident). The autopsy was made the same evening by Dr. Flexner. Anatomical diagnosis. Extensive burn. Cloudy swelling of viscera and general glandular hyperplasia. Heat destruction of red blood corpuscles. Acute splenic tumor. External appearance. Well nourished child. Burn extends over face, head, arms, thorax and anterior parts of thigh. In places the epidermis has peeled ofC, and over the trunk a number of large bullae are found con- taining clear fluid. Near the burned area the skin shows minute puncti- form ecchymoses. Thoracic cavity. Pleurae normal. Lungs slightly congested, otherwise normal. Heart, few slight ecchymoses under epicardlum, covering the auricle. Bronchial glands enlarged. Abdominal cavity. No excess of fluid. Ecchymoses beneath the serosa in places. Omentum, congested. Liver, cloudy swelling. Kidneys, cloudy swelling. Spleen, greatly enlarged, soft and dark; Malpighian bodies large, prominent and grey. Stomach apparently normal. Duodenum and jejunum normal. Ileum, follicles near valve enlarged. Large intestine, solitary follicles enlarged. Mesenteric and retroperitoneal lymphatic glands enlarged and oedematous. Axillary and inguinal glands. Enlarged, softened and congested, especi- ally the axillary. Cultures. Negative. Frozen sections. Heart muscle shows no fat. Kidney, cloudy swelling of convoluted tubules, no fat. Liver, slight cloudy swelling. Digitized by Microsoft® 162 Charles Russell Bardeen. Blood. Cover-slips from right side heart show a few fragmented red blood corpuscles. Spleen. Cover-slips show fragmented red blood corpuscles, some of which are enclosed in other cells. Tlie hardened tissues examined were from the skin, blood, lym- phatic glands, lungs, heart, liver, spleen, kidneys and pancreas. The changes noted were as follows : Shin. Changes similar to those described under & in the first case. The epithelium of the sweat glands is altered. The cell outlines are not sharp, the protoplasm is granular, and the nuclei are frag- mented, the neighboring connective tissue cell nuclei being normal. Blood. Cover-slips were made from the liver, spleen, kidney and fluid blood in the large vessels.' In these specimens neither poiki- locytosis nor fragmentation is so marked as was expected from study of the freshly prepared specimens. The leucocytosis is chiefly that of the polymorphonuclear variety, though the large mono- nuclear forms are also increased in number. Eosinophiles are not increased in number. The cover-slips made from the spleen show many cells containing fragments of corpuscles. Lymphatic glands from the thoracic and abdominal cavities all show advanced focal lesions of degeneration. Lungs. Slight congestion; the lymph nodules in the connective tissue show focal degeneration. Liver. Essentially the same as in the previous case except for small parenchymatous haemorrhages. In one area there is a more marked congestion than in the previous case. Spleen. The description given of the spleen in Case I applies here also. The degeneration in the lymphatic tissue is, however, more marked. The red corpuscles in the spleen pulp are much increased in number. Intestines. The epithelium of the small intestines is beautifully preserved in these specimens. The contrast between the abund- ance of dividing nuclei in the mucosa, where there is an increase in the number of the goblet cells, and the absence of mitotic figures in the lymphatic tissue, is most striking. The focal degeneration in the latter tissue is extreme. Eor the rest the description given of the intestines in the previous case applies here. 1 These were hardened by heat and by absolute alcohol and ether, and stained in methylene blue and eosin and in Erlich-Biondi triple stain. Digitized by Microsoft® Report of Cases. 163 Kidney. Excepting for the greater amount of congestion and the freer escape of the red blood corpuscles into the capsular spaces, the condition is much the same as in the previous case. Pancreas. Apparently normal. The following three cases came into the hospital at the same time. Four small children, left alone, managed to explode a lamp and a gasoline stove and contributed their own clothes to the con- flagration. This happened about 9 o'clock p. m. February 24th, and at 11 p. m. they were brought into the hospital. Three had died by half-past six the next morning. The fourth, somewhat older and less severely burned, recovered. Case III. Tlie patient was a girl, six years of age. She died at 6.30 a. m., nine and a half hours after the injury. The autopsy was performed by Dr. Flexner, seven and a half hours after death. Anatomical diagnosis. Burn of second and third degrees. Parenchy- matous swelling of viscera and lymphatic glands. Heat destruction of red blood corpuscles. External appearance. Well nourished child. Defects of epithelium on posterior and outer aspect of both legs, the skin being badly burned. Hands and arms severely burned, the epidermis being in part deficient, in part loosely covering an cedematous surface. Face and neck are very badly burned, the epidermis being in part absent. The eyelids are so swollen that they cannot be opened. The head is badly burned, and bullae exist beneath the scalp in places. Thoracic cavity. Pleurae normal. Lungs and bronchial glands congested. Heart, right ventricle greatly distended with fluid and clotted blood. Muscle brown in color. Thymus cloudy and congested. Lymphatic glands swollen. Abdominal cavity. No excess of fluid, intestines moderately distended. Slight injection of subserous vessels of small intestine. Liver, parenchy- matous swelling. Spleen, mahogany brown in color on section; Malpigh- ian bodies not enlarged. Kidneys, parenchymatous swelling, glomeruli visible and red. Lymphatic glands enlarged and swollen. The retro- peritoneal glands are less swollen and more congested than the mesen- teric. Intestines, in general the mucous membrane is pale. The solitary and agminated follicles, especially those just above the valve, are swollen. Stomach, the mucous membrane is slightly congested. In the region of the pylorus the swollen projecting lenticular glands give a granular ap- pearance to the part. Pancreas gray and firm. Lymphatic glands of axilla and inguinal regions are swollen and con- gested. Bone marrow of femur soft and red. Frozen sections. Liver, parenchymatous swelling, cells large and granu- lar; they contain little fat. Heart muscle free from fat. Kidneys show parenchymatous degeneration, no fat. Digitized by Microsoft® 164 Charles Bussell Bardeen. Teased bits of liver, spleen and bone-marrow stiow many fragments of red blood corpuscles witliin and without cells. The bone-marrow shows a very few fragmented red blood corpuscles. Cultures from the lung showed great numbers of minute colonies of the micrococcus lanceolatus. Spleen and heart's blood negative. The following tissues were hardened and examined: skin, bone- marrow, lymphatic glands, lung, heart, thymus, liver, spleen, stom- ach, intestines, kidney and adrenal gland. 8hin. The sections of skin from this case are like those de- scribed under Case I. One sweat gland, however, shows changes similar to those found in the epithelium of the glands in Case II. The nuclear degeneration is less marked. Bone-marrow. Besides changes similar to those found in the lymphatic tissues elsewhere, not a few cells containing fragments of erythrocytes are seen. Lung. The sections examined show early inflammation. Con- gestion is marked and there is some oedema. There is desquama- tion of the epithelium, and in the alveoli there- are many cells containing blood pigment and fragmented corpuscles. A few " shadows " are also present and some polymorphonuclear leucocy- tosis. There is marked bronchial congestion. The sections were not stained especially for micro-organisms, but it will be remem- bered that in this ease cultures from the lung showed lancet-shaped bacilli. Thymus. Aside from the normal retrogressive changes always seen in a child of this age, nothing special is to be observed except congestion, and a few areas in which there is fragmentary degen- eration like that seen in the lymphatic glands. . This focal degen- eration is not, however, extreme. Liver. The condition is similar to that found in the previous two cases. Karyokinetic figures are rarely met with in the endothe- lial cells of the capillaries. Spleen. The lesions are essentially like those in the previous cases. The degeneration of the lymphatic tissue is moderate. Stomach. The lymph follicles are much swollen and show ex- quisitely the degenerative changes described elsewhere. Other- wise the organ is practically normal except for a slight hypersemia. Intestines. Duodenum: Brunner's glands normal, great swell- ing and degeneration of all lymphatic tissue. Ileum: extensive lymphatic swelling and degeneration; slight hyperzemia. Digitized by Microsoft® Report of Oases. 165 Kidney. Essentially the changes described in the former cases. There is perhaps a somewhat greater escape of red blood corpuscles in this case, especially into the capsular spaces. Case IV. The patient, a girl of eight years of age, died at 6.15 a. m., February 25, nine and a quarter hours after the accident. The autopsy was performed at 3.30 p. m. by Dr. Flexner. Anatomical diagnosis. Burn of second and third degree, parenchymatous degeneration of viscera, swelling of lymphatic glands, heat changes in the red blood corpuscles. External appearance. Spare but well nourished child. Burned especially about the face and scalp, whence the epidermis is in part removed. Much oedema of eyelids. Upper extremities severely burned and in part denuded of epithelium. Lower extremities less severely burned, but in places the epithelium Is gone. There is little reaction in the burned areas except infiltration with serum. Thoracic cavity. Pleurae normal. Lungs normal except for a slight in- terstitial emphysema and congestion. Heart, distension of right side with fluid blood and clots. Thymus, congested and csdematous. Bronchial glands swollen. Abdominal cavity. No excess of fluid, intestines moderately distended; hyperaemia of the vessels of the serosa. Peyer's patches shine through Intestine surrounded by a zone of hyperaemia. Liver, cloudy on section. Spleen, dark in color on section; Malpighian bodies numerous and perhaps enlarged. Kidneys show parenchymatous swelling. Pancreas grey and firm. Lymphatic glands swollen and somewhat hyperaemic. Retroperi- toneal glands swollen but not congested. Intestines, solitary follicles of large intestine swollen, more markedly in lower than in upper part of colon. Peyer's patches more swollen in upper part of the ileum than near the valve. No marked swelling of the follicles in the Jejunum. Mucous membrane pale throughout. Stomach and duodenum, mucous membrane pale; some swelling of the lymph foUicles. Axillary glands enlarged but not congested. Larynx, follicles beneath mucous membrane enlarged. Pharynx and tongue, follicles not particularly enlarged. Bone-marrow red and soft. Brain, sup. long, sinus contains fluid blood; meningeal vessels greatly congested; there is no oedema of the meninges. Frozen sections the same as in Case III. Cultures from spleen, heart's blood and lung negative. The hardened tissues examined were from the skin, scalp, lym- phatic glands, bone-marrow, thyroid, thymus, heart, liver, spleen, stomach, intestines, kidney, pancreas, adrenals and brain. Shin. Essentially like that described in the first case. Scalp. The hair is burned off and the epithelium forms a coag- ulated mass in which no definite cell outlines can be distinguished. Some of the nuclei, however, take stains. The connective tissue is Digitized by Microsoft® 166 Charles Russell Bardeen. cedematous, but otherwise, except just beneath the epithelium, shows no special change. The hair follicles, the sebaceous and sweat glands seem normal. The oedema of the subcutaneous tissue is very marked. The blood-vessels are similar to those in the burned skin elsewhere. Brain. Parts of the cortex and of the optic thalamus were har- dened in Miiller's fluid and in formalin and were treated with a modified Golgi impregnation and carmine stains. The Golgi speci- mens unfortunately did not turn out well. In the other specimens nothing of note was seen. There was no thrombosis in the speci- mens examined, nor was there noticeable congestion. Lymphatic glands, bone-marrow, thymus, stomach and intestines show essentially the lesions described in Case III. The following tissues show essentially the lesions described in Case I: kidney; liver (in addition a few capillaries are, however, packed full of leucocytes) ; spleen (but the lymph tissue is in a more advanced stage of degeneration). Heart muscle, pancreas and adrenal show no noteworthy changes. Case V. The patient was a girl aged 16 months. She died at 1.25 a. m., February 25, four and one-half hours after the injury. The autopsy was performed at 5 p. m., February 25, by Dr. Blumer. Anatomical diagnosis. Burn of second and third degree, parenchymatous changes in viscera and lymphatic glands; heat changes in red blood cor- puscles. External appearance. Well nourished child. Burns extend over face, ears, both arms, legs, thighs and buttocks. Over the face there are areas denuded of epithelium, and oedema of the eyelids and lips is present. In the skin of the thorax and abdomen are numerous eechymoses, pin-point to pin-head in size. Thoracic cavity. Pleurse normal. Lungs normal except for slight conges- tion; some mucus in bronchial tubes and a slight interstitial emphysema. Heart, slight amount of a yellow fluid in pericardial cavity, but both layers of pericardium smooth. Right side of heart distended and filled with fluid blood and clots. Muscle pale brown in color. Thymus slightly con- gested. Bronchial glands swollen. AMfiminal cavity. No excess of fluid. Intestines normal in appearance except for the Peyer's patches which shine through the wall. Bach patch is surrounded by a hypersemic zone. Liver shows parenchymatous swell- ing and on the surface a yellowish mottling. Spleen deep red in color on section, slightly swollen; Malpighian corpuscles enlarged. Kidneys pale and cloudy, glomeruli pale. Adrenals normal. Lymphatic glands swollen, especially the mesenteric glands about the caecum. Intestines, lymphoid tissue as in the other cases much swollen, espec- ially towards the valve. The mucous membrane Is pale except in duode- Digitized by Microsoft® Lesions in Lymphatic Tissues. 167 num and upper jejunum, where it is bile stained. The mucous membrane of the stomach shows a granular appearance at the pyloric end, owing to the swelling of the solitary follicles. Axillary glands swollen and somewhat congested. Bone-marrow chocolate brown in color and very soft. Tonsils and back of tongue show swelling of lymphoid tissue. Pharyns and larynx, the lymph follicles are much enlarged. Frozen sections, essentially as in preceding cases. Cultures from spleen, heart's blood and lung negative. Sections of skin, lymphatic glands, thymus, lungs, heart, liver, spleen, tongue and tonsil, stomach, intestines and kidney were examined with the f oUoAving results : Blood. In general the blood is modified as in the other cases, but more intensely. Lymphatic Glands. Degenerative changes in many glands well marked. Congestion is perhaps more noticeable than in the other cases. Thymus. Apparently normal. Lungs. Slight congestion and desquamation of epithelial cells. Slight bronchitis. Heart. No degeneration seen in the muscle fibres. Spleen. The fragmentation of the red blood corpuscles is ex- treme. The degeneration of the lymphatic elements is not so far advanced as in some of the other cases. Tongue and Tonsil. The section was made so as to include parts of both. In the tongue nothing especial was noted. In the tonsil the degenerative changes seen in the lymphatic tissue throughout the body were noted. Stomach. The swelling of the lymphatic tissue is marked. The actual fragmentation has not progressed far. Intestines. The lymphatic tissue is greatly swollen and is the seat of the degenerative changes so often mentioned in connection with these cases. III. The Alterations Found in the Lymphatic Tissues. But little attention has hitherto been paid to the pathological changes produced in the lymphatic tissues of the body by superfi- cial bums. Swelling of the lymphatic follicles of the intestinal mucosa was noted by Avdakoff in dogs experimentally burned, and Digitized by Microsoft® 168 Charles Russell Bardeen. is also reported several times in the autopsy reports collected by Sclijerning. v. Lesser noted that the lymphatic glands were often enlarged in the dogs used in his experiments. Schjerning, Fraen- kel and others have reported cases in human beings fatally burned in which lymphatic glands have been found enlarged. Foa ' in his experiments on animals found that if the animal survived the burn- ing some days there were found post-mortem follicular enteritis and certain peculiar alterations in the bone-marrow. These latter changes consisted ia the disappearance of fat and, in certain areas, of nucleated red blood corpuscles. There was found a great in- crease in the number of the large c'ell elements. There was also a tendency in certain areas for the medullary cells to become fused (focal degeneration?). The lymphatic tissue in our cases, as has so often been noted, was most markedly affected and in an interesting and specific man- ner. Wherever lymphocytes were seen collected into nodular masses, from the small nodules in Glisson's capsule in the liver to the largest lymphatic glands, these alterations appeared. In places the changes were so slight as to be found only after very careful study; in other places they were clearly visible to the naked eye. Study of different sections made from glands variously affected gave rise to the conviction that the various steps in the main pro- cess of degeneration in the gland could be followed. I shall there- fore describe the stages of alteration noted in different sections as if consecutive, noting first the appearance of the least affected areas and proceeding thence to the areas showing the most extreme degeneration. A general oedema throughout the gland, but especially marked at the germinal centres and in the swollen lymph sinuses, seems to be the earliest stage of the process. This oedema is sometimes ac- companied by slight venous and capillary congestion. It is in this stage, if at any, that there is an increased activity of cell reproduc- tion by indirect cell division. At this stage nuclear figures can always be seen, but it is doubtful if they are really present in greater number than in the normal gland. In the later stages karyokinetic figures are very rarely seen. Almost coincident with the oedema, the cells, especially those at the germinal centre, begin to swell as if there were an intraproto- ^ Revista Sper., vli., p. 135. Digitized by Microsoft® Lesions in Lymphatic Tissues. 169 plasmic as well as an intercellular oedema. There are always cells at the germinal centre larger than the usual lymphocytes, but the swollen cells which now appear are quite different in their general morphology. The protoplasm becomes coarse and granular, some- times vacuolated, and the nucleus, at first vesicular, takes on the form of knotted irregular bands of chromatin. Soon these go to pieces, scattering about small and large bits of a chromatin material which stains deeply in the basic dyes. The germinal centre meanwhile expands until it reaches a size large enough to strike the naked eye (1 to 2 mm.). The proto- plasm breaking up forms masses of a granular, vacuolated material without nuclei, though bits of nuclear fragments may be discerned. Fat is usually absent in this degenerating material. In our cases no fibrin was seen. Meanwhile large flattened cells similar to those which line the lymph sinuses appear, particularly in the germinal centres, and exhibit a most marked phagocytic action, rapidly engulfing the nuclear fragments and other debris of the fragmenting leucocytes. It is probable that these endothelial cells exist normally within the lymph nodule as well as at its borders, where they line the perifolli- cular lymph sinuses. Some of the larger leucocytes appear also to act as scavengers, but the main phagocytic action is carried on by these endothelial cells.'' The appearance of a lymph follicle in which the process has reached an advanced stage is most striking. Such a follicle is represented in the illustration accompanying this article. At the centre of the follicle the large flat endothelial cells form the most prominent feature. Fragments of protoplasm and nuclei lie upon and within these cells, and here and there the wall of a blood cap- illary may be seen. In places a few erythrocytes have escaped, only to be engulfed by the flat phagocytic cells. Extending out from this centre is an area marked by leucocytes in all stages of degeneration. In some a slight swelling of the cell body is the main alteration. In others the nuclei are becoming vacuolated or are beginning to fragment. Other cells have lost all traces of nuclei, and the protoplasm of the cell body is becoming fused with that of neighboring cells. In places cells appear to be undergoing ^ These cells appear identical with those which Rindfleish found in simi- lar lesions in typhoid fever and called " typhoid cells." Digitized by Microsoft® 170 Charles Bussell Bardeen. dmsion in a crude, irregular manner, tlie nucleus and cell body appearing to divide simultaneously into two or more unequal parts. But more often the degeneration is too rapid and extreme to give rise to tlie belief tbat the process is one of cell multiplication. Be- yond and encircling this area of extreme degeneration lies a zone of lymphocytes, for the most part slightly swollen, but otherwise nor- mal in appearance. And then comes a zone of " normal " lympho- cytes closely packed together, in many places filling the area which in the normal lymphatic gland so often appears plainly as a sinus or lymph channel. Many of the lymphocytes in the lymph sinus are swollen. Karyo- kinetic figures are at times seen here, and sometimes the degenera- tion appears to extend inwards from the sinus as well as outwards from the centre of the follicle. In these instances marked degener- ative changes are seen in the cells bordering the sinus. In a few instances large numbers of eosinophiles are seen within the lymphatic glands. The most striking changes occur, as I have described, within the lymph follicles. But in the lymph cords similar though more dif- fuse areas of degeneration are to be seen. The swelling of the glands is to be ascribed almost wholly, if not wholly, to the oedema, to the swelling of the individual cells and to the extensive fragmentation of the latter. In an area of a given size in a swollen gland there are fewer lymphocytes than in a cor- responding area of an unaffected gland. In the Malpighian corpuscles of the spleen the same changes are seen as in the lymphatic gland. The corpuscles become enlarged from the swelling of cells and the subsequent degenerative process which begins at the centre of the follicle. It is impossible to be sure whether lymph cells gather from the general pulp and collect about the Malpighian corpuscles, as described by Barbacci in diph- theria. Single cells and small groups of cells may be seen degen- erating in all parts of the pulp, but well marked areas of degenera- tion are confined to the centres of the Malpighian bodies. Karyo- kinesis is rarely seen. In the bone-marrow there are similar areas of focal degeneration. The protoplasm of the cell bodies in these areas becomes swollen, neighboring cells fuse, and the nuclei become fragmented and dis- torted. There seems to be, however, a normal or increased number Digitized by Microsoft® Lesions of Lymphatic Tissues. 171 of nucleated red corpuscles, otherwise the changes are not unlike those described by Foa in the bone-marrow of dogs. In the alimentary tract the lymph nodules and follicles are strikingly altered. In the swollen tonsils areas of degeneration identical with those seen in the lymphatic glands are found. In the stomach the swollen follicles give a granular appearance to the gastric mucosa, and the microscope reveals in these swollen folli- cles most extensive areas of degeneration. But the most severe effect of burns on the lymphatic apparatus is exhibited in the intes- tines. The follicles, solitary and agminated, were in all cases so swollen as to extend above the surface of the mucosa and laterally into the adjacent membrane. Yet on microscopic examination practically no cell division can be made out in the lymphatic tissue. The degeneration of the lymph cells in these follicles is like that seen in the lymphatic glands, though the process is less focalized, normal and altered cells being much intermingled. The areas of gross alteration in the Peyer's patches are much larger than any focal areas seen in the most altered lymphatic glands. In the lym- phatic tissue of the villi scattered cells and groups of cells can be found undergoing degeneration in the same manner as in the spleen pulp. Flexner has suggested ' that the focal pathological effects result- ing from the action of certain poisons on the body may in some way be related to the capillary circulation. It has seemed to me that it is probable that such a relationship is present in the follicles of the lymphatic glands in these cases. It is, for instance, inter- esting to note that the severest changes in the lymphatic gland begin just at the region where a terminal artery breaks up into capillaries and where therefore the blood plasma is given special opportunity for the diffusion of its contents. Most of the capil- laries seem to have intact walls; the capillary endothelium is very granular. In places, as has been noted, a few red blood corpuscles have escaped, only to be engulfed by the epithelioid phagocytes." ' Johns Hopkins Hospital Reports, vol. vi. ' Calvert (Anatom. Anzeiger, vol. xiii, 1897) has recently shown that in the lymphatic gland of the dog an artery runs to the centre of the lymph follicle and there breaks up into capillaries which radiate towards the periphery of the follicle and empty into collecting veins running just inside the perifollicular sinuses. There is every indication that a similar condi- tion prevails in the human lymphatic gland. The blood therefore in the Digitized by Microsoft® 172 Charles Russell Bardeen. It seems not unfair to assume that in our cases of skin burn a toxine-holding plasma escaped with more than normal rapidity near the centre of the follicle. This rapid flow of plasma has given rise to the oedematous swelling and has tended to sweep the lympho- cytes into the perifollicular lymph sinus. At the same time the noxious materials contained in the blood and escaping plasma have had the destructive effect on the lymphocytes already described in some detail. It is not impossible that the destructive changes in- duced in the lymphocytes indicate an abnormal and fruitless attempt at cell reproduction. The exact nature of these focal pathological alterations in the lymphatic tissue can be determined only by careful experimental work. But in spite of this we have logical grounds for assuming that these alterations are due to poisonous substances circulating in the blood, since nearly identical changes have been found in the lymphatic glands of children who have died from diphtheria and other acute infectious diseases in which it is believed that toxines circulate in the blood. Again similar lesions can be produced ex- perimentally in animals by the injection of ricin, abiin, the diph- theria toxine and similar complex organic poisons.^ We have there- fore in these lesions in the lymphatic glands good objective proof that toxines of a highly virulent nature must have been circulating in the blood of the children whose tissues we have been studying.'' In 1876 Bizzozero described focal areas of degeneration in the spleen and in the lymphatic follicles of the intestines in persons dead from diph- lymph follicle circulates from the centre of the follicle towards the peri- phery. And so also the plasma, escaping from the capillaries near the centre of the follicle, must have a general direction towards the perifolli- cular lymph sinus. It is worthy of note that the region of greatest repro- ductive activity, the " germinal centre," lies close to the point where the follicular artery terminates. ' For a description of the nature of these substances and their action on the body see Flexner, J. H. H. Reports, Vol. vi. I may here with propriety perhaps refer more especially to the changes described in the lymphatic tissue. A full bibliography of the literature of this subject is given in Flexner's article. ' The rapidity with which the lesions in our cases were developed is one of their most Interesting features. How soon these specific lesions might be produced it is hard to judge. In the child which died soonest, and only 4 hours after the burn, the lymphatic lesions and parenchymatous changes were well marked. Schjerning reports that in a child which died half an hour after the bum, marked swelling of the Intestinal follicles and of the mesenteric glands was seen. He, however, thought this due to catarrhal enteritis existing before the burn. Digitized by Microsoft® Lesions of Lymphatic Tissues. 173 theria. Tlie lymphatic tissue in general was found much swollen, and in the midst of the swollen tissue degeneration was noted, which seemed to consist of swelling of the lymph cells and breaking up of the protoplasm and nuclei. In 1884 Arnold described these areas of degeneration as con- structive rather than destructive. The general process he considers a peculiar form of indirect nuclear and cell division. He had previously described a similar form of reproductive activity as occurring in bone- marrow. He called it indirect fragmentation. The focal areas of de- generation after acute diseases he showed occurred at the very centre of normal reproductive activity, the so-called " germinal centres." Arnold found evidences of indirect division also in these areas. In the lymphatic tissue of the spleen and lymphatic glands he described in these cases two main types of cells, large cells with nuclei at first vesicu- lar, later rich in chromatin, and small cells with nuclei rich in chromatin. Many cells fail to correspond closely to either type. He found three main types of nuclear figures in the cells undergoing indirect fragmentation. There were large figures rich in chromatin, small figures rich in chromatin, and small figures poor in chromatin. The size of the cell corresponded roughly with that of the nucleus. Several daughter cells may be formed from these dividing cells and there may be protoplasm left over to degen- erate and go to pieces. In our cases similar appearances were seen, but we take them to be degeneration phenomena. Stilling laid special stress on the reproductive growth at the centre of the follicles in the spleen and also described degenerative changes occurring there. Oertel in 1887 described the histological lesions due to diphtheria in more detail. He pointed out the occurrence of phagocytosis and, in long stand- ing cases, of hyaline degeneration. He described cell division of the " fragmentation " type of Arnold, but found no true Indirect division. Mueller foimd, in addition to the lesions previously described, fatty de- generation in the lymphatic cells. Babes and Welch and Flexner extended still further the knowledge of the histological changes produced by the diphtheria toxalbumin, basing their work on experiments on animals. The latter described focal areas of necrosis in the spleen, liver, intestinal canal, kidney, lymphatic glands, heart, muscle, etc. Bullock and Schmorl showed that the degeneration is often so exten- sive in the lymphatic tissue that the protoplasm runs together and there may be a fibrin network formed in this confused mass. Katzenstein could find no true hyperplasia in the spleen and lymphatic glands in these cases. Barbacci has recently gone over the whole ground. He describes espec- ially the appearances found in the Malpighian bodies of the spleen in cases of human diphtheritic infection, pointing out that these changes correspond closely with those seen In the lymphatic glands. The swelling of the Malpighian bodies he ascribes to two main causes: 1. Infiltration of cells from the general pulp into the " germinal centres " and about the Malpighian bodies. 2. Oedema, which may be general and diffuse, but is especially collected at the periphery or near the centre of the follicle. Other histological points noted in the Malpighian bodies in these cases are: Epithelioid cells In the centre of the follicles; occasional congestion of the blood-vessels; occasional nuclear division even where the degeneration is active; extreme degeneration in the lymph cells, giving rise to nuclear Digitized by Microsoft® 174 Charles Russell Bardeen. destruction and to the formation of necrotic material; phagocytes contain- ing nuclear fragments; hyaline degeneration; and rarely fibrin. In the spleen pulp Barbacci noted especially cell hyperplasia, capillary haemorrhage, chromatin blocks (the end result of the destruction of the leucocytes of the blood), some karyoklnesis and cell degeneration similar to that of the Malpighian bodies but not in large areas. In the lymphatic glands, as I have said, the changes described by Bar- bacci are essentially those seen in the Malpighian bodies of the spleen. In the glands, however, hyperaemia is more common. Barbacci concludes by pointing out that the diphtheria poison has a great affinity for the nuclei of the leucocytes, for liver cells, etc. The white blood corpuscles are attacked in the blood, spleen, lymphatic glands and bone-marrow. The results of this action on the leucocytes of the blood are seen in the nuclear fragments in the spleen pulp. The liver nuclei tend rather to swell and fade than to fragment. I have given at some length a summary of the chief lesions produced by the diphtheritic poison in the spleen and lymph glands, because they are so strikingly like the lesions seen in our cases as to make it seem most probable that a similar poison has been at work here. In this connection the changes described by Flexner as resulting after ricin poisoning (in the guinea-pig) are also of interest. Lymphatic glands: hsemorrhages, vessels dilated and packed with ery- throcytes, often extreme nuclear fragmentation, some karyoklnesis. Intestinal lymph apparatus: much cell degeneration, some increase in the number of cells, cell elements of the villi destroyed. Spleen: Malpighian bodies show similar changes to the lymphatic glands. Liver: capillary endothelial cells fragmented; leucocytes likewise. Focal coagulation necrosis; other areas of simple death; cell debris in the lymph channels of the interlobular connective tissue; thrombosis. IV. The Probable Cause of Death in the Oases Studied. In Part I we reviewed at some length tlie many theories tliat have been held concerning the cause of death after superficial bums. Most of these we found to be supported by very insuificient evi- dence. The three hypotheses which seemed to have the most war- rant were those based on the ideas of vaso-motor changes, of throm- bosis, and of a toxaemia. It is not unlikely that all three are import ant factors in producing the fatal symptoms following burns. A fourth factor, direct injury of the internal organs by the heat, is probably important only in those cases where the burning imme- diately results in death. How important a part the nervous system may play in the path- ological changes following burns it is not possible to say. Too little is known of its influence in general constitutional aflections, so that it would seem better to seek for objective evidence of other causal Digitized by Microsoft® Probable Cause of Death. IT 5 factors before forming ingenious hypotlieses. In our cases all tlie pathological alterations found in the tissues may be accounted for witbout assuming that tbe nervous system was an active factor in the process. Of course, however, such activity cannot be excluded. These pathological changes are to be ascribed to alterations in the blood. Though certain of the erythrocytes are altered morphologi- cally, we would refer neither the pathological lesions found after death nor the clinical symptoms seen before death to destroyed red corpuscles. Nor does thrombosis, which seems to have been so prominent a feature in the pathological changes in the dogs experi- mentally burned by Silbermann, seem to have been important in our cases. The thrombi were few in number except in the skin, and unimportant in distribution. The alteration in the blood, to which we would refer the lesions found in our cases, we rather hold to be the presence in the plasma of poisonous substances. The nature of these substances and their mode of origin are mere matters of conjecture. "We do not at present possess methods which can be relied upon to furnish them in satisfactory form. That they exist we may safely assume from the lesions, the nature of which we have already so fully discussed. "We feel fairly certain that death in each of the five cases studied by us was the result of an acute toxaemia. "We think that the possibility of a toxaemia after exten- sive superficial burns should be taken into account in the treatment of similar cases.' V. Bibliography.' Ajello and Parascandolo : Gazzetta degli ospedali e delle cliniche, Mlano, XVII, pp. 866-872, 1896. [Keview, Oentralblatt f. innere Med. (1896), p. 1303.J ' Since working up the cases described above I have had the opportunity of studying the tissues from the bodies of two adults whose death was due to superficial burns. In each case lesions similar to those described above were found, but the lesions seemed less marked in the lymphatic tissue of the adults than they were in those of the children. We purposely forego a discussion of such other aspects of the general subject as the relation of superficial burns to gastric and duodenal ulcer- ation; to the manner of the injury, as by heated oil, water, and other sub- stances. = Only the more important articles treating of experiments on animals, or giving statistical summaries of autopsy reports, or finally, very com- plete accounts of individual autopsies, are referred to here. For a list of Digitized by Microsoft® 176 Charles Bussell Bardeen. AydakofC: (a) Dissertation, St. Petersburg, 1876. (b) Medic. Vestnik, XYI, p. 4, St. Petersburg, 1876. Baraduc: Des causes de la mort a la suite des brulures superficielles. Paris, 1862. Baumeister: Dissertation, Bonn, 1869, pp. 31. Billroth: Arcb. f. klin. Ohinurgie, VI, pp. 406-408, 1865. Boyer and Guinard: Des brulures, Paris, 1895, pp. 186. Bunzeli: Arch. f. exp. Patb. u. Pbarmakol. Leipzig, 1896, XXXVII, pp. 445-466. Oatiano: (a) Vircbow's Arcb., LXXXVII, pp. 345-363, 1882. (b) AUgem. Wiener medic. Zeitung, XXVII, pp. 271-285, 1882. Cumin: Edinburgb Medic, and Surgio. Journ., XIX, pp. 337-344, 1823. Curling: Acute ulceration of tbe duodenum. Medicb-Cbirurgical Transactions, XXV, pp. 260-281. London, 1842. Degranges: Journ. de medec. de Bordeaux, XIII, pp. 385, 577, 705, 1855. Dupuytren: Legons orales, IV, pp. 503-604, 1839. Ericbsen: London Medic. Gazette, 1843, pp. 544-553, 588-593. Talk: (a) Arcb. f. Anatomie, Pbysiologie u. wissenscb. Medizin. Leipzig, 1870, pp. 374-394. (b) Vircbow's Arcbiv, LIII, pp. 27-69, 1871. (c) Atlanta Medic, and Surg. Journ., X, p. 288, 1872-73. Feltz: Gazette d. Hopitaux, XLIII, p. 229. Paris, 1870. Fiscber: Lebrbucb der allgem. Cbirurgie, Stuttgart, 1887, pp. 142- 153. Foa, Pio : Eivista sperimentale, VII, 1881. Med. leg. , pp. 1 3 5-143 . Foa and Pellacani: Pt. I and II in year VI of Eivista, p. 195. FoUin: Traite de patbologie extern., I, p. 521, 1860. Fraenkel, Deutscb. medic. Wcbscbft. Leipsic, XV, p. 22, 1889. Guensburg: Ztscbrft. f. klin. Medizin. Breslau, 1850, pp. 401-415. Heyf elder: Jabrbucb der deutscben Medizin und Cbirurgie, X, 2, pp. 57-61. Hannau, 1825. most of the autopsies reported previously to 1883 see Schjerning's article. He gives references to the literature of eases In which the body was burned after death, to those where death took place during the burning, and to those cases where more than half an hour intervened between the burning and death. In the last class of cases he gives in addition a short summary of the pathological report of each case. Digitized by Microsoft® Bibliography. 177 Hocli: (a) "Wiener medic. Wchschrft., XLIII, pp. 737-741, 1893. (b) Wiener med. Blatter, XVIII, p. 183, 1895. Holmes: Bums and scalds, System of Surgery, I, pp. 723-752. London, 1860. Hoppe-Seyler: Zeitschrift f. physiolog. Chemie, V, 1881. Horrocks: Saprsemia in burns, Lancet, 2, p. 868. London, 1891. Kijanitzin: (a) CMrurg. Vestnik. St. Petersburg, 1893. (b) Vir- cbow's Arcbiv, CXXXI, pp. 436-467, 1893. (c) Arcb.. de medeciue experimental, etc., VI, pp. 731-768. Paris, 1894. Klebs: Miincbener JSTaturforscberversammlung, 1877. Krieger: Untersuchung iiber Entstehung der entziind. Krankbeiten. Strassburg, 1876. Kuebne: Lebrbucb der physiolog. Chemie, 1868, p. 61. Lascbkewitscb: Arcb. f. Anat. und Pbysiologie, 1868, p. 61. V. Lesser: Virebow's Arcbiv, LXXIX, pp. 248-310, 1880. Long: London Medical G-azette, I, p. 743, 1840. Lustgarten: "Wiener klin. "Wcbscbrft., 1891, No. 29, pp. 528-531. (Also given before tbe New York Dermatological Society, April 28, 1891.) Lustig: Medicinische Zeitscbrift der versammten Heilkunde, 1860. Maas: Verbandlung des Obirurg. Congress, 1881. Maison: These de Paris, 1875. Markonet: Laitop Kbirurg. Obsb. v. Moskvai, IV, p. 252. Moskow, 1881. Markusfeld und Steinbaus: Centralblatt f. allgem. Pathologic, etc., VI, pp. 1-4. Jena, 1895. Mendel: (a) Vierteljabrscbrift f. gerichtliche Medicin, XIII, pp. 93-139. Berlia, 1870. (b) Analyse des annales d'hygiene publique et de medecine legale, XXXIX, 1873. Morton: Encyclopedie international de Chirurgie, 1883. Passavant: (a) Deutsche Kritik:, X, pp. 348-365. Berlin, 1858. (b) Schmidt's Jahrbuch, CII, p. 216. Patak;: Combustio; ulcus duodenalis perforans. Orvosi. hetil., XXIX, pp. 248-250. Budapest, 1885. Pawlowsky: (a) Chir. Laitop., Moskow, XIV., pp. 559-563, 1894. (b) Atti d. XI Cong. med. intemaz., 1894, Koma, 1895 IV Cbirurg., p. 267. Pflanze: Dissertation, Greifswald, 1893, pp. 34. Ponfick: (a) Berliner klin. Wcbscbrft, 1876, No. 17. (b) Amtl. Digitized by Microsoft® 1Y8 Charles Russell Bardeen. Ber. ii. d. Versamml. deutsch. ISTaturf. u. Aerzte, Miinoken, 1877, pp. 259-261. (c) Berliner klin. Wchschrft., 1883, No. 26. Pouchet: Exper. sur la congelation des animaux. Rouen, 1865. Eeiss, W.: (a) Wiener med. Wchschrft., XLIII, pp. 59-61, 1893. (b) Arch. f. Dermatologie und Syphilis, Erganzungsheft, 1893. Remy: These de Paris, 1835. Roger, H. : Qiielques effets des excitations cutanees, etc.. Arch, de Physiologic, 1893, p. 17. Salvioli: (a) Arch, per le scienze medic, XV, pp. 157-191, Torino et Palermo, 1891. (b) Arch, italiennes de biologie, XY, 1891. (c) YirchoVs Archiv, OXXV, 1891. Schjerning: Vierteljahrschrift f. gerichtliche Medicin, N. P., XLl, pp. 24-66 and 273-300; XLII, pp. 66-104, 1884-1885. Schlesinger: Virchow's Archiv, OXXX, p. 150, 1893. Schneider: Medic. Annalen, X, pp. 140-164. Heidelberg, 1844. Seliger: Vierteljahrschrift f. gerichtliche Medicin, XLIV, 1887. Seydel: Vierteljahrschrift f. gerichtliche Medicin, XL VIII, pp. 253-263, 1891. Silbermann, O. : (a) Centralblatt f. die medic. Wissenschaften, XXVII, p. 513. Berlin, 1889. (b) Virchow's Archiv, CXIX, pp. 488-523, 1890. (c) Jahresbericht des saehsisches Gesell- schaft f . vaterlandische Oultur, LXXI, I Abtheikmg medic. Section, pp. 52-55. Breslau, 1893-1894. Sonnenburg: (a) Deutsche Zeitschrift f. Chirurgie, IX, pp. 138- 159. Leipzig, 1878. (b) Verbrennung und Erfreiung. Stuttgart, 1879. Spiegler: Wiener med. Blatt., 1896, XIX, pp. 259, 277, 194, 310. Stilet: (a) Boston Medical and Surgical Journal, LXX, June 18, 1864. (b) Schmidt's Jahrbuch, CXLI, p. 104, 1869. Tappeiner: Centralblatt f. die medic. Wissenschaften, 1881. Treichler: Schweizer Zeitschrift f. Medic, Chirurg., etc. Ziirich, 1853, pp. 229-235. Trojanoff: Dissertation, St. Petersburg, 1882. Tschmarke, P.: Deutsche Zeitschr. f. Chir. Leipzig, 1896, XLIV, pp. 346-392. Welti: Inaug. Diss., Zurich, 1889. (b) Correspondenzblatt fiir schweizer Aertze, 1889. (c) Beitrag zur pathologischer Ana- Digitized by Microsoft® Bibliography. 179 tomie, etc., IV, pp. 519-556. Jena, 1889. (d) Drei Falle vooi Verbremnuigstodes, Centralblatt fiir allgem. Patliologie. Jena, 1890, pp. 537-550. Werner: Zeitschrift fiir Wundarzte, pp. 82-91, XX. Stuttgart, 1867. WertKheim: (a) "Wiener medic. Presse, VIII, pp. 1237-1239, 1867. (b) Wiener medic. Wocbenblatt, 1867, p. 144. (c) Woehen- blatt d. k. k. Gesellschaft der Aerzte in Wien, 1868, l^o. 13. (d) Wiener medic. Presse, IX, p. 309, 1868. (e) Ibidem, p. 605. (f) Oesterreichische medic. Zeitung, XVI, p. 38, 1868. (g) Wiener medic. Wocbenschrift, XVIII, p. 826, 1868. (h) Medic. Jabrbncb, XVI, pp. 36-46. Wien, 1868. (i) Vir- cbow's Arcbiv, 1886, Winkelmann: Inaug. Diss., Erlangen, 1893. Zolotareff : Medic. Pribar Mossk Sborniku. St. Petersburg, 1887, p. 329. Digitized by Microsoft® Digitized by Microsoft® Digitized by Microsoft® Digitized by Microsoft® Digitized by Microsoft® Digitized by Microsoft® Digitized by Microsoft® Digitized by Microsoft® Digitized by Microsoft® Digitized by Microsoft® Digitized by Microsoft®