'■^hhiiniii\i\i\iKil'u(\yi\.i,t\{. i.it..;.. ■ :v.-. ■.;j-.nr.unjmjwv,.'.> {?: :<*us;?i$et0)i;tfWpm, w NATIONAL LIBRARY OF MEDICINE Bethesda, Maryland If' ■ Gift of Alan Banov and Jane Banov Bergen From the Library of Leon Banov, Jr., M.D.. Charleston, South Carolina *• * p.. 6791 rf £*#. (P. >jo 0 §1 w "S'S p M-S si ■g-a A ■a " K Iw P B . o «w £ 0 Is M «! "cla h! a S t= a* fc ga «13^ II bone, tendons, and peripheral nerves. Complete restoration of a peripheral nerve frequently takes place after resection of more than an CICATRIZATION. 21 inch of its continuity. In subcutaneous tenotomy the tendon-ends may be kept separated for two or more inches, and yet after a few months it would be difficult to ascertain, even after the most careful examination, the site of operation. The fractured ends of a broken bone may be completely separated by lateral displacement during the entire time required in the healing process, and yet they are firmly united by the interposition of a connecting bridge of new bone. In other tissues endowed with less reparative energy, as for instance the muscular fibre, a slight separation results in the formation of cicatricial tissue between the anatomical structure which it is the intention to unite. By cicatri- zation is therefore understood the completion of the reparative process, and the term does not necessarily imply the formation of a permanent cicatrix. An ideal healing culminates in the formation of tissue which effects a physiological restitution of a defect caused by injury or disease. As a rule, it can be stated that the result will be satisfactory in proportion to the amount of granulation tissue produced or required in the process of repair. In an aseptic wound the reparative material will not be in excess of the local demand, and the demand will depend on the degree of accuracy of approximation of the surfaces of the wound. Cicatrization begins in the ganulation tissue nearest the pre- formed vessels; that is, the margins and surface of the wound. The embryonal connective-tissue cells, or fibroblasts, as they are called, at first round, become elongated with thread-like prolongations from the extremities. The new connective tissue contracts, thus bringing the margins of the wound or granulating surface in closer apposition, and by its constricting effect assisting in the obliteration of superfluous vessels. The cicatrix or scar will be large if the process of granulation has been in excess of the demand, or if a large defect had to be healed by the deposition or interposition of a large quantity of cicatricial material. Large scars should be prevented, if possible, by appropriate treatment, as from the contraction they give rise to distressing deformities, and from their low vitality they furnish a permanent predisposition to ulcer- ative processes and not infrequently become the seat of malignant Fig. 16.—Embryonal Connective- tissue Cell Undergoing Transfor- mation into Mature State. (Ziegler.) A, the cell-body; still contains a considerable amount of protoplasm, which, however, gradually di- minishes toward D, where it represents a mature connective-tissue cell with a very small amount of protoplasm surrounded by connective-tissue fibres. 22 PRINCIPLES OF SURGERY. disease. After the healing of any ulcer of considerable size upon the mucous surface of any of the hollow viscera the cicatricial contraction often gives rise to the formation of strictures. Nerves appear to form in granulations, as these are often exceedingly tender to the touch. Their existence, however, has not been demonstrated. The pain and tenderness may be caused by force being transmitted to subjacent nerves. According to Vanderkolk, no lymphatic vessels are present in granula- tion tissue. During the process of cicatrization all the embryonal cell- elements undergo transformation into mature tissue, the fibroblasts are converted into connective tissue, the angioblasts into vessels, the myoblasts into muscle-fibres, the osteoblasts into bone, etc., each histo- logical element represented in the wound or defect furnishing the material for its own repair. EPIDERMIZATION. A wound of the external sur- face of the body can be said to have healed after the completion of epi- dermization. In accordance with the general law of succession of cells, epidermization takes place ex- clusively by proliferation of pre- formed epithelial cells. The new epithelial cells have a more or less rounded shape, and cover the granu- lations from the margins of the wound, where the new skin appears Fial7--WFZXol™rCmS as a bluish-pink pellicle. At first a, old epithelial ceiis upon edge of wound of skin, with they do not readily adhere to the proliferation of nucleus. J J granulations, but appear to cover them (Fig. 15, E') ; later, however, they throw down long processes which penetrate the granulations, and in this way obtain a permanent foothold. New epithelial cells possess amoeboid movements, may become detached from the epithelial matrix, and wander some distance and form perma- nent attachments, and in such an event an independent centre of epider- mization is established. Migration of epithelial cells was first observed and described by Klebs in superficial wounds in the skin of the frog. The irregular projections of the new skin over the granulations, so frequently observed during the healing of wounds by granulation, is undoubtedly often due to such a displacement of embryonal epithelial cells. In granulating surfaces following destruction of the skin by burns, caustics, or ulceration, independent centres of epidermization are often ��99999 POSITIVE INDICATIONS IN THE TREATMENT OF WOUNDS. 23 seen in the midst of the field of granulations. In such cases the entire thickness of the skin at some points has not been destroyed, and epi- thelial proliferation takes place from remaining remnants of glands, as is well shown at F and G in Fig. 15. The granulations in the immediate vicinity of the zone of epidermization become reduced in size, the blood- vessels are diminished in number, and the subjacent fibroblasts are rapidly converted into connective tissue. In wounds of the skin which heal without visible granulations the papillae are absent from the cicatrix, even although it be broad from subsequent yielding to traction. In wounds healing by open granulations new papillae are formed in the new skin, because the capillary loops atrophy downward and become the papillary vessels. Epidermization and cicatrization are favorably influ- enced by measures which secure for the wound an aseptic condition throughout, and by keeping the delicate granulations covered with pro- tective silk until the wound is completely healed. POSITIVE INDICATIONS IN THE TREATMENT OF WOUNDS, WITH SPECIAL REFERENCE TO SECURE UNION BY FIRST INTENTION. Absolute Asepsis.—Absolute asepsis can only be secured by strictest antiseptic measures. Surgical cleanliness is more than ordinary clean- liness. Antiseptic precautions are employed for the purpose of securing for the wound and everything that is brought in contact with it an aseptic condition. The mechanical removal of microbes from the field of opera- tion by shaving and washing with warm water and potash-soap should be as thorough as possible, but cannot be relied upon in securing asepsis. The surface must be disinfected with a reliable germicidal solution, either a l-to-1000 solution of corrosive sublimate or a 4-per-cent. solution of carbolic acid. Accidental wounds must always be considered as infected wounds, and a faithful effort must be made to render them aseptic by exposing, if possible, the entire wounded surface to the direct action of one of these solutions, while the surface for a considerable distance around it is also disinfected. Recently, a weak solution of the double cyanide of mercury and zinc has been recommended by Sir Joseph Lister as an antiseptic, and, from his experimental investigations and clinical experience, it appears that this substance possesses an advantage over carbolic acid, corrosive sublimate, and other antiseptics, as it exerts an inhibitory effect upon microbes which still may remain in the wound or its immediate vicinity, which prevents them from multiplying in the tissues or in the dressing. The hands of the operator and his assistants are to be cleansed by washing in warm water and potash-soap, and then disinfected in a l-to-1000 sublimate solution, and, lastly, washing in abso- 24 PRINCIPLES OF SURGERY. lute alcohol. Special care is to be exercised in cleansing and disinfecting the space under the finger-nails. On each side of the wound or field of operation a towel wrung out of an antiseptic solution is spread smoothly, in order that, during the operation, instruments and sponges will not be contaminated by being brought in contact with non-aseptic clothing or surface. None but sterilized sponges are to be used, and, in the absence of such, pieces of aseptic gauze, folded into convenient shape, should be used as substitutes. The cheapest and most reliable method of disinfection of instruments is to boil them for five minutes- and then place them upon an aseptic towel, ready for use. If these anti- septic precautions have been faithfully carried out, sterilized water can be used for irrigation during the operation, or the dry method of operat- ing recently introduced into practice by Landerer can be followed In operating upon aseptic tissues or in the treatment of aseptic wounds* In the operative treatment of suppurative affections, irrigation with a l-to-5000 solution of sublimate must be frequently resorted to during the operation, and, in the removal of tubercular products, irrigation with an aqueous solution of the tincture of iodine, made by adding enough of the tincture to sterilized water to impart to the solution a sherry color, should be used. CAREFUL HJEMOSTASIS. The presence of a blood-clot between the surfaces of the wound is objectionable for the following reasons : 1. It separates mechanically the surfaces which it is intended to unite. 2. It serves as a culture medium for micro-organisms, which, if in contact with living tissue, might remain harmless. 3. It gives rise to tension, and consequently becomes pro- ductive of pain and an undue degree of reflex irritation. For years, von Bergmann has insisted that careful arrest of haemorrhage is one of the most urgent and important indications in the treatment of wounds, and his teachings merit the attention of every prudent surgeon. Bleeding points should be tied with sterilized catgut or silk. A number of sur- geons have discarded catgut, as it is more difficult to render it aseptic than silk. The latter can be readily sterilized by boiling. The haemor- rhage that so often interferes with an ideal healing of the wound is the capillary or parenchymatous oozing, and this should always be carefully arrested before the wound is sutured. The following measures should be resorted to in controlling this form of bleeding, and in the order named: 1. Position. 2. Surface compression. 3. Hot-water irrigation. 4. Anti- septic tampon. 1. In wounds of the extremities, capillary oozing is usually promptly arrested by holding the limb in a perpendicular position. In this position the intraarterial pressure is diminished and the return of venous blood ACCURATE SUTURING. 25 favored, both of which are important elements in diminishing the amount of blood in the capillary vessels. In order to produce the desired effect, this position should be maintained for fifteen to twenty minutes, and the limb should be kept in this position for at least six hours after the operation. 2. Surface pressure with a flat sponge or a compress mechanically arrests the bleeding, and the capillary vessels, partly or completely emptied of blood, are placed in a more favorable condition for the forma- tion of a thrombus. After an amputation, for instance, the sponge or compress is applied to the surface of the cut muscles and the flaps are laid over it, and compression with two hands applied, with the limb in a perpendicular position before the elastic constrictor is removed. Com- pression, continued in this manner for ten or fifteen minutes, will usually be successful in completely arresting parenchymatous bleeding. 3. Irrigation with water at a temperature sufficiently high to coagu- late the albumen on the surface of the wound seals mechanically the cut vessels, and, at the sa»e time, produces a localized anaemia by contract- ing the terminal art#-ia,l branches. A temperature of 120° F. will answer for this purpose. 4. Styptics should never be employed in arresting bleeding from a recent wound. If the procedures mentioned fail in accomplishing the desired object, the wound should not be sutured until haemorrhage has been completely checked by the use of the antiseptic tampon. The wound is packed with iodoform gauze, and the customary dressing is applied in such a manner as to exercise uniform gentle pressure. After twenty-four hours the dressing and tampon are removed, and the wound closed with sutures. In such cases secondary suturing is of great value in securing a speedy and satisfactory healing of the wound. ACCURATE SUTURING. Brilliant operators are not always the best surgeons. The best results in surgery follow the one who is most painstaking in following out the minutest details. This assertion applies most forcibly in the treatment of wounds. The surgeon here occupies the position of handmaid to the vis medicatrix naturae, and in the exercise of his duties must do all in his power to tax only to a minimum extent the regenerative resources of the wounded tissues. In the treatment of wounds it becomes his imperative duty, not only to unite the surfaces of the wound accurately and neatly, but to unite, whenever it becomes necessary, tissues of the same anatomical structure and physiological function. Divided nerves, tendons, muscles, fascia, must be separately united with buried sutures before the wound is closed by the ordinary interrupted or continuous 26 PRINCIPLES OF SURGERY. suture. When several nerves or tendons have been divided in the same wound, great care must be exercised to unite the ends of the same nerve or tendon. Accurate approximation of a deep wound is impossible without the buried suture. Several rows of these sutures may be re- quired. Reliable catgut should be preferred for the deep sutures, but if this material is not at hand fine silk can be used. The best materials for the ordinary interrupted sutures are silk or silk-worm gut. Separate sutures for the skin are usually required in order to approximate the superficial margins of the wound accurately. If the surgeon has reason to believe that the wound is aseptic, drainage should be dispensed with, because the manner of suturing, as just described, guards against the occurrence of " dead spaces." An absorbent antiseptic compress, com- posed of a few layers of iodoform gauze and a thick layer of salicylated cotton, or sublimated moss or wood-wool, is the most appropriate dress- ing for such cases. The bandage to retain this dressing is applied in such manner as to exercise uniform equable compression,—an important element in affording support to the injured vessels and in securing rest for the parts involved in the injury. PHYSIOLOGICAL REST. In the after-treatment of a wound nothing is more important than to secure for the parts which have been mechanically united, as far as possible, physiological rest. The importance of rest in the prevention and treatment of inflammation has been prominently brought forward by Hilton, and his teachings have resulted in a great deal of good in the treatment of inflammatory surgical affections. If one of the extremities is the seat of the wound, immobilization upon a splint or with a plaster- of-Paris dressing, in such a position as to relax the muscles involved in the wound, is of paramount importance. The injured part must be kept in a position which will favor a normal blood-supply and prevent passive hyperemia. A wound properly dressed should not be disturbed until union has taken place. If any one of the three most important indica- tions for a change of dressing—pain, rise in temperature, and saturation of the dressing with wound-secretions—do not arise, the first dressing is allowed to remain for eight days to six weeks, according to the location, character, or size of the wound. In wounds of the gastro-intestinal canal, physiological rest is secured by abstinence from food, and, if necessary, peristalsis is diminished by a few doses of opium. In wounds of the bladder distention of the organ is prevented by the introduction and retention of a catheter. In wounds of the brain or its envelopes, rest is secured by exclusion of light and by enforcing quietude in the patient's room. UNION BY SECONDARY INTENTION. 27 UNION BY SECONDARY INTENTION. In an aseptic wound all the new material resulting from proliferation of the fixed tissue-cells is used in the process of repair, and the time for healing of the wound will depend on the anatomical structure of the part injured and the amount of material required to form a bridge of living tissue between the divided parts. As long as the wound heals without destruction of any of the new tissue-elements by specific microbic causes, it is proper to speak of a union by primary intention, whether the healing is completed in three or four days, or whether it is protracted for months until the ultimate object of wound treatment has been reached. From a pathological, and even from a practical, stand- point, it is not correct to include, under the head of healing by the second intention, aseptic wounds that, on account of want of proper approximation, or on account of loss of tissue, have of necessity to heal by granulation, with infected wounds in which the regenerative processes are disturbed by suppuration. In a suppurating wound the embryonal cells which are destined to become transformed into new tissue are exposed to the destructive action of pus-microbes and their ptomaines, their protoplasm is destroyed, and they become one of the histological sources of pus-corpuscles. The cells on the surface of the wound, being most distant from the vascular supply, possess the least power of resist- ance to the action of pus-microbes, and on this account, as well as from the greater number of pus-microbes on the surface of the wound than in the deeper tissues, they are converted into pus-corpuscles. As long as suppuration remains active the superficial layer of granulation cells are destroyed, and as soon as other embryonal cells take their place the process is repeated, and thus the healing of the wound is indefinitely delayed. When a favorable change takes place in the wound, either spon- taneously or from the employment of antiseptic measures, suppura- tion is diminished, the granulations become firmer and more vascular, and cicatrization and epidermization now progress in a satisfactory manner. Such a favorable change in the condition of the wound can be readily explained after the use of such agents as are known to destroy the microbic cause of the suppuration when brought in contact with the wound. In such a case we would naturally expect that, with the removal, destruction, or rendering inert of the pus-microbes, the embryonal cells would remain attached to the point where they were produced, and would soon be converted into tissue resembling the matrix which produced them. Spontaneous cessation of suppuration, and with it the conversion of a surface covered with dead material into a healthy granulating sur- face, would indicate either that the virulence of the pus-microbes had 28 PRINCIPLES OF. SURGERY. become attenuated, that the soil was no longer congenial for their multi- plication, or finally that the resistance on the part of the tissues to then- pathogenic action had become increased. That tissue resistance has a potent influence in neutralizing and modifying the action of pathogenic micro-organisms has been observed clinically and demonstrated experi- mentally. Suppurating wounds are graver affections, and are more difficult to manage in the aged and in badly-nourished persons, as well as in patients debilitated from excesses and other protracted diseases. A good circulation of the part is an important element in counteracting the cause of suppuration. A chronic varicose ulcer of the leg that suppurates freely, as long as the patient continues to use the limb, is often transformed into a healthy granulation surface after a few days of rest in bed, with the affected limb in an elevated position. TREATMENT OF SUPPURATING WOUNDS, WITH SPECIAL REFERENCE TO HASTENING THE PROCESS OF REPAIR. In the treatment of an accidental wound, which always must be regarded as a septic wound, or in the management of a wound where the antiseptic precautions have failed, no time should be lost in securing for the wound and its vicinity an aseptic condition by thorough disinfection. The surroundings of the wound are disinfected in the same manner as for an operation. The wound is exposed as thoroughly as possible to direct treatment by enlarging it over recesses otherwise inaccessible, after which it is thoroughly irrigated with a solution of sublimate (1 to 2000). If the granulations are copious and flabby they must be removed with Volkmann's sharp spoon, and after the bleeding has ceased a 12 per-cent. solution of chloride of zinc is applied; after a few minutes the surplus fluid is washed away by irrigation with the sublimate solu- tion. The wound is now dried, sutured, and drained. Drainage in these cases is a necessary evil, as the surgeon can never feel certain that he has succeeded in obtaining perfect asepsis. If the wound is extensive, or if pus has been burrowing in different directions along the deep tissues, as in cases of compound fracture where a thorough disinfection of every part of the wound, as described above, is impossible or imprac- ticable, constant irrigation with a saturated solution of acetate of aluminum should be instituted and continued until the wound has been rendered aseptic. Acetate of aluminum is a reliable antiseptic, is non- toxic, and penetrates the tissues deeply. The treatment most appro- priate for a recent aseptic wound is to be adopted as soon as suppuration has ceased and the general symptoms at the same time point to an aseptic condition. SUTURING OF GRANULATING WOUNDS. 29 SUTURING OF GRANULATING WOUNDS. If union by primary intention has failed to take place for any reason in wounds which can be closed by suturing, a second attempt can be made to approximate the surfaces with sutures with fair prospects of success as soon as the granulations are in an aseptic condition. Aseptic granulating surfaces when brought in contact unite rapidly, as vascular connections between the new capillary loops are established in a remark- ably short time, and the wound then heals in the same manner as after primary suturing. The cases best adapted for secondary suturing are those where suppuration has ceased, the granulations have become small and firm,—in short, wounds in which cicatrization has commenced. The technique in the treatment of such wounds is the same as in cases of aseptic recent wounds. The advantages of this method of dealing with wounds that have failed to unite are pronounced when the wound is deep and the margins can be coaptated without much tension. Buried sutures can be used for the same purpose and with the same benefit as in the treatment of recent wounds. Before the surfaces are brought in contact with the sutures it is important to disinfect and dry the granulations thoroughly. As secondary suturing is applicable only in the treatment of such wounds where we have every reason to assume that an aseptic condition exists, or can be secured by disinfection, the whole wound should be carefully closed and drainage must be dispensed with, in order to obtain rapid healing of the entire wound. It has been recently suggested by Kahn that in extensive defects of the skin a covering for the wound can be obtained by sliding of the skin, after undermining it for some distance in a direction most suitable. That this procedure is applicable onby under circumstances when the surgeon is sure of asepsis is to be taken for granted, as otherwise it might be followed by gangrene and still greater loss of tissue. CHAPTER II. Regeneration of Different Tissues. In connection with the subject of healing of wounds it is very important for the student to familiarize himself with the vegetative capacity of the different tissues of the body in order to estimate with some degree of accuracy the part taken Iry each tissue in the reparative processes which take place after an injury or disease. No positive proof has yet been furnished that the leucocytes or any other of the cellular elements of the blood take any active part in the restoration of lost parts. It does not appear to me reasonable or logical that such an indifferent cell as the leucocyte should ever become transformed directly into-a fixed tissue-cell, and it is still more improbable that it should be possessed with such a diverse vegetative capacity as to undergo a transi- tion in one place into a connective-tissue cell, in another into bone, and still another into a muscle-fibre. It is much more rational to assume, in the repair of an injury and in the regeneration of a part destro}Ted by disease, that the universal law of legitimate succession of cells asserts itself, according to which the reparative process is initiated and completed by homologous cell proliferation. In the following pages experimental and clinical proofs will be advanced which will at least tend to establish the truth of this assertion. NON-VASCULAR TISSUE. The part taken by blood-vessels in regenerative processes is well shown in the healing of wounds of non-vascular tissue. Large wounds of the cornea and cartilage can only heal after a blood-supply has been established through new vessels from the nearest vascular district. Rapid vascularization of the non-vascular tissues is alwa} s observed when the wound has become infected. Cornea.—The normal cornea contains no blood-vessels, but vascular spaces, which form a system of channels for the circulation of the plasma- fluid. In 1863 Recklinghausen discovered in these spaces migrating corpuscles, resembling in size and shape the white blood-corpuscle, which he regarded as offsprings of the corneal corpuscles. Later, Cohnheim showed that these wandering cells were leucocytes which had escaped from the pericorneal capillary vessels and had found their way into these (31) 32 PRINCIPLES OF SURGERY. channels. In traumatic keratitis these spaces become blocked with leucocytes, and they constitute largely the primary product of inflam- matory exudation long before the fixed cells of the cornea could have yielded such an amount of cellular elements. Strube and His studied experimentally the healing of wounds of the cornea and traumatic kera- titis. They injured the cornea of rabbits by cutting and cauterization. As the cornea is freely supplied with nerves, they observed as one of the earliest tissue changes a reflex paretic dilatation of the marginal blood- vessels. The marginal hyperemia was followed by the formation of new blood-vessels in the direction of the seat of injury. The early opacity around the wound and the space between the wound and the advancing channels are caused by the presence of leucocytes in the vascular spaces ; later, to proliferation of the corneal corpuscles. That leucocytes enter the plasma-canals when the cornea is irritated has been definitely settled by Cohnheim by one of his most ingenious experiments. He injected finety-divided carmine suspended in an acid, or precipitated aniline into the dorsal lymph-sacs of frogs, with the result that when he irritated the cornea, a few days later, leucoc3Ttes stained with the pigment-material appeared at the margin of the cornea where cell-migration was known to appear first. He found a rapid increase of corneal corpuscles in the animal subjected to experimentation; thus, in one instance, eighteen hours after the injury, he found, in spaces normally occupied by one corpuscle, as many as 20 to 30 3roung cells closely packed together. Hamilton regards as the first change in an irritated cornea an in- crease of the plasma-current which may destroy the endothelial lining of the canals, and according to this observer cell-migration into the corneal spaces occurs later. Unimpaired innervation of the cornea is an important factor in the prompt healing of wounds of this structure, as it is well known that in patients suffering from glaucoma, and in the aged, wounds of the cornea heal often in a very unsatisfactory manner. An aseptic wound of a normal cornea heals without opacity; the new corneal corpuscles, after they attain maturity, transmit light as perfectly as the cells from which they are produced. Imperfect restoration of tissue is to be expected when the regenerative process is complicated by a suppurative inflammation with considerable destruction of tissue. Gussenbauer incised the cornea in rabbits half-way between the centre and its margin to the extent of half a line to a line, and found, in exam- ining the specimens after twenty-four hours, that no union had taken place. The wound-surfaces at this time were glued together by an inter- posed substance. The surfaces of the wound were in close contact at a point corresponding to the middle portion of the cornea, and the gap widened toward each of its surfaces so that the temporary cement- NON-VASCULAR TISSUE. 33 substance represented two cones with their apices directed toward each other and the bases toward the surfaces. On staining the specimens with chloride of gold it was found that this substance contained cells which were most numerous toward the surfaces of the cornea. The cor- neal corpuscles on the cut surfaces were seen to be enlarged and presenting different stages of cell-division. Instead of round the corpuscles were spindle-shaped, some containing one nucleus, others two nuclei; intercellu- lar substance granular. In specimens eight days old the space between the cut surfaces was occupied almost exclusively by new corneal corpuscles, and the edges of the wound could no longer be clearly defined. During cicatrization of the wound the number of cells is diminished, while in form and size they resemble more and more the mature corneal corpuscles from which they were derived. In a non-penetrating incised wound of the cornea the gap is filled Fig. 18.—Corneal Corpuscles in a State of Proliferation. (Senftleben.) A, old corneal corpuscles with one or two nuclei and young offshoots, B and C. up after a few days with young cells derived from the cylindrical cells of the deepest layer of the corneal epithelia. If the wound has penetrated, the posterior third of the wound gaps toward the anterior chamber of the eye, and is first plugged with the products of coagulation necrosis, which is later replaced by epithelial cells from the membrana Descemeti (Fig. 19, C), while the anterior por- tion is occupied by epithelial cells the same as in the non-penetrating wounds. At the end of the first week the corneal corpuscles begin to proliferate, and the cells from this source gradually displace the epithe- lial cells and bring about the definitive healing of the wound. As wounds of the cornea are not sutured, the surgeon should aim to secure approxi- mation by removing coagulated blood if present, and b}' correcting any dis- placements which may be present by direct measures, and finally b}r apply- ing a dressing which will exert uniform and equable elastic compression. 3 34 PRINCIPLES OF SURGERY. Although the antiseptic treatment cannot be carried out with the same precision in the treatment of wounds of the cornea as in other localities, it is at least the duty of the surgeon to use only sterilized instruments and aseptic sponges, and to employ such mild antiseptic solutions as will at least exercise an inhibitory influence upon pathogenic micro-organisms that may be present in the wound or upon the surface of the eye. Cartilage.—Cartilage is in every sense of the word a non-vascular struc- ture, as even the plasma-channels found in the cornea are absent here. Plasma diffusion must take place between or through the cells. It is un- Fig. 19.—Wound of Cornea, (von Wyss.) A-A', new corneal corpuscles; B-A', temporary plug of fibrin; C, epithelia from membrana Descemeti. doubtedly on account of the limited provisions for nutritive supply that the vegetative capacity of this tissue is so exceedingly low. Normal cartilage when injured is unable to repair the defect. The process of healing of wounds of cartilage was first studied experimentally by Redfern. In one experiment he found the wound almost unchanged after twenty-nine days. In one specimen, where the healing process had been completed, he found the defect repaired by connective tissue. The microscopical description of the healing process corresponded with that given by Goodsir of inflammatory processes in this structure. Along the margins Vascular Tissue. 35 of the wound the cartilage-cells multiply and the cement-substance is dissolved. No new cartilage-cells are produced, and the space is occu- pied by connective tissue. Vascularization toward the seat of injury from the marginal vessels of the perichondrium takes place in the same manner as in the cornea. Reitz traced the formation of connective tissue from the cartilage-cells in tracheotomy wounds in rabbits. He observed, after the cement-substance had become dissolved, that the cartilage-cells were transformed into spindle-cells, and later into connective tissue. He found the gap between the divided cartilage-ring filled with such cells a few days after the wound had been inflicted, and explains the discrep- ancy between the results he obtained and those described by Redfern on the ground of the close proximity of vascular supply in his case and the remoteness of vessels from the wound studied by Redfern, as the latter experimented on articular cartilage. Gussenbauer studied the repair of cartilage wounds after incising subcutaneously costal cartilage. In wounds twenty-four hours old a triangular gap was found filled with fibrin and blood-corpuscles. No change was found at this time in the cartilage- cells and cement-substance. The cells of the perichondrium increased in volume and changed in form. Gussenbauer was unable to verify the observation made by Reitz in wounds of trachea, that cartilage-cells are transformed into connective-tissue cells, and believes that the ammonia used by Reitz to provoke croupous pneumonia, by its introduction into the bronchial tubes through the tracheal wound, may have modified the result. He traces tissue proliferation almost exclusively to the peri- chondrium, the cells of which were found in all stages of division and development, while only a few of the cartilage-cells presented evidences of segmentation. Dorner studied not only the manner of repair of simple incised wounds of cartilage, but also produced more complicated injuries, and invariably found that the perichondrium took a more active part in the process of healing than the cartilage-cells. Wounds of fibro- and reticulated cartilage heal in the same manner as wounds of hyaline cartilage. The histological changes observed by Redfern, Dorner, and Gussenbauer during the repair of wounds of cartilage are descriptive of the changes which attend chondritis. VASCULAR TISSUE. The healing of wounds of vascular tissue is accomplished more rapidly than of non-vascular tissue, as the primary wound-secretion, which is derived mostly from the wounded vessels, forms a temporary cement-substance which glues the parts together,—a condition which renders material assistance in maintaining coaptation,—while the direct blood-supply to the injured part cannot fail in increasing the vegetative i 36 PRINCIPLES OF SURGERY. capacity of the cells, and, lastly, the leucocytes present in the recent wound serve as food for the cells, which are undergoing karyokinetic changes. As a rule, to which there are few exceptions, it may be stated that the rapidity with which the healing process is completed is propor- tionate to the vascularity of the wounded part. For instance, wounds of the fingers heal much more rapidly than wounds of the arm or fore- arm, and wounds of the face more rapidly than wounds of the neck. Karyomitotic changes are first noticed in the nuclei of cells in close proximity to blood-vessels. In studying the healing of wounds of vascular tissue, Graser noticed that the connective-tissue cells a little distance from the surface of the wound were first to show evidences of karyokinetic changes; hence, it is apparent that the reparative process is initiated in cells most favorably located in reference to an abundant blood-supply, which corresponds to the location of capillary vessels which are undergoing dilatation prior to the formation of new blood- vessels. Regeneration of tissue takes place most rapidly in parts where new blood-vessels are developed early, rapidly, and abundantly. The healing process is retarded or completely suspended when the capillary vessels, new and old, are seriously altered by inflammation. Surface Epithelia.—Epithelial cells in a normal condition receive no direct blood-supply, but their relations to the subjacent vascular tissue are so intimate, and their proliferation in the healing of surface wounds and in the repair of defects caused by pathological conditions is so largely dependent on the development of new blood-vessels, that the study of their regeneration among the vascular tissues appears appro- priate. In the consideration of this subject of epidermization, it has been shown that epithelial cells are derived exclusively from an epithelial matrix, either from the margin of the wound or an islet of the epiblast buried among the granulations. Regeneration of epithelial cells of the hypoblast takes place in a similar manner as has been described in epidermization of a wound of the cutaneous surface. Of special interest is the rapid regeneration of the gastro-intestinal mucous membrane. A recent gastric or intestinal ulcer presents elevated and swollen margins, and as long as this condition remains the healing process fails to become established until the swelling subsides, and paving of the granulations with epithelial cells is postponed until the surface of the ulcer is nearly on the same level with the surrounding border of the mucous membrane. Griffini and Vassale made gastric fistula in dogs for the purpose of studying directly, and during the life of the animals, the process of repair of wounds of the mucous membrane of the stomach. Through the fistula they made superficial wounds of the inner surface of the organ, and from their observations they satisfied themselves that VASCULAR TISSUE. 37 healing takes place rapidly, and that regeneration of epithelial cells occurs in the peptic glands, where even as early as the third day the epithelial cells showed evidences of active proliferation. The new epithelial cells spread over the interglandular spaces, while a part of the glandular structure is lost during the process of healing. In traumatic defects where the glands have been excised with the mucous membrane the epithelial covering of the granulating surface is derived from the preformed epithelial cells of the mucous membrane bordering the wound. At a later stage new glands are formed by karyomitotic cellular changes after the normal type of development of glands in the embryo. Even the youngest glands have an outlet, and the structure increases in depth by extension of mitotic changes in that direction. Pepsin-secreting cells are found only after the glands have attained nearly their normal depth. In one instance they were found only partly developed on the fortieth day. Connective-tissue proliferation takes no essential part in the growth and development of the new glands. Visceral wounds of the stomach heal kindly and rapidly. Even gunshot wounds of this organ, when made with a small bullet, may heal without surgical interference, more especially if at the time the injury has been inflicted the stomach is empty and all food is withheld for a few days. A strict diet is important in the treatment of wounds or ulcers of the stomach, as Leube has obtained excellent results from treatment of chronic ulcers of this organ by an exclusive milk diet. Griffini also made the observation that the traumatic defects which he produced in the interior of the stomach of dogs healed most rapidly when food was withheld entirely for a few days, and later on nothing but milk was allowed. From these observa- tions and experiments it is evident that the young cells are unfavorably affected by the action of the gastric juice. Quincke has demonstrated experimentally, which has been a long- known and familiar clinical fact, that anaemia retards regeneration of the gastro-intestinal mucous membrane. In two dogs a gastric fistula was made, and through it a defect of the mucous lining was made of the same size in both animals. One of the animals was in perfect health, and healing was completed in eighteen days. The other dog was anaemic, and the healing process was prolonged thirty-one days. In the healing of an ulcer of the stomach or any portion of the intestinal canal the epithelial cells are first to take an active part in establishing a process of repair, the connective-tissue cells entering later upon their part of tissue production. The healing process terminates most satisfactorily when only a small amount of connective tissue is formed and the epithelial covering is completed in a short time, as such a scar represents almost to perfection the normal tissue it has replaced. If a large 38 PRINCIPLES OF SURGERY. quantity of granulation tissue is produced by the connective tissue, and the formation of the epithelial covering is delayed for a long time, or is imperfectly accomplished, there is great danger of subsequent cicatricial contraction of the new tissue producing a stricture. The best possible prophylactic means against the occurrence of strictures under such circumstances are such dietetic and therapeutic measures as will secure for the ulcerated or wounded surface such favorable conditions as will expedite the paving of the surface with epithelial cells and limit the production of cicatricial tissue. TRANSPLANTATION OF SKIN. Epidermization of a large granulation surface is a slow process, even under the most favorable circumstances, and the resulting cicatrix is often large, gives rise to contractions, and not infrequently becomes the seat of keloid or ulcerative processes subsequently. Modern surgery offers means by which this tedious process can be materially shortened, and healing is accomplished by the formation of a more satisfactory scar. Skin-grafting to Expedite the Healing of Granulating Surfaces.—In 18T0 Reverdin discovered that small, thin pieces of superficial skin, transplanted upon a healthy, granulating surface, formed, in a short time, organic connections with the granulations, and that epidermization pro- ceeded independently from such transplanted islets of skin. Later, Schwenninger demonstrated, by his experiments, that hairs could similarly be transferred to a granulating surface. An open, granulating wound or ulcer can be covered over with epidermis in a short time by resorting to Reverdin's method of transplantation of skin. The most essential condition for success is an aseptic condition of the granulations. In suppurating wounds this method of treatment is not applicable until suppuration has ceased and the granulations are small and firm. The part from which the skin is to be taken, in preference the thigh or arm, should be shaved and disinfected. The only instruments required for cutting and transferring the skin is an ordinary sewing-needle fixed in a needle-holder, or, what is still better, a pair of haemostatic forceps and a sharp razor. With the needle the skin is transfixed, and with a razor a thin section the size of the circumference of a split pea is removed and at once transferred to the granulating surface with the needle in such a manner that the cut surface is brought accurately in contact with the granulations. As the detached portion of skin always curls toward the raw surface at its margins, it must be carefully flattened out with the point of one or two needles, care being taken to imbed it well among the granulations without causing any bleeding. The grafts are planted in rows, commencing near the border and leaving small spaces between TRANSPLANTATION OF SKIN. 39 the separate grafts. Each row of grafts is then separately protected with a narrow strip of protective silk, and a thick, antiseptic compress is applied and retained by a bandage, which should exercise uniform gentle compression. The dressing should not be removed in less than a week. At this time the grafts will not only have become firmly attached to the subjacent surface, but each of them has become surrounded with a zone of new epithelial cells. As each graft now constitutes an inde- pendent centre of epithelial proliferation, the remaining portion of the granulation surface soon becomes paved by new epithelial cells, and epidermization and cicatrization are rapidly completed. The results obtained by this method of treatment have not always been such as to satisfy the earlier expectations. The new skin is but a poor substitute for the normal structure. Epidermization is hastened, and the results are better than after-healing without skin-grafting, but the ideal result, the formation of tissue resembling true skin, is not obtainable by this method of skin transplantation. Skin-grafting in the Treatment of Recent Wounds.—If after an operation or injury it is found that a too extensive defect of the skin renders approximation by suturing impossible, the surgeon has it now in his power to supply the defect at once by taking large skin-grafts from another part of the body, or from another person, and planting them in the form of a mosaic upon the raw surface. This method of skin-grafting in the treatment of extensive superficial wounds, as after the extirpation of a lupus, or a surface epithelioma, was devised by Thiersch. Experience has shown that grafts of the whole thickness of the skin, and an inch square, if planted smoothly upon the raw surface and kept uninterruptedly in contact with the wound by an appropriate dressing, not only retain their vitality, but enter rapidly into organic connections with the part with which they have been brought into con- tact, and, at the same time, their anatomical and physiological properties are maintained to perfection. Thiersch found that after eighteen hours they were supplied with new blood-vessels, which could be successfully injected from the vessels of the part to which they had become adherent. This method of transplantation of skin is now extensively practiced in connection with plastic operations about the face. For such purposes the skin is taken from the region of the trochanters, as the skin here is almost or entirely devoid of hair. All bleeding from the wound to be covered with the grafts is carefully arrested by surface pressure before the grafts are planted, as it is necessary to secure accurate coaptation of the wound-surfaces in order to secure a favorable result. The modern method of performing rhinoplasty furnishes a good illustration of this method of skin transplantation. 40 PRINCIPLES OF SURGERY. As a matter of course, success by this method of skin transplanta- tion can only be expected when the wound and grafts are aseptic, and the parts are kept in this condition at least until vascularization of the grafts has taken place. After the grafts have been planted the treat- ment of the wound is the same as in Reverdin's method. During the after-treatment it is important to secure rest for the part, and to prevent, by appropriate means of fixation, even the slightest displacement of the grafts in any direction. A good plan is to apply a thin plaster-of-Paris Fig. 20.—Rhinoplasty and Transplantation of Large Skin-grafts. (Thiersch.) A, A, skin-flaps from face turned inward and covered with large flap from forehead, C after C, and B after B'. Defects covered with mosaic of large skin-grafts from trochanteric region. bandage over the dressing. Schede has substituted Thiersch's for Re- verdin's method in the treatment of granulating surfaces by skin-graft- ing, and the results have been very gratifying. The granulating surface is transformed into a recent aseptic wound by removing the granulations with a sharp spoon. After all bleeding has ceased the wound is covered with large skin-grafts in the manner described. The skin obtained after this method of transplantation presents a normal appearance. I have repeatedly seen that, after excision of an epithelioma of the frontal or parietal region, a defect the size of the palm of the hand was healed CONNECTIVE TISSUE. 41 completely in less than three weeks by using Thiersch's grafts. This method of skin-grafting must be a welcome resource to the oculists in the operative removal of tuberculous lesions and malignant affections of the eyelids, as well as in the treatment of some forms of ectropion. Transplantation of Mucous Membrane.—In the treatment of traumatic or ulcerative defects of accessible mucous membranes, it would seem that restoration of the defect by transplantation of grafts of mucous membrane, if found feasible, would be the ideal treatment. Wolfler has recently shown that such a method of treatment is not only practicable, but has resorted to it successfully in the treatment of obstinate strictures of the urethra. After excision of the cicatrix at the seat of resection he sutured a circular graft of mucous membrane to each end of the resected urethra, and had the satisfaction to observe that the graft not only retained its vitality, but became adherent and constituted an essential part of the new portion of the urethra. Wolfe has also suc- ceeded in transplanting the whole of the tissues of the conjunctiva of the rabbit onto that of man in order to fill a defect caused by cicatricial contraction. This method of dealing with large defects of mucous surfaces accessible to direct treatment holds out many inducements for future imitation. The difficulties in the way of equal uniform success in the transplantation of grafts of mucous membrane, as in skin trans- plantation, are owing to the location of the seat of operation. In the former instance it must alwa3?s be such as to preclude the possibility of securing perfect asepsis on the one hand, and the impossibility of apply- ing an efficient protective dressing; at the same time, it is also more difficult to obtain the proper material for the grafting. CONNECTIVE TISSUE. The granulations seen upon a wound or ulcerating surface are formed almost exclusively by the transformation of mature connective tissue into embryonal tissue, the cellular elements of which they are composed being embryonal connective-tissue cells. This transition of mature into embryonal cells is accomplished by karyokinesis. As con- nective tissue is found almost in every part and organ of the body, it takes an active part in the repair of all wounds, and when the more im- portant tissues in the wound cannot be approximated for organic union to take place its greater vegetative capacity enables it to produce a large amount of new material, which later forms a connecting bridge of cica- tricial tissue. For instance, in a transverse wound of a muscle, where it is often difficult, if not impossible, to keep the divided ends sufficiently approximated for the wound to heal by the interposition of new muscle- cells, the gap is spanned by a band of connective tissue, which, if not 42 PRINCIPLES OF SURGERY. completely, at least partially, restores the function of the muscle by fur- nishing it with two additional fixed points of attachment. Graser has shown that the first karyokinetic changes are seen in connective-tissue cells some distance from the surface of the wound, and that the new cells reach the surface with the new blood-vessels, where they constitute the granulation tissue. In aseptic wounds, where cicatrization progresses rapidly, the embryonal connective-tissue cells, or granulation cells, are short-lived, as they are rapidly transformed into mature connective tissue, which here constitutes the cicatrix. In suppurating wounds, the super- ficial layer of embryonal cells are brought in contact with the pus- microbes and their ptomaines, which destroy the protoplasm of the cells, when they are transformed into pus-corpuscles; while those nearer the blood-vessels retain their vitality and capacity of undergoing cicatrization. BLOOD-VESSELS. Wounds of large blood-vessels, with few exceptions, require such measures in their treatment which completely arrest the circulation, and which aim at permanent obliteration of the lumen by the usual method of cell proliferation and cicatrization. A wound of an artery, if accessi- ble to direct treatment, should be treated by cutting the vessel completely across and applying a ligature to each end. A small wound of a large vein can be treated successfully, under favorable conditions, by closing it with a lateral ligature. With a tenaculum the margins of the wound are transfixed, and by making slight traction the vein-wall is raised, and around the base of the little cone thus formed a fine catgut ligature is applied. If the wound remains aseptic, the mural thrombosis at the seat of ligation is slight, and closure of the wound is effected without oblitera- tion of the lumen of the vessel. A wound of a blood-vessel usually terminates, spontaneously or through the intervention of art, in perma- nent interruption of the circulation by the formation of an intravascular cicatrix. For many years it has been maintained that obliteration of a vessel after injury, disease, or ligature resulted from what was termed " organization of the thrombus." It was believed that the thrombus be- came vascular either from the lumen of the vessel or the vasa vasorum, and that the histological elements in the thrombus took an active part in the production of the intra-vascular cicatrix. Numerous experimental investigations by different authors, undertaken for the purpose of demon- strating that in wounds of blood-vessels healing takes place in the same manner as in the wounds of other tissues, have shown that the blood-clot always occupies only a passive role, and, if present, is only in the way of a speedy definitive closure, which invariably is effected by prolifera- tion from the fixed cells of the vessel-wall. Eliminating the thrombus BLOOD-VESSELS. 43 as an active agent in the obliterating process, we can say that union be- tween the tissues which are brought in contact by the ligature takes place by tissue proliferation from the walls of the vessel itself. In the true sense of the word, direct or immediate union is as impossible here as in any other wound, and, like everywhere else, the intra-vascular cica- trix is formed from tissue derived from the tissue of the injured vessel- wall. In case the inner tunics are severed by the ligature, the lacerated surfaces are brought in contact with the adventitia, and repair takes place as in other tissues which are largely composed of connective tissue, the process extending from both sides of the ligature, where endothelia Partly-formed connective Vasa vasorum. lutima. tissue from endothelia. Fig. 21.—Microscopical Appearances of the Interior of Artery of Dog Forty-nine Days after Ligation. Transverse Section through Border of Artery, x 240. assist in the process of cicatrization. If, on the other hand, the con- tinuity of the vessel is not destroyed by the ligature, and the intima is simply brought in contact without being ruptured, the new cells from the connective tissue perforate the endothelial lining, and the new elements of the latter join in the reparative process by being converted from their embryonal state into connective tissue. The histological changes in the interior of veins undergoing obliteration are the same as in arteries, the new material of which the cicatrix is composed being derived exclusively from the endothelial and connective-tissue cells. 44 PRINCIPLES OP SURGERY. J. Collins Warren, who has done excellent work in studying experi- mentally the healing of arteries after ligature, maintains that he has seen sufficient evidence in his specimens that the muscle-cells in the tunica media take an active part in the process of repair. The same author compares the process of healing in arteries to the formation of callus after fracture, and hence calls the intra-vascular material the internal and the extra-vascular the external callus. The numerous experiments of the author on ligation of arteries and veins have demonstrated, to his own satisfaction, that the most speedy obliteration of a vessel is obtained if Proliferation of connective tissue. Fig. 22.—Microscopical Appearances of the Interior of Vftn ot r»n« SETOSE #0FRTTT0NLlT2r- T--VERTSEERIS°ERC?I0^FNP0AFR?0F the vessel is rendered bloodless by the application of two ligatures. The ligatures are applied with sufficient firmness to obliterate the lumen of the vessel without rupturing any of its coats. After ligation the walls of the vessel became thickened so that, a few weeks after the ligatures had been applied, the vessel presented a spindle shape, tapering toward each side, a condition entirely due to the formation of new material _ the external callus of Warren. The bloodless space between the Matures is obliterated in a short time by cells which enter it from the vessel-wall In the obliteration of veins and ligation of arteries in their con- tinuity, the double ligature, including a bloodless space about i inch in BLOOD-VESSELS. 45 length, places the tissues in the most favorable conditions for speedy definitive closure by an intra-vascular cicatrix. When the vessel is ex- posed catgut should be used, but in the subcutaneous ligation of veins silk is preferable. Since the introduction of antiseptic surges and the aseptic ligature, secondary haemorrhage has become an exceedingly rare accident, and, when it does occur, it is in wounds where the antiseptic measures have failed. A vessel in an aseptic wound, tied with an aseptic ligature, becomes in a few hours the seat of a regenerative process which effectually guards against the possibility of haemorrhage, even if the mechanical obstruction caused by the ligature should be removed after a few days. The aseptic ligature, applied under strict antiseptic precau- tions, has been advantageous in other directions. The older surgeons always expected, after ligating an artery in its continuity, that the thrombus would extend on the proximal side to the nearest collateral branch, and on this account they were alwaj*s anxious to secure a space of an inch or more between the ligature and the nearest large collateral Fig. 23.—Femoral Artery of Dog Fifty Days after Double Ligation with Silk. Below, Transverse Section showing Bloodless Space Filled with Cicatricial Material. (Natural Size.) branch, in order to prevent secondary haemorrhage. The aseptic ligature is never followed by such extensive thrombosis, and the intra-vascular cicatrix is often exceedingly narrow,—in fact, almost linear. The limited thrombosis and the prompt formation of an intra-vascular cicatrix place the surgeon now in a position that he can ligate a large artery, close to a collateral branch or near a point of bifurcation, without a particle of fear of incurring secondary haemorrhage. In the ligation of veins the aseptic ligature has dispersed all fear of suppurative thrombo-phlebitis and pyaemia,—complications which were formerly so much feared, even after insignificant operations on veins. In the repair of wounds union between the divided ends of blood-vessels is probably never effected. The vessel- ends are temporarily closed either by tying with a ligature or by the formation of a thrombus, the former being the case when vessels of some size have been divided, the latter being accomplished usually spontane- ously in vessels which give rise to parenchymatous haemorrhage. In either instance the ends of the vessel are, later, permanently sealed by the formation of a cicatrix by proliferation of fixed tissue-cells, the endo* 46 PRINCIPLES OF SURGERY. thelia, and connective-tissue cells. The interrupted circulation between the two sides of the wound is restored indirectly through collateral branches, which are always new blood-vessels. The angioblasts in the injured capillary vessels assume active tissue proliferation within twenty- four hours after the injury has occurred, and through them, almost exclu- sively, the new blood-vessels are formed in the shape of loops, which, coming as they do from both sides, establish the vascular connection between the two surfaces of the wound. Many of these new blood-vessels disappear after the consummation of the reparative process, while others remain as permanent collateral vessels between the closed ends of the old blood-vessels permanently separated by the injury. MUSCLES. It is only quite recently that it has been ascertained that a divided muscle can unite, under favorable circumstances, by interposition of new muscular tissue between the divided ends. It was formerly believed that healing was always accomplished by the formation of connective tissue, and that the ends of the cut muscle remained permanently sepa- rated by a bridge of cicatricial tissue. The theory that connective tissue can be transformed into muscular tissue is untenable, since Pflueger has demonstrated the minute structure of muscular fibre. Kolliker has shown that the fibrillae in the muscle fibre constitute the real ground- substance. Rabl ascertained, by his embryological researches, that the muscular tissue is derived from a distinct portion of the mesoblast, and consequently proved that at a very early period of embryonal life an absolute difference takes place between muscular and connective tissue. Heterotopic muscular structures must, therefore, be looked upon, not as products of connective-tissue proliferation, but as a growth from a dis- placed embryonal matrix of muscular tissue. The vegetative capacity of muscle-cells, striped and unstriped, is quite limited, as compared with some of the other tissues, so that if the ends of a muscle that has been cut transversely are separated for more than an inch complete restoration of the continuity of the muscle is not attaind, and the two ends are connected by a band of connective tissue. If, during the healing of the wound, the cut surfaces of the muscle are kept in accurate contact, and even if a gap of half an inch exist between them, restoration ad integrum takes place by proliferation of the muscle- elements near the seat of injury. Non-striated Muscular Fibre.—Stilling and Pfitzner, as well as Busachi, have shown that unstriped muscular fibres multiply by indirect division of their nuclei, and in the repair of wounds of this tissue new fibres are produced exclusively by this method. These authors studied MUSCLES. 47 the karyokinetic changes in the muscular fibres of the triton taeniatus. They observed, after the division of the nucleus in the usual manner by kar}rokinesis, that as the new nuclei separated and approached the poles of the cell the protoplasm of the cell-body at the transverse axis became narrower, showing a well-marked constriction, which would indicate that subsequently cell-division occurred. Herczel witnessed similar changes in the hypertrophic muscular coat of the intestines on the proximal side of strictures. In defects caused by the injury, removal, or destruction of unstriped muscular fibres, regeneration takes place only from the margins, while the centre at first is occupied by connective tissue. The new muscular fibres are at first irregularly arranged, and it is only toward the completion of the healing process that the new tissue repre- sents to perfection the mature muscular fibres. Klebs is of the opinion that the leucocytes serve as food for the cells which undergo karyokinetic changes. Striated Muscular Fibre.—0. Weber, as early as 1854, claimed that in the healing of wounds new muscular fibres are produced,but, in accord- ance with the views which then prevailed, believed they were derived from connective tissue. Wittich saw, in hibernating frogs, new fibres which he believed had developed from the cells of the internal peri- mysium. In 1865, after an examination of a genuine myoma strio- cellulare, Buhl expressed the opinion that new muscular fibres are produced from old fibres. In the same year Waldej'er discovered the muscle-cell sheath, and he regarded the cell inclosed by it as a derivative of the nucleus of the fibre, but, with Zeuker and others, he still regarded the perimysium as the source of new muscular fibres. In 1868 E. Neumann made the observation that after section or laceration of a muscle the ends of the fibres became the seat of active tissue changes, which resulted in the formation of what he termed muscle-buds. These muscle-buds were not only found at the ends of the fibres, but also on their sides; at first they were seen to be composed of numerous nuclei and protoplasm, while later they were transformed into striated fibres. The sarcolemma is such a delicate structure that new cells which form within it readily find their way through it, and appear upon its outer surface in the shape of buds, as described by Neumann. Tizzoni has recently investigated the karyokinetic changes in the nuclei or sarcoblasts in the perimysium during the repair of muscle wounds. The first evidences of cell proliferation were seen in the nuclei or myoblasts nearest the seat of injury, and proliferation took place in fibres which had undergone degeneration as well as in those which pre- sented a striated appearance. Leven found, during the first twenty-four hours after injury, an increase of nuclei of the sarcolemma sheath. These 48 PRINCIPLES OF SURGERY. new nuclei are arranged in the form of rows and heaps, and by mutual pressure are flattened. Many of these new elements present karyokinetic figures, and around them protoplasm is deposited, and the new cells become spindle-shaped. The new cells increase in number from the third to the fourth da}', so that at this time from five to six can be seen under one field. Klebs studied regeneration of muscle in young guinea-pigs after puncturing subcutaneously the gastrocnemius muscle. He came to the following conclusions: A portion of the muscular fibres die and shrink, and in this condition they can be stained more deeply with haematoxylin than the others. Such fibres are completely removed by absorption within the first four days. In the fibres which remain striated Fig. 24.—Muscular Fibres Near a "Wound in a State of Proliferation (O. Weber). A, contused end of muscular fibre ; B, muscular fibre retracted within sarcolemma, the latter terminating in a sharp point; C, old fibre degenerated into a colloid mass; D, young nuclei between and upon fibres; E, nuclei surrounded by cell-protoplasm; F, new cell, showing stations- G new muscular fibre. ' ' the fibrillae become plainer, and in them the regenerative process can be distinctly seen. The nuclei increase in number, and are packed densely together, but at this stage he was unable to detect any evidences of karyokinesis. During this stage Steudel was also unable to detect any appearances which indicated indirect cell division. These young cells are called sarcoblasts by Klebs, and their transformation into muscle-fibres is effected by aggregation around them of a very thin layer of proto- plasm. The youngest cells are round, and the change into spindle form is gradual. The new cells are arranged in rows between the old muscular fibre (Fig. 24, between G and B). Some authors believe that the sarco- blasts unite end to end, and that the muscular fibre is formed in this BONE. 49 manner. Kraske and Klebs maintain that muscular fibres result from a single cell by gradual elongation of the cell-body. In the regeneration of the muscular fibres of the heart after injury, Martinti and Bonome witnessed karyomitotic changes in the interior of the sheath of numerous fibres, while in others where degenerative changes had taken place no such changes could be seen. In wounds of the heart of old rats kaiyo- mitosis commences five to six days after the injury, and does not last longer than six to seven days, and results only in incomplete regener- ation. In myocarditis the formation of new muscular fibres has been observed by Virchow, Boettcher, and Waldeyer. Muscle Suture.—In the treatment of recent wounds special pains should be taken to secure accurate approximation between the ends of divided muscles. For this purpose special means must be employed when large muscles have been divided transversely. In such cases the retraction which follows gives rise to great separation, which can only be overcome by suturing respective ends separately with buried animal sutures. Great care is necessary not to invert the margins, but to unite the cut surfaces throughout, using for this purpose, if necessarj*,as many as six sutures, which must include considerable tissue in order to prevent their tearing through. In muscles supplied with a well-marked sheath this should be sutured separately. In the after-treatment it is necessary to place the limb in such a position that will relax the sutured muscles, and to secure immobility of the limb in this position by a proper me- chanical support, which should not be removed until the healing process is completed, in order to prevent subsequent diastasis between the sutured ends. When it is desirable to elongate a contracted muscle in the correction of deformities, as in the treatment of torticollis, the con- tracted muscle should be exposed by incision, and after section a suture a distance is applied. A number of heavy catgut sutures will answer an excellent purpose, as they will maintain fixation of the separated ends in a desirable position, and will furnish an admirable scaffolding for the new connective-tissue cells, which, later on, are transformed into a tendon which permanently connects the retracted ends of the divided muscle. BONE. The granulation material by which the fractured bone unites is called callus. According to the location of this material around, within, or be- tween the fragments, we speak of an external, internal, or intermediate callus. The external or provisional callus is abundant, as a rule, where the broken bone is surrounded by a. thick cushion of soft parts, and when the fragments are not well immobilized. It forms early and disappears gradually after the fracture has united. The internal or medullary callus, 4 50 PRINCIPLES OF SURGERY. which takes the place of the medullary tissue in fractures of the shaft of the long bones, serves a useful purpose as a means of fixation of the fragments, and is also removed in the course of time after union has taken place, and with its disappearance the medullary cavity is restored. The intermediate or definitive callus is the material interposed between the broken surfaces, and which is transformed into permanent tissue. Callus is the product of cell proliferation of those tissue-elements which are directly concerned in the growth and development of bone. Duhamel de Monceau attributed to the periosteum and endosteum the function of producing callus. Haller and his prosector, Detlef, be- lieved that the periosteum takes no part in the regeneration of bone, but that callus is derived from the fractured ends of the bone, more especially the myeloid tissue. Dupuytren maintained that the periosteum and the paraperiosteal connective tissue were bone-producing tissues. Cruveil- hier claimed that the lacerated soft tissues around the fractured bone- ends, the periosteum, connective tissue, muscles, tendons, etc., furnished the material for the callus. Flourens claimed that the periosteum alone could produce new bone. Rokitansky asserted that callus is developed directly from bone and its connective tissue, including the periosteum. From his own experimental work, R. Hein came to the conclusion that regeneration of bone takes place from connective tissue in and around bone and the periosteum. According to Virchow, callus is produced from connective tissue outside of the bone, as well as from the medullary tissue. Hofmokl con- sidered as sources of callus formation the periosteum, bone, and mar- row. Gegenbauer takes the ground that bone is produced directly from connective tissue. He asserts that Sharpey's fibres, if traced carefully, can be seen springing from a bony point between the Haversian canals, from which point they radiate toward both sides into the lamellar sys- tems. The fibres form net-works, and at points of intersection bone- cells are produced, and a deposit of lamellae takes place around the connective-tissue fibres. It is now generally conceded that the provisional callus is the prod- uct of tissue proliferation from the periosteum, while the definitive or permanent callus is produced directly from the medullary tissue. The provisional callus is nature's splint, its only object being to immobilize the parts until the definitive callus firmly and permanently unites the fragments. The temporary callus is an accidental product, and appears earliest and most copiously where the paraperiosteal tissues are most abundant and motion between the fragments greatest; the intermediate or permanent callae is produced later, and is transformed into permanent tissue. Oilier and Buchholtz, in their experiments on transplantation of BONE. 51 periosteum, found that the transplanted tissue first produced cartilage, which later was transformed into bone; but they also ascertained that such bone disappeared again unless it formed in a place where bone nor- mally exists. Cohnheim and Maas came to the same conclusion from their experiments on intra-venous transplantation of periosteal grafts. It is possible that special cells (Mastzellen) are the active agents in the removal of tissue in places where it has no physiological existence. Fig. 25.—Section through Callus Fifty-two Hours after Fracture of Ulna from Rabbit. Beginning Formation of Osteoid Tissue. (Bajardi.) A, cortical portion of bone; B, osteoid tissue; C, beginning of formation of a lamella, surrounded by osteoblasts; D, periosteum. (Hartnack, Obj. 8.) Macewen has maintained for 3-ears that bone grows only from bone, and the results obtained by applying this principle in practice speaks strongly in favor of this supposition. That medullary tissue alone can produce bone has been experimentally demonstrated by Burns. The osteoblasts from which bone production alone can take place are found in the periosteum, more especially its inner layer, the cambium, and in the interior of bone. Regeneration of bone from these cells takes place in two ways,—either the cells are transformed into an osteoid tissue, or 52 PRINCIPLES OF SURGERY. they are first changed into cartilage-cells, and the latter at a later stage undergo ossification. The osteoblasts in the periosteum, and, to a lesser extent, those in the central medullary cavity, produce bone by this indi- rect method, while in other places ossification is effected in a more direct way by the osteoblasts being transformed into an osteoid substance. In the normal regeneration of bone, cartilage plays an important part. As the bone-cells disappear, or at least lose their nuclei where cartilage- cells form, it is probable that the cartilage-cells represent structures in- termediate between osteoblasts and bone-cells. Cartilage is abundant R M Fig. 26.—Transverse Section through Callus of Tibia of Rabbit Forty Days after Fracture, with External Resorption. (Maas.) P, periosteum, much thickened; R, giant cells or osteoklasts; G, blood-vessels; M, medullary resorption spaces ; K, compact portion of bone. where union is retarded, and especially in cases of pseudarthrosis. During ossification the hyaline cement-substance between the cartilage- cells is dissolved, and the space gives way to lamellae, while the cells are transformed into bone-cells. According to Krafft, multiplication of the bone-producing cells of the periosteum can be seen twenty to thirty hours after fracture, in the shape of karyokinetic figures in the nuclei of the cells, while somewhat later the same figures are to be seen in the endothelia lining the blood-vessels. The new cartilage-cells also multiply by karyokinesis. Like in the healing of wounds in soft parts, the cells on the surface of the fracture take no part in the process of BONE. 53 regeneration, as their proliferation capacity has been destroyed by the trauma as well as the sudden diminution of the vascular supply. Osteo- porosis at the seat of regeneration is always present, and results from the action of another kind of cells discovered by Kolliker,—the osteo- klasts. Robin described them as myeloplaques. They are found in Howship's lacunae where resorption takes place. The osteoklasts appear to be nothing else but myeloid cells which have lost their bone-producing function ; they are in reality hyperplastic osteoblasts. Absorption of bone takes place because these cells do not produce bone. There is no reason to believe that these cells are altered bone-cells, as no intermediate forms have been found. Ziegler does not assign much influence to these cells in the resorption of bone. Wegner has shown that in pathological processes in bone where resorption takes place they are arranged along the sides of blood-vessels, and on this account he believed they were derived from the vessel-wall. Klebs is of the opinion that the osteoklasts may secrete a chemical substance which decalcifies the bone. Resorption of superfluous callus is accomplished undoubtedly by the action of osteoklasts, an exceedingly useful function, as by it form and strength of the broken bone are restored. According to Meyer the architectural structure of the spongiosa, after the healing of a fracture, adapts itself to the new conditions, so that the new traction and pressure-curves are arranged in such a manner as will resist the greatest degree of force. This capacitj' of adaptation is present to a very high degree in bone. Abnormal and Defective Callus.—Callus may be formed in excess of local requirements after a fracture, and yet no union take place. The osteoblasts respond promptly to the stimulus created by the trauma, karyokinetic changes occur early, new cells are formed with great rapidity, and a large mass of new material is deposited at the seat of fracture, but bony consolidation does not occur because the new tissue does not undergo ossification. The normal development of cells is arrested at an early stage, and the chemical process upon which ossifica- tion depends are delayed or fail to appear altogether. Prompt bony union does not only imply that the osteoblasts at the seat of fracture should undergo karyokinetic changes and multiply, but that the new tissue must be placed under the influence of favorable chemical conditions which will enable it to be transformed into bone. A few years ago B. von Langenbeck reported 2 cases of fracture of the femur, where he resorted to amputation of the thigh under the belief that the luxuriant callus, which formed in each case at the seat of fracture, was a sarcoma. Microscopical examination in both instances showed that the swelling was composed of cells which are found in callus 54 PRINCIPLES OF SURGERY. at an early stage of its formation, without any evidences of ossification of the new material. The causes of delayed ossification are not known, but, as in a number of instances of profuse callus formation and delayed union a vigorous antisyphilitic course of treatment produced favorable results, it appears that the virus of syphilis may at least be one of them. We know that in gummata the same conditions prevail in the persistence of tissue in its embryonal state for an indefinite period of time, or until the syphilitic virus has been removed or neutralized by proper anti- syphilitic treatment. In cases where no such cause for the delay of the transition of callus into bone can be surmised, the internal administration of minute doses of phosphorus should be tried. Kassowitz produced osteoporosis in animals experimentally by large doses of phosphorus, while minute doses produced an opposite effect. He recommended the remedy in small doses in the treatment of rickets, and since then it has been ex- tensively used in the treatment of this disease, and with the best results. The action of this drug undoubtedly would produce a favorable effect upon the osteoid material, in hastening its transition from the embryonal into a mature state. Defective callus formation will necessarily follow a fracture if the osteoblasts fail to enter upon an active process of cell proliferation. These are the cases where the surgeon resorts to local measures, which are intended to stimulate the cells to increased activity. Fractures of the lower extremities which have failed to unite as long as the patient is kept in bed often unite promptly after he is allowed to walk around on crutches, the favorable change being brought about by an increased blood-supply to the seat of fracture. Dumreicher suggested that the local blood-supply could be increased by applying a compress and bandage above and below the seat of fracture, while Helferich more recently, and with the same object in view, advised moderate constriction with an elastic bandage applied in such a manner as not to interfere with the arterial circulation. Rubbing of the frag- ments forcibly against each other is an old method of treating delayed union, and has often been sufficient to rouse the dormant osteoblasts into active cell proliferation. The distinguished Brainard made the treatment of delayed union a special study during many years of his useful life, and devised a new method of treatment, the subcutaneous drilling of the ends of the fragments, which has been extensively prac- ticed, and has jnelded most excellent results. The drilling of the ends of the broken bone has a most decided effect in stimulating the sluggish separative process, as it produces osteoporosis and increases the vascu- larity of the parts, both of these conditions being well calculated to increase the local nutrition. Dieffenbach went one step farther, and BONE. 55 advised the use of ivory nails, which were allowed to remain until they became loose and dropped out. The term non-union is a relative one, as in some fractures this condition may have been reached in three to four months, while others may unite after a year. In a fracture of the femur in a healthy man, who came under the author's observation, that had not united a year after the accident, bony consolidation took place after this time without any operative inter- ference. In another case bony union did not occur until nearly two years after the fracture had taken place. When a pseudarthrosis has once become established, all measures which have been found useful in the treatment of delayed union are useless, and the only rational treatment in such cases consists in transforming the old fracture into a recent one. The ends of the fragments are exposed, the interposed ligamentous structures—muscles or tendons—or false joint excised, and the ends vivified in such a manner as to furnish large surfaces for apposition. The bone should never be cut transversely, but always obliquely, or, what is still better, Volkmann's step-operation should be done wherever the existing conditions make this possible. Direct fixation of the frag- ments with aseptic bone or ivory nails should alwa}rs be practiced, as by this expedient we are able to secure greater immobility between the fragments, and at the same time the perforations and the presence of the foreign bodies cannot fail in imparting an additional stimulus to the tissues which will expedite the process of repair. The frequency with which non-union is met with after intra-capsular fracture of the neck of the femur has almost by universal consent been attributed to defective callus formation. It has been claimed that in such a fracture, occurring as it usually does in persons advanced in life, callus production is always defective, and, as the upper fragment is but scantily supplied with blood-vessels, it was asserted that it was not in a condition to take an active part in the reparative process. The author made numerous experiments on animals, fracturing the neck of the femur within the limits of the capsular ligament, and as long as the fracture was treated in the customary way bony union was never attained. He then resorted to direct means of fixation by transfixing both fragments with an absorbable nail, and with this treatment succeeded in obtain- ing bony union in the majority of cases. Since that time he has treated fractures of the neck of the femur by immediate reduction and permanent fixation with a plaster-of-Paris splint, with pressure over the trochanter major in the direction of the axis of the neck of the femur with a compress and set-screw, the latter passing through a splint which is incorporated in the plaster-of-Paris dressing. With this treatment he has obtained bony union in a number of instances, 56 PRINCIPLES OF SURGERY. where all the signs and symptoms pointed to a fracture within the capsular ligament. It is a well-established clinical fact that in the aged other fractures unite readily, and pseudarthrosis is exceedingly uncommon, excepting after this fracture; and the writer is satisfied that this undesirable result occurs more in consequence of improper treatment than defective callus production. If the fragments can be brought in accurate apposition soon after the accident has occurred, and coaptation can be maintained uninterruptedly for three months by an appropriate dressing, bony union can be secured not only in exceptional, but in the majority of, cases. In the treatment of fractures, as in the treatment of wounds of the soft parts, accurate coaptation and effective fixation should be aimed at so as to place the parts in the most favorable conditions to unite by the smallest possible amount of new material. GLANDS. Griffini studied regeneration of testicle-substance in frogs, dogs, chickens, and guinea-pigs. He excised a wedge-shaped piece under strict antiseptic precautions, and killed the animals in from three to seventy- five days. Examination of the specimens showed that an increase of tubuli seminiferi had invariably taken place. They appeared to have originated as blind pouches from pre-existing tubules. Tizzoni has also observed, in his experiments on dogs, production of new gland-tissue during the healing of wounds of the liver and after partial excision of this organ. The same author studied experimentally regeneration of the spleen-tissue, and found that this occurred after partial and complete extirpation, the new tissue being made up of elements in connection with blood-vessels of the adjacent peritoneum. After complete extirpation of the organ the new spleens appear as nodules of a brownish color, which are attached to the vessels of the peritoneum, and develop around new buds of these vessels. The beginning of such a minute spleen appears as an accumulation of new loose connective tissue, in the meshes of which lymph-corpuscles are found ; later, follicles and pulp-substance appear, with a corresponding arrangement of blood-vessels. As these little organs always appear about the hilus of the spleen, they cannot be supernumerary spleens. After excision of wedge-shaped pieces of the spleen, foimation of new spleen-tissue has also been observed upon the omentum at a point opposite the wound and independently from tissue proliferation in the wound. Reproduction of tissue therefore takes place in the same manner as in the regeneration of lymphatic tissue. After the removal of the entire spleen, tissue proliferation takes place in the adjacent Wood-vessels, the product of which corresponds with normal CENTRAL NERVOUS SYSTEM. 57 splenic tissue, and doubtless possesses the same physiological functions. As the immediate result of such proliferation an altered condition of the vessels must be accepted, as the blood-vessels of the omentum and peri- toneum correspond with the fundus of the stomach. Mayer claimed regenerative capacity for the pulp of the spleen, but he may have been deceived by the presence of lymphatic glands of the color of the spleen at the seat of extirpation. Picard and Malassez, Bizzozero and Salvioli, and finally Tizzoni and Fileti showed that after splenectony a diminu- tion of the blood-corpuscles is observed first, but as the new spleen-tissue is produced their number again increases. Baier and Bacialli have shown, by their experimental investigations, that new lymphatic tissue is rapidly produced after partial as well as after complete removal of a lymphatic gland. In the regeneration of this tissue the adjacent adipose tissue appeared to take an active part. According to Baier, the adipose tissue is first infiltrated with leucocytes, while Bacialli saw new endo- thelial cells and lymph-spaces develop from the connective-tissue cells, after having seen mitotic figures in the nuclei. After complete extirpa- tion of a lymphatic gland, reproduction of lymphoid structure in all probability does not take place from any other but lymphatic tissue, and the new gland-tissue is the product of tissue proliferation from the cut ends of lymphatic vessels. CENTRAL NERVOUS SYSTEM. The central nervous sj'stern is built up partly from the mesoblast and partly from the epibk-st. The stellate and spider-shaped cells are derived from the mesoblast, while the neuroglia and the nerve-cells proper spring from the neuroblast, a part of the epiblast, which, in the embryo, is located nearest the middle axis. The neuroglia represent channels of nutrition, which are formed only at a time when the neuro- blastic tissues have reached the height of their development. The mesoblastic portion of the brain and spinal cord does not increase dur- ing the healing of a wound of these parts. In pathological conditions, however, as in cases of multiple sclerosis, the stellate and spider-shaped elements proliferate so actively that the nerve-cells are completely dis- placed by the new product. Many authors have expressed their doubts as to the possibility of regeneration of brain-tissue after injury or dis- ease, while others have gone to the opposite extreme, and claim that complete repair can take place in cases of extensive defects. Yoit claims that in pigeons he has observed complete restoration of both structure and function after extirpation of the entire cerebrum. While large de- fects are not repaired, the regenerative capacity of the nervous elements cannot be doubted, and such a doubt would come in cc-unict with a 58 PRINCIPLES OF SURGERY. general law. Regeneration of the cerebral nervous system comprises the production of new ganglia-cells and neuroglia, the latter consisting of a fine net-work, sometimes of nervous, at others of basis, substance. During the healing of every wound of the brain the observer can satisfy himself that the neuroglia possesses a high capacity of reproduction, as well-marked karyokinetic changes can be seen during the first twenty- four hours after the injury. The new cells are very abundant, and arrange themselves in groups. More difficult is the demonstration of the same changes in the ganglia-cells, but Mondino (1886) and Coen (1887) have given descriptions of these cells which leave no further doubt that they also multiply by karyokinesis. Klebs has also observed karyokinetic figures in the nuclei of ganglia-cells during the repair of injuries of the brain. In the embryo, increase of ganglia-cells by karyokinesis has been witnessed t)y Pfitzner, Uskoff, Rauber, Merk, and Cattani. It is true that brain wounds heal with some defects, but this applies to extensive injuries in which the regenerative capacity of the brain-substance is not equal to the emergency; hence, only a part of the defect is repaired. Klebs gives an accurate account of his examination on the reparative process in two cases of brain injury,—one recent, the other of long stand- ing. Microscopical examination of the tissues from the seat of injury in both cases showed that new tissue had been produced. He found many new cells from the neuroglia which he is inclined to believe may func- tionally take the place of ganglia-cells. The same author made numerous experiments on .young animals for the purpose of studying the process of healing in wounds of the brain. With an aseptic needle the brain was punctured. No symptoms followed the injury. The brain was examined from two to four days after puncture ; only slight meningeal haemorrhage. The needle-track in the brain not closed. Mitotic changes were found not in the cells in the immediate neighborhood of the punc- ture, but in the cells corresponding to from the second to the fifth row from it. In the same place were found an accumulation of resting nuclei. Mitotic cell proliferation of injured cells was found completed on the fourth day. Ganglia-cells undoubtedly increase in number in the same manner. He found no leucocytes in the brain, and believes that those that must have been present had been appropriated as food by the cells which had undergone karyokinetic changes. The gray matter of the surface of the brain is composed of numerous but exceedingly small cells, and their numerous connections would indicate great reproductive capacit}r. Peripheral Nerves.—When Cruikshank suggested the possibility of restoring physiological function in a divided nerve by suturing, his con- temporaries regarded the suggestion as an absurdity. Since that time CENTRAL NERVOUS SYSTEM. 59 the subject of nerve regeneration has engaged the attention of some of tb« best men in the profession, and from the knowledge which has thus accumulated it is safe to repeat the statement made by Vanlair recently, that " the surgeon who neglects to suture a divided nerve commits the s?me mistake as he who neglects to reduce a fracture or fails to unite a divided tendon." Regeneration of a nerve takes place exclusively from pre-existing nerve-fibres. Schwann's sheath isolates the nerve-fibre so thoroughly from the mesoblast that it would be almost impossible for the latter to take any direct or active part in the regeneration of the former. The neuroblasts from which tissue proliferation takes place are found within the nerve-sheath. Confluence of the new nerve-elements within the neurolemma does not take place, as, according to Cattani, they receive envelopes from the medulla. Section of a motor fibre is at once followed by degeneration of the motor terminal palate ; hence, degen- eration and regeneration in the divided nerve and the muscles supplied by it are parallel processes. Degeneration and regeneration have been studied in nerves that were stretched, lacerated, or completely cut across, and the histological processes were found almost identical in all of these conditions. The study of degenerative and regenerative processes side by side in injured nerves has thrown much light upon their minute anatomy. The medullated peripheral nerve-fibre is composed essentially of Schwann's sheath, the axis-cylinder, and a fluid which appears as a periaxial layer. Klebs looks upon this fluid as a sort of nervous endo- lymph, which, b}r virtue of its great mobility, takes part in the nutrition of the nerve. The space which contains the fluid, being between the axis-cylinder and the sheath, serves not only the purpose of a channel for the fluid, but also for the dissemination of movable elements, as, for instance, migration corpuscles. Leucocytes are only present in any considerable number in pathological conditions. Schwann's sheath is composed of connective tissue. The large oval nuclei, containing each one or two shining nucleoli, which are attached to its inner side, are the neuroblasts. It is as yet not definitely settled whether the portion of nerve between two of Ranvier's constrictions is composed of one or more cells. Klebs is inclined to accept the view that such a space is represented by one cell, and if several nuclei are present they are the product of nuclear segmentation. The nuclei must be regarded in the light of peripheral nerve-cells. The specific functional contents of a nerve-fibre are the axis-cylinder, the endolymph, and medulla. The first two are continuous with the neighboring elements, but not so the medul- lary sheath. The medullary sheath is a very complicated structure. The masses of fat are held together, and are inclosed by a frame work of keratin. Finer keratin threads unite both sheaths in the form of Golgi's 60 PRINCIPLES OF SURGERY. spirals, which are present in the funnels of Schmidt-Lautermann's med- ullary spaces ; besides, numerous transverse threads are strung out in zigzag shape between the sheaths. The constituent parts of the medul- lary portion of the nerve-fibre can disappear separately ; if the medullary fat is removed by absorption, the keratin frame-work becomes visible,—a condition which is present during the early stages of neuritis parenchy- matosa; if the keratin frame-work is dissolved, the fat appears in drops, as can be seen during the degeneration of a nerve after section. The axis-cylinder is a pre-existing structure, which, however, can be only distinctly outlined against the medullary sheath and endolymph by post-mortem influences. Its structure, in the larger medullated fibres at least, is not simple, but is composed of fine fibrillae, held together by an amorphous, gelatinous substance. Physiologically, this part of the nerve must be regarded as a complex of different conductors, which only differ by the qualities of motility and sensibility. Regeneration of a periph- eral nerve-fibre is a regular typical process, as far as it serves as a substitute for lost elements of a nerve. The process resembles the physiological growth of a nerve which always occurs only in connection with the central nervous system. If the separation between the nerve- ends exceeds an inch, restoration of its continuity without assistance cannot take place. In such an event the ends become bulbous, the medullary substance in the distal portion undergoes degeneration, and the axis-cylinder becomes more and more indistinct. The same changes take place in the nerve-ends after amputation. When a nerve is simply divided, and there is no loss of substance, the ends remaining in close contact, function is established in a remarkably short time. In two instances Gluck observed perfect function within twenty-four hours. He concludes that the granulation tissue must have been the means of con- duction in these cases. In his experiments on the sciatic nerve in fowls, where he divided the nerve and immediately sutured with catgut, func- tion was restored in from fifty to eighty-six hours. Waller and Vanlair are of the opinion that regeneration proceeds entirely from the proximal end. Colasanti claims that degeneration of the peripheral end only extends as far as the next Ranvier's ring, while Tizzoni found that degeneration extends from the seat of injury in both directions, only that it is more marked on the distal side. Most of the recent writers on the subject assert that when a piece of the nerve is resected the entire nerve on the distal side undergoes degeneration, while, if the nerve is only divided, and the ends are immediately sutured, at least a number of the nerve-fibres retain their integrity. Eichhorst and others, who have made regeneration of the nerves a special study, are of the opinion that the nerve-fibres of both ends participate in the process of repair, CENTRAL NERVOUS SYSTEM. 61 and that regeneration commences with degeneration. Eichhorst believes that regeneration takes place exclusively by splitting of the axis-cylinder within Schwann's sheath, so that the latter in the course of time becomes distended with them. Continuity is restored by the central fibrils being pushed outward through the cicatrix to meet the peripheral, and coales- cence follows. Beueke, on the other hand, traced the origin of the new fibres to protoplasm of the neuroblasts, which are transformed into delicate fibrils, which become surrounded by a coating of myeline, the future medulla. It is more probable that regeneration of a nerve takes place by the latter method. After a trauma, reproduc- tion of the axis-cylinder always follows. Accord- ing to a number of investigators who have studied this subject, several axis-cylinders are formed within each Schwann's sheath, each of which is surrounded by a separate medullary sheath. It is difficult to ascertain whether these new fibres, growing out of one of the old fibres, again become united some distance toward the periphery, or whether they remain isolated to their point of peripheral distribution. After nerve section, the axis-cylinder swells at the cut end and becomes striated; this swelling, however, is not an active process, but the result of imbibition of stagnant endolymph. The longitudinal striations and for- mation of vacuoles which have been described by Tizzoni are due to the same cause. The gran- ular appearance is brought about by disintegra- tion of the fibrillar The old axis-cylinder breaks down into isolated fragments, which, in part at least, are removed by leucocytes, which at this time have made their appearance. With such extensive destructive changes in the axis-cylinder it is difficult to conceive how regeneration of this structure could take place in the manner described by Eichhorst. The only histological elements within the fibre-sheath exempt from degeneration are the nuclei of the inner surface of the sheath, the neuro- blasts, and from these regeneration takes place. At the seat of regeneration the nerve is enlarged from the accumu- lation of the products of tissue proliferation within the neurolemma sheaths. The first stage of regeneration of a nerve is initiated by multiplica- Fig. 27.—Nerve-fibre in a State of Regenera- tion Fifty to Seventy Hours after Injury. (Gluck.) A, proliferation of neuroblasts; B, spindle-cell, which, becoming confluent with similar cells from both sides, unites the nerve-fibres; C, rows of spindle-cells, forming amyelinic nerve-fibres; D, younjj amyeloid cells, formed from nuclei of neurolemma. 62 PRINCIPLES OF SURGERY. tion of the neuroblasts and increase of protoplasm. The nuclei increase to double their normal size and then divide into two or more. Division of nuclei probably takes place by karyokinesis. The protoplasm is gran- ular, and is stained a reddish color with neutral picrocarmine. The nerve-fibre originates from the protoplasm, and, according to Tizzoni, in the form of separate pieces, around which already can be distinguished a medullary sheath and transparent contents. In other cases there may be a direct connection between the old and new axis-cylinder. Longitudi- nal striation of the axis-cylinder prob- ably takes place at a time when the fibre has formed a direct connection with dis- tant parts, the seat of active physiologi- cal processes. Leucocytes have been found within the neurolemma by Tizzoni and Korybut-Daskiewicz, while Neumann de- nies their presence in this locality. Cattani believes that they are present within the fibre-sheath after nerve-stretching, and can be found as far as the motor ganglia of the cord. Nerves of different function, when united, will undergo repair and establish useful conductors for the transmission of nerve force. The late Professor Gunn estab- lished the correctness of this assertion by a series of interesting experiments on dogs. Early functional results after nerve suture are often fallacious, as the function at- tributed to sutured nerves may be per^ formed by other nerves which reach over such areas ; and, again, the peripheral mani- festation may be the result of physical con- duction of the irritation, and apparent motor recoveries may be stimulated by the action of muscles other than those supplied by the sutured nerve. Fig. 28.—Longitudinal Section through Nerve Twenty-one Days after Injury, show- ing Medullated and Non- medullated Nerve-fibres with Round Cells between them. (Gluck.) NERVE SUTURE. Nerve suture was first performed by Baudens in 1836, with negative result. The procedure was revived by Nelaton in 1863, and the follow- ing year by Langier. The first operations were made with fine silk sutures, which were not cut short, and subsequently came away by suppura- tion. 0. Weber advised to unite the nerve-ends by passing the sutures, not through the nerve-substance, but only through the connective tissue NERVE SUTURE. 63 surrounding the nerve,—the paraneurotic suture. Experience, however, has shown that transfixion of the nerve-ends by the sutures does not give rise to pain, and does not interfere with the normal reparative processes, and at the same time, by resorting to this direct method of suturing, more perfect coaptation is secured. In the case of large nerves, it is advisable to re-inforce the direct sutures with a number of para- neurotic sutures. The best material for the sutures is aseptic catgut. An ordinary sewing-needle with a dull point is preferable to a surgical needle, as it is more sure to pass through the nerve without injuring the fibres. From one to three direct sutures, according to the size of the nerve, are applied, and from three to six paraneurotic sutures. The needle is passed straight through the nerve on each side, one-eighth to one-fourth of an inch from the ends, and care must be exercised, in tying the sutures, to bring the cut surfaces in accurate apposition, and not to tie the sutures too tightly,as by doing so the nerve-ends are liable to become displaced by overlapping. In tying the paraneurotic sutures the necessary precautions must be taken to pre- vent the margins of the sheath from insinuating themselves between the nerve-ends. Primary Nerve Suture.—A primary nerve suture is one used to unite a nerve immediately or soon after the injury has occurred, and before any degenerative changes have taken place. It should always be resorted to in the treatment of accidental wounds where one or more nerves have been divided, also where in operations a nerve has been divided accidentally, and, finally, in cases where a neurectomy for pathological conditions cannot be avoided. The results after primary suture have been very satisfactory. Bruns has collected 71 cases from different sources, and in more than 33 per cent, of the number function was restored. As suppuration in a wound where a nerve has been sutured would, in all probability, cause tearing out of the sutures and displacement of the nerve-ends, it is of the greatest practical importance to secure for such wounds an aseptic condition and to obtain primary union throughout, and consequently no provision for drainage should be made. If the wound-surfaces cannot be approximated, and a greater or less space has to fill up by granulation, a bundle of catgut threads can be used for a capillary drain, in order to avoid tension from the accu- mulation of blood or the primary wound-secretion. Secondary Nerve Suture.—When a divided nerve fails to unite, the Fig. 29.—Nerve Suture, showing Applica- tion of Direct and Paraneurotic Su- tures. 64 PRINCIPLES OF SURGERY. ends become bulbous, are usually found imbedded in a mass of cica- tricial tissue, and separated from each other from 1 to 2 or more inches. Function below the point of division is completely lost; the distal por- tion of the nerve itself, being no longer in connection with the central nervous system, undergoes degeneration, and the muscles supplied by the injured nerve become atrophic and useless. The reuniting of such a nerve is done by the secondary suture. Experience has shown that function can be restored by this procedure years after the injury. Jessop vivified the nerve-ends and applied sutures nine years after in- jury of the median nerve, and restored function. Langenbeck sutured the sciatic nerve two years after division ; sensation returned in three days, and, later, motion. As a rule, sensibility returns first after nerve suture, followed considerably later by restoration of motor function. The most speedy restoration of function, both sensory and motor, after secondary suture is reported by Tillaux. He operated on the median nerve three years after division. The ends were found imbedded in a cicatrix and separated from each other 4 centimetres. The ends were vivified and sutured. He claimed that physiological function was re- stored completely three hours after the operation. There can be no doubt of the ultimate recovery of nerve function in this case, but that this should have been attained in three hours appears next to impossible. Enough has been said to show that secondary nerve suture can be re- sorted to with good prospects of success years after an injury, but for well-known reasons it should not be postponed after it has become evi- dent that union has failed to take place. Unnecessary delay is danger- ous, because when a nerve has become permanently disconnected from the central nervous system muscular degeneration goes hand in hand with degeneration of the distal portion of the nerve, and the longer the operation is delayed the greater the length of time required to complete the regeneration of the nerve and the muscles. The first secondary nerve suture was made by Nelaton in 1865. In Germany, the first opera- tion was made by Guster Simon in 1876, and he was followed by Lan- genbeck the following year. In 1884, Bruns found 33 recorded cases, and in 24 of this number the result was satisfactory. As a rule, sensa- tion returned gradually in from two to four weeks, while motion did not return until three weeks to three months after the operation. Complete restoration of function was seldom completed until half a year to one year after the operation. As in cases which require secondary suture the nerve- ends are sealed with a mass of cicatricial tissue, it is always necessary to resect the ends, after which the sutures are applied in the same manner as in primary nerve suture. Both nerve-ends must be freed from all cicatricial adhesions before approximation is attempted, and, if this NERVE SUTURE. 65 cannot be readily done on account of previous retraction, both ends are carefully stretched and sufficient elongation secured so as to prevent any tension upon the sutures. A great deal can be done to prevent tension, by placing the limb in such a position as will relax the nerve; for in- stance, flexion of the hand and forearm in suturing the ulnar, median, or musculo-spiral, and flexion of the leg and extension of thigh after re- uniting the sciatic. The position of the limb most favorable for the union of a sutured nerve is best secured by a plaster-of-Paris dressing, which is allowed to remain not only till the external wound is healed, but until the nerve has firmly united. When a nerve has suffered at the seat of injury a considerable loss of substance, it is often found impossible to bring their ends in contact by nerve-stretching and position of limb, and in such cases restoration of continuity becomes an exceedingly difficult task. Le'tie'vant suggested that the defect in such cases should be cor- rected by a neuroplastic operation. He proposed that a flap should be taken from each end sufficiently long that, when turned toward each other, they could be sutured at the middle of the defect, thus making a connecting bridge of nerve-tissue between the separated nerves. As could be expected, in a case where he performed this operation the result was negative. In a case operated on by Tillmanns after this method, partial restoration of function was established three and a half months after the operation. The success in this case was probably not the result of conduction of nerve force along the fibres of the flaps, but the pro- duction of new fibres across the gap, perhaps through the tissues com- posing the temporary bridge. From his experiments on animals, Gluck came to the conclusion that nerve defects could be corrected by trans- plantation of nerves ; that is, inserting a piece of nerve from an animal, corresponding in size to the nerve to be reunited, between the nerve ends, and uniting it with them with sutures. He reports a number of success- ful experiments on chickens, filling the gap with a nerve taken from rabbits. Philipeaux and Vulpian, from their own researches, came to the conclusion that a transplanted nerve always degenerates and dis- appears, and that restoration of structure and function only takes place by regeneration from the nerve-ends. It is probable that the methods of nerve restoration devised by Le'tie'vant and Gluck are useful in reunit- ing separated nerve-ends in the same manner as the suture a distance of catgut suggested by Assaky. The interposition of an aseptic, absorbable substance like catgut or nerve-tissue serves as a temporary scaffolding for the products of tissue proliferation from the nerve-ends, which at the same time determines the direction for the new material, providing the shortest route to meet the same material from the other side. When catgut is employed, two or three sutures are used, so that the combined 6 66 PRINCIPLES OF SURGERY. size of the strings will at least approximately correspond to the size of the nerve. Vanlair, who believes that regeneration of a nerve takes place exclusively from the proximal end, resected a piece of the sciatic nerve in dogs, and then sutured both ends of the nerve to the ends of a decalcified-bone tube, which in length corresponded to the section of nerve removed. From the results of his experiments, 10 in number, he became satisfied that continuity of the nerve was restored by the new nerve-fibres from the proximal end growing into the tunnel, bridging the defect in a comparatively short time, as they had no resistance to over- come, and uniting with the end of the nerve on the opposite side of the tube. It appears to the author that this method of overcoming the difficulties of reuniting nerve-ends widely apart is not only an ingenious procedure, but, if applied in practice, promises better results than any other method heretofore proposed. In certain cases where the distal end cannot be found, or where the separation is so great that none of the methods of approximation so far devised hold out any inducements of a successful issue, Letievant suggested the idea of grafting the central end upon the intact trunk of a neighboring nerve. This operation failed in his hands, but Tillaux and Tillmanns, slightly modifying the method, were suc- cessful. In Tillmanns' case the ulnar nerve had been divided, the ends were found separated 4^ centimetres, and the proximal end was grafted upon the median nerve. Sensation returned in a month, and by using electricity and massage recovery was complete a year later. Nerve- grafting, as advocated by Letievant, should only be resorted to after implantation of a decalcified-bone tube between the nerve-ends has been tried and proved a failure, or in cases where the defect is very extensive, or, finally, if, after the most diligent search, the distal end cannot be found. Restoration of function does not always follow after the con- tinuity of a nerve has been restored by operative measures. Ehrmann has reported such a case. The radial nerve was divided below the elbow and failed to unite. Complete paralysis of all the muscles supplied by this nerve. After the lapse of seven months the nerve was exposed, and the ends, which were 5 centimetres apart, were vivified and sutured. Seven months after the operation, no improvement. The nerve was again exposed at the former site of operation, and it was found that union had taken place, but the nerve was compressed by a firm cicatrix 2 or 3 centimetres in length. The nerve was relieved from its imprisonment, and when the faradic current was applied all the muscles supplied by the nerve responded. Four months later, complete recovery. This case reminds us of the importance of securing healing of the nerve and wound with as little cicatricial tissue as possible, which can only be done by absolute asepsis and careful attention to suturing of the wound. CHAPTER III. Inflammation. The subject of inflammation is one of deep interest both to the stu- dent and practitioner, as it initiates the former into the field of general and special pathology, and the latter meets with it daily in some form in his practice. We have already set apart from inflammation those numer- ous processes by which injuries or defects are repaired without destruc- tion of any of the new tissue-elements which have been described in the first chapter under the head of Regeneration. From a scientific and practical stand-point, it is exceedingly important to draw a distinct line between the series of tissue changes which attend regenerative processes, uncomplicated by the action of pathogenic bacteria, and true inflamma- tion, which is always caused by the presence of one or more kinds of patho- genic microbes. As compared with true inflammation it has been custom- ary for quite a number of years to speak of regeneration as a plastic or regenerative, inflammatory process; but the term inflammation in the future should be limited to the series of histologiccl changes which ensue in the living body from the presence and action of specific micro-organ- isms, while the word regeneration should be used to designate the histo- logical changes which take place in tissues which have been primarily in an aseptic condition or have been rendered so after the inflammation has subsided. From this it will be seen that the study of inflammation is intimately and inseparably associated with a consideration of the new science of bacteriology. For most forms of inflammation the presence of a specific micro-organism has been demonstrated, and its etiological relationship established by cultivation and inoculation experiments; and in the few inflammatory diseases where no such positive proofs can be furnished we have, from analogy and circumstantial evidence, reason to suspect the presence of undiscovered microbes. Inflammation, in the widest and most comprehensive meaning of the word, should be made to embrace pathological conditions which are caused by the action of patho- genic microbes or their ptomaines upon the histological elements of the blood and the fixed tissue-cells. A correct definition of inflammation, which should embody the etiological, anatomical, and pathological char- acteristics of the disease from our present knowledge of the subject, cannot be given, as many important points connected with the compli- (67) 68 PRINCIPLES OF SURGERY. cated processes await explanation by future investigation. Sanderson defines inflammation as " the succession of changes which occur in a living tissue when it is injured, provided that the injury is not of such a degree as at once to destroy its structure and vitality." As we have restricted the term inflammation to the succession of changes which occurs in a liv- ing tissue from the action of pathogenic microbes or their ptomaines, this definition would cover processes which, for reasons already given, we have considered as instances of tissue proliferation unattended by any of the characteristic features of inflammation. J. Bland Sutton uses the term inflammation in a more restricted sense in coining the following definition: " It is the method by which an organism attempts to render inert noxious elements introduced from without or arising within it." As nothing is said of the method, the most important part of the definition, it certainly cannot be said to cover the whole ground. The conception of the true nature of inflammation for the present, at least, must remain symptomatic. Asa rule, inflammation subsides as soon as the primary cause has disappeared or has been rendered inactive, as is well shown by the spontaneous disappearance of febrile disturbances in the general in- fective diseases, and the subsequent rapid repair of the local lesions which characterize them. If an acute inflammation become chronic, either from a diminution of the quantitative or qualitative intensity of the primary cause, or from the tissues becoming accustomed to its action, it is sometimes difficult to tell whether the primary cause has disappeared or has ceased to act, or whether it is still present and active. In chronic inflammation the most reliable indications of the presence and potency of the primary bacterial cause are acute exacerbations, as chronic inflam- mation only consists of a series of acute inflammatory processes which repeat themselves at larger or shorter intervals. The differences between an acute and chronic inflammation are not in kind, but in degree. The complicated processes which characterize inflammation can be studied most profitably by considering separately and conjointly the symptoms to which they give rise, which Galen enumerated as calor, rubor, dolor et tumor, to which may now be added the functio Isesa of modern authors. The study of the objective and subjective manifestations of inflammation should be preceded by a short description of THE HISTOLOGICAL ELEMENTS WHICH ARE DIRECTLY CONCERNED IN THE INFLAMMATORY PROCESS. Capillary Vessels.—The most important histological changes in in- flammation, acute or chronic, transpire within, and in the immediate vicinity of, capillary vessels. The smallest arteries and veins, the ves- sels on either side of the capillaries, undergo changes, and the disturb- HISTOLOGICAL ELEMENTS IN THE INFLAMMATORY PROCESS. 69 ance of circulation within them constitutes a part of the picture of in- flammation, but it is in the capillaries that the most serious disturbances occur; it is here where the noxae are brought in closest contact with the para-vascular tissues, and it is here where the inflammatory exudation and transudation take place. The capillaries are minute vessels, or rather channels, which connect the arteries and veins, the walls of which are composed of a thin, elastic, endothelial membrane ; that is, a single layer of nucleated cells held together by an amorphous cement-substance. In Fig. 30.—Capillary Vessels of the Frog's Mesentery, Stained with Ni- trate of Silver only ; the Wall of the Vessel is Viewed from the Sur- face, and is Seen to Consist of Elongated Endothelial Cells, Marked by their Outlines only; the Nucleus of the Individual Cells is not Shown. (Klein.) silver-stained specimens the cement-substance appears as dark lines which outline the boundaries of the cells. The shape of the cells is more or less elongated, with pointed ex- tremities, and their outline smooth or sinuous. The nuclei of these cells are oval, situated either about the middle of the cell or near one ex- tremity. The nucleus contains within a well-defined membrane a net-work of chromatin threads, but no nucleolus. When the capillaries undergo alteration and distention, as in inflammation, the cement-substance yields in many places ; in consequence of this minute openings appear, called by Arnold stigmata, which become gradually enlarged into stomata. 70 PRINCIPLES OF SURGERY. Winiwarter found that by injecting inflamed capillaries the contents of the vessel escaped through these openings. Through these openings emigration of leucocytes takes place, and when the inflammation is very intense the red corpuscles escape,—a process which Strieker has named diapedesis. If the capillary vessels, through which emigration has been going on, be stained with nitrate of silver, it is seen that the emigration is limited to the interstitial cement-substance of the endothelial wall. (Purves.) Klein has shown that the walls of all capillary vessels in the adult state form a direct connection with the process of the connective-tissue corpuscles of the surrounding tissue,—a matter of great interest in studying the relationship between the capillary vessels and the sur- rounding connective-tissue spaces. Blood-corpuscles.—The blood-corpuscles frequently serve as carriers of the microbic cause of the inflammation; they block the lumen of inflamed capillary vessels, partially or completely, and constitute the histological elements of the primary exudation. The element of the blood which is more intimately associated with the histology of inflammation is the I. Leucocyte, or White Blood-corpuscle.— This is a nucleated, spherical, transparent mass of protoplasm, without a limiting membrane or Tig^u™— leucocyte, envelope. Heitzmann made the discovery that PBOT5piAKICUsrawGs^ it is composed of a reticulum of protoplasmic (Kiem.) strings, with a hyaline substance in the meshes. The nucleus shows a similar structure, and its net-work is continuous with that of the cell-body. Strieker and Klein, as well as a number of other histologists, have adopted Heitzmann's views in reference to the minute anatomy of the leucocyte. The reticulated structure is well shown by staining with chloride of gold, which stains the protoplasmic strings, but not the interstitial substance. The leucocyte is endowed with intrinsic power of locomotion,—amoeboid movements,—a function which is performed by the reticulum. Wharton Jones discovered motion of protoplasm in leucocytes of human blood as early as 1846. In 1862 Haeckel showed that the white blood-corpuscles absorb pigment-granules, —a process which can only take place by amoeboid movements, which by change of form of cell bring the foreign material into its interior by inclusion. These observations enabled Cohnheim to demonstrate later that the white blood-corpuscles found in the vascular spaces of the cornea were derived from the blood; in other words, to establish the fact of emigration of leucocytes through the inflamed wall of capillaries. The HISTOLOGICAL ELEMENTS IN THE INFLAMMATORY PROCESS. 71 amoeboid movements of the colorless corpuscles can be well observed for hours in the moist chamber on the warm stage. The movements of a leucocyte are peculiar. The first effort consists of a protrusion of a hyaline film. This is withdrawn, and another is protruded; in the next moment this is diminished to a very minute process, whereas, on the opposite side, a new, broad process appears. After this the corpuscle is seen to throw out processes of various length and thickness, and thus to alter its shape in a considerable manner. By virtue of the amoeboid movement of leucocytes they move from place to place independently of the blood or plasma current. This independent locomotion enables them to pass through the small opening in the wall of inflamed capillaries, and, after they have reached the para-vascular tissues, to travel along connective- tissue spaces until arrested by some mechanical obstruction. If pigment-material, in a finely-divided state, is mixed with blood, either before or after withdrawing it from the vessels, the projections thrown out by the leucocytes inclose the particles brought in contact with it, and the granules reach in this manner the interior of the leuco- cytes, and are variously distributed according to the shape and move- ments of the protoplasm. Microbes reach the interior of the leucocytes in the same manner. In cases of intra-vascular infection the emigra- tion corpuscles convey with them inflamed capillaries into the tissues surrounding them. 2. Red Blood-corpuscle.—The colored blood-corpuscle serves less frequently as a carrier of microbes than the leucocyte, as it does not possess amoeboid movements. For the same reason it is not found so constantly as a component part of the inflammatory exudation, as its transit through the capillary wall is entirely a passive process, and is accomplished only by the vis a tergo in case the stomata are sufficiently large to permit its passage. The presence of numerous colored corpus- cles in the exudation is an indication of great acuity and intensity of the inflammation,—conditions causing serious and extensive alterations of the capillary wall. The escape of whole blood through a capillary vessel greatly damaged by the cause of the inflammation is called rhexis. Fig. 32.—Change of Forms of a Moving Leucocyte by Amoeboid Move- ments. (Klein.) the microbes through the wall of 72 PRINCIPLES OF SURGERY. 3. Third Corpuscle.—A third cellular element in the blood, the third corpuscle, was discovered by Max Schultze, in 1865. He described it as a small, colorless sphere or granule. Elaborate descriptions of this corpuscle were given by Hayem, in 1878, and Bizzozero, in 1882. Hayem, from his observations, believed that these minute structures represented young colored blood-corpuscles, and hence named them hsematoblasts. Bizzozero entered his protest against this theory and called them blood-plates (Blutpldttchen). Under the microscope they appear as minute, faintly-colored blood-corpuscles. They seem to Fig. 33. (Eberth and Schimmelbusch.) 1. Third corpuscle. A, natural appearance when seen on surface and on edge; B, C, C, D, and E, appearance presented by them during coagulation. 2. Shows the little heaps of granules formed by them after coagulation (Hayem). 3. A small blood-vessel as stasis is approaching. A, third corpuscles in periphery of stream; B, colored blood-corpuscles; C, leucocyte. possess a little stroma like the red blood-corpuscles, but contain no nucleus and are devoid of any cell-membrane. What appears as a nucleus is, according to Hayem, an optical defect. Hayem estimates that they are forty times more numerous in man than the leucocytes, and twenty times more abundant than the colored corpuscles. As there has been no positive proof furnished that the third corpuscle is an embryonal red blood-corpuscle, and as it has been shown that blood-corpuscles are produced from the fixed cells of blood- producing organs, as, for instance, the spleen and medullary tissue, it is HISTOLOGICAL ELEMENTS IN THE INFLAMMATORY PROCESS. 73 advisable not to apply to it the term hsematoblasts, but to designate it from the remaining two morphological elements of the blood numerically by calling it the third corpuscle. Under a higher power the third corpuscle can be readily recognized in the blood-stream of capillary vessels in the mesentery or web of a frog. In blood withdrawn from a vessel it is destroyed as soon as coagulation sets in; hence it disappears almost immediately after it leaves the blood-vessel. In order to study it outside of the body, means must be employed to prevent coagulation, which can be done by mixing the blood with the following solution, recommended by Hayem :— Distilled water,.......200.00 cubic centimetres. Sodic chloride,.......1.00 gramme. Sodie sulphate,.......5.00 grammes. Mercury bichloride,......0.50 gramme. From a needle-puncture the blood is allowed to mix with the solu- tion in the proportion of about 1 to 20 up to 1 to 100. In this mixture the third corpuscle will retain its shape and size for twelve to twenty- four hours. The third corpuscle is a fibrin-producing structure, and, as such, it takes an active part in the formation and growth of intra-vascular blood-clots. The white mural thrombus, produced intra vitam, is com- posed almost exclusively of this element of the blood. If, from a trauma or disease the endothelial lining of a blood-vessel is injured and the smooth surface becomes uneven, the third corpuscles, #oating in the peripheral portion of the axial current, come in contact with projecting points, and are arrested and become attached to the vessel-wall, la}Ter after layer is added, and in this manner the mural thrombus is formed. On the surface of recent wounds they appear in large numbers, lose their fibrin ferment, and give rise to the formation of fibrin, which acts both as a haemostatic and temporary cement-substance. In inflammation the third corpuscle escapes through the capillary wall in the same manner as the red corpuscles, but, on account of its smaller size, its peripheral loca- tion in the blood-stream, and its greater abundance, it is numerically more abundant in the inflammatory exudation. The fibrin in inflamed tissues is undoubtedly derived largely from this source. 4. Fixed Tissue-cells.—The fixed tissue-cells behave differently in the inflamed part, according to the intensity and nature of the primary microbic cause. The microbes, or their ptomaines, may possess such intense local toxic properties as to destroy their vitality directly when the inflammation results in necrosis, as is the case in the centre of an ordinary furuncle, and on a larger scale in cases of progressive phleg- monous inflammation. The fixed tissue-cells may be destroyed by starvation, by the primary inflammatory exudation being so abundant as 74 PRINCIPLES OF SURGERY. to obstruct the circulation in the inflamed part. If the cause of the in- flammation is less intense, as is the case in chronic inflammation, the fixed tissue-cells are brought in direct contact with the microbes which produced the inflammation, and active tissue proliferation is the result, and this furnishes the bulk of the inflammatory product. The histo- logical structure of tubercle furnishes a good illustration of the part taken by the fixed tissue-cells in chronic inflammation. In chronic sup- purative inflammation the fixed tissue-cells are. first transformed into embryonal tissue, and, as the protoplasm of the new cells is destroyed by the ptomaines of pus-microbes, they are converted into pus-corpuscles. A passive role in the inflammatory process was assigned to the fixed tissue-cells by Boerhave, who regarded stasis as the essential feature of inflammation; by Andral, who believed that hypersemia was the char- acteristic pathological condition in an inflamed part; and by Rokitansky, who taught that exudation constituted the most important element in all inflammatory lesions. Yirchow located the primary seat of inflam- mation in the fixed tissue-cells, and asserted that nutritive or formative irritation occurred in them independently of vessels or nerves. He maintained that the more the cells were disposed to take up nutritive material the greater the danger that they themselves would be destroyed. Remaining faithful to the doctrine that inflammation is only caused by the presence and action of a specific microbic cause, we shall find that the more acut»the process the less the probability that the fixed tissue- cells take an active part, and that the more chronic the inflammation the greater the amount of the new material that has been derived from the fixed tissue-cells, and the smaller the quantity of vascular exudation. SYMPTOMS OF INFLAMMATION. The structural changes caused by inflammation give rise to a char- acteristic complexus of symptoms,—pain, redness, swelling, heat, and suspension,—elimination or perversion of function. These symptoms vary in intensity, according to the nature of the primary cause and the anatomical structure and location of the tissues affected. One or more of the symptoms enumerated may be absent, when the existence of in- flammation must be ascertained by a more careful study of those pre- sented. In acute inflammation the symptoms appear in rapid succession or almost simultaneously, while in the chronic form they come on slowly, often almost insidiously, and frequently one or more are wanting, even when the disease which those that are present represent is far ad- vanced. The number and intensity of the individual symptoms vary not only according to the virulence of the primary microbic cause, but are also modified by the resisting capacity of the individual and the SYMPTOMS OF INFLAMMATION. 75 tissues affected. We speak of a complete or partial immunity to certain microbic diseases, and of a general or local, hereditary or acquired, dis- position. For diagnostic purposes the symptoms must be studied in- dividually and collectively, and with special reference to their etiology and the location and structure of the inflamed tissues or organ. (a) Pain.—Pain is one of the most variable symptoms of inflamma- tion. It is caused by traction or pressure to which sensitive nerve-fila- ments are subjected in the inflamed tissues, and probably also, in some instances at least, by extension of the inflammatory process to the structure of the nerves themselves. Some patients are more sensitive to pain than others. The same extent and degree of inflammation of the same part giving rise to sensation of discomfort in a torpid person may cause excruciating pain in patients with a nervous temperament. As the degree of pain will depend largely upon the number of sensitive nerves present in the inflamed area and the amount of exudation, we would naturally expect to find pain a prominent symptom in inflamma- tions of unyielding tissue freely supplied by sensitive nerves. This, as a rule, is the case. Pain is a distressing sj^mptom in cases of phleg- monous inflammation of the fascia and tendon-sheaths of the fingers and palm of the hand. Pain is the most conspicuous symptom in periostitis and inflammation of the serous membranes. Wherever the inflammatory exudation appears rapidly in parts freely supplied with sensitive nerves, pain from tension appears as one of the foremost s}rmptoms, and con- tinues without intermission until tension is relieved. In acute suppu- rative osteomyelitis intense pain is present from the very commencement of the disease, and continues unabated until tension is removed by operative procedures, or by the escape of inflammatory product, through some defect in the bone, into the more yielding paraperiosteal tissues. The pain is throbbing, sometimes synchronously, with the pulse in acute circumscribed phlegmonous inflammation. It is sharp and lancinating in inflammation of serous membranes. It is described as a burning sensation in inflammation of the skin. The pain is of a dull, aching, boring character in deep-seated inflammation, especially in the interior of bone. Nocturnal exacerbation of pain is a common occurrence, and seldom absent in painful typhlitic affections. The pain is not always referred by the patient to the seat of inflammation, as in the early stages of coxitis it is not in the hip, but over the inner aspect of the knee, and in inflammatory affections of the nerves the pain radiates along the pe- ripheral branches, and is usually felt most severely some distance from the seat of the disease. In ascertaining the existence and exact location of a deep-seated inflammation, tenderness is a more valuable symptom than spontaneous pain. Tenderness is the pain elicited by pressure. If the 76 PRINCIPLES OF SURGERY. inflamed part is tender on pressure and accessible to palpation, the area of tenderness will correspond to the extent of the inflammation. During the beginning of an attack of phlegmonous inflammation the surgeon is able to locate the affection accurately, by searching for the point where the tenderness is most acute, and the same symptom will indicate to him, earlier than any other, the direction in which the process is extending. In periostitis the area of tenderness will show whether the inflammation is circumscribed or diffuse. The existence of circumscribed points of tenderness about the epiphyses of the long bones is almost a certain in- dication of central osseous tuberculosis, and, at the same time, furnishes a reliable guide in their early operative treatment. Firm pressure relieves pain in nervous hysterical patients, while it aggravates it when it is caused by inflammation. On the other hand, superficial pressure made with the tips of the fingers increases the suffering in parts the seat of functional disturbance, while it does«not materially affect the pain resulting from inflammatory lesions. (b) Redness.—The composition of normal blood is admirably adapted for the passage of this fluid through capillary vessels. As long as the relation of corpuscular elements to the blood-plasma remains normal, and the intima of the blood-vessels remains intact, and the vis a tergo is adequate, there is no tendency to capillary obstruction. If the capillary circulation in the mesentery of a frog is examined under a microscope, there is no difficulty in distinguishing two currents,—the axial and peripheral. The axial or central current is rapid and conveys the red corpuscles, which have the same specific gravity as the blood- plasma, while the peripheral current between the axial and vessel-wall is considerably slower, and in this current the colorless corpuscles are conveyed, their rotating motion being due to their coming in contact with the wall of the vessel. D. J. Hamilton has shown, by numerous experiments, that in fluids holding in suspension solid particles passing through capillary tubes the heaviest particles are carried along the central current, while those specifically lighter than the fluid seek the peripheral current. The leucocytes are specifically lighter than the fluid in which they are contained; hence they are forced into the space be- tween the axial current and the vessel-wall (Fig. 33, C). The third cor- puscle, probably for the same reasons, moves also in the peripheral stream. The colorless corpuscles accumulate more in the peripheral stream when the current is feeble than when it is rapid. This fact is of great importance in the study of the altered circulation when the capil- lary vessels are in a state of inflammation. The accumulation of color- less corpuscles in the peripheral stream in inflamed capillary vessels, according to Thoma, Eberth, and Schimmelbusch, is owing to the slow- SYMPTOMS OF INFLAMMATION. 77 ness of the current, which, although insufficient to propel the specifically light, colorless corpuscles, is still competent to force onward the less- resisting and specifically heavier-colored corpuscles. Eberth and Schimmelbusch state that in the vessels of a warm- blooded animal four kinds of stream are noticed, in accordance with its velocity : (1) the normal stream, in which the axial current and periph- eral zone are readily recognizable; (2) a slow stream, in which the leucocytes accumulate in the periphery ; (3) a still slower stream, in which the third corpuscles also leave the axis and accumulate in the periphery, and in which, these observers assert, the leucocytes become less numerous ; and (4) a stream so slow as to approach stagnation, in which all the elements of the blood are indiscriminately mixed. From the above it can be seen that all general and local conditions which tend to diminish the velocity of the blood-current in the capillary vessels are productive of accumulation of the colorless corpuscles and of the third corpuscle in the peripheral stream,—a condition which greatly aggravates the existing local impediments to capillary circulation, and when well advanced, by encroaching more and more upon the central stream, will result in complete stasis. Redness as a symptom of inflammation signifies an excess of blood in the part, and the terms used to indicate its existence are hypereemia and congestion, while complete arrest of the capillary circulation is expressed by the word stasis. Accurately speak- ing, hyperaemia should be used to designate that condition of the circu- lation where the part not only contains an increased amount of blood, but where an increased amount of blood flows to and returnsyVom the part, —an exalted physiological process; while the word congestion literally means onl}r an accumulation of blood in a part,—a condition owing to some form of local or distant mechanical obstruction. The condition giving rise to redness, hjrperaemia, congestion, and stasis should not be studied only from descriptions, but in order to be understood they should be seen. This can be readily done by producing artificially an inflammation in a transparent part of some lower animal, preferably the frog, and studying the circulation in the inflamed part step by step under the microscope. For this purpose experimenters have usually selected the frog's web, mesentery, tongue, lung, and bladder, and the tadpole's tail. For general use the frog's web should be selected, as the preparations for this experiment are very simple. Inflammation is provoked by cauterizing the web with a needle heated to a red heat, or by applying with a small plug of cotton some powerful irritant, as ammonia, tincture of cantharides, or croton-oil, or by touching the surface with a sharp stick of nitrate of silver. Hamilton gives the following directions for making the experiment: "Nothing more is 78 PRINCIPLES OF SURGERY. necessary than a piece of tin or other soft metal, about l£ to 2 inches broad and about 6 to 8 inches long, or, what is better, a thin piece of hard wood of the same dimensions. At the end where the web is to be stretched it should not be so broad. From the narrow end of this a V-shaped piece is cut out, over which the web is to be spread. The frog should first be curarized, as this does not interfere with the circulation, provided that the solution employed be not too strong. The ^W of a grain, in watery solution, injected under the skin, is sufficient. Chloral may be substituted. Caton recommends a solution of 4 grains to the drachm. As many minims should be injected subcutaneously as the Fig. 34.—Normal Circulation in Frog's Web. (Landerer.) A artery B vein; C, capillaries. Vessels covered by a net-work of polygonal epithelial cells of web, in ' ' ' which pigmented cells are not represented. frog is drachms in weight. The injection is made under the skin of the back with an ordinary hypodermic syringe. The animal is laid on the piece of metal or wood, and, the web being stretched over the cleft at the end, the toes are held by tying a piece of thin thread to them and fixing the ends into a fine slit cut in the metal or wood." The micro- scope is so arranged and adjusted that the field of observation will cor- respond to the point of irritation. A sufficiently high power is used so that the different corpuscular elements in the capillary stream can be readily seen and recognized. In order to witness the different stages of the in- flammatory process it is necessary to continue the observation for hours. SYMPTOMS OF INFLAMMATION. 79 Any one of the irritants mentioned applied to the frog's web will produce in the capillaries over a limited area a series of changes which are always present in inflammation, and a description of them will repre- sent what takes place in capillaries the seat of inflammatory process of bacterial origin; almost simultaneously with the application of the irritant a momentary contraction of the vessel occurs, caused by the stimulation of the vaso-contractor nerves, which is followed by dilata- tion, with increased velocity of the capillary current,—a true hyperemia. The bright-red color of the hyperemic part at this stage, according to Fig. 35.—Capillaries of Frog's Web in a State of Hyperemia soon after Application of Irritant. (Landerer.) A, artery; B, vein; C, capillaries. Recklinghausen, is due to increase in the rapidity of the blood-current but, as the color of the blood indicates a diminished expenditure of oxygen and a smaller quantity of carbon in the blood, increased velocity alone would not explain this change. Diminished alkalescence in the inflamed tissues may reduce the amount of oxygen used, as is the case in glands during active secretion, where Claude Bernard showed that defective oxygenation is always present. At this stage the corpuscular elements circulate in their respective streams, and the whole picture is one of increased physiological activity. Dilatation of the vessels follows contraction so quickly that it would be difficult to explain it as a para- 80 PRINCIPLES OF SURGERY. lytic phenomenon. Its early outset and the rapidity with which it ap- pears would point to a neurotic cause, traceable to the action of ganglia in the vessel-wall. It has not yet been satisfactorily explained whether this early dilatation of the vessel is due to vasomotor paralysis or irritation of the vaso-dilators, but it is more probable that it is caused by the vaso-dilators, while, later, paralysis from overdistention occurs. Division of the sympathetic in the neck brings about increased vascu- larity, but no inflammation. The difference between dilatation of an inflamed vessel and the dilatation following division of the sympathetic consists in alteration of the capillary wall, in the former instance pro- duced by the action of the causes which induced the inflammation, while in the latter the dilatation is a purely nervous phenomenon, unattended by other pathological conditions of the vessel-wall. Disturbances of the circulation alone are not sufficient to bring about the local changes which are characteristic of inflammation; if the velocity of the blood-current is greatly diminished by purely mechanical or nervous causes, mural implantation of the white corpuscles may take place, but emigration does not occur on account of the absence of the essential condition which gives rise to it,—alteration of the capillary wall. Dilatation is first noticed in the smallest arteries, afterward in the veins and capillaries, and keeps increasing from fifteen minutes to two hours. The vessels often enlarge to double their normal calibre. During the stage of dilatation many of the capillaries which were small or con- tained but little blood become visible, which greatly adds to the turgidity and redness of the inflamed part. As long as the acceleration of the capillary current continues, the different corpuscles move in their respec- tive currents. The white corpuscles that are mingled with the colored are washed along with the latter in the central stream without finding their way into the slower side-current which propels the leucocytes and the third corpuscles. The leucocytes in the peripheral stream appear more numerous, and skip along by more rapid rotatory movements. At this time the circulation has reached its greatest speed, and the tissues present every appearance of well-marked hypersemia. In from fifteen minutes to two hours from the time the irritant was applied, intra-vascular changes are noticed which are calculated to impede the capillary current. The first link in the chain of local causes which obstruct the capillary circulation consists of a crowded condition of the vessels from a greater accumulation of the different corpuscles, which is soon followed by a greater separation of the leucocytes from the central current and their greater accumulation in the peripheral stream, where they often become arranged in heaps and little masses. This change is first observed in the small veins, and somewhat later, and to a lesser extent, in the smallest SYMPTOMS OF INFLAMMATION. 81 arteries. Separation of the blood-corpuscles is the necessary outcome of slowing of the stream from greater accumulation. In the peripheral zone of leucocytes the next source of obstruction is created. Some of the colorless corpuscles become momentarily attached to the capillary wall, when they are again detached by the force of the current, or are rolled away by another leucocyte. As the process advances it appears as though the viscosity of the leucocytes was increasing constantly, as more and more of them become adherent, while fewer are again detached. The lumen of the vessel is narrowed more and more by mural implanta- tion of the leucocytes. The small veins now assume an appearance as if the internal surface of their wall were paved with leucocytes, while in the capillaries a similar adhesion of the leucocytes to the wall is noticed. At this stage it often appears as though complete obstruction would occur every moment, the capillary stream becoming completely arrested for a moment, and the current may even move in an opposite direction, when the obstruction is again overcome and the current moves once more in the right direction. The smallest arteries exert themselves to the utmost to clear the way, and pulsations can be seen where in a normal condition they are absent. Hyperemia has now given way to congestion. An intra-vascular obstruction has given rise to accumulation of blood on the proximal side of the inflamed vessel. Increasing slowing of the current gives rise to greater accumulation of leucoc}'tes, which become firmly adherent to the capillary wall, narrowing the vessel more and more until the space for the axial current becomes too small for the pass- age of the red corpuscles, when complete arrest of the circulation takes place. Congestion has resulted in stasis. As soon as complete stasis has taken place the colorless corpuscles become mixed with the red cor- puscles which are forced into the mass of the white, while by amoeboid movements the latter wander toward the centre of the vessel and mix freely with those which were moving in the central current. The most advanced stages of vascular disturbance are, of course, noticed first where the irritant was applied, so that when complete stasis has taken place in the centre a zone of congestion surrounds this, while more distant ves- sels still present every indication of active hyperemia. Redness is most marked where hyperemia is extant; that is, in parts containing a maxi- mum amount of arterial blood. As soon as congestion sets in, the blood- corpuscles, red and white, do no longer pass through the vessel with the same rapidity and number, and the redness gives way to a bluish tinge, which becomes well marked and does not give way to pressure when complete stasis has occurred. The blood in the stagnated vessels, accord- ing to Paget, has little tendency to coagulate ; hence the possibility of resistutio ad integrum of the circulation after subsidence of the acute 6 82 PRINCIPLES OF SURGERY. symptoms. Complete stasis occurs first in such capillaries where the vis a tergo is greatly diminished by a circuitous route from an artery to a vein, and increases in the direction in which the blood-current is slowest. In warm-blooded animals the phenomena of inflammation do not differ materially from those observed in the frog's web, except as re- gards the presence and disposition of the third corpuscles. According to Eberth and Schimmelbusch, in warm-blooded animals the third cor puscles in the normal capillary circulation move along with the colored corpuscles in the axial current, and hence they maintain that they must be of nearly the same specific gravity. A few of the leucocytes, mixed with the colored corpuscles and the third corpuscles, are found in the central stream, but the majority of them are propelled by the peripheral stream, which, according to those observers, is from ten to twenty times slower than the central or axial current. With the slowing of the stream from alteration of the capillary wall and subsequent intra-vascular condi- tions, separation of the corpuscles takes place in the same manner as has been described in the frog's web; the leucocytes and third corpuscles leave the central stream and accumulate in the slower peripheral zone of capillary stream, where they give rise to a greater degree of slowing of the column of blood by the formation of intra-vascular obstruction, which, if sufficient in degree, finally arrests the central current, thus causing stasis. The inflammatory process in warm-blooded animals can be studied advantageously in the artificially-inflamed omentum of young animals, especially the guinea-pig, as the omentum in these animals is exceedingly delicate and transparent. The animal is narcotized by injecting sub- cutaneously 3 grains of hydrate of chloral for a full-grown animal. As the animal, with the exception of the head, is to be kept immersed in a physiological solution of salt kept at a temperature of the body in a large vat with a glass bottom, it is wrapped in a sheet of gutta-percha tissue long enough to overlap the head, and made so as to inclose a funnel-like space through which it may breathe. An opening is made in the cover- ing at a point corresponding to the abdominal incision, through which the omentum is withdrawn. The object-glass of the microscope is im- mersed in the solution, and the omentum laid over a slide without fasten- ing it. The vat is made so that it will fit on to the stand of an ordinary microscope, so that the light can be readily adjusted. Two tubes, one to convey the salt solution into the vat and another to conduct it away, are attached at opposite sides. These can be connected with a vessel whose temperature is kept constant by means of a thermostat and Bunsen burner. (c) Swelling.—The primary swelling in inflammation is due to dila- tation of blood-vessels, and its degree will depend on the vascularity of SYMPTOMS OF INFLAMMATION. 83 the part inflamed. The more numerous the blood-vessels, the greater the swelling from this cause. As the inflamed blood-vessels will often dilate within two hours to double their normal calibre, the primary swelling in vascular organs in a state of acute inflammation will come on quickly, and will give rise to a not inconsiderable enlargement of the inflamed part. If during this stage of inflammation the tissues are incised, haemorrhage is profuse, and the emptying of turgid blood-vessels by this means has a prompt effect in diminishing the swelling. Nancrede has shown by his investigations that local depletion, during the hyperemic stage of inflammation, exercises a favorable influence in unloading the distended blood-vessels and in modifying the intensity of the subse- quent conditions in the inflamed tissues. It is also during this stage that the application of cold proves a beneficial resource in the treatment of acute inflammation, as under its effects the distended blood-vessels contract, and in consequence of the diminution of the vascularity of the inflamed part the primary inflammatory swelling is diminished. I. Inflammatory Exudation.—A moderate amount of swelling is present in all regenerative processes, as dilatation of the vessels neces- sarily precedes the increased physiological activity of the tissue, and the embryonal material required in the reparative process occupies a larger volume than the mature tissue it is intended to replace. Inflammation is characterized by the presence of a superabundance of cells. The cause which has produced the inflammation has, by its direct action upon the capillary wall, produced such alterations of its structure as to render it more porous, hence permeable to the passage of the inclosed cellular elements of the blood. The albuminous cement-substance which holds together the endothelial cells disintegrates at different points, and through these small defects, the stigmata and stomata, the blood-cor- puscles find their way through the capillary wall into the surrounding lymph and connective-tissue spaces. In acute inflammation the inflam- matory exudation consists principally in the extra-vascular accumulation of blood-corpuscles which have passed through the injured capillary wall. The rapidity with which the inflammatory exudation appears will depend on the intensity of alteration of the capillary wall and the speed with which the blood-corpuscles escape into the surrounding tissues. In chronic inflammation exudation takes place slowly, and the histological elements of the inflammatory swelling are derived mostly from the fixed tissue-cells. Emigration of Leucocytes.—The passage of a leucocyte through a defect in the capillary wall is called emigration,—the wandering of such a cell from a place where it has a normal existence into a territory where, in a condition of health, it is seldom met with. After it has made its 84 PRINCIPLES OF SURGERY. escape from the capillary vessel it is called an emigration or wandering corpuscle. John Hunter came very near being the discoverer of emigra- tion of leucocytes during his researches on inflammation. He incised the tunica vaginalis in animals, and inserted a tallow plug, which he removed after short intervals, and examined the fluid upon its surface under the microscope. He found in this fluid, a short time after the in- cision was made, round, white cells, which could have been nothing else but wandering leucocytes. The credit for having demonstrated the porosity of the capillary wall and the escape of the colorless corpuscles unquestionably belongs to Waller. This author observed emigration in the tongue of the frog as early as 1846, and strongly maintained that the inflammatory exudates were composed largely of leucocytes, in opposition to the blastema theory of formation of pus and other inflammatory products. In 1849 Addison clearly pointed out the relationship of the color- less corpuscles and the corpuscles lying around the vessel in inflamed parts, as becomes evident from the following sentences from his work on " Consumption and Scrofula:" " During inflammation—using the word in the general sense here indicated—there is more or less marked increase of the colorless elements and protoplasm in the part affected. At first —in the first stage—these elements adhere but slightly along the inner margin or boundary of the nutrient vessels, and are therefore still within the influence of the circulating current, belonging, as it were, at this period as much, or rather more, to the blood than to the fixed solid. Secondly—in the second stage—they are more firmly fixed in the walls of the vessels, and, therefore, now without the influence of the circu- lating current. Thirdly—in the third stage—new elements appear at the outer border of the vessels, where they add to the texture, form a new product, or are liberated as an excretion." Recklinghausen found wandering corpuscles in the vascular spaces of the cornea, but he believed that they were a product of tissue pro- liferation from the fixed corneal corpuscles. Our modern knowledge of emigration of leucocytes is founded almost exclusively upon the labors of Cohnheim. This observer demonstrated, in the year 1867, by his own ingenious experiments, that the wandering corpuscles discovered by Recklinghausen in the vascular spaces of the cornea were leucocytes which had escaped from capillary vessels and had wandered into the cornea. He based his statements on the results of an experiment which could leave no room for discussion. He injected finely-divided pigment- material directly into the circulation of an animal, and somewhat later produced artificially a keratitis. In examining the cornea he found the vascular spaces nearest the margin of the cornea crowded with leuco- SYMPTOMS OF INFLAMMATION. 85 cytes loaded with pigment-granules. There could be only one conclu- sion,—that the leucocytes, which had become charged with pigment- granules in the general circulation, had passed through the capillary vessels at a point nearest the seat of irritation; in other words, the capillary vessels which took part in the traumatic keratitis furnished the primary inflammatory exudation. A slight irritation of a frog's webb will only produce an active hyperemia, and in a short time the circulation returns to normal without any emigration of leucocytes having taken place. In such cases the irritant has been of such a nature or of such mild action as not to produce the necessary alteration of the capillary wall for mural implantation and emigration to take place. Zahn has shown that if the mesentery of an animal is exposed, but carefully protected against injury, emigration of leucocytes does not take place for seven or eight hours, while the remaining disturbances of the circulation indicate the existence of inflammation. If, however, the frog's web or tongue is cauterized with a sharp-pointed pencil of nitrate of silver the necessary conditions for an acute inflammation are created, and the minute eschar is soon surrounded by vessels showing the differ- ent stages of the inflammatory process, from active hyperemia to com- plete stasis. Emigration of leucocytes takes place most actively in capillaries partly obstructed by mural aggregation of these elements, and the process is arrested as soon as the circulation has come to a complete standstill. The following conditions must be present and are essential for emigration of leucocytes : 1. Alteration of capillary wall. 2. Mural implantation of leucocytes. 3. Permeability of lumen of capillary vessel. 4. Amoeboid movements of leucocytes. 1. Alteration of capillary wall has been repeatedly enumerated as the most important feature of inflammation, and without such a change the rapid escape of leucocytes as we find it in inflammation would be utterly impossible. The cause which has produced the inflammation produces such a degree of softening in the cement-substance as to enable its penetration by the leucocytes between the endothelial cells, or, as some of the authors claim, localized minute defects cause the formation of small openings through which the leucocytes escape. 2. Mural implantation of leucocytes is an equally essential condition, as without it the leucocytes, which are at any rate larger in circumference than the supposed openings through which they escape, would be rolled over these minute defects by the sluggish peripheral stream, and emigra- tion would not take place. Increased adhesiveness or viscosity of the leucocytes is supposed to play an important part in the occurrence of mural implantation. According to Hering, mural fixation of the leuco- 86 PRINCIPLES OF SURGERY. cytes is effected by fine projections, which are thrown out on their sur- face, and which insinuate themselves into the small crevices of the rough- ened intima. Mural implantation cannot take place as long as the capil- lary stream retains its normal velocity ; hence, slowing of the peripheral current is the first and most important cause. The slower the peripheral stream, the more readily does mural implantation occur, and the greater the tendency to aggregation of leucocytes along and near the capillary wall. The rapid transudation of the plasma of the blood through the defective capillary is undoubtedly another cause of impediment of prog- ress and final adhesion of leucocytes to the inner surface of the capil- lary vessel. Finally, mural fixation of leuco- cytes is effected by the changed condition of the protoplasm of the leucocytes and the inner surface of the capillary wall by the action of the essential cause which produced the inflam- mation. 3. It has been shown that emigration of leucocytes is most active where the capillary circulation has become impeded, but not ar- rested, and that the process is arrested with the occurrence of complete stasis ; hence, it ap- pears that the intra-vascular pressure is one of the factors in this process. Hering and Schklarewsky maintained that the leucocytes are entirely passive structures in their passage through the capillary wall, that they are forced through defects in the wall exclusively by the intra-vascular pressure. That emigration is not such a simple process is evident, as there would be in such case a larger representation of colored corpuscles in the inflammatory exudation. The blood-pressure assists in the extrusion of leuco- cytes that have penetrated the capillary wall, but, without changes in their form, would not be adequate to force them through the minute openings or the softened cement-substance. 4. Leucocytes, in order to pass through an inflamed capillary wall, must possess amoeboid movements; hence, only living leucocytes are capable of migration. After the leucocyte has become implanted upon the inner surface of the capillary wall it penetrates the softened cement-substance by throwing out projections, or one of these projections insinuates itself into one of the minute foramina, and as the intra-mural portion increases Fig. Pass- 8.—Leucocyte ing through Capillary Wall. (Landerer.) A, leucocyte attached to capillary wall by delicate processes; higher up it has penetrated the capillary woJl by a large projection; B, half of the leuco- cyte outside of the capillary wall drag- ging the balance after it. SYMPTOMS OF INFLAMMATION. 87 in size the balance of the leucocyte is drawn toward it; this step is greatly aided by the blood-pressure, which pushes the intra-vascular por- tion in the direction of the growing projection, until by its own exertions, and aided by the vis a tergo, it has finished its journey through the capil- lary wall, and has reached the para-vascular lymph or connective-tissue spaces, where it constitutes the most important element of the inflam- matory exudation. In the inflamed capillaries of the frog's web, under the microscope, this process of emigration can be readily followed, and leucocytes can be seen in the same field in various stages of transit through the wall, and finally liberated in the para-vascular spaces. Fre- quently one leucocyte after another can be seen passing through the same place,—a fact which points strongly to the existence of well-defined circumscribed defects in the capillary wall. As the escaped leucocytes accumulate outside of the capillary vessels, some of them can be seen to change their location by the same forces which have been active in their passage through the vessel-wall,—amoeboid movements and stream of parenchyma fluid. Diapedesis.—This word was devised by Strieker to designate the passage of colored corpuscles through the inflamed vessel-wall. If there could be any doubt as to the existence of minute openings in the inflamed capillary wall in the consideration of emigration of leucocytes, this doubt must be effectually dispelled when the passage of colored corpuscles through the capillary wall can be demonstrated under the microscope. Experimental research and clinical observation have shown that when the inflammatory action is very intense red corpuscles form no inconsid- erable part of the inflammatory exudation. As the colored corpuscles possess no amoeboid movements, their passage through the capillary wall must be an entirely passive process ; they are extruded through pre- formed openings or through an exceedingly soft cement-substance by the intra-vascular pressure. It is possible that they are forced through pas- sages made by the emigration corpuscles. It is well known that at first only leucocytes are found outside of the capillary vessels, that the colored corpuscles appear later, and that, while leucocytes also pass through the smallest veins, the colored corpuscles escape only through capillary vessels (Fig. 37, D). Arnold noticed that red corpuscles floating in the capillary stream, when they arrived opposite a stomata, were drawn toward the opening of the transudation stream. Diapedesis becomes a prominent feature where the inflammatory process is very acute, consequently where extensive alteration of the vessel-walls has taken place. In such instances the colored corpuscles are so numerous in the exudation as to impart to it a hsemorrhagic 88 PRINCIPLES OF SURGERY. appearance. An abundant escape of colored corpuscles in inflammation is technically called rhexis. The third corpuscles are extruded through the inflamed capillary wall in the same passive way as the colored corpuscles. The primary inflammatory exudation consists of the corpuscular elements of the blood which escape through the porous capillary wall, the products of their disintegration, and blood-plasma. The latter will be again referred to under the head of Transudation. The presence of the solid constituents of the blood differentiates the inflammatory exuda- tion from an ordinary hydropic or oedematous swelling. The question Fig. 37.—Inflammation of Frog's Web at Stage where Capillary Stream is Impeded by Commencing Emigration. (Landerer.) A, small artery; B, small vein; C, capillaries; D, red corpuscles which have escaped from capillary by diapedesii. rises, What becomes of the corpuscular elements after they have left the general circulation ? The most favorable termination of the inflamma- tory process consists in the preservation of the vitality of the cellular elements outside of the blood-vessels and their return into the general circulation by a process which is called immigration. This probably seldom, if ever, takes place in the case of the colored and third cor- puscles, both of which possess no amoeboid movements and undergo molecular disintegration, and the granular detritus is removed by absorp- tion. The leucocytes which have retained their vitality can return into the circulation either by re-entering the capillaries which they have left, SYMPTOMS OF INFLAMMATION. 89 after the acute symptoms have subsided and the capillaries have been cleared of the mural thrombi, or by a more indirect route through the lymphatic vessels. The latter route is probably the most frequent. If the blood-corpuscles contain the microbic cause of the inflammation in sufficient quantity and intensity to destroy their protoplasm, they fur- nish the necessary nutrient medium for the growth and development of the microbe outside of the vessel-wall, thus bringing it in direct contact with the para-vascular tissues, which then become the seat of infection. In such instances the cellular elements of the primary inflammatory exu- dation are dead tissue, and act or are disposed of as such. In acute suppurative inflammation the leucocytes which have escaped are con- verted into pus-corpuscles. The emigration corpuscle under no circum- stances assumes a tissue-producing function. When inflammatory proc- esses result in the formation of new tissue, this function is performed by fixed tissue-cells which have been stimulated to a state of activity by the increased nutritive conditions incident to some form of inflamma- tion. The albumen, which is always present in considerable quantity in every inflammatory exudation, furnishes an additional nutrient supply, and thus assists the process of cell proliferation; this is especially the case with the globulins. The filtrate which percolates through the in- flamed capillary wall contains coagulable substances, which, in hydropic fluids, are less abundant. The emigration corpuscles, which disintegrate soon after they have left the capillary vessels, furnish fibrin ferment. Fibrin production in the tissues is suspended as soon as the product of emigration has become copious. The third corpuscles furnish another source of fibrin production. In suppurative inflammation fibrin forma- tion does not take place. Where no fibrin forms in the exudation, the supposition lies near that the fibrin-producers are taken up by the cells, or that the fibrin which had already been produced is liquefied and assimilated by them. If the inflamed vessels are surrounded only by a few leucocytes, the latter are destroyed and liberate fibrin ferment; if abundant, they are move resistant and destroy albuminous substances. Weigert asserted that cell necrosis resulted in the formation of fibrin, as the dead cells furnish the fibrin ferment. That fibrin production does not always attend inflammation can only be explained by the supposition that the fibrin-producers are assimilated as soon as they have left the blood-channels. If the cells which furnish the fibrin come in contact with necrotic tissue, such an assimilation is prevented and fibrin is formed. Fibrin production, however, may take place without cell necro- sis, as is the case upon inflamed serous surfaces. Its occurrence in this particular locality can only be explained by the absence of assimilation of the cells which yield the fibrin ferment. The cellular constituents 90 PRINCIPLES OF SURGERY. and fibrin of the inflammatory exudation impart to it one of its charac- teristic clinical features,—a sense of firmness,—which is well marked in proportion to the predominance of these over the fluid portion. Inflammatory Transudation.—The liquid portion of the blood which escapes through the damaged wall of inflamed capillary vessels is called inflammatory transudation. The same causes which are necessary to extrude the non-amoeboid corpuscular elements of the blood constitute also the conditions which enable a part of the blood-plasma to leave the capillary stream. Increased porosity of the capillar}' wall is the most important of them. As soon as the capillary wall has become abnor- mally permeable the blood-pressure forces the fluid through the minute pores into the surrounding connective tissue, or, if the inflammation is located in a mucous or serous membrane, upon the surface. In deep- seated inflammation the transuded fluid freely percolates through the connective-tissue spaces, and gives rise to one of the well-known symp- toms of inflammation,—the inflammatory oedema. The transudation is always more widely diffused than the exudation. Recent bacteriological researches have shown that, while in the tissues, at the seat of exuda- tion, the presence of the microbic cause of the inflammation can be readily demonstrated by microscopical examination and cultivation ex- periments, the oedema fluid some distance from them was found free from micro-organisms. The escape of blood-plasma in inflammation is a proc- ess which resembles percolation through a porous membrane. As the blood-plasma contains fibrinogen and fibrino-plastic material, its presence in the tissues or upon inflamed serous or mucous membranes is impor- tant in the production of fibrin. In some instances the inflammatory product is greatly changed by the presence of a copious transudation, and the inflamed part then presents more the appearance of oedema than inflammation. This is well shown by the two clinical varieties of anthrax. The expression serous inflammation is used to indicate the predominance of transudation over exudation in some forms of inflammation. The liquid transudate predominates over the exudate in some forms of sup- purative inflammation (purulent oedema of Pirogoff), also when the circulation is feeble, as in the aged and in anaemic individuals. The addition of mucus alters the character of an exudation or a transudation, as* may be seen when a mucous membrane is the seat of inflammation. Serous transudation often precedes mucous exudation, as in cases of acute catarrhal inflammation of the nasal passages. After the acute symptoms of inflammation have subsided and the capillary circulation has been restored, the transuded fluid is absorbed, and with its absorp- tion the inflammatory oedema disappears. In suppurative inflammation the transudation becomes the pus-serum. SYMPTOMS OF INFLAMMATION. 91 (d) Heat.—Increase of temperature of the inflamed part is the result of increased afflux of blood and the accompanying augmentation of physiological processes. Cohnheim showed experimentally that inflam- mation, without an increased blood-supply, does not give rise to an increase of temperature. John Hunter was already aware that the temperature at the seat of inflammation is never in excess of the tem- perature of the blood. Heat is both a subjective and objective symptom. In acute inflammation of the skin, or a mucous membrane, the patient often complains of a distressing burning or scalding sensation, which is often effectually relieved by cold applications. The surface thermometer is sometimes an important instrument in setting a differential diagnosis between a deep-seated chronic inflammation and a malignant tumor. Diminution of temperature may indicate either a favorable change or complete arrest of circulation in the inflamed part, in the first instance showing that resolution is in progress, in the latter commencing the speed}' occurrence of gangrene. (e) Disturbance of Function.—As inflammation, wherever it occurs, consists essentially of increased nutritive changes in the tissues, result- ing in consequence of a more abundant blood-supply and an exaggerated vegetative capacity of the cells, it may lead to at least a temporary in- crease of function. This is always the case in inflammation of mucous membranes, where, as one of the prominent clinical features, we observe an increased secretion of mucus usually preceded and accompanied by a more or less profuse transudation. Parenchymatous inflammation in glands usually produces sudden diminution and often complete suppres- sion of secretion. Acute suppurative osteomyelitis is attended by almost complete suspension of all the functions of the affected limb. Myositis arrests the contractility of the muscles affected. The pain caused by an inflammation may interfere with the functions of adjacent organs, as may be seen in the fixed chest-wall in cases of acute pleuritis, and in fixa- tion of the abdominal walls, with diminished or suspended respiratory movements of the diaphragm, in cases of peritonitis. The accumulation of inflammatory products may prove a serious obstacle to important functions, and often constitutes a direct cause of death, as in cases of intra-cranial inflammation, where death is more frequently caused by com- pression of the brain than destruction of the contents of the cranial cavity ; and the accumulation of serum or pus in the pleural cavity or pericardium, where a fatal termination can often be traced to mechanical causes from the presence of a copious effusion. Diminution of function often affords the earliest indication of the existence of a deep-seated chronic inflam- mation, as is evident from the slight limp which ushers in a coxitis or the imperfect flexion and extension in chronic inflammation of joints other than the hip-joint. CHAPTER IV. Inflammation (continued). MODIFICATION OF INFLAMMATION BY THE ANATOMICAL STRUCTURE AND LOCATION OF THE INFLAMED TISSUE. The clinical course and pathological conditions of inflammatory processes are materially modified not only by the primary cause, but also by the anatomical structure and location of the inflamed tissues. Inflammation of serous or mucous surfaces has a tendency to spread in a peripheral direction, and, as a rule, remains superficial, and the exuda- tion and transudation are poured out in the direction offering the least resistance; that is, upon the free surface. In tissues that are dense and unyielding the swelling, for physical reasons, is limited, and the inflam- matory products give rise to tension, which may arrest the circulation completely and cause necrosis, as is the case in acute suppurative osteo- myelitis. When the area of inflammation is supplied with an abundance of connective tissue the swelling often attains enormous dimensions in a short time, as may be seen in every case of phlegmonous inflammation of the deep-seated connective tissue of the extremities, neck, chest, and abdomen. Acute inflammation of organs that are exceedingly vascular gives rise to an early and abundant exudation, as can be demonstrated in every case of croupous pneumonia and acute nephritis. Inflammation of non-vascular tissue is accompanied by the formation of new blood- vessels, which grow in the direction of the seat of inflammation from the nearest vascular district. Some tissues are more disposed to inflamma- tion than others; thus, the connective tissue is more frequently the seat of acute inflammation than muscles, and the medullary tissue than the bone-substance proper, and most causes which give rise to chronic inflammation are known to select certain organs and tissues in preference to others. PARENCHYMATOUS INFLAMMATION. In the study of the cardinal symptoms of inflammation special attention was given to the part taken in the inflammatory process by the capillary vessels and the blood-corpuscles. Alteration of the capillary wall was alluded to as the most important pathological condition, as (93) 94 PRINCIPLES OF SURGERY. upon it depends the emigration of the corpuscular elements of the blood and the occurrence of the inflammatory transudation, which together constitute the primary inflammatory swelling. Incidentally it was stated that as soon as the cause which gave rise to the inflammation is brought in direct contact with the fixed tissue-cells, these take part in the in- flammatory process and contribute their share to the inflammatory exu- dation. Inflammation is said to be parenchymatous when the parenchyma of an organ is the primary seat of inflammatory changes, as when the secreting structures of a gland are implicated from the beginning. In all such instances the blood-vessels which furnish the vascular supply have undergone the characteristic changes which have been described, and with few exceptions the microbes have been conveyed to the parenchyma through them. The cloudy swelling of parenchyma cells is either an evidence of the existence of degenerative changes, or it denotes the beginning of coagulation necrosis from the specific effect of patho- genic microbes upon their protoplasm. A cloudy appearance of cells is one of the first manifestations of the presence of a parenchymatous in- flammation. Lesion of connective tissue or parenchyma cells is next to alteration of capillary wall, and emigration of blood-corpuscles the most important pathological condition of inflammation, and, as far as the ultimate result is concerned, the most important, as extensive destruction of parenchyma cells will result in suspension of function, and death of the organ affected is one of vital importance. As soon as the fixed tissue- cells outside of the vessel-wall have become implicated their physiological resistance is diminished,—a condition which cannot fail in aggravating the existing vascular disturbances. Landerer maintains that the normal elasticity of the tissues surrounding the capillary vessels is an essential factor in preserving the equilibrium between the intra-vascular pressure and the surrounding tissues in a normal condition of the circulation. This mechanical theory of inflammation is founded upon the supposition that this normal elasticity of the para-vascular tissues is diminished by the causes which give rise to inflammation, and that when this has occurred the capillary walls have lost their outer support, in consequence of which they become dilated, and hyperaemia, slowing of blood-current, emigration, and transudation follow as the result of purely mechanical causes. Ingenious as yiis theory may appear, it cannot explain the complicated processes which characterize inflammation. The train of pathological conditions which attend inflammation must be regarded as effects of a common microbic cause upon the capillary wall, their con- tents, and the fixed tissue-cells outside of the capillary vessels. In parenchymatous inflammation the cause has reached the parenchyma cells, either directly, as when microbes are brought in contact with a INTERSTITIAL INFLAMMATION. 95 mucous surface, become attached to and penetrate the parenchyma cells, multiply in their interior, and, later, reach the connective tissue and blood-vessels, or, what is more common, the microbes reach the paren- chyma through the circulation. In both instances the capillary vessels and the connective tissues between them and the parenchyma cells take an active part in the inflammatory process. The microbes may be present in such great number or may possess such intensely virulent properties as to destroy the parenchyma cells, as is the case in diphtheritic inflammation of mucous membranes. When less intense in their action the parenchyma cells proliferate, and the embryonal cells, being less re- sistant, succumb later, as when suppuration occurs in the parenchyma of an organ, or they remain indefinitely in their embryonal state, as can be readily verified by examining the different forms of chronic inflam- matory swellings,—the so-called granulomata. INTERSTITIAL INFLAMMATION. In this form of inflammation the connective tissue is the seat of cell emigration and tissue proliferation. Many of the microbes select the connective-tissue spaces; they locate and multiply here, and the inflam- matory product is composed almost exclusively of emigration corpuscles and embrj'onal connective-tissue cells. Tubercle and gummata present such a histological structure. Phlegmonous inflammation represents the acute form of connective-tissue inflammation. If the connective tissue of an organ become the seat of an inflammatory hyperplasia the paren- chyma suffers, either in consequence of pressure or, later, from cicatricial contraction and the inevitable diminution of blood-supply incident to this condition. Parenchymatous inflammation of an organ is preceded or followed by interstitial inflammation, and a primarily interstitial in- flammation sooner or later involves the surrounding tissue by direct extension of the inflammatory process, or indirectly the mechanical causes; hence, as a rule, it is anatomically and even etiologically not always possible to differentiate between these two forms of inflammation, nor is such a distinction of much practical importance. HEMORRHAGIC INFLAMMATION. A few colored corpuscles escape through the capillary wall in almost every case of acute inflammation, but their presence in the exudation can only be determined by the use of the microscope. When they are present in sufficient number to impart to the exudation a bloody tinge, we speak of a haemorrhagic exudation or transudation. A haemorrhagic transudation into the pleural, pericardial, or peritoneal cavity usually indicates the existence of a tubercular or malignant disease of the 96 PRINCIPLES OF SURGERY. respective serous membranes. In cases of acute inflammation with haem- orrhagic exudation, the quantity of the effused blood will be a sign by which we can at least approximately estimate the extent of alteration of the capillary wall. Rhexis can only take place when the capillary wall at some point has been completely broken down and an opening of con- siderable size has formed through which a small stream from the axial current can escape. Aside of the nature and intensity of the primary cause of the inflammation, haemorrhagic inflammation is more likely to be met with in persons debilitated from other diseases, in the aged, and in patients suffering from diseases which obstruct the circulation, such as valvular disease of the heart, cirrhosis of the liver, emplvysema of the lungs, and chronic affections of the kidney. The presence of blood in a transudation or exudation is always a grave sign, and as such should always be taken into careful consideration in rendering a prognosis. SUPPURATIVE INFLAMMATION. In suppurative inflammation at least a part of the exudation is transformed into pus. Transformation of the cellular portion of the exudation, the leucocytes and embryonal cells, into pus-corpuscles is due to the destructive effect upon their protoplasm of the pus-microbes and their ptomaines, while the transudate becomes the pus-serum. Suppu- rative inflammation occurs either as the result of a primary or secondary infection with pus-microbes. In primary infection with pus-microbes the leucocytes most remote from the blood-vessels, and which have been exposed longest to the specific action of the pus-microbes and their ptomaines, are converted first into pus-corpuscles, while the fixed tissue- ce^ls are first transformed into embryonal cells before the same cause, by destruction of their protoplasm, changes them into similar structures. In suppurative inflammation due to secondary infection, the pus-microbes act upon embryonal cells which owe their origin to an antecedent infec- tion with another microbe of milder pathogenic qualities, as can be seen when tubercular granulations or a gumma undergo suppuration. Sup- purative inflammation, in all of its aspects, will be fully considered in the chapter on Suppuration. INFLAMMATION OF SEROUS MEMBRANES. Inflammation of the serous membranes has been called exudative, adhesive, suppurative, or serous, according to the character of the in- flammatory product. In most inflammatory affections of the serous membranes the surface becomes covered with a copious exudation, which is composed of leucocytes, fibrin, and the products of tissue proliferation of the endothelial and connective-tissue cell. The leucocytes and third INFLAMMATION OF SEROUS MEMBRANES. 97 corpuscles are rapidly destroyed as they reach the surface, and the fibrin ferment and fibrino-plastic material which are liberated form, on com- bining with the fibrinogen of the blood-plasma, fibrin. The inflamed membrane is often covered by a thick layer of fibrin, which is firmly adherent to the surface by means of new blood-vessels and granulation tissue which have grown into it. The endothelial cells take an active Fig 38 —Germinating Endothelium, Omentum of Young Dog. Acute Peritonitis. Silver-staining, X 350. (Hamilton.) A natural endothelium covering wall of a mesh; B, D, endothelial cells beginning to germinate; C, a chain of germinating cells extending across a fenestra; E, mass of germinating endothelial cells. part in the inflammation, and in case the new product from this source is converted into connective tissue a permanent adhesion forms. In some instances the endothelial cells are destroyed and desquamation takes place, which leaves the subjacent connective tissue exposed. In such cases the superficial dilated capillaries have lost an important sup- port, and transudation takes place freely. D. J. Hamilton has studied 7 98 PRINCIPLES OF SURGERY. the histological changes which occur in periostitis by producing this disease artificially in young dogs. Besides desquamation, he has seen the endothelial cells multiply by division of the nucleus. The new cells resemble the ordinary granulation or embryonal cells. The connective tissue between the endothelial lining and the blood-vessels Fig. 39.—Omentum of Young Dog, Experimentally Inflamed. X 450. (Hamilton.) A, pyriform cell, probably of endothelial origin, sprouting from wall of a fenestra (S) of the membrane; C, capillary, surrounded by extravasated leucocytes; V, small vein, in similar condition. undergoes tissue proliferation, and the new cells reach the surface and mingle with those derived from the endothelial lining, so that the inflamed surface becomes covered with a layer of granulation tissue. The granu- lations, accompanied by dilated or new blood-vessels, penetrate into the fibrinous exudation, which is removed in the same manner as a thrombus INFLAMMATION OF SEROUS MEMBRANES. 99 in a blood-vessel undergoing obliteration. Permanent adhesions and obliteration of serous cavities are affected by the granulation tissue, which removes the inflammatory exudation and establishes an organic union between opposing inflamed membranes. If the fixed tissue-cells do not participate actively in the inflammatory process, the exudation becomes absorbed in the course of time, and the endothelial lining is repaired; thus the temporary adhesions are removed, and the normal Fig. 40.—Acute Pleurisy. X 300. (Hamilton.) A, A, net-work of fibrin; B, an effused leucocyte; C, laminae of fibrin lying adjacent to the plenra (F); D, small round cells effused into the pleura; E, distended blood-vessel of the superficial layer of pleura. relations existing between the serous membrane and inclosea viscera are restored. The blending of the corpuscular elements of the inflammatory exudation of a serous membrane with the product of tissue proliferation of the endothelial cells is well shown in Fig. 39. The pathological anatomy of acute inflammation of a serous mem- brane at an early stage is well represented in Fig. 40. The scarcity of leucocytes in the fibrin in the specimen represented by this illustration was undoubtedly due to their rapid destruction as 100 PRINCIPLES OF SURGERY. soon as they reached the surface, which resulted in the formation of a copious deposit of fibrin. The round cells in the subpleural connective tissue are effused leucoc}rtes. Sufficient time does not seem to have elapsed for any marked changes to have occurred in the fixed tissue-cells. In suppurative inflammation of a serous membrane, if life is sufficiently prolonged, the leucocytes and embryonal cells are transformed into pus- corpuscles, and in this manner empyema, pyocardium, and purulent peritonitis are produced. The introduction of pus-microbes in sufficient quantity into the abdominal cavity, the power of absorption of which has been reduced by an antecedent affection or an accompanying trauma, will produce such a rapidly fatal peritonitis that the peritoneum, on post- mortem examination, will show little, if any, macroscopical lesions. Death in such cases results from acute septic infection. When life is pro- longed for several days, the post-mortem reveals all the evidences of a fibrino-plastic peritonitis; that is, numerous adhesions between the intestines and the parietal peritoneum and among the intestinal loops. In purulent peritonitis the exudation often breaks down as the leuco- cytes contained in it are converted into pus-corpuscles. Tubercular peritonitis is usually attended by a copious exudation, which limits the process and encapsulates the serous transudation. If, in an inflamma- tion of a serous membrane, the transudation predominates over the exudation, the character of the process is indicated clinically by ,a subacute or chronic course and the absence of severe symptoms. Hydro- thorax often develops insidiously, and perhaps the first subjective symptom is difficulty of breathing. Tubercular peritonitis with copious circumscribed effusion has been frequently mistaken for ovarian cyst, not only because the swelling closely resembles a unilocular ovarian cyst, but also from the absence of any of the usual local symptoms which attend the usual forms of fibrino-plastic peritonitis. It appears that the causes which give rise to the form of inflammation of serous membranes do not act with sufficient intensity on the capillary wall and the para-vas- cular tissues to provoke a copious exudation and active tissue prolifera- tion, but create conditions which permit a copious transudation to take place. It has been recently a much-discussed question whether or not all cases of serous effusion into the chest are of tubercular origin. The fact remains that many cases of subacute and chronic pleurisy die subse- quently from tuberculosis, and the natural conclusion would be that the disease was primarily caused by a localized tubercular focus, which, at the time, could not be detected. It is evident that the causes which produce serous transudation do so not only by producing changes in the capillary wall which permit free transudation, but also by bringing about alterations which diminish or completely suspend the power of absorp- INFLAMMATION OF MUCOUS MEMBRANES. 101 tion ; hence, not only the occurrence of transudation, but accumulation of the liquid effused. The presence of blood in the transudation is usually an indication of the presence of tuberculosis, carcinoma, or sarcoma. INFLAMMATION OF MUCOUS MEMBRANES. Inflammation of a mucous membrane represents another variety of surface inflammation which is greatly modified by the anatomical character of the tissue the seat of the inflammatory process. We have seen that inflammation of serous membranes presents as its most charac- teristic pathological feature a plastic exudation on its surface, composed of the exuded blood-corpuscles and the products of their disintegration, which are firmly attached to the endothelial lining, which in part has been destroyed and detached by desquamation, while the cells which have retained their vitality proliferate new tissue, which mingles with and ultimately removes the exudation. The epithelial cells which line mucous membranes when in a state of inflammation are stimulated to increased activity, and consequently secrete an increased quantity of mucus, which is the characteristic pathological and clinical feature of I. CATARRHAL INFLAMMATION. Inflammation of a mucous membrane is called catarrhal as long as the product consists of an increased secretion of mucus. If a part of the mucous lining is destroyed and the discharge becomes a mixture of pus and mucus, it is no longer proper to call it a catarrhal inflammation, as the pus-microbes have wrought changes that bring the process within the legitimate sphere of suppurative inflammation. Catarrhal inflamma- tion produces a thickening of the mucous membrane by infiltration of the submucous tissue, which, if copious, may subsequently give rise to cicatricial contraction, and, if the inflammation is located in a tubular organ, to the formation of strictures. According to Virchow, a catarrhal inflammation may lead to the formation of superficial ulcers,—the so- called catarrhal ulcers. II. SUPPURATIVE INFLAMMATION. In this form of inflammation of a mucous membrane, the leucocytes which are extruded upon its surface, as well as the embryonal cells, are destroyed by the pus-microbes and are converted into pus-corpuscles, which, when mixed with the mucus secreted by the cells which have retained their pli3rsiological function, form the muco-purulent discharge. Most of the ulcers which form upon mucous surfaces result from circum- scribed necrosis or suppurative inflammation. A catarrhal inflammation very frequently precedes the suppurative form, and a circumscribed sup- 102 PRINCIPLES OF SURGERY. purating area is usually surrounded by a zone of catarrhal inflammation. Cicatricial obliteration of a tubular organ can only take place after ex- tensive defects of its mucous lining from necrotic, ulcerative, or trau- matic causes. Limited defects are repaired by regeneration of the epi- thelial cells, either from the margins of the defect or from remnants of glands. The most frequent causes of ulceration in the intestinal canal are dysentery, typhoid fever, and tuberculosis. Ulcers which result from the sudden obliteration of a small blood-vessel by thrombosis or embolism are met with after extensive burns in the upper portion of the small in- testine and in the stomach in chlorotic females. A strange form of •perforative enteritis has recently been described by Mikulicz. A similar case was operated on in the Zurich Klinik, and a careful description of the pathological conditions found at the necropsy has been given by Klebs. He found multiple perforations in a circumscribed portion of the jejunum, and only a few of them had been found and closed by the surgeon who performed the operation. The perforations on the peri- toneal side were covered by a plastic exudation. The lumen of the intestine corresponding to the affected portion was considerably enlarged. Mucous membrane not much changed in appearance, but, on close inspec- tion, a number of small defects, partly hidden under the folds, were de- tected, and were found to correspond with the covered defects on the outer surface. On microscopical examination, it was found that the villi and mucous membrane were softened and denuded of the epithelial lining and infiltrated with cells over a considerable distance beyond the per- forations. The most marked changes were found in the submucous tissue, which was also much softened, and the scanty intercellular substance was found traversed by wide spaces in which were found numerous large cells with large oval nuclei. Besides these enlarged parenchyma cells, and in their vicinity, leucocytes which had undergone fragmentation were found. As the capillary vessels were much dilated and in a con- dition of inflammation, Klebs looks upon the process as a hyperplastic parenchymatous enteritis. As the leucocytes found in the tissues pre- sented all the evidences of fragmentation, there can be but little doubt that this rare form of enteritis presents only another variety of sup- purative inflammation of the mucous membrane of the intestine. III. CROUPOUS INFLAMMATION. When inflammation of a mucous membrane is attended by the formation of a fibrinous exudation or false membrane upon its surface, it is called croupous. The formation of a fibrinous exudation upon a serous surface, we have found, is always associated with a more or less extensive destruction and desquamation of endothelial cells, and a simi- INFLAMMATION OF NON-VASCULAR TISSUE. 103 lar superficial change takes place in croupous inflammation. Weigert states that unless the epithelial surface of a mucous membrane be broken the inflammatory exudation from it will not coagulate. As croupous inflammation of a mucous membrane is probably always pro- duced by direct infection, it is probable that the micro-organisms destroy some of the epithelial cells, and as the inflammatory process penetrates deeper into the tissue, the exudation and transudation coming in contact with dead tissue on the surface, fibrin is deposited, and, becoming entan- gled with the cellular debris, it becomes adherent to the partially-abraded and uneven surface. The fibrin is arranged in layers in the form of a coarse net-work, in the meshes of which is a finer reticulum of the same, with leucocytes and embryonal cells thrown off from the surface. Some membranes contain numerous leucocytes, while in others they are de- stroyed in the process of coagulation. Separation of a false membrane takes place either by the mucus secreted by intact cells underneath it, or if the mucous lining has been completely destroyed by suppuration and granulation. It has been claimed that, pathologically, a croupous mem- brane differs from a diphtheritic exudation in that, in the former, the lining of the mucous membrane is found intact after stripping it off, while in a diphtheritic inflammation there is always found a loss of sur- face substance after removing the membrane. Upon this more apparent than real anatomical difference the discussion on the non-identity of croupous and diphtheritic inflammation rests. As superficial coagula- tion necrosis is present in all cases of croupous inflammation, and if this process is etiological^ different from diphtheritic inflammation, the pathological conditions are different only in degree and not in kind. False membranes, wherever they may form upon a mucous or serous sur- face, serve as nutrient media for micro-organisms, and the underlying surface is subjected to the risks of recurring infection from them as long as they remain. INFLAMMATION OF NON-VASCULAR TISSUE. The importance of blood-vessels in inflammation can be best shown by a study of the pathological conditions in inflammation of non-vascular tissue. The part taken by the blood-vessels and the fixed tissue-cells in the inflammatory process can be most satisfactorily demonstrated in non-vascular organs. Cornea.__Cohnheim first demonstrated emigration of the colorless blood-corpuscles in artificially-produced keratitis. He cauterized the cornea in animals, and then observed cell infiltration from its margins at a point corresponding to the nearest vascular supply. For the purpose of showing that the cells were not products of the fixed tissue-cells he 104 PRINCIPLES OF SURGERY. injected, a few days before the cauterization, finely-divided cinnabar into the circulation, and found that the leucocytes, as they escaped from the capillary vessels, contained granules of the pigment which he had in- jected. The leucocytes were seen to wander through the vascular spaces of the cornea toward the seat of cauterization. As he could observe no changes in the fixed corneal corpuscles at the seat of cauterization, he maintained that the inflammatory product was derived exclusively from the blood, and that its escape from the blood-stream depended on altera- tion of the capillary wall. He regarded the dilatation of blood-vessels, which occurs soon after the application of the irritant, as a result of reflex action, and attempted to prove, by specimens of keratitis stained with chloride of gold, that the fixed tissue-cells remained unaffected by the inflammation. Strieker maintained the opposite view, and proved, in silver-stained specimens, that the corneal corpuscles had undergone changes which indicated that they performed an active part in the in- flammation. Recklinghausen resorted to a very ingenious experiment to establish his theory regarding the origin of the wandering cells in the vascular spaces of the cornea. He cauterized the cornea of a frog, excised it immediately, and kept it under conditions favorable to cell vegetation, and found, later, wandering cells in the vascular spaces, the origin of which he traced to tissue proliferation of the corneal corpuscles after excision; but even his assistant, F. A. Hoffmann, expressed the opinion that the cells might have been leucocytes which had entered the vascular spaces before the cornea was excised. It is more than doubtful that tissue proliferation would take place in an excised cornea, even under the most favorable physical conditions. There can be no doubt whatever that the primary exudation in traumatic keratitis, as in all other forms of acute inflammation, takes place from inflamed capillary vessels, as Cohnheim has demonstrated so beautifully ; but this constitutes only a part of the phenomena which characterize inflammation in the cornea and all other tissues, as, later, the fixed tissue-cells participate in the process, and the new cells derived from them form a part of the in- flammatory products. The parenchymatous changes are even more im- portant than the vascular, as repair after subsidence of inflammation is accomplished exclusively by proliferation of the fixed tissue-cells. Eberth has demonstrated, by his accurate histological researches, that the corneal corpuscles near an eschar, made for the purpose of producing a keratitis, multiply by karyokinesis, and regeneration is effected exclu- sively by the embryonal cells derived from this source. The corneal corpuscles possess a high vegetative capacity, resembling in this respect the connective tissue, to which they bear a strong resemblance, having a similar embryological origin, and receive their nutritive supply through INFLAMMATION OF NON-VASCULAR TISSUE. 105 a system of lymph-channels or vascular spaces which are in intimate relationship with the sclerotic vessels at the border of the cornea. The plasma or lymph-channel in the cornea are loosely filled with a liquid albuminoid substance, in which can be seen, even in a normal condition, occasionally a lymph-corpuscle. In artificial keratitis these channels are first packed with leucocytes, which escape from the congested capillaries at the limbus corneae, enter them directly, and wander toward the seat of irritation far in advance of the new blood-vessels. Infiltra- tion of the cornea with leucocytes gives rise to cloudiness. At first Cohnheim claimed that infiltration of the cornea always occurred from the periphery, but in some of the later experiments on the corneae of spring frogs he noticed cell accumulation around the central eschar made with a sharp pencil of nitrate of silver, and, as he was absolutely opposed to the idea that the corneal corpuscles could take any active part in the process, he came to the forced conclusion that the cellular elements of the conjunctival fluid were increased, and that these had wandered into the cornea through the lesion at the centre. Strieker has observed karyomitotic changes in the corneal corpuscles surrounding a central eschar as early as three hours after cauterization, and after twenty-four to forty-eight hours cell proliferation was seen to be present all around the inflamed area. From what different authors have written on the subject of artificial keratitis, which, of course, must be accepted as a fair representative of the clinical forms of this disease, it becomes apparent that the first evidence of inflammation is an increased amount of fluid in the vascular spaces, causing distention and, consequently, swelling of the cornea. As the plasma canals become distended the cells lining them are in part de- stroyed, and the fluid escapes between two laminae and forces them partly asunder. (Fig. 41, C, C.) At this time the endothelial cells and corneal corpuscles undergo tissue proliferation, and the new cells form part of the inflammator}' product. With the breaking down of the vascular spaces resulting in lymph stasis, accumulation of lymph-corpuscles also takes place, by which another cellular element is added to the inflamma- tory product. The plasma channels and artificially-formed spaces between laminae are now blocked with leucocytes, lymph-corpuscles, and embryonal cells. If the irritation is prolonged for a sufficient length of time, vascularization of the inflamed cornea will take place in the course of one or two weeks by the formation of new vessels from pre-existing sclerotic vessels at the corneal border. The new blood-vessels grow in the direction of the seat of irritation, occupying a triangular field, with the apex directed toward the centre, the base corresponding to the limbus corneae. The vascular portion of such a cornea is called a pannus. In 106 PRINCIPLES OF SURGERY. suppurative keratitis the emigration corpuscles undergo fragmentation and are converted into pus-corpuscles; at the same time the embryonal cells exposed to the action of the pus-microbes furnish another histo- logical source for pus production. The fibrous tissue within the sup- purating area necroses on account of the disturbed nutrition and the toxic effect of the pus-microbes and their ptomaines, and an abscess results. Vascularization of an inflamed cornea furnishes one of the Fig. 41.—Artificial Keratitis, Kitten. Silver-staining, X 450. (Hamilton.) A, isolated and nucleated cell; B, a group of snch still retaining something of the shape of a plasma canal; C, C, plasma canals breaking into fragments; D, the fibrous basis of the lamellae, or the ground- substance. most beautiful illustrations of the presence of protective resources in the organism, which, when called upon to meet different emergencies, render material aid in the prevention or limitation of destructive proc- esses. Every oculist is familiar with the fact that extensive suppurative keratitis manifests no tendency to reparative action when conditions are present that retard or completely prevent the formation of a pannus. As soon as the process of repair has been completed the new vessels dis- INFLAMMATION OF NON-VASCULAR TISSUE. 107 appear, leaving a transparent cornea if the defect has been within the limits of the regenerative capacity of the tissues; in case the loss of substance has been too great for complete restoration of structure and function, healing is accomplished by the formation of ordinary cicatricial tissue, which results in the formation of a scar—a permanent opacity of the cornea. In keratitis without suppuration, or attended by a limited ulceration, the cloudiness of the cornea resulting from cell infiltration and the presence of embryonal cells in moderate abundance, transparency is restored with the removal of the wandering cells by granular degenera- tion and absorption, or their return into the circulation, and the repair of the lesion by the transformation of the embryonal cells into mature, perfect, corneal tissue. Cartilage.—Cartilage is a structure not only devoid of blood-vessels, but also of any kind of vascular spaces for plasma circulation. Nutrition must here take place by inter- and intra- cellular diffusion of plasma. In its structure it resembles the cornea. On account of the absence of any direct or indirect connection of cartilage tissue with the vessels of the perichondrium all regenerative processes are slow and imperfect, and the inflammatory lesions, which only occasionally are found here as a primary affection, are noted for their chronicity. Artificial chondritis was studied by Goodsir and Redfern. Certain parenchymatous changes were noted at different times after cauterization of articular cartilage. They consist essentially in the enlargement of the cartilage-cells, with increase of the nuclei, or of peculiar corpuscles contained in them, or with fatty degen- eration of their contents and fading or similar degeneration of their nuclei. The hyaline intercellular substance at the same time splits up, and softens into a gelatinous and finely molecular and dotted substance. When molecular disintegration or ulceration of cartilage takes place, the enlarged cartilage-cells on the surface are liberated, and the cement-sub- stance disappears in a similar manner after having undergone liquefaction. Kiiss stated that he had recognized, in articular cartilage under the influ- ence of irritants, certain fibrous transformations, and believed that he had seen, in one case, changes taking place within the cartilage-cells. If articular cartilage be examined in the neighborhood of an ulcerated spot, a complete separation of the fibres, the existence of which in its lami- nated structure was demonstrated by Thin, by a special method of silver-staining, and its reversion to ordinary white fibrous tissue can be readily made out. Weber describes new vessels as extending not only over the surface of the ulcerating cartilage, but afterward penetrating its substance. In long-standing ulceration of cartilage a well-marked pannous condition is usually found present, which has resulted from the development of new 108 PRINCIPLES OF SURGERY. blood-vessels from the vessels of the perichondrium, which grow in the direction of the inflammatory focus in the same manner as in keratitis. Defects of cartilage caused by inflammation, like defects resulting from a trauma, are only partially repaired on account of the low vegetative capacity of the cartilage-cells, and the product of tissue proliferation is transformed into connective tissue. PHAGOCYTOSIS. It has been known for a long time that absorbable aseptic tissues in the living body are capable of removal by the action of certain cells. The absorption of aseptic catgut ligatures by leucocytes and embryonal cells, which accumulate around it and, later, infiltrate it, affords a good illustration of this. Metschnikoff has introduced the term phagocytosis to designate a process by which leucocytes and other cells remove dead material and destroy or digest pathogenic micro-organisms. The cells which perform these functions he calls phagocytes. The leucocytes are called mikrophagi, and the fixed tissue-cells, which are capable of per- forming the same function, makrophagi. Pigment-granules, minute fragments of tissue, and microbes gain entrance into a cell, either by the projections which are thrown out by amoeboid cells surrounding and inclosing them (intussusception), or, in the absence of amoeboid move- ments, by a special property of the cells, by which they take up into their protoplasm solid particles of various kinds. The cells which are known to possess phagocytic properties are the leucocytes, mucous cor- puscles, connective-tissue cells, endothelia of blood-vessels and lymphatic vessels, alveolar epithelium of the lungs, and the cells of the spleen, bone, marrow, and lymphatic glands. Metschnikoff studied first phago- cytosis in the tail of the tadpole, and found that the separation of this organ at the time this animal is developed into a frog is accomplished by leucocytes. At a time when the hind legs begin to bud the leucocytes migrate into the tail, and at the point where separation is to take place they attack the tissues, minute fragments of which may be seen in the interior of their protoplasm. In the daphnia, the common water-flea, he studied the destruction of a fungus with which these insects are prone to be infected,—by the mikrophagi. When phagocytosis proved success- ful he witnessed the destruction of the fungus in the interior of leuco- cytes ; on the other hand, when the fungi were present in such large numbers that the leucocytes were unable to destroy or digest them, the daphnia died. Next, he investigated phagocytosis in a number of diseases,—erysipelas, anthrax, relapsing fever, and tuberculosis. In erysipelas the cocci are first attacked by the leucocytes filling the lymph- spaces, and, later, by the fixed connective-tissue cells. In the path of PHAGOCYTOSIS. 109 destruction he saw leucocytes loaded with cocci, the latter showing various stages of dissolution. The connective-tissue cells were also engaged in the removal of disintegrated leucocytes. In fatal cases of erysipelas the streptococci multiplied with such great rapidity that the phagocytes were unable to cope successfully with the disease. Ribbert experimented with the spores of aspergillus and mucor, and the results were such that he claimed that spores in the interior of leucocytes, the connective tissue of the liver, and the giant cells which develop in the liver and in the lungs are destroyed, but that their destruction is not owing so much to phagocytic action of the cells as to the exclusion from them of nourishment for the spores, particularly of oxygen. Laer injected into the lungs through the trachea cultures of the staphylo- coccus in rabbits, with the result of causing a catarrhal inflammation. The cocci were removed by leucocytes and the embryonal epithelia of the alveoli. During the first week these cells contained many cocci, but during the second week they disappeared in the cells, and the animals recovered. Metschnikoff's doctrine of phagocytosis has met with violent oppo- sition by a number of eminent pathologists, and foremost among them we find Baumgarten. In a number of publications, this author has taken a positive and firm stand against the claim that cells have the power to digest or destroy the microbes which inhabit their protoplasm. Holmfeld, Bitter, Prudden, and Nuttal have also arrayed themselves against Metschnikoff. With some modifications Klebs is a believer in phagocytosis. In a very interesting paper on this subject, Osier gives the result of his own observations on the phagocytic action of the cells lining the bronchial tubes and the alveoli of the lungs. He shows very conclusively how minute foreign particles are eliminated by means of the phagocytic action of the cells. In connection with the subject of inflammation, the doctrine of phagocytosis should be employed in a wider sense than was assigned to it by Metschnikoff. In the first place, the accumulation of leucocytes at the seat of inflammation must be consid- ered in the light of a mechanical barrier, an attempt to protect the tis- sues against infection. Unfortunately, in acute inflammation, this wall is usuany more apparent than real, as the microbes become diffused through the plasma-stream, and are transported by the leucocytes them- selves ; hence the progressive nature of the process. The connective- tissue proliferation proves more successful than emigration in limiting the dissemination of micro-organisms in the tissues, as the new cells, as long as they remain attached to the matrix which produces them, remain stationary, and mechanically block the avenues through which dissem- ination takes place. It is the impermeable wall of granulation tissue no PRINCIPLES OF SURGERY. which surrounds a suppurating depot, which finally limits suppurative inflammation. In the next place, the phagocytes are scavengers which remove foreign dead particles from the tissues. Langhans was the first to show that extravasated blood did not simply disintegrate and disap- pear, but that the connective-tissue elements were actively at work, and that many of the colored corpuscles disappear in their interior. Rosen- berger implanted stained aseptic tissue into the abdominal cavity of animals, and, on examining the parts a few weeks later, found that not only had the tissues been completely removed by leucocytes, but he was able to follow the course of the leucocytes, after they had left the feeding-ground, by colored lines, all of which were seen to radiate from the place where the stained tissue had been fixed. In different pathological conditions where tissue proliferation was in process, Klebs could find positive evidence that wandering cells which had undergone fragmentation had been appropriated by the embryonal cells as food, as fragments of the nuclear chromatin of the leucoc3rtes could be discov- ered in the protoplasm of the new cells. In the reparative process which follows the subsidence of inflammation, a great deal of cellular debris is to be removed, and this work is performed by the phagocytes, notably by the fixed tissue-cells in a state of proliferation. The vege- tative capacity of the cells is augmented by the reception into their protoplasm of nutritive material furnished them by cells which have succumbed in the struggle. Metschnikoff believed that the destruction of micro-organisms in the interior of phagocytes was an active process, and that the protoplasm had a sort of a digestive action upon them. To prove the correctness of this supposition, he made some experiments with the bacillus of tuberculosis. He injected a pure culture of the bacilli into the subcutaneous tissue of white rats, and, later, produced artificially suppuration at the seat of injection. Two months later he found bacilli in the pus-corpuscles in an unchanged condition, and with- out having lost their power of reproduction. As in other experiments he had witnessed the destruction and disappearance of the same bacillus in living cells, he concluded that phagocytosis is an active process which can only take place in a living cell, and is suspended with the death of the cell. There are few at this time who regard the destruction and dis- appearance of microbes in phagocytes as an act of digestion. If, how- ever, microbes in the interior of phagocytes are rendered harmless, or disintegrate and disappear, this fact is an important one, and it is im- material in what way this result is obtained, whether the microbes are digested by the protoplasm, or whether some chemical substance in the cell-body exerts an inhibitory effect upon them, or, finally, whether for want of a proper nutrient material they are starved, as it were. The CHRONIC INFLAMMATION. Ill results of experimental research have furnished positive evidence that infective processes terminate most favorably where the conditions described as phagocytosis are accomplished most satisfactorily. When the struggle between a microbe and a phagocyte turns out in favor of the latter, the microbe does not multiply in the protoplasm, or ceases to do so before the protoplasm is destroyed, and, as the microbe cannot leave without dissolution of the cell, it remains within its narrow confinement and is destroyed, either by some as yet unknown chemical substance or dies from starvation ; in either event the vitality of the cell is not impaired, and the microbe disintegrates and disappears. (Fig. 42, A.) If the conditions for the growth and development of the microbe in the protoplasm of the cell are more favorable, intra-cellular multiplication of the microbe takes place, the ptomaines which are Fig. 42.—Phagocytosis. Struggle between Anthrax Bacillus and Leucocyte. A, successful phagocytosis; B, unsuccessful phagocytosis. eliminated produce coagulation necrosis in the protoplasm, the cell disintegrates, and the intra-cellular culture is liberated in an active con- dition (Fig. 42, B). In cases of unsuccessful warfare of the phagocytes against invading micro-organisms, the mechanical obstruction composed of emigration corpuscles and embryonal cells is broken down, and the rapid increase of micro-organisms at the seat of inflammation gives rise to extensive local and often general infection. From a practical stand- point it can be said that all therapeutic measures which influence favor- ably the process of phagocytosis, in the broadest meaning of this word, are calculated to exert a potent influence in arresting or limiting infective processes. CHRONIC INFLAMMATION. Chronic inflammation differs from the acute form only in degree. The vascular changes which have been described come on slowly, and 112 PRINCIPLES OF SURGERY. are never as marked as in acute inflammation, and on this account the emigration of blood-corpuscles occurs slowly, and in some instances it is entirely wanting. The inflammatory product is largely, and in some cases exclusively, composed of embryonal cells derived from fixed tissue-cells. The noxae, which excite chronic inflammation are such that exert their deleterious effect more on the tissue-cells directly than the capillary vessels. Their primary action on the tissues consists in increasing the vegetative capacity of the cells; hence, mature cells are transformed into embryonal or granulation tissue and remain in this condition as long as the noxae exist, and retain their pathogenic qualities or otherwise until the new celis undergo retrograde metamorphosis. If in a chronic inflammation degeneration of the embryonal cells has not taken place, and the primary cause has ceased to act, the new tissue is either removed by absorption or is converted into mature tissue, in which event the inflammation has resulted in hyperplasia. Syphilitic gummata, which are composed almost exclusively of embryonal tissue, disappear promptly under a vigorous antisyphilitic treatment, because by such treatment the micro-organisms which have caused the lesion are either destroyed or at least have been deprived for the time being of their pathogenic properties. Chronic inflammation is represented by that large class of affections which are included under the name granulomata. These swellings, irre- spective of their primary microbic cause, are composed of what is known as granulation tissue. Some pathologists have been inclined to classify them with tumors, because their development is seldom attended by well-marked symptoms of inflammation, and in their methods of regional and general dissemination they bear a close resemblance to the malignant tumors. Their obstinacy to successful treatment does not depend upon any malignant qualities of the tissues of which they are composed, but upon the difficulty of eliminating or rendering inert the primary cause by internal medication or operative procedures. All granulomata are inflammatory in their origin, and under the microscope present all the characteristic appearances of inflammation. Histologically they are composed of embryonal cells which correspond to the type of the tissues in which or from which they have developed. In a tubercular nodule we find giant cells, epithelioid cells, the ordinary granulation cell, and leucocytes. Actinomycotic swellings are composed almost exclusively of embryonal connective tissue. Many of the granulo- mata contain Ehrlich's plasma-cells (Mastzellen), of unknown origin, composed of a fineby-granular mass around a vesicular nucleus. On staining with aniline colors, the nucleus remains unchanged, while the granules are deeply stained. The cells are about the size of a leucocyte, Chronic inflammation. 113 either spherical or somewhat elongated in shape. In some cases the outer portion of the inflammatory product, being sufficiently remote from the infected area, is converted into a firm connective-tissue capsule, which limits the extension of infection, while in its interior, from the presence of the specific micro-organisms, but probably more on account of inadequate blood-supply the tissues undergo rapid retrograde degenerative changes. Secondary infection in a granuloma, either through the circulation, or, what is more common, from without, through some minute infection- atrium, is a not uncommon occurrence. Secondary infection almost always means localization of pus-microbes in the granulation tissue and a breaking down of the latter into pus-corpuscles. The serious conse- quences which follow suppurative inflammation of a gumma developing after incision made upon a wrong diagnosis is well known. Infection of a large tubercular depot with pus-microbes after incision without proper antiseptic precautions, or after spontaneous evacuation, is followed by destruction of the remaining granulations, profuse suppuration, and not infrequently by death from sepsis. Actinomycosis gives rise to a large granuloma without any tendency to suppuration until infection takes place with pus-microbes, when the granulations melt away rapidly, leaving a deep ulcer with ragged, undermined margins, and a speedy extension of the combined infective processes following in its course the connective tissue. The secondary infection, however, may prove beneficial and become the means of complete elimination of the products and micro-organisms of the primary infection. In this way a localized tubercular lesion is sometimes cured spontaneously by suppuration. A suppurative inflam- mation of a tuberculous gland of the neck is often followed by complete removal of the bacilli-containing tissues and a permanent cure. All chronic inflammatory processes are attended by recurring attacks of acute exacerbations. If during these attacks in the periphery of the chronically-inflamed area a more active cell proliferation is initiated, the conditions for a more successful phagocytosis are improved and the acute attack has proved a curative measure. The surgeon often resorts to measures which result in the transfor- mation of chronic into an acute inflammation, in imitation of nature's efforts in the same direction. In illustration of this, I will only mention ignipuncture. The fenestration of a chronic inflammatory swelling under strict antiseptic precautions has proved a valuable therapeutic measure by securing drainage, but more especially because around each tubular eschar made with the needle-point of a Paquelin cautery a zone of active tissue proliferation is created, and the new tissue, by under* 8 114 PRINCIPLES OF SURGERY. going transformation into cicatricial tissue, serves a useful purpose in starving out microbes that have escaped the cautery. Another instruc- tive instance of the benefits which accrue from the substitution of an acute for a chronic inflammation is found in the use of jequirity in ophthalmic practice. The powdered bean or some other preparation of this drug, when brought in contact with the conjunctiva, produces a violent inflammation which has frequently proved a curative measure in the treatment of trachoma and some forms of pannus of the cornea. One of the ways in which an acute inflammation acts beneficially in promoting the process of resolution in tissues the seat of a chronic inflammation is by its stimulating action on the capillary vessels. The active hypersemia may become the means of clearing partially-obstructed capillary vessels of implanted colorless corpuscles, and thus remove from the weakened tissues not only the mechanical causes which have main- tained the chronic congestion, but also the intra-vascular cause of the inflammation—the microbes. When the infected corpuscles reach the general circulation there is a chance for more effective phagocytosis and elimination of the microbes through one or more of the excretory organs. SYMPTOMS AND DIAGNOSIS OF INFLAMMATION. For practical purposes, inflammation may be divided into acute, subacute, and chronic, according to the intensity of symptoms and the time required to reach one of its terminations. The nature of the pri- mary cause determines the course and nature of the inflammation. The microbes of suppuration, erysipelas, anthrax, glanders, tetanus, and gonorrhoea cause acute affections, while the micro-organisms of tubercu- losis, lepra, and actinomycosis cause lesions which are noted for their chronicity. Acute inflammation may become subacute and finally chronic, as in suppurative osteomyelitis, where, if the disease is multiple, in the first bone affected it pursues a very acute course ; while often in the successive bones attacked it is less intense, and not infrequently in the last bone involved it appears as a chronic affection. A chronic in- flammation may be followed by a subacute or acute attack, as is fre- quently observed in tuberculosis complicated by secondary infection with pus-microbes. In acute inflammation the local and general symp- toms are so well marked that no difficulties are in the way of recogniz- ing its existence, and it only remains to decide upon its character. The fever which attends the inflammation is only a symptom, and indicates the introduction into the general circulation of phlogistic substances from the products of exudation or the fixed tissue-cells which have undergone pathological changes. Microbes that cause acute inflamma- tion differ greatly as to the amount or intensity of action of the phlo- SYMPTOMS AND DIAGNOSIS OF INFLAMMATION. 115 gistic substances which they produce in the inflamed tissues affected; also exert an important influence in modifying the febrile disturbance. Suppuration caused by the micrococcus pyogenes tenuis is not attended by so high a temperature as when produced by the staphylococcus or streptococcus. The rise in temperature which accompanies inflammation is due either to the introduction into the circulation of fibrin ferment resulting from the destruction of leucocytes or the production of pto- maines by the specific action of microbes on the tissues, which act as phlogistic substances when introduced into the general circulation,—a fact which has been abundantly demonstrated by clinical observation and experimental research. As soon as the causes which have produced the rise in temperature in inflammation have been rendered inert by phago- cytosis, or have been eliminated with the removal of the inflammatory product, the fever subsides. The general disturbances, such as headache, vomiting, loss of appetite, thirst, and the ever-present feeling of lassitude which attends acute inflammation of all kinds, are caused by the fever and the presence of toxic substances in the blood. The symptoms of inflammation, which have been described at length, must be studied sep- arately and conjointly in each form of inflammation, and their individual and mutual significance carefully estimated. A local rise in temperature is of more diagnostic value in ascertaining the existence of inflammation than fever, as the latter can be caused by the absorption of fibrin ferment from any causes which destroy the colorless blood-corpuscles and the absorption of the products of tissue disintegration in malignant tumors ; while a permanent increase of the temperature at the seat of the disease denotes almost infallibly the existence of inflammation. In reference to the extension of the inflammatory process, it can be said that this will be influenced by the anatomical structure of the part involved and the manner of diffusion of the microbe which causes the inflammation. If a mucous or serous surface is affected, infection is prone to spread rapidly by continuity of tissue and the mechanical dissemination of the microbes on the surface in the mucous secretion, and by the movements of one serous surface upon the other. In erysipelas the inflammation spreads rapidly, as the microbe is diffused through the lymphatics and connective- tissue spaces. In phlegmonous inflammation the pus-microbes find no mechanical barriers, and are rapidly distributed over a larger area through the connective-tissue spaces. The same manner of diffusion is observed in anthrax if the bacillus finds ingress into a part supplied with an abundance of loose cellular tissue, while the disease remains circumscribed and presents itself in an indurated form if it is located in tissues which do not present such favorable anatomical conditions for extension of the local invasion. The nature of the inflammatory product 116 PRINCIPLES OF SURGERY. always answers to the specific action of the microbe as the tissues which caused the inflammation. Thus, an inflammation caused by pus- microbes will result in the formation of pus; while the microbes which produce chronic inflammation, as a rule, only convert the pre-existing mature into embryonal tissue. The microbes which have a short exist- ence in the tissues may give rise only to intense hyperemia and a mod- erate emigration of the colored blood-corpuscles, as, for instance, the streptococcus of erysipelas. The genuine, uncomplicated erysipelatous inflammation is of such short duration that perfect restoration of the parts is accomplished in a few days. PROGNOSIS. The most favorable termination of inflammation is resolution, with restitutio ad integrum of structure and function of the tissues which were the seat of the inflammatory process. Resolution is only possible if the emigration of blood-corpuscles is moderate in quantity and none of the cellular elements of the exudate are transformed into pus-corpuscles. If exudation take place rapidly, the connective-tissue spaces are com- pletely blocked with the emigration corpuscles and the products of coagulation necrosis, which seriously impairs or completely arrests plasma circulation, and, by pressure upon the blood-vessels, may interfere with the capillary circulation to such an extent as to cause necrosis. Resolution, as has been previously stated, signifies that, after subsidence of the symptoms of inflammation, the part is left in a condition capable of removing the inflammatory product and of repairing the damage done. Many of the leucocytes which have retained their vitality immigrate back into the general circulation either through the walls of capillaries or, what is more frequent, through the lymphatic system. The remain- ing leucocytes and colored corpuscles undergo degeneration and are removed by absorption. Fibrin which has formed in the tissues is trans- formed into a granular mass, and is removed in a similar manner. Embryonal cells which have become detached, or have been damaged by the inflammation, are also removed by absorption after they have under- gone granular degeneration. The transudation is removed by absorp- tion as soon as capillary circulation is restored and the connective-tissue spaces have been cleared of their cellular contents. The capillary wall is repaired, and any tissue defects are restored by proliferation of the fixed tissue-cells. The inflammatory exudate may prove a source of danger when, by its mechanical pressure, it interferes with the function of important organs, as the brain, heart, or lungs. A moderate transu- dation within the skull from inflammation of any of the meninges can produce death from compression of the brain; a pericardial effusion, TREATMENT. 117 when sufficient in amount to interfere mechanically with the action of the heart, causes death by syncope; and a copious effusion into the pleural cavity, especially if it come on rapidly, may impair respiration to such an extent as to result in death from apncea. A slight croupous exudation upon the vocal cords or oedema about the entrance to the larynx destroj's life by preventing, in a purely mechanical way, the en- trance into the lungs of an adequate quantit}- of air. Inflammation is greatly modified b}r the age and general condition of the patient. Infants and persons advanced in years possess little power of resistance, and, when attacked by inflammation, the disease is prone to become diffuse and lead to serious pathological changes. The same can be said of persons who have been debilitated b}r antecedent diseases or intemperate habits. The greatest danger in the different forms of inflammation, as far as life is concerned, consists in the introduction into the general cir- culation of septic material produced in the inflamed part by the action of microbes on the tissues. This general infection, occurring in the course of a localized inflammation, appears either as a symptomatic fever, which disappears with the subsidence of the local process, or as a pro- gressive septicaemia, pyaemia, or septico-pyaemia. The latter diseases will be considered in separate chapters. Tubercular affections are always attended by the danger incident to extension of the process to other organs by dissemination of bacilli through the lymphatic channels or blood-vessels. Chronic suppuration finally causes amyloid degeneration of important organs, and death ensues from this cause. In summing up what has been said under this head, it is evident that the prognosis rests mainly upon the intrinsic pathogenic qualities of the microbe which has caused the inflammation ; the anatomical structure, location, and physio- logical importance of the part or organ inflamed; the general condition of the patient, and the accessibility to and feasibility of treating the disease by direct radical surgical means. TREATMENT. As inflammation per se is no disease, but an effort on the part of the organism and the tissues affected to eliminate or render harmless the primary cause, the treatment must be, in each individual case, purely symptomatic. A proper appreciation of the nature and tendencies of inflammation is an essential prerequisite to rational treatment. In surgery the prophylactic treatment of inflammation is the most important and satisfactory. The prevention of inflammation in accidental and oper- ation wounds by strict antiseptic precautions has made modern surgery what it is. The surgeon has it now in his power, by resorting to anti- septic measures, to prevent the innumerable and formerly too often fatal 118 PRINCIPLES OF SURGERY. wound complications. Lister has inaugurated a new era in surgery, and his work, as well as that of his early enthusiastic followers, has been the means of saving annually thousands of lives. The mortality of even the most desperate operations where the antiseptic treatment can be followed to perfection has been so much reduced that operative surgery has received a new impetus, and operations are devised and put in prac- tice almost daily which formerly would have been looked upon as a freak of imagination or the outcome of a diseased brain. The prophy- lactic treatment of inflammation in dealing with wounds, or other avenues through which infection can take place, consists of securing for the place deprived of the effective protection against the entrance of patho- genic micro-organisms—the intact skin or mucous membrane—an aseptic condition by antiseptic measures, and to bring in contact with it only things that have been thoroughly sterilized. In inflammation without an external tangible infection-atrium we must take it for granted that microbes have entered the circulation through slight defects, the existence of which, perhaps, the patient does not remember, and which have left no appreciable marks of their former existence, or infection has taken place through some of the appendages of the skin, or through a mucous membrane, with localization of the microbes in a part or organ previously prepared for their reception and growth; that is, in a location presenting a locus minoris resistentise. Recognizing the fact that inflammation, wherever it occurs, is pro- duced by the action upon the vessel-wall and the tissues outside of it of specific micro-organisms, it would appear that the most rational indica- tion for treatment would be to resort to such means which would destroy the microbes in the tissues as soon as their presence is manifested by their action. This would imply the saturation of the inflamed tissues with ger- micidal solutions,which from laboratory experiments are known to be effec- tive in destroying such microbes ; hence, it has been advised to resort to Parenchymatous Injections.—This method of treatment was strongly advised and extensively practiced by Heuter long before the direct relationship between certain microbes and definite forms of inflammation had been demonstrated. Heuter claimed that every inflammation was caused by certain noxae introduced from without, and which he aimed to destroy by saturating the inflamed tissues with an antiseptic solution. His favorite remedy was a 3- to 5-per-cent. solution of carbolic acid. The instrument which he used was an ordinary Pravaz syringe, with a long needle provided with a number of small lateral openings. In adults he injected as much as 10 grammes at a time of a 3-per-cent. solution. In using this method in the treatment of large, granulating, tubercular foci he employed what he termed an infusor, composed of a graduated glass TREATMENT. 119 cylinder, joined with the needle by means of a rubber tube. By this method of injection the fluid diffused itself through the soft, granular mass by its own weight. In the treatment of tubercular lesions Heuter claimed for the parenchymatous injections of carbolic acid great curative powers. Rational as this method of treatment appears, it has not yielded the results that were anticipated. The living tissues cannot be compared with a test-tube. Nitrate of silver, iodine, permanganate of potassa, corrosive sublimate, and other potent germicidal agents have been used since, but the results, on the whole, have been anything but satisfactory. If this method of treatment is to be successful in the treatment of acute inflammation, it must be instituted at an early stage, at a time when only a limited area of tissue has been infected, as, under such circumstances, if the area of infection could be accurately outlined, it would be possible to saturate the tissues with an antiseptic solution without running the risk of killing the patient by administering a toxic dose of the drug employed, which might be the case if a larger area were treated in a similar manner. If we remember that the microbes are diffused through- out the entire exudation, and constitute the most important element of the inflammatory product, it is easy to understand that sterilization of the inflamed tissues by means of parenchymatous injections is not an easy task, and we are then in a position to realize why this method of treatment has not proved more uniformly successful. Most of the germi- cidal agents heretofore employed in this manner, when brought in contact with the tissues, form compounds which prevent further diffusion, and therefore each needle-puncture sterilizes only a very small portion of the inflamed district. It is possible that in the future non-toxic, but at the same time effective germicidal, substances will be discovered which can be used in larger quantities, and in this event the treatment of inflamma- tion by parenchymatous injections will have a wide range of application, and will be practiced with better success. At present this method has a limited field of application in the treatment of the various forms of in- flammation. Under no circumstances should the amount of the drug used exceed the dose which it would be safe to administer internally, and the danger of a poisonous dose should be remembered in repeating the injection. An ordinary hypodermic syringe with a long needle can be used in making the injection. That the needle and syringe should be perfectly aseptic is to be understood as a matter of course, as unclean instruments have often been the means of conveying a fatal disease. Multiple punctures are to be preferred, as in this manner, by using the same amount of fluid, more tissue can be saturated than by a single puncture. Before making the punctures the surface must be disinfected. The object should be to bring the antiseptic solution in contact with as 120 PRINCIPLES OF SURGERY. much of the injected tissues as possible, and if the disease show a ten- dency to spread it is advisable to go beyond the zone of infection, as, for instance, in cases of erysipelas and anthrax. Many accessible tuber- cular affections are greatly benefited by parenchymatous injections of carbolic acid. Recently, intra-articular and parenchymatous injections of iodoform have been strongly recommended in the treatment of articu- lar and other forms of surgical tuberculosis. Antiphlogistic Treatment.—An erroneous conception of the nature and tendencies of inflammation has for centuries induced the ablest teachers and practitioners to advocate and practice what they termed the antiphlogistic treatment of inflammation. This included blood-letting, cupping, leeching, and the internal use of emetics and cathartics. It was urged that as inflammation was attended by an increase of heat, swelling, and redness, such remedies should be employed as will reduce arterial tension. Venesection is now seldom, if ever, resorted to in the treat- ment of any form of inflammation. An unimpaired vis a tergo is one of the best means to prevent stasis within the inflamed capillaries, and practical experience has shown that all remedies and agents which diminish the intra-arterial tension only diminish the prospects for a favorable termination of the inflammation. Cohnheim showed experi- mentally that the threatened stasis in the exposed mesentery of the frog was avoided by injecting into one of the veins 1 centimetre of a &-per- cent. solution of sodic chloride. If, under similar conditions, a consider- able quantity of blood is abstracted, the congestion can be seen to terminate in a short time in complete stasis. While venesection in the treatment of inflammation has been discarded, the direct abstraction of blood from the inflamed part hss proved a useful therapeutic resource. Genzmer showed that in the inflamed mucous membrane of a frog scari- fication hastened resolution. In order to be of benefit the scarification must be made through the inflamed part, so as to unload directly the dilated and engorged capillary vessels, and on this account this method of treatment is only applicable when the inflammation is superficial and affects accessible parts. Leeches should never be used, as infection from this source has frequently resulted disastrously. The scarification used for cupping is difficult to keep aseptic, and the number and depth of the scarifications to be made are not under the control of the surgeon, and for these reasons this instrument has only an historical interest and antiquarian value. The scarification should be made with a sharp scalpel, and the bleeding encouraged by applying warm water. Scarification is followed by great relief in inflammation of accessible mucous membranes, and has recently been very strongly recommended in the treatment of erysipelas for the purpose of preventing the extension of this disease. TREATMENT. 121 In the different forms of septic inflammation attended by severe general symptoms the gastro-intestinal canal often participates in the process, and vomiting and diarrhoea become conspicuous and often dis- tressing symptoms. These symptoms should not be checked, as they indicate an attempt on the part of the organism to eliminate through the gastro-intestinal mucous membrane microbes and ptomaines which have reached it through the general circulation. The surgeon should assist this effort by administering a few doses of calomel, followed by a saline cathartic, which will often control the vomiting and diarrhoea more promptly by removing the cause than medicines employed to arrest the process of elimination. Physiological Rest.—One of the most urgent indications in the treat- ment of inflammation is to secure for the part affected a condition approaching physiological rest. In ulcerative affections of the gastro- intestinal canal the patient should abstain from taking food by the stomach. Fixation of the chest by means of broad strips of adhesive plaster affords great relief in pleuritis. An inflamed point must be im- mobilized by some kind of a splint. A chronic cystitis usually yields to supra-pubic or perineal drainage of the bladder after all other measures have failed. In inflammatory affections of the eye exclusion of light is one of the most essential features of successful treatment. Patients suffering from inflammatory affections of the tonsils, pharynx, and larynx should use their voice as little as possible. In cases of acute inflammation of the brain or its envelopes the patients must be kept in a dark room, and absolute quietude enforced. Elevation of Inflamed Part.—From the diminished vis a tergo on the distal side of the capillary vessels, venous engorgement is as pronounced as increased arterial tension on the proximal side of the inflamed capillary vessels, and elevation of the inflamed part improves the vascular dis- turbances by the force of gravitation favoring the return of venous blood. The importance of elevation of the inflamed part becomes manifest in the treatment of inflammatory affections of the extremities. In phlegmonous inflammation of the hands or feet the throbbing pain is always aggravated if the limb is kept in a dependent position, and promptly relieved upon placing it in an elevated position. Elevation not only alleviates the pain, but is at the same time the most effective means of removing the oedematous swelling. If necessarj* elevation can be combined with suspension in order to secure more perfect rest for the inflamed part. In severe acute inflammation it is not only necessary to secure rest for the part inflamed, but of the whole body, and in such cases the patient must observe the recumbent position in bed, as all muscular movements and all unnecessary strain upon the blood-vessels 122 principles of Surgery. cannot but be productive of harm by favoring the ingress into the circu- lation of micro-organisms and their ptomaines from the seat of inflam- mation, or, perhaps, result in embolism from detachment of a portion of a thrombus,—an accident which possibly might not have occurred otherwise. Application of Cold.—Cold has been resorted to indiscriminately and empirically in the treatment of inflammation. Cold is a potent agent for good or harm, according to the stage of inflammation during which it is applied. The sensation of heat, both subjective and objective, naturally suggested the use of this remedy. The application of cold is of great benefit during the earliest stage of inflammation, at a time when exuda- tion is only beginning and the capillary vessels are dilated and only partially obstructed. Cold, when applied under these circumstances, becomes a valuable remedial agent (1) by producing contraction of the small blood-vessels ; (2) by producing at least an inhibitory effect upon the micro-organisms in the inflamed tissues. The contraction of blood- vessels which takes place under the application of cold has a tendency to clear the capillaries of their contents and to prevent further mural implantation. Micro-organisms can only multiply at a certain tempera- ture, and if this can be kept at a point low enough to prevent their in- crease in the tissues by the application of cold this agent fulfills one of the causal indications in the treatment of inflammation. If, however, stasis has already taken place in the capillaries first affected the applica- tion of cold will prove harmful, as it will tend to prevent the formation of an adequate collateral circulation. Cold acts most beneficially when the inflammation is located in the superficial parts, but its prolonged use will reach even deep-seated structures, as the pleura, peritoneum, the brain and its envelopes, the joints and bones. When it appears desirable to resort to the use of cold, this remedy should be applied in the form of an ice-bag. The part to which the ice-bag is to be applied can be covered with several layers of a wet towel, as otherwise the prolonged use of the direct application of ice may freeze the skin. The sensations of the patient can actually be taken as' a safe guide as to the length of time it should be continued. Antiseptic Fomentations.—The ordinary filthy poultice of flaxseed, slippery elm, bread and milk, has no longer a place among the resources of the aseptic surgeon. The common poultice is a hot-bed for bacteria, and, as such, it should be discarded. In the treatment of an ordinary furuncle with poultices, I am sure that almost every surgeon must have seen occasionally the development of innumerable minute daughter- furuncles in the surface covered by the poultice. In phlegmonous in- flammation of the fingers or hand the prolonged use of the poultice is TREATMENT. 123 followed by maceration of the skin, extensive oedema of the superficial structures, a flabby condition of the granulation,—in fact, all the evidences which point to the poultice as a means of favoring the extension of the infective process. When inflammation has passed beyond the stage where cold exercises a favorable influence, or where cold applications in- crease the suffering, warm antiseptic fomentations should be employed. The surface to which they are to be applied should be thoroughly cleansed with warm water and potash soap. The antiseptic solution to be used should be selected according to the age of the patient, or the area affected, with a special view of guarding against the absorption of a toxic dose of the drug employed. Acetate of aluminum, in the strength of 1 per cent, dissolved in sterilized water, is a safe preparation under all circumstances. Boracic and salicylic acid are efficient and safe preparations. Greater care is necessary in the use of carbolic acid and corrosive sublimate, as, when concentrated solutions of these drugs are used for any length of time in infants, the aged, or persons suffering from organic disease of the kidneys, there is danger of poisoning from absorption through the intact skin. In children and marantic persons it is safer to use acetate of aluminum, salicylic or boracic acid, and re- serve the more potent antiseptics for adults suffering from circumscribed inflammatory lesions. Hot fomentations act as derivatives and favor the formation of collateral circulation; at the same time they relieve pain. A number of layers of hygroscopic gauze or flannel cloth are wrung out of one of these antiseptic solutions and applied over the affected part, and for the purpose of retaining the heat and of preventing evaporation of the solution the compress is to be covered either with gutta-percha, rubber sheeting, or macintosh cloth, and the dressing is retained by an appropriate bandage. The compress is removed two or three times a day, again wrung out of the hot solution, and re-applied as before. Absorption through the skin of the antiseptic substance used may have a direct influence in diminishing the intensity of the cause which pro- duced the inflammation, and prepares, in an admirable manner, the field for any operation which may become necessary in the future. Antipyretics.—If the rise in temperature which attends many of the acute inflammatory affections is due to the introduction into the circu- lation of phlogistic substances which are produced by the action of the micro-organisms in the inflamed tissues, it is not difficult to conceive that its artificial reduction by the internal use of chemical substances is not followed by any permanent benefit. The rational treatment of the fever consists of such local measures as will remove its cause. Antifebrin, antipyrin, salicylated soda, quinine, and other antipyretic drugs, when employed in large doses, will usually reduce the temperature several 121 PRINCIPLES OF SURGERY. degrees for a few hours, but this is always accomplished at the expense of the forces which are laboring to clear obstructed paths, and on this account their use has resulted in more harm than good to the patient. Quinine is the least objectionable of the drugs which have been men- tioned, and in the beginning of an inflammation, by its known tonic effect on the small blood-vessels, when administered in a large dose, has a favorable effect in preventing rapid dilatation of and stasis within the capillary vessels. If used at all, it should be given in a decided dose,— 1 gramme, in solution,—immediately or soon after the development of the first symptoms. Sponging the surface of the body with warm water or the use of warm baths are the most rational antipyretics, as these simple measures do not weaken the heart's action, while they have a decided effect on the temperature, and at the same time add to the comfort of the patient and favor the elimination of microbes through the excretory organs of the skin. As the kidneys are known to eliminate micro- organisms that reach them through the general circulation, their func- tion should be carefully inquired into, and if the secretion of the urine is scanty, diuretics, like liq. amnion, acet., or acetate of potash should be given. Stimulants.—Just as soon as symptoms of sepsis develop in the course of an inflammation, alcoholic stimulants should be freely admin- istered to meet in time the dangers incident to heart-failure. Stimulants have largely taken the place of antiphlogistics at the present time in the treatment of septic inflammations. Brandy, cognac, or whisky, not in measured doses, but given in quantities large enough to produce the de- sired effect on the heart, are given at intervals of one or two hours. Cham- pagne is a more diffusible stimulant, and is to be resorted to when the stomach does not tolerate other alcoholics. In chronic cases, Tokayer or Greek sherry are to be preferred. In wasting diseases, a good quality of beer, ale, or porter will do excellent service. In cases where, from any cause, the heart's action is suddenly diminished, camphor or musk can be administered subcutaneously to bridge over the time for the employment of more substantial stimulants. Diet.—The treatment of inflammation by starvation has been abol- ished long ago. The strength of the patient must be sustained in time by a nutritious, well-selected diet. Animal broths, beef-tea, and milk should be freely given from the very beginning, and if more substantial food can be digested it should not be withheld. Oysters, eggs, fine- scraped raw meat, or rare roast are excellent articles of food for patients whose strength is being undermined by debilitating, suppurative affec- tions. If the stomach does not retain food, the patient should be nour- ished by rectal enemata of peptonized milk and beef-tea in quantities TREATMENT. 125 not exceeding 4 ounces, given alternately, every eight hours. Ripe oranges and grapes are most always grateful to the patient, and their use should never be prohibited, unless the gastro-intestinal canal is the seat of inflammation. Tonics and Alteratives.—In protracted inflammatory affections tonic doses of quinine are indicated. Tincture of chloride of iron is an excel- lent remedy after the acute febrile symptoms have subsided. Under similar circumstances, one or more of the bitter tonics can be given with benefit if the appetite is defective. If there is any history of specific disease, a thorough antisyphilitic treatment will often produce a marked effect for the better on the inflammatory process. Catarrhal inflamma- tion in rheumatic patients is favorably influenced by antirheumatic rem- edies. Syphilitic lesions are to be treated by potassic iodide and small doses of corrosive sublimate. Tubercular affections call for arseniate of iron, syrup of iodide of iron, and, if the patient's stomach can tolerate it, pure codliver-oil. The latter drug should be given alone, and not in emulsion, in gradually-increasing doses an hour and a half after each meal. Anodynes.—Remedies to relieve pain must always be used with caution, as in painful chronic affections their prolonged use frequently engender a habit. The cause of pain must be sought for, and, if possible, removed by local measures. In acute inflammation, pain indicates ten- sion in the inflamed part, and prompt relief is obtained by subcutaneous incision. Periostitis and paronychia should be treated by this method. In superficial inflammations scarification answers the same purpose. If opiates are used, a decided dose is better than smaller doses frequently repeated. The anodyne effect of opium is increased by the addition of a minute dose of atropine. Chloral and potassic bromide are to be pre- ferred to opium to relieve the pain of intra-cranial lesions. Phenacetine in ^-gramme doses is a very excellent anodyne in cases of peripheral neuritis. Inhalations of chloroform to allay intense pain should never be resorted to except by the direction of and under the personal supervision of a competent physician. Massage.—In chronic inflammatory affections systematic massage, scientifically practiced, is an exceedingly important and valuable thera- peutic resource. It stimulates the surrounding vessels to increased action, and exerts a potent influence in restoring the normal circulation in the affected capillary vessels, and always promotes absorption. The masseur should be instructed to apply some absorbent preparation before makino- the manipulations, as the endermic use of absorbent drugs in this manner will increase the efficacy of the treatment. A drachm of potassic iodide or half a drachm of iodoform to an ounce of lanolin will be an 126 PRINCIPLES OF SURGERY. excellent preparation for this purpose. Cold and hot douches, passive and active motion, combined with massage, will often expedite a cure. Counter-Irritation.—Like so many other time-honored methods of treatment, counter-irritation in the treatment of acute inflammation has almost entirely gone out of use. In chronic inflammation, blistering and painting with the tincture of iodine will at least satisfy the patient, if no good result from them ; and if he does not recover, he is at least prevented from passing into the hands of charlatans until the time has arrived to resort to more effective and radical measures. Kocher praises the appli- cation of the actual cautery in the treatment of chronic tubercular osteo- myelitis and synovitis. The seton and moxa have fallen into well- merited disuse for all time to come. Ignipuncture.—In many chronic affections, where the inflammatory exudation remains stationary for a long time, multiple punctures with the needle-point of a Paquelin cautery, made under strict antiseptic pre- cautions, will have a prompt effect in diminishing the primary cause, as well as in promoting absorption. CHAPTER V. Pathogenic Bacteria. Bacteria, micro-organisms, microbes, and germs are synonymous terms for certain minute, microscopical, vegetable organisms which, when introduced into the living body, produce the fever and the tissue changes described in the preceding chapter. For a time it was claimed that these minute organisms belonged to the animal kingdom, as some of them were seen to possess spontaneous movements; but now it is gener- ally agreed that they are minute plants, and botanists have made great progress in perfecting a scientific classification. Among the men who have developed this part of botany, the names of Cohn, Zopf, and Nageli stand pre-eminent. CLASSIFICATION. The pathogenic bacteria which will claim our attention belong to the class known as schizomycetes (Spaltpilze). In diameter they vary from 0.001 to 0.004 millimetre, and are composed largely of an albu- minoid substance called by Nencki myco-protein. Toward the periphery this substance becomes firmer, and forms a gelatinous envelope, a sort of a membrane, which is said to contain cellulose, and, in some instances, even fatty material. The outer surface of bacteria is frequently cov- ered with a viscid substance, by which many of them are often held together in a mass or group, technically called zoo'gloea. Each bacterium represents a cell, although the presence of a nucleus, or something repre- senting such a structure, has not been demonstrated ; but its cellular structure is made evident by its intrinsic power of germination or repro- duction when surrounded by the necessary conditions for its growth. Some of the bacteria are provided with processes, or cilia, by which, when suspended in a fluid, movements are accomplished ; in others motion is entirely dependent on molecular movements described by Brown. Nageli, and formerly Billroth, claimed that all bacteria had a common botanical source, and that the different forms and actions only represented alteration of form of action of the same plant at different stages of development and under different circumstances,—in other words, that a coccus could be transformed into a bacillus, and vice versa; and that in one instance the same plant caused fermentation, in another putrefaction, and that all infective diseases were caused by the same (127) 128 PRINCIPLES OF SURGERY. microbe. Buchner maintained that, by cultivation in different nutrient media, he was able to transform the dangerous bacillus of anthrax into • •• • • • • s-Vv 2 -7- •••• %3 j A__. „ — 3 J f $. \£. #3 ,^,3 v/ - Y \j *. Fig. 43.—Different Forms of Bacteria. (Baumgarten.) A, cocci; B, bacilli; C, spirilli. the harmless bacillus subtilis, and, again, the latter into the former. Cultivation and inoculation experiments on a large scale by most careful MULTIPLICATION OF BACTERIA. 129 observers have shown conclusively that such transformations never take place, and that each microbe not only always retains its shape, but also its specific pathogenic properties. Pus- and other microbes have been cultivated through thirty and more generations without suffering any morphological deviations or losing any of their inherent characteristic pathogenic properties. The three principal forms of bacteria discovered up to the present time, and which have been demonstrated as causes of disease, are: (1) the ball (coccus); (2) rod (bacillus); (3) corkscrew (spirillum). As illustrations for these different forms, de Bary very appropriately takes the billiard-ball, lead-pencil, and corkscrew. The surgeon has to deal only with the two first forms,—the cocci and bacilli. Modifications of form are frequently met with, as an oblong coccus closely resembles a short bacillus, and a short, broad bacillus with rounded ends approaches the coccus form. Again, a double coccus, or diplococcus, with ill-defined constriction at the point of junction, might, from superficial examination, be mistaken for a bacillus (Fig. 43, A, 2). More than 2 cocci in a row, or a chain of cocci, are called a streptococcus (A, 3). Four cocci arranged in the form of a square are called a micro- coccus tetragones (A, 4). Cocci arranged in the form of a bunch of grapes are called streptococci (A, 6). An irregular mass of cocci, when at rest and held together by a viscid substance, is described as a zoogloea. MULTIPLICATION OF BACTERIA. Bacteria multiply with great rapidity in tissues presenting favorable conditions for their growth, or in proper nutrient media kept at a tempera- ture approaching that of the body. Multiplication takes place either by fission or segmentation, by the production of spores, or by both of these methods. The bacillus of anthrax multiplies by fission in the bod}-, by spores outside of the body. Fission.—The round or globular bacteria,—the cocci,—as far as we know, multiply only by fission. The cell elongates prior to segmenta- tion, when a constriction appears in the centre, which, by becoming deeper and deeper, finally results in complete division of the cell into two equal halves, which soon attain the size of the mother-cell, and, in turn, again undergo the same process. If the new cells remain adherent, and arrange themselves in the form of a chain, a streptococcus is formed. Fliigge observed complete division of a coccus in bouillon, kept at a tem- perature of 35° C, in twenty minutes. If it should require one hour to complete segmentation and for the new cell to attain maturity, a single coccus multiplying by fission, according to Colin, during one day, would produce sixteen millions of cocci, and at the end of the second day the product would represent two hundred and eighty-one billions in number, 9 130 PRINCIPLES OF SURGERY. and at the end of three days the extraordinary number of forty-seven trillions would be reached. Rod bacteria which reproduce themselves by fission undergo transverse segmentation in the middle, and after com- plete separation each segment grows to the size of the parent-cell before the process repeats itself. Spores.—The spores of bacteria represent the seed of flowering plants. Each spore develops into a bacterium, and thus one crop after another is produced, the multiplication increasing with the number of bacteria in the soil. Most of the bacilli multiply by spores. Fructifica- tion again takes place, either within the protoplasm of the cell (endospore) or at one or both extremities of the cell (endspore). Fructification is often preceded by a rapid elonga- tion of the bacillus. Multiple endospores usually form in one bacillus simultaneously. The first evidences of the formation of spores within the protoplasm of a bacillus is indicated by the appear- ance of circumscribed points of cloudiness at equi- distant points. After the expiration of twenty hours the bacil- lus appears like a string of pearls, each segment of which represents a fully-developed spore. After \this the segments separate and each spore develops into a bacillus. If the bacillus reproduce itself by a single endospore, it does not elongate before fructification, but increases in diameter, especially in the centre, so that it assumes the shape of a spindle; while, equidistant from its ends, changes are observed in the protoplasm which indicate the beginning of spore formation. If the bacillus multiply by ter- minal fructification, one or both of its ends enlarge, become club-shaped, and the spores pass through the same stages of development as the endospores, and they are liberated in the same man- ner by liquefaction of the cell-membrane surrounding them. Bacteriol- ogists are familiar with the fact that spores possess a greater power of resistance to germicidal agents than the bacilli which produced them. Mature bacteria are always destroyed by a temperature of 77° C.; most of them succumb when exposed to a heat of 50° to 55° C. On the other hand, some of the spores are known to survive a temperature of 100° to 120° C. Sternberg has determined the thermal death-point of the following bacteria:— Fig. 44.—Endogenous Spore Produc- tion in Bacillus Anthracis Culti- vated upon Meat- Infusion Peptone- Gelatin. X 950. (Baumgarten.) CULTIVATION OF BACTERIA. 131 so Fahr. Bacillus anthracis (Chaveau),.......129.20° Bacillus-anthracis spores,........212.0° Bacillus tuberculosis (Schill and Hischer), . . . . 212.0° Staphylococcus albus,.........143.6° Staphylococcus pyogenes aureus,.......136.4° Staphylococcus pyogenes citreus,.......143.6° Streptococcus erysipelatosus,.......129.2° Gonococcus, ........... 140.0° In all experiments, with the exception of the bacillus of tuberculosis, the microbe was subjected to the specified heat for ten minutes; the tubercle bacillus was destroyed in four minutes. Such resisting spores are often not destroyed by boiling continued for several minutes, and yield only slowly and frequently imperfectly to germicidal chemical agents. Surgeons are aware that such spores may re- main dormant in the body for }Tears without giving rise to any symptoms until aroused to activity by surround- i 2 3 ing conditions favorable to their growth and development, fig. 45.—Spore of Bacillus of Anthrax. CULTIVATION OF BACTERIA. Bar"™' {De rr,, _ ... . . . . S, ripe spore be- The first cultivation experiments were made with fore germination; 1, 2, 3, three successive fluid nutrient substances, such as bouillon, different |ta0^3.°3f ge0™in^ng animal broths, and solutions of sugar. Koch introduced solid nutrient media, which not only serve as food for the bacteria, but at the same time present the great advantage that the colonies can be seen with the naked eye, and their microscopical appearances, as well as the visible action of the bacteria on the nutrient substance, often are sufficient to convey reliable information to enable the observer to form a positive conclusion in reference to the kind of microbes of which the colonies are composed. In fluid nutrient media the bacteria cause tur- bidity, or they appear as a thin film on the surface; or zoogloea masses show themselves as swimming flocculi; or, finally, when the fluid has been exhausted of its nutrient supply the spores settle at the bottom of the vessel and appear as a pulvurulent deposit. Upon solid nutrient media each kind of bacteria appear as isolated, distinct colonies, and as such can be recognized by the naked-eye appearances. The substance used first by Koch as a solid medium, and which is now used more than any other, was gelatin. Later, a jelly-like substance called agar-agar, obtained from several sea-weeds on the coasts of Japan and India, was found superior to gelatin where a higher than ordinary temperature was required to cultivate certain microbes. Edington prefers a gelatin made of Irish moss to agar-agar, as it is more transparent. Some microbes that will not grow upon gelatin vegetate luxuriantly on solid blood-serum. The tubercle bacillus grows 132 PRINCIPLES OF SURGERY. equally well upon solid blood-serum and glycerin agar-agar. This latter substance is easily prepared and is made by adding 6 per cent, of pure glycerin to the ordinary agar medium. The busy practitioner, who has no time to prepare the media used in laboratory work, can do good bacteriological work by using sterilized potato or bread-paste. The potato is the best medium for the cultiva- tion of chromogenous bacteria, or such as secrete a coloring matter, as upon this substance the color is preserved. The potato is scrubbed with a hard brush under a stream of water. It is then left in a solution of corrosive sublimate (1 to 1000) for an hour or so to disinfect its surface. With a knife rendered sterile by passing it through the flame of a Fig. 48..-Gelatin Cultures following Surface Inoculation. (Fliigge.) Bunsen lamp, a quadrilateral piece is cut from the centre, and is rapidly transferred on the knife to a glass capsule previously sterilized by heat. Capsule and potato are next placed in steam sterilizer, when the simple apparatus is ready for inoculation. Inoculation is done by charging the point of an aseptic needle with the culture, or substance containing the microbes, and after lifting the capsule half up a number of streaks are made with the needle upon the surface of the potato. A potato-paste, made by adding a sufficient quantity of distilled water to the interior portion of boiled potatoes to make a paste, is used in the same manner and answers the same purpose as sterilized raw potato. Bread-paste is made of stale, coarse bread, thoroughly dried in an oven, but not roasted. It is pulverized in a clean mortar and the powder CULTIVATION OF BACTERIA. 133 made into a paste by adding distilled water. The paste is transferred to sterile glass capsules and used in the same manner as potato-paste. If it is employed for the culture of bacteria, it must be neutralized with a solution of carbonate of soda. Some microbes possess the faculty of liquefying the gelatin; others remain as solid cultures upon the surface of the medium, or in its interior. Free access of oxygen to the seat of inoculation is essential for the growth of some microbes, and these were termed by Pasteur aerobiontic, while those that germinate with exclusion of oxygen he called anaerobiontic. The former class germinate on the surface of the media with or without liquefaction of the soil. If microbes of this kind are inoculated by scratching the surface of the medium with Fig. 47.—Cultures in Gelatin growing in the Track made by the Needle. (Fliigge.) the point of a needle charged with them, the culture appears first at isolated points (Fig. 46, A), which by increase in size become confluent and occupy as a solid mass the whole track made by the needle (B, C). In making inoculations with anaerobiontic bacteria the gelatin is punctured with a needle, charged as before, to "some depth, and isolated colonies appear in the track made by the needle, which by confluence form a continuous, uninterrupted culture the whole depth of the needle, which increases in diameter by extension in a peripheral direction. Superficial cultures are called streak cultures; deep cultures, stab cultures. All cultivation experiments must, of course, be conducted under strictest antiseptic precautions, as otherwise there is great danger of 134 PRINCIPLES OF SURGERY. contamination of the cultures by the accidental ingress of other microbes, especially of some forms of fungi. ESSENTIAL CONDITION FOR GROWTH OF BACTERIA. For the germination of bacteria, besides a proper nutrient substance the other conditions which enable the growth of other plants from seed are necessary, viz., moisture and a certain degree of heat. Inspissation of solid nutrient medium arrests further development of a culture. Bacteria cannot grow upon a perfectly dry medium. Most microbes germinate best at a temperature corresponding to blood-heat, but in this respect the different kinds show great variance, as some vegetate at 10° C, while the growth of others will continue at 65° C. Acids appear to produce an inhibitory effect on the process of germination. Laplace has utilized this fact and advises the addition of citric acid to solutions of corrosive sublimate to intensify its germicidal properties. It is well known that the gastric juice suspends the growth of most bacteria. Bacteria which live on dead substances exclusively are called sapro- phytes. Bacteria which feed on dead substances and can exist in the living tissues only at a certain stage of development are called facultative parasites, in comparison with the obligatory parasites, which multiply exclusively in the living tissues. As representatives of the former can be enumerated the bacillus of anthrax and cholera, which, under favor- able conditions, can multiply outside of the body, while the bacillus of tuberculosis germinates only in the living body. ACTION OF BACTERIA ON TISSUES OF THE BODY. The action of pathogenic bacteria on the tissues is a twofold one. In the first place, they abstract from the body a part of its essential constituents; for example, albuminous substances, carbohydrates, oxy- gen, etc. These substances are not only taken from the fluids of the body, as the blood and lymph, but also directly from the protoplasm of the cells. In the second place, they produce in the body toxic agents from their action on the albuminoid substances. The decomposition of albuminoid substances by the action of bacteria results in the formation of ammonia and its deritatives, the different amines, C02, H2S, indol, scatol, phenol, asparagin, leucin, tyrosine, etc. Ptomaines.—The common name for the toxic substances of bacterial origin is ptomaines. Brieger has isolated a number of ptomaines from cultures of different bacteria, and Hoffa is now engaged in the same kind of work. Vaughn, of this country, has written a valuable work on this subject, which should be read by all who wish to become familiar with modern surgical pathology. Brieger has isolated a number of toxic INOCULATION EXPERIMENTS. 135 alkaloids, cadaverin, neurin, muscarin,and mydalein, which are intensely toxic, while the derivatives of ammonia-dimethylamin, trimethylamin, and triathylamin are much less dangerous substances. The ptomaines, being soluble substances, are readily absorbed, and when introduced into the circulation produce fever and symptoms of sepsis. The ptomaines of the bacillus of tetanus act principally upon the central nervous sys- tem, producing characteristic tonic and clonic spasms of definite groups of muscles. The ptomaines also produce a definite local effect,—thus, the ptomaines of pus-microbes transform the leucocytes and embryonal cells into pus-corpuscles, those of the microbe of progressive gangrene destroy the protoplasm of the cell-body directly, while the toxic sub- stances of the microbes of chronic infective diseases transform the fixed tissue-cells into embryonal or granulation cells. Some of the microbes remain in the tissue at the seat of infection ; others localize in the lymphatic channels, while, finally, others enter the general circulation and multiply in distant organs. The production of ptomaines usually takes place in the tissues in which localization takes place. INOCULATION EXPERIMENTS. The mouse, rat, rabbit, guinea-pig, and dog are the animals usually selected for this purpose. Inoculations are made either with pure cul- tures, which are injected by means of a sterilized hypodermatic syringe, or infected tissues are implanted under strict antiseptic precautions. Injections of pure cultures are made either into the subcutaneous tissue or one of the large serous cavities, the pleural or peritoneal cavity. The same localities are generally selected for inoculation by means of im- plantation of infected tissue. For instance, granulation tissue from tubercular lesions is either introduced into a small pocket made in the subcutaneous tissue in the inguinal region of a guinea-pig, or a small fragment is inserted into the pleural or peritoneal cavity through a small incision. Before the incision is made it is absolutely necessary to shave the surface and disinfect it in the usual way. After the implantation is made the wound is closed by suturing with fine catgut, after which it is sealed with collodium. In the course of two or three weeks the subcu- taneous graft has become the centre of a local tubercular focus, which soon gives rise to regional infection through the lymphatic vessels, to be followed at the end of five or six weeks by general diffuse miliary tuber- culosis. In cases where it is impossible to make a differential diagnosis between a syphilitic and tubercular lesion, inoculation of a guinea-pig with a fragment of the granulation tissue will furnish positive informa- tion in the course of a few weeks. If the lesion is syphilitic, the result of the inoculation will be negative; if it is tubercular, local, regional, 136 PRINCIPLES OF SURGERY. and general infection will follow in regular order. In making implanta- tion experiments from animal to animal, it is necessary to remove the graft immediately, or soon after death, and to resort to the necessary precautions to prevent contamination during its conveyance from the dead to the living animal. In bacterial diseases which affect the blood, inoculation can be practiced by injecting blood, abstracted from the in- fected animal, into the subcutaneous tissue or general circulation of a healthy animal, with the effect of reproducing the disease. Anthrax and septicaemia of mice furnish good illustrations of this class of diseases. ATTENUATION OF PATHOGENIC BACTERIA. Pasteur opened a wide field for investigation in preventive medicine by his introduction of prophylactic inoculations. He experimented first with the microbe of chicken-cholera and the bacillus of anthrax. The microbe of fowl-cholera was cultivated in chicken-bouillon for three, four, five, or eight months. He found that by this time the virus becomes so attenuated that, when injected into a healthy chicken, it kills only in exceptional cases. Experience showed that attenuation only occurred when the culture is freely exposed to atmospheric air, and therefore Pasteur believed that the prolonged contact of the culture with oxygen diminished its virulence. Chickens inoculated with wCak cultures were rendered immune to the action of the active virus. The same author made the discovery that the anthrax bacillus, cultivated in the same way at a temperature ranging between 40° and 43° C, loses its virulence gradually, so that on the ninth day it is rendered harmless. Inoculation with attenuated cultures protected sheep against the active virus. Koch, Gaff ky, and Loeffler found that a culture of anthrax bacilli twenty days old, attenuated at a temperature of 42° to 46° C, was still sufficiently strong to kill mice, but had little effect on guinea-pigs and sheep. A culture twelve days old killed guinea-pigs, but not sheep. It proves fatal to sheep up to six days of cultivation. Their views in reference to the cause of attenuation differ from Pasteur's, who regards oxygen as the active agent, while these observers attribute it exclusively to the high temperature. They succeeded, like Pasteur, by using attenu- ated cultures in protecting, in most cases, sheep against the action of virulent cultures. In his practical work Pasteur uses two strengths of mitigated virus. The milder vaccine is a culture fifteen to twenty days old ; the stronger vaccine is from ten to twelve days old. Sheep are inoculated first with the milder vaccine, and after an interval of twelve to fifteen days the stronger culture is used. Animals thus treated are either entirely immune to anthrax, or, if they contract the disease, it assumes a mild type. Other methods of attenuation of active cultures THERAPEUTIC INOCULATION. 137 to be used for prophylactic inoculations have been devised, but, as they appear to have been put only to a limited extent to practical tests, they will be only briefly mentioned here. Sanderson found that the bacillus of anthrax loses much of its virulence when passed through the system of a guinea-pig. Toussaint and Chaveau found that the action of a temperature of from 50° to 55° C, continued for five to twenty minutes, greatly diminishes the virulence of the bacillus of anthrax. For the attenuation of spores a temperature of 80° C. is required. Paul Bert showed that oxygen, under a pressure of from 20 to 40 centimetres, destroys the bacillus of anthrax. Toussaint, Chamberland and Roux, and Klein made experiments to determine the influence of chemical agents in effecting attenuation of active cultures, and their work has shown that the virulence of some bacteria can be greatly diminished and even entirely suspended by this method of treatment. Arloing asserts that anthrax bacilli, exposed to a bright sunlight in a liquid medium, gradually part with their toxic qualities. More accurate knowledge and greater experience in this interesting field of prophylactic inoculations will undoubtedly lead to important results in the near future. THERAPEUTIC INOCULATION. Therapeutic inoculations have been put to a practical test upon a knowledge obtained from laboratory work, that direct antagonism exists among certain kinds of micro-organisms. Emmerich's experiments on rabbits have demonstrated the value of the streptococcus of erysipelas as a protective and curative agent in anthrax in these animals. In one series of experiments the rabbits were first inoculated with a large quantity of a reliable culture of the microbe of erysipelas, and then, two to fourteen days later, the animals were infected with a pure culture of the anthrax bacillus. Of 15 animals treated in this way, 7 recovered, while all the control animals inoculated only with anthrax died ; of the 7 animals which died after double infection, some succumbed to the anthrax bacillus and some to the streptococcus'of erysipelas. Thera- peutic inoculations with cultures of the microbe of erysipelas in animals suffering from anthrax were less successful. Garre has studied antag- onism among bacteria on culture soils. He made many careful experi- ments to determine the growth of a culture on different nutrient media, by removal of the entire culture with a minute spade and inoculation of the same soil with another microbe. From the results obtained thus far he has ascertained that some microbes affect the soil favorably for the growth of other varieties, while others render it sterile. For example, a culture medium impregnated with the ptomaines of the bacillus fluorescens putidus remains perfectly sterile when inoculated with pus- 138 PRINCIPLES OF SURGERY. microbes. These investigations have an important practical bearing, as future research may not only show the way to secure immunit}' from in- fection by pathogenic microbes by prophylactic inoculations with harm- less microbes, but may likewise establish a system of rational and effective treatment by inoculations of cultures of antagonistic bacteria for therapeutic purposes. Therapeutic inoculations with potent cultures have also been made with some success in the treatment of inoperable malignant tumors. In a recent publication on this subject Bruns gives the result of 22 cases of malignant growths, including 1 that came under his own observation that passed through an attack of erysipelas. Bruns's case was one of melanosarcoma of the breast, in which a final cure followed the attack. Out of 5 sarcomata, 3 were permanently cured, while the other 2 were diminished in size, but soon returned to their former size. The effect of the erysipelatous invasion proved negative in 6 cases, in which the diagnosis between carcinoma and sarcoma could not be positively made, as also in 3 cases of ulcerative epithelioma. It is stated that in cicatricial keloid and lymphomata the attack of erysipelas proved curative. BACTERIA OUTSIDE OF THE BODY. Bacteriology has rendered the term miasma obsolete. All infective diseases are now traced to an organic contagium. Most of the bacteria are ectogenous; that is, they exist, and, under favorable circumstances, multiply outside of the body. The microbe of syphilis, in all probability, is an endogenous parasite. Auto-infection is a misapplied term, as nearly all, if not all, infective diseases are caused by the introduction into the body of pathogenic bacteria from without. Some microbes exist in the soil, and as they or their spores may exist in an active condition for an indefinite period of time, or even germinate there, they give rise to endemics of infective diseases. The anthrax bacillus, the bacillus of tetanus, and the actinomyces can be included in this category. Other microbes are diffused over large territories through water-courses, as the bacillus of typhoid fever and cholera. Finally, some bacteria, like pus- microbes, appear to be ubiquitous, being present everywhere and at all times. Of all substances which serve as a carrier of microbes, the atmospheric air is the most important, because it is present everywhere on the surface of the globe, and no one can exclude himself from it. In a dry state, pathogenic bacteria move with the currents of air and attach themselves again to the solid or fluid substances with which they come in contact. Although most of the pathogenic bacteria under ordinary circumstances do not reproduce themselves outside the body, their resistance to heat and cold, moisture and dryness, is so great that they retain their disease-producing qualities often for an indefinite period of PRESENCE OF PATHOGENIC BACTERIA IN THE HEALTHY BODY. 139 time, and after their entrance into the body, and meeting with a proper nutrient medium, they exert their specific pathogenic effects. From a practical stand-point it is important to remember that infection takes place by the entrance into the tissues or body of micro-organisms from without through some defect of the skin or mucous membranes, hence by contact entrance of bacteria into the body. As a rule, to which there are few exceptions, bacteria are introduced into the body through a wound abrasion, or ulceration of the skin or a mucous membrane. Such a defect or gateway is called an infection-atrium. A healthy, granulating surface furnishes almost as secure a protection against infection as the skin, but when the granulations are destroyed or injured infection is again liable to occur. On this account probing of a fistulous canal has not infrequently resulted in aggravation of the local symptoms, and even in general infection. Kiister reports 2 cases where patients who had undergone an operation for hydrocele by incision, and who were permitted to leave the hospital before the wound had completely healed, died subsequently from sepsis caused by careless after-treatment of the granulating surface. Most of the microbes, after they have become deposited upon an absorbing surface, exercise first their pathogenic qualities at the seat of primary localization. The action of some of them always remains local. If the infection spread, it does so by dis- semination of the microbes over a surface, along the connective tissue, or through the lymphatics or blood-vessels. There is no reason to doubt that bacteria can gain entrance into the tissues and the circulation by passing through intact mucous membranes in the same manner as minute particles of inorganic material, like coal-, marble-, and ivory- dust. This brings up the question of the PRESENCE OF PATHOGENIC BACTERIA IN THE HEALTHY BODY. It still remains a disputed question whether pathogenic micro- organisms can exist in the body without giving rise to disease. It has been definitely ascertained, by experimental research, that many of the pathogenic microbes are harmless as long as they remain in the circu- lating blood, and that their specific pathogenic action only becomes evident after localization has taken place in some part of the body, in a soil prepared by injury or disease for their reproduction. It has also been conclusively shown, by clinical experience, that pathogenic spores may remain in the healthy body, in a dormant condition, for an indefi- nite period of time, until, by some accidental pathological changes, the tissues in which they may exist have been prepared for their germina- tion. Numerous experiments will be cited elsewhere, in which injections of pure cultures directly into the circulation produced no ill effects in 140 PRINCIPLES OF SURGERY. healthy animals, but when previous to the injection,or soon after, an injury was inflicted in some part of the body, localization occurred at the seat of trauma, and in the locus minoris resistentiae thus created the microbes pro- duced their specific pathogenic effects. From these remarks it is reason- able to assume that pathogenic microbes may and do exist in the healthy body without necessarily giving rise to disease, especially if, as is well known, they are being constantly eliminated through the excretory organs. Bizzozero could not detect bacteria of any kind in animals soon after birth, but in the lymph-follicles of the caecum in healthy rabbits he found numerous micro-organisms. They were seen mostly in the protoplasm of cells,—a condition which would indicate that they are transferred from the intestinal canal into the closed lymph-follicle through the medium of migrating cells. In the human subject, Ribbert found micro-organisms in the interior of the epithelia lining the intestinal canal, but they were absent in the submucosa. Perhaps the epithelial cells in this locality take the part of phagocytes. Zahor examined the blood, testicle, heart, and spleen of a healthy rabbit, and found in fresh as well as in hardened sections, after staining with methyl-violet, cocci, and here and there rods. The same examinations, with like results, were made on the organs of a young cat. Fodor introduced directly into the circulation of rabbits pathogenic bacteria, in order to study their effects on the tissues and manner of elimination. As a rule, he found they had completely disap- peared from the blood after twenty-four hours. He believes that the bacteria are destroyed in the circulation by the blood-corpuscles. The same author maintains that the power of the blood to destroy bacteria is not diminished by a moderate degree of anaemia, but is lessened when diluted with water, as, when this is done, the microbes are destroyed more slowly and with greater difficulty. Watson-Che3rne found, in his experiments made for the purpose of ascertaining the presence of micro- organisms in the living tissues, that while they were not present when the animal was in good condition, yet if the vitality of the animal was depressed, say, by administering large doses of phosphorus for some time, microbes could be found at times in the blood and tissues of the body. Again, it has been found that, while some micro-organisms when introduced into the living body in small number disappear after a short time, when a large quantity of the culture is introduced the tissues of the body are injured by the pre-existing ptomaines and the microbes re- tain their vitality and often cause inflammation of the organ in which they locate. The conditions, then, upon which depend the preservation of health in the event of the entrance of pathogenic microbes into the body, are : 1. The number of microbes introduced. 2. Absence of a locus minoris resistentiae. 3. Active elimination through the excretory organs. LOCALIZATION OF BACTERIA. 141 LOCALIZATION OF BACTERIA. Every surgeon has had frequent opportunities to observe cases in which a slight subcutaneous injury was followed by a destructive inflam- mation,—an inflammation not caused by the trauma alone, but by the trauma giving rise to localization of pathogenic microbes in the tissues altered by the injury. Thus, Chaveau has shown experimentally that a subcutaneous contusion furnishes an excellent condition for the locali- zation of pathogenic bacteria carried to the part by the circulating- blood. When he injected a putrid fluid directly into the circulation of young rams shortly before crushing subcutaneouuly one of the testicles, the injured organ always became the seat of septic gangrene, while with- out such injection the testicle disappeared completely by necrobiosis and absorption. Gangrene only occurred if the putrid fluid contained bacteria; it did not take place when the injected fluid had been sterilized by filtration. Extensive subcutaneous injuries, as severe contusions, rupture of tendons or muscles, and comminuted fractures, are not fol- lowed by suppuration unless the injured tissues become subsequently the seat of infection with pus-microbes. A patient may have been the sub- ject of tubercular infection for an indefinite period of time, and yet may present the appearances of ordinary health, until some slight injury determines localization of the bacillus in the part injured,—an occur- rence which is followed by a localized tuberculosis from which, later, regional and general dissemination takes place, to which the patient finally succumbs, unless the tubercular focus is removed by an early operation. These facts suggest very strongly that, in the hypothetical cases, suppuration and tuberculosis would not have occurred in the part injured without the injury, and that the injury certainly would not have produced suppuration or tuberculosis unless the respective patients had been infected previously with specific micro-organisms. The injury in these cases created a so-called locus minoris resistentiae, which may signify one of two things : (1) Diminution or suspension of the vital resistance on the part of the injured tissues to the action of pathogenic microbes; or (2) the injury so alters the tissues that bacteria, which were present in the circulation without having given rise to symptoms, become arrested, and find at the same time at the seat of localization the necessary conditions for their reproduction. Heuber studied experi- mentally the effect of chemical irritation of tissues in determining locali- zation of the bacillus of anthrax. The experiments were made on rabbits, in which by the external application of croton-oil to the ear he produced a tissue-lesion by the inflammation which followed. One ear was thus treated, the other being left in a normal condition in order to compare the results of localization of anthrax bacilli in inflamed and normal 142 PRINCIPLES OF SURGERY. vessels. As soon as the inflammation was established, a pure culture of anthrax bacilli was inserted subcutaneously at the root of the tail; this place was selected in order to make the infection as far as possible from the inflamed ear. In some cases the croton-oil was applied after the inoculation. Immediately after the death of the animal, both ears were cut off and carefully preserved for subsequent examination, and, at the same time, serum and blood were separately taken from the inflamed ear and preserved in sterilized glass tubes. The results of a number of these experiments enabled the author to assert that in all stages of the inflammation the bacilli were never found outside the walls of the capillary blood-vessels in the crotonized ear. Their number within the blood-vessels depended upon the condition of the inflamed vessels. During the first stage of inflammation, marked by oedema without suppuration, more bacilli were found within the in- flamed vessels than in the corresponding vessels of the opposite ear. During the suppurative stage the bacilli disappeared from the vessels. During the third stage, when granulations commenced to form, a com- plete change was again observed in the bacteriological condition of the inflamed part. The height of this stage is reached on the tenth day. During this stage the bacilli re-appear in the inflamed tissue, where they can be seen in considerable number, especially in the interior of new capillary vessels. During cicatrization the number of bacilli in a cor- responding area of both ears was about the same. From these observations the author concludes that the bacillus of anthrax finds, in a soil prepared by inflammatian induced with croton-oil, a locus minoris resistentiae, which presents more favorable conditions for its localization and growth than the tissues in other parts of the body. Suppuration appeared to neutralize the anthracic process by the destruc- tive effect of the pus-ptomaines upon the bacilli. The conclusions which he has drawn from his experiments may be summarized as follows: Localization of pre-existing micro-organisms in tissues prepared by injury or disease takes place, provided that the necessary conditions for their growth are present. In looking over different pathological conditions we frequently meet with a so-called locus minoris resistentiae; at any rate, if we search only for that which should mean what has been described above, it is not difficult to conceive how slight injuries, wounds, contusions, etc., should in this manner give rise to serious affections. But not only do direct tissue-lesions, as haemorrhage, necrosis, hyperaemia, fractures, etc., act in this manner, but a variety of pathological conditions of a general nature may serve the same purpose, as imperfect digestion, enfeebled circulation and respira- tion, and particularly irregular distribution of blood resulting from LOCALIZATION OF BACTERIA. 143 exposure to cold. All these ill-defined conditions belong here, and through their instrumentalities the localization of infective microbes is favored. In secondary or mixed infection the microbes which exist in the tissues first prepare the soil for the arrest and germination of other bacteria which may reach the circulation. Muskatbliith studied experimentally the fate of anthrax bacilli when introduced directly into the trachea by injection through the larynx, or through a tracheotomy wound. From the results which he obtained he concludes that the bacilli can enter the circulation through the bronchial mucous membrane, and that the juice-canals and lymphatics are the channels through which the infection takes place. It appeared strange to the author that no bacilli could be found in leucocytes, but always only in epithelial cells. Final localization of the bacilli which have entered the circulation through the lungs takes place in distant organs by implantation upon the endothelial lining of the capillary vessels. Other experimenters affirm that if the anthrax bacilli are injected in moderate quantities into the circulation of animals, they disappear soon from the blood without having produced any pathogenic effects; but, if in animals thus infected a contusion is produced in some part of the body, the bacilli pass out of the injured vessels into the connective tissue along with the blood, germinate there, and soon cause the formation of the characteristic inflammatory product, the disease becomes diffused, and the animals die of anthrax. Localization of the bacillus of tubercu- losis affords an interesting subject for experimental research and clinical study. The late distinguished Professor von Volkmann, from an extensive clinical experience, came long ago to the important and practical con- clusion that a severe trauma seldom, if ever, gives rise to tuberculosis at the seat of injury; and, on the other hand, that in cases where tuber- culosis develops in consequence of any injury, the trauma is always slight, sometimes almost insignificant. The experience of almost every surgeon will agree with these statements. Volkmann maintains that the active tissue changes which follow a severe trauma during the reparative process counteract the growth and propagation of the bacillus. Luecke attributes to exposure to cold an important role in the causation of tubercular and other infective forms of inflammation, as he asserts that the sudden diminution of blood-supply to the cutaneous surface causes internal congestions, which favor the localization of pathogenic microbes in some one of the congested organs, otherwise predisposed to the specific inflammation. Schiiller studied the localization of the tubercular virus experimentally in the same manner as others have studied the locali- zation of pus-microbes. He inoculated animals with the products of 144 PRINCIPLES OF SURGERY. tubercular inflammation, subsequently produced contusions and sprains of joints, and observed that localization usually occurred at the seat 01 injury. If the tubercular virus was introduced b}r inhalation, the same typical lesions occurred in the injured joints as when infection was prac- ticed in a more direct manner. In all cases the product of the local joint-lesion corresponded with the character of the material introduced through some remote point. Surgeons are well aware of the danger of general infection following an injury to a part or an organ the seat of local tuberculosis, more particularly in cases of tubercular disease of joints treated by brisement force. Numerous cases are recorded where this procedure was followed within a few days b}T general miliary tuber- culosis and a speedy death. In all cases where a local tuberculosis develops in consequence of an injury, we must take it for granted that the injured part contained the essential cause of the disease, the bacillus of Koch, and that the lesions caused by the trauma created the necessary conditions for its reproduction; or, if the injured tissues at the time are sterile, that they serve the purpose of a locus minoris resistentiae for bacilli which might reach them through the circulation. The frequency with which suppuration occurs without any visible infection-atrium has led bacteriologists to investigate with special care and diligence localiza- tion of pus-microbes. Rosenbach ascertained, bjr numerous experiments, that acute suppu- rative osteomyelitis could only be produced by injecting pus-microbes directly into the circulation and by injuring the medullary tissue a few days before or after the inoculation. Kocher, Becker, and Krause repeated the experiments of Rosenbach, and came essentially to the same conclusions. Both Kocher and Rosenbach look upon the altered circulation in the injured part as the essential condition which determines localization of the pus-microbes floating in the blood-current; at the same time they admit that the immediate tissue-lesions, haemorrhage, and necrosis may have the same effect. Upon the same theory, Kocher explains the occurrence of traumatic suppurative strumitis in a hyper- plastic struma. If non-septic pus is injected into the circulation of healthy animals in moderate quantities no serious results are produced, as the pus-microbes are soon eliminated through the kidneys. If, how- ever, the pus-microbes attach themselves in the circulation to some foreign substance which prevents such elimination, suppuration will follow. A number of experiments made, among others by Ribbert, on the production of myo- and endo- carditis in rabbits, have shown that abscesses can be produced in other organs if the pj^ogenic microbes are attached to foreign bodies which cannot pass through the pulmonary capillaries. Thus, Ribbert was able to produce myocarditis by using a LOCALIZATION OF BACTERIA. 145 cultivation of staphylococcus pyogenes aureus on potato, if he took the precaution, in removing the culture from the surface of the potato, to scrape off also the superficial surface of the potato itself. The particles of potato injected with the microbes determined suppuration by causing localization of the microbes, as the foreign bodies were too large to pass through the capillary vessels and were not capable of removal by absorption. The influence of a trauma in determining localization of microbes circulating in the blood is well shown by the experiments which have been made to produce, artificially, endocarditis in animals. O. Rosen- bach made the first experiments of this kind. He observed, in his experiments on animals and in post-mortem examinations in cases of ulcerative endocarditis, microbic emboli in the valves of the heart and in the infarcts of other organs, and classifies this affection with pyaemia. The more frequent occurrence of endocarditis in the left side of the heart than the right he explains by assuming that the microbes find a better soil in the arterial blood, as when the affection occurs in the foetus during intra-uterine life, when the blood in both sides of the heart is of about the same composition, the valves in both sides are affected with the same frequency. Orth and Wyssokowitsch found that staphylococci could be injected into the blood of a rabbit without apparent injury to it, but if before the injection a slight mechanical injury was inflicted on one of the valves of the heart, typical endocarditis was at once produced. The injury was produced with a small rod, which was introduced into the jugular vein on the right side. The endocardial lesion always corresponded to the seat of the injury. Similar results were obtained by Frankel and Sanger. Rinne came to different conclusions in reference to injured tissues serving as a locus minoris resistentiae in the causation of inflammation due to the presence of microbes. He injected pure cultures of the different kinds of pus-microbes directly into the circulation of animals, and found that, as a rule, no harm resulted. In rabbits he injected from 2 to 3 Pravaz syringefuls of unfiltered, distilled water, holding in suspension pure cultures, and, after repeating this dose several times, inflicted all kinds of subcutaneous lesions without causing suppuration. Only in a few instances were pyaemic metastases observed, and these occurred usually only in cases where undiluted gelatin cultures were used. In several dogs he made subcutaneous fractures and then injected large doses of cultures of pus-microbes, suspended in distilled water, into the peritoneal cavity, but no suppuration occurred at the seat of trauma. In six rabbits he fractured the femur subcutaneously and then injected pure cultures into the jugular, or one of the auricular, veins, but 10 146 PRINCIPLES OF SURGERY. only in one of them did osteomyelitis occur at the seat of fracture. In two experiments where he injected osteomyelitic pus diluted with distilled water the seat of fracture suppurated, and in these cases abscesses were also found in the heart-muscle and the kidne}rs at the autopsy. It is difficult to explain the discrepancy between the results obtained by Rinne and the other experimenters who have been quoted, as the same kind of animals and inoculation material were used, and the experiments were conducted in the same manner. The fact remains, and is abundantly vouched for by clinical experience, that a subcutaneous injury, if the tissues remain sterile, does not give rise to inflammation, and that many inflammatory processes are established immediately or soon after an injury, and in the inflammatory product the presence of patho- genic bacteria can be demonstrated by microscopical examination, cultiva- tion, and inoculation experiments. A number of well-authenticated cases of osteomyelitis after simple subcutaneous fracture have been recorded where the infection could be traced to a slight peripheral suppurative lesion. The same can be said of many cases of suppurative osteo- myelitis which occur without fracture, where the exciting cause can be referred to some slight injury, or exposure to cold, and the essential cause can be located in some pus-producing lesion in a distant part, and having no direct vascular connections with the suppurating medullary tissue. From a scientific and practical stand-point, it is important to recognize the existence of local conditions in the tissues created by a trauma, or antecedent pathological conditions, to explain the localization of floating microbes and the production of local affections by their uniform presence and constant pathogenic action. SECONDARY OR MIXED INFECTION. Antecedent pathological products may serve the same purpose in the body as a trauma in the determination of localization of pathogenic microbes. Suppuration in a tumor, or a hyperplastic gland with an intact cutaneous covering, indicates that in the tumor or swelling pus- microbes have been arrested, and that they have been deposited in a soil adapted to their germination and the exercise of their pathogenic qualities. The atypical vascularization in tumors and the partial obstruction in the lumen of blood-vessels in inflammatory swellings cannot fail in creating conditions which determine filtration of bacteria- containing blood. If the pre-existing pathological product is the result of a previous infection, and serves as a medium for localization of another kind of pathogenic microbes, we speak of the combined process due to the presence of two varieties of micro-organisms as a mixed infection. The first positive proof of the existence of a secondary or mixed infec- SECONDARY OR MIXED INFECTION. 147 tion was furnished by Brieger and Ehrlich. These observers saw a malignant oedema develop at the point where musk was injected hypo- dermatically in a severe case of typhoid fever. They found that in such cases a predisposition is established by an existing disease to the growth and reproduction of micro-organisms, which may have been previously present in the organism without producing any pathological lesions. Koch, in his article on " The Etiology of Tuberculosis," alludes to the occurrence of mixed infection, as he states that he saw at the same time bacilli and micrococci present in the same tubercular lesion. In reference to the occurrence of micrococci in tubercular deposits in the lungs and spleen, he explained their presence upon the supposition that they entered the circulation through ulcerations of the tongue, and that they became arrested in the capillary vessels, which had lost their normal resisting power by the tubercular process. Bumm maintains that in some patients secondary infection is a purely accidental occurrence, as, for example, a tuberculous patient can be attacked with erysipelas; a lying-in woman suffering from gonorrhoea may become the subject of septic infection. Another and practically more important variet}T of mixed infection he speaks of where a more direct relation exists between the different microbes, in the sense that the one precedes the other and prepares the soil for the growth of the latter. These forms are characterized by being constantly associated with certain definite microbes. The pneu- mococcus may prepare the soil for fructification of the bacillus of tuber- culosis or the microbes of suppuration in individuals that otherwise would have been immune to the action of these micro-organisms. The gonococcus can also modify the mucous membrane of the genito-nrinary tract in such a manner as to render easy the invasion of other pathogenic microbes. Gonorrhoeal infection of the vulvovaginal gland furnishes a good illustration. As long as the infection remains purely gonorrhoeal, the acute suppurative stage is followed by a chronic stage which may last for several months, the swelling gradually subsides, and subsequently atrophy and sclerosis of the gland follow. If, however, purulent infec- tion is added to the gonorrhoea, the gland soon becomes enlarged and tender, and suppuration follows. In the abscess and its vicinit}7 no gonococci can be found; the pus only contains pyogenic microbes, which exterminated the gonococci. Cystitis which accompanies gonorrhoea is, again, a variety of mixed infection. The stratified epithelium of the bladder is impenetrable to the gonococcus. According to Bumm the cystitis is maintained by another species of microbe resembling the gonococcus, but differing from it by taking a 148 PRINCIPLES OF SURGERY. different staining. The gonococcus expends its action on the superficial layers of the mucous membrane exclusively. Suppurative parametritis following gonorrhoea is analogous to a gonorrhoeic bubo, which is always caused by a secondary infection with pus-microbes. A valuable contri- bution to our knowledge of mixed infection has recently been made by Babes. His investigations consist of a series of bacteriological studies of the tissues of children who died of infectious diseases. Within a few hours after death fragments of tissue were removed from different organs which, under strict antiseptic precautions, were imbedded in sterilized culture material. In acute infectious diseases, such as diph- theria and scarlatina, cultures from the spleen, kidneys, liver, lungs, and blood yielded numerous colonies of streptococci, putrefactive bacteria, capsule cocci, more rarely staphylococci and various bacilli. Of special interest are his researches on the manner of localization and extension of the secondary invasion after different primary diseases. In 8 cadavers he found one or more species of bacteria in the internal organs. In a case of septic omphalitis he found the bacillus of green pus. In 6 cases of different forms of infectious disease the streptococcus pyogenes could be cultivated from the tissues, and only in 1 was the yellow pus-microbe present in the culture. Various putrefactive bacilli were cultivated from 5 cases. In some instances he was able to demonstrate the point at which the different secondary invasions had taken place. Thus, in a caae of sepsis after scarlatina, in which streptococci were found in every part of the body, a streptococcus pneumoniae was found in the lower portion of the left lung, while a number of foci in the upper portion of the opposite lung contained only bacilli. Frankel and Freudenberg cultivated from internal organs of 3 patients who had died of scarlatina the streptococcus p}'ogenes, and they maintain that the presence of this microbe is evidence that a secondary infection takes place through the diseased mucous membrane of the pharynx. Schnitzler, after having observed and carefully studied a number of cases, has come to the conclusion that syphilitic ulcerations of the larynx may pass into tubercular, as the syphilitic ulcer furnishes a good culture soil for the bacillus of tuberculosis. Heuber attributes the occurrence of suppuration and gangrene in croupous pneumonia, phlegmonous inflammation and suppuration in enr- sipelas, and suppuration in tubercular processes to secondary infection with pus-microbes. As the bacillus of tuberculosis and the streptococcus of erysipelas do not possess the property of converting leucocytes and embryonal cells into pus-corpuscles, suppuration, if it does occur in these diseases, can only be accounted for by admitting the existence of a secondary infection with pus-microbes. ELIMINATION OF PATHOGENIC BACTERIA. 149 The important question presents itself whether, in cases of mixed infection, the two or more kinds of microbes enter the organism at the same time, or whether primary infection prepares the way for the en- trance and fructification of the microbes which produce the secondary infection. Pus-microbes being present at all times and everywhere, and perhaps gaining entrance into the body more readily than others, it is very easy to understand why secondary infection by them is most fre- quently observed. Rosenbach frequently found in pus more than one kind of pyogenic microbe. He often cultivated from the same pus two kinds of staphylococci, or one variety of staphylococci with streptococci. While antagonism among some bacteria has been shown to exist, others prepare the soil for the growth of a different variety, and in such in- stances it is not difficult to conceive that secondary infection is of fre- quent occurrence. For instance, any microbe that will convert mature tissue into embryonal cells abbreviates and lightens the work of pus- microbes in converting fixed tissue-cells into pus-corpuscles. ELIMINATION OF PATHOGENIC BACTERIA. Having described the different ways in which pathogenic bacteria enter the body, it now remains to show in what manner they are disposed of in the event no harm follows, or the patient recovers from the disease which they produced. The probable existence of disease-producing micro-organisms in the healthy body and the spontaneous subsidence of many infective processes make it important to consider the ways and means by which they are rendered harmless in the living body, or are removed by elimination through some of the excretory organs. In all infective processes in which life is not destroyed, and the products of inflammation do not find their way to the surface spontaneously or by operative treatment, the microbes are either destroyed in the blood and the tissues by phagocytosis or are eliminated through some of the excre- tory organs in an active state. The rapid disappearance of most microbes from the blood when injected into the circulation of healthy animals would indicate that an active warfare is instituted against them by the colored corpuscles of the blood, in which the microbes are defeated,— that is, destroyed. If some of the microbes pass through the capillary blood-vessels and come in direct contact with the fixed tissue-cells, a similar struggle ensues between them and the tissue-cells, and if the latter are victorious the microbes are destroyed. Successful phagocytosis must therefore be considered as the most efficient and desirable way of dispos- ing of pathogenic bacteria after they have entered the tissues or the general circulation. But should phagocytosis prove unsuccessful in de- stroying the microbes which have reached the blood, there is still another 150 PRINCIPLES OF SURGERY. way in which the unassisted resources of the organism can deal with them successfully, viz., elimination through one or more of the excretory organs. The critical discharges of the ancient authors—profuse sweat- ing, diarrhoea, and copious secretion of urine—in the light of modern science have received a different significance, as they are now regarded as efforts of the vis medicatrix naturae to throw off the cause which pro- duced the disease,—the pathogenic microbes and their ptomaines. The kidneys and the mucous membrane of the intestinal canal are the organs most concerned in the process of elimination. That microbes in an active state are eliminated by the kidnej^s is shown by various observa- tions, and this is an important point to remember as probably explain- ing certain cases of pyelitis occurring in patients who have never had any instrument passed, and in whom the urethra and bladder are perfectly normal. The salivary glands, more especially the parotid, occasionally take part in the elimination of pus-microbes, thus offering an explanation of the not infrequent occurrence of abscesses in this gland after suppura- tion elsewhere. The frequency with which the kidneys are affected in cases of tuberculosis furnishes an evidence that elimination of bacilli takes place through these organs. Philipowicz produced tuberculosis in animals by injecting urine taken from tubercular subjects into the peri- toneal cavity. Neumann found the specific microbes in the urine in cases of typhus, septicaemia, and pyaemia. In a case of acute endocarditis and osteonvyelitis he cultivated from the urine the staphylococcus pyogenes aureus. He asserts that the micro-organisms which circulate in the blood localize in the capillary vessels of the kidney, where they often cause minute multiple lesions without implication of the entire paren- chyma of the organ. Through the altered tissues some of the microbes enter the tubuli uriniferi, and are washed away with the urine. Phili- powicz found bacilli in the urine in anthrax and glanders. Schweiger has shown conclusively, by his bacteriological researches, that the urine from scarlatinal patients is contagious; for varicella, typhus recurrens, and malaria the same holds true. Schweiger regards all kidney-lesions occurring in the course of infective diseases of microbic origin. To prove that microbes pass through the kidneys, he cultivated a bacillus which Reimann discovered in the pus of ozaena. This bacillus is stained an intense green color in a culture of gelatin and agar after twenty-four hours. A culture of this bacillus was diluted with a physiological solu- tion of salt and injected directly into the circulation. The experiments were made on a dog, cat, and rabbit. A certain length of time inter- vened between the injection and the appearance of bacilli in the urine, as though, somewhere on their way, an obstacle had been met with. At first only isolated bacilli were found in the urine, but later on they DIRECT TRANSMISSION OF PATHOGENIC BACTERIA. 151 appeared in larger numbers. Bacteriological examinations of milk have shown that different kinds of pathogenic bacteria are eliminated through the mammary gland. The chapter on Bacteria would not be complete without at least alluding briefly to what is known in reference to DIRECT TRANSMISSION OF PATHOGENIC BACTERIA FROM PARENTS TO FffiTUS. That many of the infectious surgical diseases are hereditary has been admitted by the best authorities for a long time, and many theories have been advanced to explain their transmission from parents to child. The modern views on this subject may be narrowed down to two suppo- sitions : 1. Transmission from parents to child of a predisposition to certain diseases. 2. Direct transmission from parents to foetus of the essential cause of the disease. The supposed hereditary predisposition is interpreted as meaning some congenital anatomical or physiological defects in the tissues, which render the organisms unduly susceptible to the action of post-natal microbic infection. The existence of minute anatomical defects of blood-vessels, lymphatic vessels and glands, con- nective-tissue spaces, etc., has been advanced in explanation of a greater liability of infection with floating microbes, which enter the circulation after birth. An inherited defective vital resistance on the part of the tissues to the action of bacteria is also considered by many in the light of a con- genital influence in the causation of disease. The above-mentioned conditions are recognized, but no satisfactory, demonstrative, or experi- mental proofs of their existence have as yet been furnished, and yet the immunity of some animals to certain diseases cannot be explained in any other way than in attributing to the tissues anatomical or physiological properties which protect the organism against the action of certain micro-organisms, which, in other animals not so protected by inherited qualities, produce a serious or fatal disease. Clinical observation also teaches us that a great difference exists among different persons in refer- ence to the degree of susceptibility to the same form of infection. In many persons, for instance, inoculation with a pure culture of tubercle bacilli would be a perfectly harmless procedure; in some it would be followed by a localized tubercular process, which in the course of time might heal spontaneously ; while in a few, rendered more susceptible to this form of infection by hereditary or acquired causes, inoculation with the same number of bacilli would be followed by a severe form of local tuberculosis, soon to be followed by regional and general dissemination and death. The same can be said of nearly all, if not all, infectious diseases. If their existence has not been demonstrated, we are, neverthe- 152 PRINCIPLES OF SURGERY. less, forced to accept the influence of certain as yet unknown conditions inherent in the tissues, and which are often traceable to a congenital cause or causes, which favor or resist post-natal microbic diseases. During the last few years some progress has been made in showing that hereditary diseases, in many instances at least, are due to a more direct cause— transmission from parents to foetus of the essential cause of the disease— pathogenic microbes. Although our knowledge of the intra-uterine origin of microbic diseases is as yet imperfect, there can be no doubt that future study and research will clear up many dark points, and fur- nish satisfactory demonstrative explanations of the direct and indirect hereditary influences in the causation of disease. It is well known that small-pox, measles, and scarlatina are directly transmissible from mother to foetus. Numerous well-authenticated cases of these diseases occur- ring in newborn children have been recorded. Lebedeff reports a case of premature birth which occurred eight days after the mother had recovered from erysipelas. The child died ten minutes after birth, and the author found Fehleissen's streptococcus in the lymphatic vessels, in the diseased skin, and in the umbilical cord, but none in the placenta. The author believes that the streptococci were transported from the lymphatic vessels of the lower extremities of the mother through the lymphatics of the uterus into the placental vessels, and from the mater- nal into the foetal circulation. Ahlfeld and Marchand report the case of a woman who presented no symptoms of disease except a moderate pallor and tympanitic distention of the abdomen. After a normal labor she gave birth to her second child ; eight hours after delivery the patient died in collapse, for which no cause could be found. The autopsy re- vealed anthrax as the cause of death. The child died four days after birth from the same cause. The mother, as was later ascertained, con- tracted the disease in sorting horse-hair, and the child was infected directly through the placental circulation. Sangalli found the bacilli of anthrax in the blood of a foetus from a woman who had died of anthrax. In opposition to Golzi and others, he affirms that the transmission of the disease from mother to foetus could only have taken place by the passage of the bacilli or spores from the maternal to the foetal circulation through the placental vessels. Netter reports a carefully-observed case of direct transmission of the diplococcus of pneumonia from mother to foetus. The mother was a Vl-para, pregnant eight months, when she was attacked with croupous pneumonia, which terminated on the seventh day in recovery. On the ninth day after the attack she was delivered of a living child. The child died on the fifth day after birth. The autopsy revealed lobar pneumonia involving the right upper lobe, double fibrinous pleuritis, pericarditis, suppurative meningitis, and otitis media on both DIRECT TRANSMISSION OF PATHOGENIC BACTERIA. 153 sides. Bacteriological examination of the different inflammatory products, as well as of the blood taken from the left ventricle, showed the presence of Frankel's diplococcus pneumoniae. One of the strongest evidences of direct transmission of pathogenic microbes from mother to foetus through the placental circulation is the often-quoted observation made by Johne. An eight months' foetus was taken from a cow, the subject of advanced tuberculosis. No tuberculous products were found in the placenta or the uterus, but in the lower lobe of the right lung of the foetus a nodule the size of a pea was detected, containing four caseous centres. The bronchial glands were tubercular. The liver contained numerous miliary nodules, All the lesions presented under the micro- scope the characteristic histological structure of tubercle. Jani has examined the healthy sexual organs of nine phthisical patients for tubercle bacilli. No bacilli were found, in any of these, in the semen from the vesiculae seminalis, but, on the other hand, in 5 out of 8 cases, a few were found in the testicle, and in 4 out of 6 in the prostate gland. He further examined two women who died of pulmonary phthisis, the ovaries in both presenting negative results. In one case of chronic pulmonary phthisis, with extensive intestinal tuberculosis, he examined the Fallopian tubes, and found tubercle bacilli. He believes that the tuberculous virus can be transmitted from parents to offspring in one of two ways : 1. Through the semen of the male. 2. Through the migration of bacilli into the uterus from the abdominal cavity. The frequency with which the Fallopian tubes are the seat of tuberculous lesions make it more than probable that the ovum, on its way from the ovaries to the uterine cavity, is infected with bacilli. It also requires no stretch of the imagination to understand how the spermatozoa in the testicle or on its way to the vesiculae seminalis can be contaminated with bacilli, and thus the disease directly transmitted from father to foetus. That syphilis is a microbic disease can no longer be doubted, and that it is one of the diseases which is most frequently transmitted from parents to offspring is well known. That pathogenic micro-organisms may exist in the blood of ap- parently healthy mothers without doing any harm is well illustrated by children who have been born suffering from suppurative osteo- myelitis, while the mothers, through whose blood only the micro- organisms could have come, showed no evidences of disease. Rosenbach reports such a case in his artice on acute osteomyelitis. Transmission of microbic diseases through the placental circulation has been made the subject of experimental inquiry. Strauss and Chamberland experimented on guinea-pigs to prove that intra-uterine transmission of anthrax from mother to offspring is possible. Gravid animals were inoculated with 154 PRINCIPLES OF SURGERY. the virus of anthrax, and the foetuses examined immediately after death. Blood taken from the cavities of the heart and liver, examined under the microscope, never showed bacilli. Cultivation experiments were made with the foetal blood in veal-bouillon, and these proved that in some instances the blood of all foetuses from the same mother contained bacilli; sometimes from the same litter all cultures remained sterile, while in some the blood of only one foetus would yield a positive result. From these experiments the authors came to the conclusion that the tissues of the placenta offer no insurmountable obstacle to the passage of the bacillus of anthrax from the maternal into the foetal circulation. Kowbassoff came to more positive results in his experiments. In all of his experiments the foetuses of the infected animals contracted the dis- ease in utero. He also found that time played an important role as far as the number of bacilli in the foetus was concerned, as the longer the period which intervened between the inoculation and the death of the mother, the more numerous were the bacilli in the foetal organs, showing that the migration of microbes from the maternal to the foetal side of the placenta is continuous. Inoculation with attenuated virus proved that intra-uterine transmission took place more slowly. Inoculation of gravid animals with a very strong culture nearly always proved fatal to the foetuses. Manzeri believes that direct transmission of microbes from mother to foetus through normal placental vessels is impossible. As the result of an extensive study of the literature of this subject and of original experiments, he has come to the conclusions that no formed elements naturally pass out of the mother's blood into the foetal circula- tion. Cinnabar, Indian ink, carmine, and other finely-divided pigment materials were injected into the jugular veins of animals far advanced in pregnancy, but in no case could any trace of the substance employed be found in the foetus. According to his views, passage of formed elements can only occur when the placenta becomes diseased by inflammation, or is partially detached so that the walls of the villi are destroyed. He maintains that only under these conditions can pathogenic micro- organisms be transmitted from the mother into the foetal blood. Most all authors agree that when extravasations or other pathological processes occur in the placental attachment, the direct entrance of microbes from the maternal into the foetal circulation is not only possible, but a probable occurrence. Abnormality of the placental circulation must, therefore, be recognized as a condition which favors the occurrence of hereditary microbic disease. Both clinical observation and experimental research leave no room for doubt that in some infectious diseases, at least, heredity is traceable to direct transmission of the specific microbes, either by means of transportation by the spermatozoa to the ovumt or by their DIRECT TRANSMISSION OF PATHOGENIC BACTERIA. 155 entrance through the thin wall which separates the maternal from the foetal circulation. It is no more difficult to explain the migration of microbes through such a thin septum than their transportation from one tissue to another, and from organ to organ in other parts of the bod3r, more especially as the anatomical conditions for mural implantation in the placental vessels are most favorable for such an occurrence. CHAPTER VI. Necrosis. Necrosis, gangrene, mortification, and sphacelus are terms used synonymously to indicate the death of a part. English and American writers have usually restricted the meaning of the word necrosis to death of bone, while the remaining terms were used to express the same con- dition affecting the soft tissues. Recently a sharp distinction has been made between necrosis and gangrene from an etiological stand-point, according to which necrosis is said to have taken place when the circu- lation and nutritive changes in a part have completely ceased to be followed by gangrene as soon as saprophytic bacteria invade it and give rise to putrefaction. Death of bone will never be described as gangrene, and the moist putrefactive form of gangrene of the soft tissues will, in all probability, be never designated by the term necrosis. Necrosis of bone takes place in the same manner and results from the same causes as gangrene of the soft parts, and on this account there does not appear to be sufficient reasons to apply different terms to identical processes occurring in different anatomical structures; and yet by long usage they have become so intimately associated with the anatomical character of the part affected that it is difficult, for the present at least, to drop either. In modern literature we speak of necrosis of the soft tissues when the dead structures do not undergo putrefaction; that is, when this process takes place in the internal organs not readily accessible to putrefactive bacteria. In its extent necrosis varies greatly; it may involve an entire limb, an entire organ, or may be limited to a single cell. As a physiological process it occurs everywhere in the tissues, being limited, however, to individual cells incident to the wear and tear of the body, the pulling down and building up of the tissues, the cells that are lost being replaced by the normal process of regeneration. A simple, numerically increased cell necrosis, without normal restitution, leads to atrophy,—necrosis atrophica. When all the cells of a part undergo death simultaneously, the circulation corresponding to the area of dead tissue is arrested completely, and with this absolute ischaemia, plasma circula- tion, and all functions are, of course, completely suspended,—a serious pathological condition. A total necrosis has occurred. (157) 158 PRINCIPLES OF SURGERY. ETIOLOGY. Necrosis is a condition, not a disease. As a symptom it represents a local condition which has been brought about by different causes. The most frequent causes of necrosis are the following:— Inflammation.—Inflammation may produce necrosis in two different ways : 1. Exudation and transudation take place so rapidly that com- plete stasis is produced by the extra-vascular pressure. 2. The bacterial cause of the inflammation is present in such large quantities that the vitality of the tissue is destroyed directly from this cause. If during an acute inflammation the capillary walls undergo such serious alteration that within a few hours or days the connective-tissue spaces become so densely packed with the corpuscular elements of the blood that the plasma circulation is greatly impeded or completely arrested, the primary inflammatory product encroaches upon the capillary vessels to such an extent as to completely arrest the already sluggish circulation. If such a copious and rapidly-forming inflammatory exudate give rise to complete stasis over a considerable area, the extent of the resulting necrosis will correspond to the district deprived of the requisite blood-supply. The same bacteria which produce inflammation frequently, if present in sufficient quantities, also cause cell necrosis. Ogston maintains that the staphylococci invade the tissues in the form of dense, round masses, which advance like clouds of a dense vapor, and, coming in contact with the tissues, induce necrosis, the cells, nuclei, and intercellular sub- stance being changed into a homogeneous, wax-like substance before purulent liquefaction occurs. On the other hand, the streptococci of suppuration invade the intercellular spaces, the nuclei of the cells re- maining visible. Bonone found the staphylococcus pyogenes aureus in such metastatic and broncho-pneumonic foci which presented a gangre- nous character. He maintains that the staphylococcus at first produces in the lungs a necrosis by its multiplication, and that suppurative in flammation follows later around the necrotic tissue. Putrefaction of the dead tissue develops in consequence of the entrance of saprophytic bacilli through the bronchial tubes. He verified these assertions by experiments. He obtained pure cultures of the yellow coccus from such pulmonary foci made by intra-parenchymatous pulmonary injections, and succeeded in producing artificially identical lesions in the lungs of animals. The same result was obtained by the intra-venous introduction of small particles of elder-pith impregnated with pure cultures of the yellow staphylococcus. The gangrenous foci produced by emboli con- taminated with the yellow coccus presented a characteristic appearance. The centre of such foci, at an early stage, is composed of necrotic tissue and remnants of dead leucocytes. The dead tissue is surrounded by a ETIOLOGY. 159 granular zone, which is again inclosed by a haemorrhagic zone, and beyond this an area of catarrhal pneumonia. The staphylococci occupy the central portion and from here invade the granular zone, where putre- factive bacteria are also found. The pus-microbes do not reach the haemorrhagic zone, or the tissues the seat of catarrhal pneumonia. As Bonone was unable to produce gangrene of the lung, either by parenchy- matous injections of other bacteria, as the pneumococcus or mikrosporon septicum, or by aseptic emboli of elder-pith, he naturally came to the conclusion that the gangrene resulted from the specific effect of the yellow coccus. He compares gangrene of the lung with furuncle of the skin from an etiological stand-point. There can be no doubt that the primary effect of pus-microbes, when brought in contact with living tissue, under certain circumstances, is to produce necrosis before sufficient time has elapsed for parenchymatous inflammation to become established. This occurs in gangrene of the lung, furuncles, carbuncles, and endo- carditis bacteritica staphylococcica. In the ordinary connective-tissue abscess, however, the connective-tissue cell undergoes the ordinary in- flammatory changes before the}' are converted into pus-corpuscles, and if gangrene occur it is owing as much to mechanical obstruction to the circulation caused by a copious exudate as to the local toxic effects of the pus-microbes and their ptomaines. This difference in the action of pus-microbes on the tissues depends largely upon the rapidity with which they multiply at the point of primary localization. If the microbes are rapidly reproduced the chemical substances which they produce in the tissues are present in such large quantities that they destroy the cell protoplasm, and cell necrosis takes place as the result of their primary action ; if the microbes multiply with less rapidity their effect on the tissues is less severe, and parenchymatous inflammation is produced instead of necrosis. Bonone used large quantities of pus-microbes in his injections, and the infected emboli caused circulatory disturbances, which only could favor rapid reproduction at the point of primary localization. Passet and Liibbert repeated his experiments, but used more diluted cultures, and probably on this account they were never successful in producing gangrene of the lung, while they frequently observed the development of a pulmonary abscess. The centre of a furuncle, as well as a carbuncle, is occupied by a mass of dead connective tissue, which later becomes detached by suppurative inflammation. The connective tissue in these cases is killed by the bacterial cause of the suppurative inflammation, which, toward the periphery, appears to become mitigated so that, behind the suppurating zone, a wall of granu- lation tissue is established which limits further extension of the disease. 160 PRINCIPLES OF SURGERY. Specific Bacteria.—All bacteria which can produce an inflammation sufficiently severe to completely arrest circulation can become an indirect cause of necrosis. Among these can be included the pus- microbes and the bacillus of anthrax. The necrosis which occurs regu- larly almost in every case of anthrax is probably due to the intensity of the inflammation resulting from the presence of the anthrax bacillus, to secondary infection with pus-microbes, or to the combined effect of both microbes. The absence of necrosis in artificially-produced anthrax, when pus-microbes are excluded by the strictest antiseptic precautions, does not prove that the anthrax bacilli possess no necrotic effect on the tissues, as in such instances death follows so soon that not sufficient time intervenes between the inoculation and the death of the animal for the local inflammation to terminate in necrosis. Necrosis is, however, much more likely to occur if the anthracic infection is complicated by the presence of pus-microbes. It is well known that certain chemical substances have the power to produce cell necrosis independently of their action to excite inflammation. Digitoxin, a poisonous principle of digitalis, is one of these. The primary effect of this substance on the tissues is to produce cell necrosis. We should expect that some of the ptomaines possess similar properties. Orthmann made some very inter- esting experiments in this direction with pus-microbes. He inoculated both corneae in rabbits by making a puncture with a needle infected with a pure culture of the streptococcus pyogenes. One of the eyes was irri- gated for ten minutes with a warm physiological solution of salt, by using an apparatus constructed for this special purpose. In the eye not thus treated a suppurative keratitis was initiated by the leucocytes from the conjunctival sac reaching the infected field, while in the cornea treated by irrigation the streptococci invaded the vascular spaces, and, multiplying with great rapidity, produced by their accumulation dilata- tion of the spaces and necrosis of the fixed tissue-cells. In most of these cases the central necrosis led to perforation of the cornea and complete destruction of the eye. As the corneal corpuscles in the necrotic area had lost their nuclei and the parenchyma cells showed no signs of inflammation, we cannot escape the conclusion that cell necrosis was induced by the direct action of the ptomaines, elabo- rated by the masses of streptococci in the vascular spaces. The most conclusive proof of the destructive effect of ptomaines on the tissues has been furnished by the great master and founder of modern bacteriology, Robert Koch. In his experiments on septicaemia in mice he found, besides bacilli, a micrococcus in the neighborhood of the place of injec- tion. Of the numerous kinds of bacteria contained in the putrid fluid used for injection, only the fine bacilli upon which the induction of the ETIOLOGY. 161 septicaemia depended and the chain cocci found a suitable soil in the mouse, while all the rest perished. The chain coccus was never found in the blood, but only in the tissues at the seat of infection. He found it exceedingly difficult to isolate it from the bacillus. At last he succeeded in cultivating it in the field-mouse, which, as experiments proved, is immune to the bacillus of septicaemia. The chain coccus injected into the subcutaneous tissue of the ear of the field-mouse invaded the tissues slowly, causing paleness and death of the cells without extravasation. The microbe entered and plugged the capillary vessels, but never found Fig. 48.—Experimentally-produced Growth of Streptococci in Centre of Cornea of Rabbit. Horizontal Section, X 40. (Baumgarten.) A, normal cornea; B, central necrotic portion, corresponding in outline to the star-shaped streptococci culture. its way into the general circulation. Examination of the specimens showed that progressive gangrene occurred in advance of the microbes, hence could have occurred only by the action of ptomaines diffused through the tissues ahead of the microbic invasion. Inflammation of the fixed tissue-cells occurred around the zone of gangrene, and all leucoc3'tes which reached the infected field perished. If the same animal was inoculated at the root of the tail, gangrene occurred and spread in a central direction, and resulted in death on the third da}\ The microbe did not change in its morphology or pathogenic properties after passing through a series of inoculations. Both Ogston and Rosenbach are of u 162 PRINCIPLES OF SURGERY. the opinion that the chain micrococcus with which Koch produced progressive gangrene in the field-mouse is identical with the strepto- coccus pyogenes. This question will have to be decided by future research, which must have for its object the isolation and cultivation of the chain coccus from the necrosed tissues of the field-mouse. Baum- garten is of the opinion that microbes can produce necrosis not only by the production of a tissue poison, but also by causing decomposition and by the assimilation of material necessary for cell nutrition. The expla- nation advanced by Koch ten years ago, however, appears more rational: , " Introduced by inoculation (chain cocci) into living animal tissues, they multiply, and as a part of their vegetative process they excrete soluble substances which get into the surrounding tissues by diffusion, and when greatly concentrated, as in the neighborhood of the micrococci, this product of the organisms has such a deleterious action on the cells that these perish and finally disappear completely. At a greater distance from the micrococci the poison becomes more diluted and acts less intensely, only producing inflammation and accumulation of lymph- corpuscles. Thus it happens that the micrococci are always found in the gangrenous tissue, and that in extending they are preceded by a wall of nuclei which constantly melts down on the side directed toward them, while on the opposite side it is as constantly renewed by lymph deposited afresh." An almost identical form of gangrene, as experimentally produced in the field-mouse by Koch, is occasionally met with in man. It is known as progressive gangrene, and is so called from its most conspicu- ous clinical feature—rapid extension. Before antiseptic surgery was known it frequently developed in cases of compound fracture and com- pound dislocation of large joints, and often proved the direct cause of loss of limb or life, or both. Two cases came under my own observation where it occurred after extirpation of carcinoma of the breast, in one without, and in the other with, removal of the axillary glands. In both cases the first symptoms appeared on the third day. The general symptoms were those of intense sepsis, while the local conditions resembled first what used to be called phlegmonous erysipelas. An erysipelatous blush appeared at the margins of the wound and extended rapidly in all directions, accompanied by infiltration of the deep tissues. The gangrene attacked the tissues first involved and followed the course of the phlegmonous inflammation. In spite of the most energetic local and general treatment, both patients died at the end of the first week. Rosenbach describes two cases that came under his care. In one the disease started from a small wound of a finger, the process finally extending to the lower extremities, with death on the sixth day. In ETIOLOGY. 163 the second case, the local lesion appeared first as a red induration, around which oedema developed rapidly, the skin covering the part presenting a reddish-blue discoloration before gangrene set in. This patient had an eruption of the skin over the whole surface of the body which resembled the rash of scarlatina. From the lesions of both of these cases Rosenbach cultivated upon peptone-meat gelatin the strepto- coccus pyogenes. Ogston calls this affection erysipelatoid-wound gan- grene, and always found in the gangrenous tissue the streptococcus. Gangrene produced by staphylococcus, the same author calls sloughing inflammation or inflammatory mortification. The streptococcus of erysipelas never produces gangrene, and when this complication occurs in this disease it is always a positive indication that secondary infection with pus-microbes has taken place. Putrefactive Bacteria.—Necrosis occurring from the action of any other microbes than those of putrefaction is not attended by any disa- greeable odor or other evidences of putrefaction, and, if limited in extent and protected against the invasion of saprophytes, the dead tissue may be completely removed by absorption. Putrefactive bacteria feed on dead tissue, and in the absence of such the}7 are comparative^ harmless. Putrefaction only takes place in moist gangrene, and is always caused by the invasion of dead tissue with one or more species of saprophytes. Progressive gangrene, complicated by secondary infection with sapro- phytes, is characterized by the formation of gases which give rise to emphysema. Progressive gangrene with emphysema is one of the most fatal of all wound complications, as the ptomaines elaborated by the saprophytic bacilli greatly increase the danger from sepsis. Sulphuretted hydrogen is one of the gases formed during putrefaction of necrosed tissue. Rosenbach cultivated from the infected tissues, in 2 cases of progressive gangrene with emphysema, a saprophytic bacillus with spores. Hauser cultivated from putrefying organic substances one or more kinds of the proteus, the proteus mirabilis (Zenkeri) and vulgaris. Trauma.—The vitality of a part is completely destroyed if a trauma is sufficient in intensity to arrest the circulation completely, and of such a character and extent as to render a return of it impossible. Such injuries, for instance, are caused by the passage of a car-wheel over a limb, where the skin often remains intact, while all of the deeper tissues are completely crushed. A blow against a part of the body where only a thin layer of tissue is interposed between the skin and an underlying bone may crush the subcutaneous tissue to such an extent as to preclude the possibility of a return of an adequate circulation, and necrosis follows as an inevitable result. Deep-seated contusions from the application of external violence are often attended by circulatory disturbances, which 164 PRINCIPLES OF SURGERY. necessarily result in necrosis. Necrosis of ganglion-cells following con- tusion of the brain affords a good illustration of the occurrence of traumatic necrosis at a distance from where the force was applied. In such cases the cells are separated from all their anatomical connections by the trauma, and either undergo calcification or are removed by ab- sorption. If such a contused area become the seat of a subsequent infection,suppuration or putrefaction can occur,according to the location of the part injured, infection taking place with pyogenic microbes or sapropli3'tes. In the so-called railway-spine the cell necrosis following a contusion of the spinal cord leads to remote, central, and peripheral disturbances. A trauma may be of such a nature as to inflict an injury not incompatible with the integrity of a limb, but may create conditions which subsequently result in complete obliteration of a main artery. If an artery is subjected to serious pressure or traction, the intima gives way and its lumen is subsequently obliterated by the formation of a thrombus at the seat of injur}'. In such a case the artery is at first per- meable, and the distal pulsations are unaffected until the lumen of the vessel is narrowed and finally completely obliterated by the formation of a thrombus. Professor von Wahl has called attention to an early and important symptom in these cases, the detection of which enables the surgeon to recognize the vessel injury before the appearance of the positive peripheral symptoms, viz., a bruit, which can be heard by placing the stethoscope over the seat of injury. The vessel injury in such cases is of serious import, as the contusion of the soft tissues which is usually also present retards or prevents the formation of an adequate collateral circulation, and gangrene occurs in consequence of complete interruption of the arterial circulation. A vein may be injured in a similar manner, and the venous stasis following obliteration by a thrombus may become a determining cause of gangrene of a limb, the vitality of which has been otherwise impaired by the injury. Decubitus.—Prolonged uninterrupted pressure causes necrosis by interrupting the circulation. Tight bandaging and pressure of splints have often been productive of gangrene. Bed-sores are liable to form in patients suffering from acute infectious diseases, and in persons suffering from fracture of the spine, or disease of the spinal cord ; also, in aged obese persons treated in the recumbent dorsal position for fracture of the neck of the femur. Decubitus is most prone to appear in consequence of pressure over bony prominences, and on this account we look for it in persons who are going through a long-enforced confinement in bed, first over the sacrum, the trochanteric regions, the spinous processes of the vertebrae, and the heels, parts most affected by the dorsal decubitus. The deleteri- ous effect of pressure is greatly aggravated by filthy surroundings, as ETIOLOGY. 165 under these circumstances the necrosed tissue becomes the seat of infec- tion with pus-microbes and saprophytic bacteria, which inaugurate a progressive gangrene and sepsis, often constituting the direct cause of death. It is not unusual, in cases of septic decubitus, to find the whole sacrum exposed, and in one instance that came under the author's obser- vation the spinal canal was opened and through the opening the cerebro- spinal fluid escaped, first clear, later purulent. This patient lived for several days after the cerebro-spinal fluid had commenced to escape, and before his death he presented symptoms which indicated that the menin- gitis had extended to the envelopes of the brain. Defective Arterial Blood-Supply.—The aseptic ligature, combined with the antiseptic treatment of wounds, has been the means of greatly diminishing the frequency of gangrene after ligation of the principal arteries of a limb in their continuity. Gangrene usualty occurred, not so much from the sudden interruption of the arterial blood-supply as from the septic inflammation following the operation, which interfered with the formation of a satisfactory collateral circulation. Ligation of Arteries in their Continuity.—Statistics of a number of years ago show that gangrene has followed ligation of the subclavian in the outer third in 9 per cent, of the cases reported; external iliac, 15 per cent.; common femoral, 11 per cent. The results after ligation of these vessels have much improved since the introduction of the aseptic ligature. In a healthy person with normal blood-vessels there is but little danger of gangrene following the ligation of the principal arteries of a limb with an aseptic ligature under antiseptic precautions. Gradual obliteration of an artery by a thrombus is not attended by equal danger of the occurrence of gangrene as when the same vessel is suddenty and completely blocked by impaction from the arrest of an embolus, because circulation is on a fair way of becoming established before the lumen of the vessel is completely closed, while in the latter case the demand on the collateral vessels is more urgent and sudden, and consequently the failure on their part to act as substitutes for the obliterated trunk is more frequent. Valvular disease of the heart, fatty degeneration of this organ, atheroma of the arteries,—in fact, all pathological conditions which diminish the vis a tergo are instrumental in the causation of gan- grene, when from any accidental cause or operative interference the blood-suppl}r to a limb has been diminished, or when the tissues are the seat of a progressive septic inflammation. Gradual diminution of the arterial blood-supply generally gives rise to dry gangrene, as is the case in senile gangrene, while sudden interruption of the circulation through a large artery from the application of a ligature or the impaction of an embolus is usually followed by moist gangrene. 166 PRINCIPLES OF SURGERY. Obstructed Venous Circulation.—Impeded venous circulation is fraught with as much danger, as far as the production of gangrene is concerned, as obstruction of the arterial circulation. Langenbeck was impressed with this fact so strongly that he recommended, if it became necessary to ligate one of the principal veins of an extremity near the trunk, to ligate at the same time the accompanjdng artery in order to guard against the evil results following ligation of a large vessel. Anti- septic surgery has minimized the danger of ligaturing, for instance, the axillary or femoral vein, and no surgeon at the present time would deem it necessary, or even justifiable, to ligate the corresponding arteries simply for the purpose of preventing excessive venous engorgement and of favoring the formation of an adequate venous collateral circulation. The same advantages which have resulted from antiseptic operations for the timely formation of an arterial collateral circulation after ligature of an artery are secured for the maintenance of an inadequate venous cir- culation after the ligation of a vein. Venous obstruction from patho- logical causes often proves more disastrous, as the causes which have brought about the formation of a thrombus frequently do not remain local, and the thrombus increases in length in both directions, thus rendering the formation of a collateral circulation a difficult, if not an impossible, occurrence. As venous obstruction gives rise to oedema gangrene, if it occur under these conditions, it always represents the moist variety, and is usually accompanied by putrefaction. Heat.—Heat produces pathological conditions according to the de- gree of the temperature and the length of time a part is exposed to its action. A momentary exposure even to a high temperature produces only a burn of the first degree; that is, simply an active hyperaemia and redness of the surface. If the part is exposed for a somewhat longer time the hyperaemia is followed by a superficial inflammation and blis- ters form,—a condition which is described as a burn of the second degree. In such cases the necrosis is limited to the epidermis, which is detached from the papillary layer. In burns of the third degree the deeper tis- sues are destroyed by the heat, and extensive necrosis is the result. Cohnheim determined that a temperature from 54° to 58° C. was sufficient to produce gangrene in the rabbit's ear. If he immersed the ear for a short time in water heated to this temperature, necrosis always followed. A somewhat lower temperature continued for a longer time produced the same effect. Heat produces necrosis by coagulating the cell-protoplasm, if its action is superficial; if it penetrate more deeply, the blood in the blood-vessels is coagulated, and necrosis of the tissues deprived of circulation in this manner follows as an inevitable result. Intestinal ulceration, in case of extensive burns, is also a necrotic process, caused ETIOLOGY. 167 by capillary obstruction with dead or dying blood-corpuscles derived from the burned district. It has been found experimentally that a temperature over 45° C. has a destructive effect on the blood-corpuscles. Welti ascertained that if the ear of a rabbit is kept immersed in water, gradually heated to 70° C, bleeding from the nose and haemo- globinurea followed,—symptoms which he attributed to partial or complete obstruction of capillary vessels with the third corpuscle of the blood. Cold.—The action of cold in producing necrosis is closely allied to that of heat. Frost-bites are classified the same as burns. Cold, like heat, causes gangrene by producing by its action cell necrosis and vas- cular obstruction. Cohnheim produced gangrene of the rabbit's ear by exposing it for a short time to a temperature of 16° C. The length of time a part is exposed, either to heat or cold, exerts an important influence in determining the extent and depth of the subsequent gangrene. Gangrene resulting from a burn or exposure to cold remains dry and aseptic as long as the entrance from without of pus-microbes and sapro- phytes is prevented, but with microbic- invasion suppuration and putre- faction are established. Caustics.—Chemical substances which by their local action on the tissues produce extensive cell necrosis are called caustics. Of these the strong acids and mineral salts destroy cells by causing coagulation. The necrosed tissue, or eschar, resulting from their action is firm, and the contour of the cells is well preserved. The alkaline caustics, on the other hand, dissolve the tissue elements, and the slough resulting from their application is soft. A peculiar form of necrosis of the maxillary bones occurs in persons exposed to the fumes of phosphorus. The most recent explanation of the occurrence of necrosis of the jaws in persons employed in match-factories is to the effect that the phosphorus fumes in the mouth are transformed into phosphoric acid, and that necrosis of the bone is produced by the direct action of the acid on the bone and myeloid cells, while the periosteum remains intact and produces new bone. Ergot.—The prolonged administration of ergot in large doses is attended by the risk of causing gangrene. The gangrene from ergotism is always of the dry variety. It is generally believed that it is caused by the drug keeping up an angio-spasm, which shuts off the full blood- supply to the peripheral portion of the extremities,—the most frequent seat of the gangrene. Zweifel, of Erlangen, believes that the toxic effect of ergot results in a vasomotor paresis, and that the gangrene is due to defective innervation. 168 PRINCIPLES OF SURGERY. SYMPTOMS. Internal Necrosis.—In simple cell necrosis the tissue elements may have undergone no changes in form, but the cell-protoplasm has lost its vital properties, and function has been completely arrested. Such cells present a cloudy appearance, and if the necrosis has resulted from a gradual or sudden ischaemia the part affected presents a pale appearance. In the periphery of such a necrotic area the vessels become dilated and a hyperaemic zone forms, in which the collateral circulation is to be established. If an artery in any of the internal organs is suddenly obliterated by the impaction of an embolus, the tissues supplied by the closed vessels are deprived for a time, and perhaps permanently, of their blood-supply, and in consequence of this they become pale, while around the wedge-shaped, anaemic territory the vessels concerned in the forma- tion of collateral circulation are distended to their utmost, and often yield to the increased intra-vascular pressure when extravasation of blood occurs. If the collateral circulation is not speedily established, necrosis of the tissues supplied by the obliterated vessel is the result. In mycotic cell necrosis karyolysis—that is, dissolution of the cells—usually occurs. If the cell-membrane rupture and the contents of the cell escape, we speak of a karyorhexis. Absolute ischaemia of certain parts or cell territories continued for only one to two hours is sure to result in necrosis. If any portion of the brain, intestines, or kidney is deprived of blood-suppby for this period of time, nutrition is completely sus- pended, and cell necrosis follows as an inevitable consequence. Litten ligated the renal artery in animals, and found, at the end of an hour and a half to two hours, the renal epithelia in a state of necrosis. Limited necrosis of the parenchyma of the brain may give rise to focal symptoms by which the lesion can not only be recognized, but often accurately located. Infarcts of the kidney can frequently be diagnosticated by a careful chemical and microscopical examination of the urine. A similar condition in the lungs gives rise to circumscribed catarrhal pneumonia, which can be recognized by a careful physical examination of the chest. Ulcer of the stomach, the result of a circumscribed necrosis, is attended by a complexus of symptoms pointing directly to the seat and nature of the lesion. Necrosis in internal organs is seldom followed by putrefac- tion, as saprophytes seldom reach the dead tissue. Necrosis of the lungs is sometimes followed by gangrene, by the entrance into the necrosed tissue of putrefactive bacteria from the respiratory passage. Gangrene of External Parts.—As it is often impossible to recognize during life a limited cell necrosis in the internal organs by the symptoms presented, this subject has been briefly disposed of, but the symptoma- tology of external gangrene will receive a more thorough consideration. SYMPTOMS. 169 It might appear that the recognition of the existence of gangrene of any of the external parts would require no special care or erudition. But this is not so. It is true that when gangrene is fully developed, when all the characteristic symptoms are present, a correct diagnosis can be made on first sight. But cases occur where it is exceedingly difficult to determine whether the part affected is dead or only in a state of inflammation. In illustration of this the author will only allude to the difficulties which surround the surgeon in many cases of herniotomy, when he has to determine whether it is justifiable to return a portion of intestine that has been strangulated for some time if he simply relies on the appearance of the intestine. The intestine presents a dusky, almost black appear- ance, and the casual observer might come to the conclusion that it is gangrenous, and treat it as such, when, in fact, a more careful obser- vation will soon reveal the fact that the circulation is not completely arrested, and that it is safe to return it. (a) Pain.—Sudden, severe, often excruciating pain in a limb is the first indication which announces the occurrence of embolism in one of the large arteries. In the lower extremity the embolus is often arrested at the bifurcation of the popliteal artery, but the pain extends along the whole limb, from the toes to the groin. The sudden anaemia is the cause of the pain. In senile gangrene the gradual ischaemia caused by the atheromatous degeneration of the arteries gives rise to pain and a sen- sation of numbness, which precede the gangrene for weeks or months. Acute inflammation resulting in gangrene is attended by intense pain from the very beginning; the pain abates, as a rule, with the occurrence of gangrene. Pain may be absent at the seat of necrosis, and referred to some other part or locality. In strangulated hernia the patient often suffers little or no pain at all in the swelling, but complains of a period- ical pain in the region of the umbilicus. The absence of pain and tenderness over the region of a hernia speaks rather for than against the presence of gangrene. Osteomyelitis is attended by severe pain, which is diminished or subsides with the escape of the products of inflamma- tion from the bone into the surrounding tissues. In cases of intestinal obstruction the cessation of pain, with continuance of the symptoms of obstruction, is an indication that gangrene has occurred. (b) Tenderness.—The pain elicited by pressure is a more important symptom in the diagnosis of necrosis than spontaneous pain. As long as the part suspected to be necrotic is sensitive to the touch it is a sign that necrosis has not taken place. To test the sensation of a part it is advisable to resort to puncture with an aseptic needle. Absence of pain and all sensation on puncturing the tissues with a needle is often the best argument to convince the patient and friends that necrosis has occurred. 170 PRINCIPLES OF SURGERY. (c) Temperature.—The difference in the temperature of a part threatened with gangrene has given rise to the expressions hot and cold gangrene. If gangrene follow an acute inflammation, the local tempera- ture remains high until other evidences of gangrene make their appear- ance, when the complete arrest of circulation and tissue metamorphosis result in a sudden fall of the local temperature. In gangrene following atheroma, thrombosis, embolism, and ligation of arteries the local temperature is reduced before gangrene occurs. (d) Pulse.—After ligation of the principal artery of a limb the sur- geon examines anxiously from day to day for the appearance of pulsa- tion in the distal portion of the artery,—an occurrence upon which depends the fate of the limb. The re-appearance of the pulsation in the distal part of the artery is a certain indication that collateral circulation has become established, and that gangrene will not occur. With the ap- pearance of distal pulsations the local temperature increases, and the diminished tissue metamorphosis is restored to its normal state. In em- bolism or thrombosis of a large artery, the same disturbances in the peripheral circulation of the limb are observed as after ligation. By searching for pulsation in different parts of the limb the surgeon can often locate the thrombus or embolus. If, for instance, the embolus or thrombus is located in the terminal portion of the popliteal artery, pulsa- tions of the femoral artery can be felt from Poupart's ligament down to the seat of obstruction, while no pulsations below this point can be felt until collateral circulation is established. Obliteration of an artery from pathological causes is prone to prevent the formation of an adequate collateral circulation by the growth, in both directions, of the thrombus or embolus. The pulse furnishes the most important means to follow from day to day the growth of the intra-vascular blood-clot. In senile gangrene a thrombus frequently forms in one of the smallest arteries and grows in a proximal direction, extending from the digital branches to the dorsalis pedis, to the anterior tibial, or from the plantar arteries to the posterior tibial, the popliteal, and finally the femoral. In such cases the arteries can be felt as firm cords, but pulsations are limited to the previous portion of the vessels. An embolus often becomes the centre of an enormous thrombus, which seriously impairs the chances of pres- ervation of the limb by the establishment of an early and adequate col- lateral circulation. If an embolus obstruct the popliteal artery, pulsa- tions can be felt above this point, but they disappear with the extension of the secondary thrombus in a proximal direction. (e) Swelling.—In moist gangrene the necrosed tissue imbibes moist- ure to a considerable extent, and the slough is larger than the tissue it represents. The swelling is twice more increased if gas forms in the SYMPTOMS. 171 tissues. In dry gangrene the parts shrink, become firmer, and instead of swelling there is diminution in their size as compared with their volume in a normal condition. (f) Emphysema.—The presence of emphysema in gangrenous tissue is a certain indication of the presence of gasogenic bacteria. The char- acter of putrefaction depends on the kind of saprophytes which are present in the dead tissues. The different kinds of proteus possess gas- producing properties. The proteus, according to Hauser, appears in dif- ferent forms, according to the chemical reaction of the soil upon which it grows. On acid gelatin the culture consists of cocci and short bacilli; on alkaline gelatin it grows in the form of threads, vibrios, spirilli, etc. All these different forms of proteus growing in dead tissue exposed to the atmospheric air produce sulphuretted hydrogen. Hauser cultivated the proteus from ulcerating carcinomas and bed-sores. In the cases of progressive gangrene with emphysema examined bacteriologically by Rosenbach, he found the bacillus saprogenes. Emphysema is sometimes so marked that on percussion a tympanitic resonance is elicited. When less in degree its presence can be readily recognized by pressure, which causes a crackling, crepitating sound. (g) Color.—If gangrene take place in consequence of interrupted arterial circulation, the part at first presents a preternaturally pale ap- pearance until the first visible evidences of the actual occurrence of gangrene are announced by a livid or lead color, at a point where the circulation has first been completely arrested. The lividity, when it is due to complete, irreparable capillary stasis, is not affected by pressure. Blisters containing a sanious fluid form at points where the deeper tissues have already undergone necrosis. As soon as the circulation has been completely arrested, tissue metamorphosis is at once suspended, and the further changes are entirely of a chemical nature. The colored corpus- cles of the blood undergo rapid disintegration; the coloring material is diffused through the dead tissue and into the interior of the bullae. The black color of gangrenous tissue is produced by sulphuret of iron,—a combination of sulphuretted hydrogen and haemoglobin. (h) Condition of Tissues.—The condition of the dead tissues will de- pend on the cause of the necrosis. In dry gangrene they become firmer by evaporation of the fluids. In moist gangrene they imbibe fluids and undergo maceration, becoming soft and friable. A fetid, sanious fluid escapes from the dead tissue. Adipose tissue in a condition of gangrene undergoes speedy disintegration, and free globules of fat are mixed with the sanious discharge. Maceration of tissue is considered by Ravoth as the most important condition in determining the presence of gangrene in cases of strangulated hernia. He maintains that if the tissues of the 172 PRINCIPLES OF SURGERY. intestinal wall can be readily separated and teased asunder with a dis- secting forceps there can be no doubt that gangrene has occurred. This maceration, however, takes place only some time after the circulation has ceased, and is entirely absent in necrosis of bone, cartilage, and tissues well supplied with elastic elements, as the arteries. In determining the presence of gangrene in strangulated hernia, where any doubt as to its presence exists in the mind of the operator, it is much better to liberate the strangulated gut, draw it forward and irrigate it every few minutes with a hot solution of boracic acid, which will stimulate the sluggish cir- culation, and will soon furnish reliable proof of the actual condition of the vessels and the tissues. Mechanical stimulation, of the intestinal wall is also a valuable diagnostic measure, as, if gangrene has occurred, no amount of irritation will excite peristaltic action, while with the restoration of the impeded circulation the muscular fibres will respond to irritation. (i) Odor.—Necrosed tissue does not emit any unpleasant odor unless it has become invaded with putrefactive bacteria. The almost unbearable stench which attends extensive moist gangrene is always the result of putrefactive changes. Dry gangrene is odorless. In acute inflammatory affections of the lung, where a communication has been established between the inflammatoiy focus and the bronchial tubes, the presence or absence of foetor is of great diagnostic value, as its presence speaks in favor of gangrene and its absence indicates an abscess. (j) Mummification.—By this term we mean a drying up of a gan- grenous soft part from the loss of fluids which it contains by evapora- tion. It is a state of preservation of dead tissue while still attached to the living body. It can only occur if the dead tissue is exposed to the atmospheric air, and on this account it is always absent in necrosis of internal organs. Mummification can only take place where putrefaction is absent, and, therefore, is most frequently met with where gangrene is first limited, and increases gradually by an aggregation of the causes which produce gradual diminutian of the arterial blood-supply, as in cases of senile gangrene. (k) Line of Demarcation.—The line of demarcation is the line where the further extension of gangrene has been arrested by an adequate col- lateral circulation and a wall of living granulations. Back of this line of demarcation, on the side of the living tissues, there is to be found a hyperaemic zone, which precedes and attends the regenerative process, and by which the further extension of the gangrene is prevented. In septic gangrene the line of demarcation marks the limits of the area of infection, while in aseptic gangrene it indicates the point where the vascular conditions answer the physiological requirements of the part. SYMPTOMS. 173 (I) Elimination of Gangrenous Part.—Spontaneous elimination of a gangrenous part is of frequent occurrence. The necrotic tissue may be disposed of in a spontaneous cure in three different ways : 1. Absorption of dead tissue. 2. Separation of necrosed part by granulation. 3. Separation of the sphacelus or sequestrum by suppuration. A limited quantity of necrosed aseptic tissue can be completely removed by ab- sorption in the same manner as absorbable aseptic substances are re- moved when implanted in the tissues. This is the most desirable termination of gangrene, and takes place frequently in cell necrosis of the internal organs. Such a disposal of aseptic necrosed tissue is also possible on the surface of the skin when the area does not exceed a square inch, and an aseptic condition is secured throughout. The capacity of the tissues to remove aseptic necrosed tissue is limited, and when the quantity of tissue surpasses this capacity the dead part is con- siderably diminished in size, and the balance is detached by the granula- tions which form at the line of demarcation, and is finally eliminated spontaneously or by operation. Repair after this manner of elimination is rapid and satisfactory. If infection with pus-microbes has taken place in the beginning of the lesion which has caused the necrosis, or, later, at the line of demarcation, separation of the slough takes place by means of a suppurative inflammation. In such cases the dead part is not diminished in size, and the healing, after its elimination, takes place more slowly, and the result, as a rule, is less satisfactory. Separation takes place very slowly in necrosis of bones, intermuscular connective tissue, and tendons, requiring often weeks and months before the dead tissue can be removed. (m) Liquefaction of Necrosed Tissue.—Where no putrefaction or suppuration takes place, and the amount of necrosed tissue exceeds the absorptive capacity of the surrounding tissues, liquefaction takes place, and months and years later the seat of necrosis is occupied by what appears, and has often been falsely described, as a cyst. This method of disposing of the dead tissue is observed most frequently in organs scantily supplied with connective tissue, as the brain and spinal cord and in adipose tissue. (n) Encapsulation.—A limited area of aseptic necrosed tissue, not amenable to absorption, is often rendered harmless by encapsulation. The surrounding living tissue throws out a wall of granulation tissue which is converted into connective tissue, forming a capsule around the dead tissue. This method of disposal of dead tissue frequently occurs in the internal organs. A sequestrum occasionally becomes encapsulated after the interior of an involucrum has been rendered spontaneously, or by treatment, aseptic. 174 PRINCIPLES OF SURGERY. (o) General Symptoms.—These will have reference to the loss of function caused by cell necrosis in internal organs and sepsis in external necrosis. Function will be affected according to the location and extent of cell necrosis. If cell necrosis is of mycotic origin and general it fre- quently becomes a direct cause of death. If it is limited to a single organ the symptoms will point to it as the seat of the disease. Limited areas of cell necrosis, in most of the organs, may give rise to ill-defined or no symptoms whatever, and is then completely beyond the grasp of a correct diagnosis. The most important general s}'mptoms of gangrene arise from the introduction into the general circulation from the gan- grenous part of soluble toxic substances. As this subject will be treated of more extensively in the chapter on Septicaemia, it will suffice here to make the broad but correct statement that septicaemia complicates gan- grene only when the dead tissues are infected with pus-microbes or putrefactive bacteria. Dry gangrene is, therefore, not attended by any danger of septic intoxication, while patients suffering from moist gan- grene with putrefaction die, as a rule, not from the loss of tissue from gangrene, but from sepsis incident to the gangrene. Sepsis in gangrene is usually of that variety which arises from the introduction into the circulation of preformed toxines, the symptoms subsiding with the removal of the cause, with the exception of those cases of progressive sepsis caused by infection with pus-microbes. CHAPTER VII. Necrosis (continued). PATHOLOGICAL AND CLINICAL VARIETIES OF NECROSIS. The pathological and clinical classification of necrosis is based upon its causes, location, extent, and the age of the patient. The causes of necrosis have already been considered, and it has been shown that it results either from arrest of the circulation from purely mechanical causes or from the action upon the tissues of toxic, chemical, or thermal influences which destroy the protoplasm of the cells directly. The location of the necrosis is important to remember, as when it occurs in organs inaccessible to saprophytic micro-organisms putrefaction never takes place; on the other hand, necrosis in parts accessible to atmos- pheric air is prone to be followed by putrefaction, with all the dangers which attach themselves to this condition. The extent of the gangrene has an important bearing on the prognosis, as, when the causes are such as to determine a circumscribed form of the disease, life is not in danger, while the progressive form, with few exceptions, ends in death, in spite even of the most heroic treatment. The age of the patient often deter- mines the form of gangrene, as, for instance, senile gangrene is a disease of the aged, while noma, almost without exception, attacks only children. The simplest and an exceedingly common form of necrosis is what has been described by Weigert as Coagulation Necrosis.—This is essentially a cell necrosis. It is called coagulation necrosis because the tissues present the appearance of coagulated albumen, and also on account of the process resembling coagulation of the blood. Coagulation necrosis is probably identical with, or, at any rate, nearly allied to, the hyaline degeneration of Reck- linghausen and fibrinous degeneration of E. Wagner. The chemical process which results in coagulation necrosis is as yet imperfectly under- stood. Weigert maintains that the cell-protoplasm and, perhaps, all albumen-containing substances are converted by it into a substance re- sembling fibrin. Macroscopically, tissues which have undergone this form of necrosis present a yellowish or whitish appearance, and are of variable consistence. Under the microscope the cells either appear un- changed in form or their place is occupied by thread-like fragments and (175) 176 PRINCIPLES OF SURGERY. granular material. Weigert lays down as the earliest change witnessed in a cell undergoing coagulation necrosis disappearance of the nucleus, which is the case twelve to twenty-four hours after the process com- menced. Fibrin is a product of coagulation necrosis of the blood. According to Alexander Schmidt, during the coagulation of blood the colorless corpuscles disappear ; the product of their destruction is fibrin ferment and fibrino-plastic material, which, with the fibrinogen of the plasma, form fibrin. Isolated cells destroyed by coagulation necrosis exfoliate, and are transformed into a homogeneous granular substance, which, according to circumstances, is removed by absorption, or becomes encapsulated. Cell necrosis en masse is often followed by calcification, and on surfaces by ulceration. The transformation of a tubercular product into a cheesy mass is the result of coagulation necrosis. As essential conditions for coagulation necrosis to occur Weigert enumer- ates : 1. Death of tissue-cells. 2. Presence of plasma-fluids. 3. Tissues must contain coagulable substances. Coagulation necrosis is retarded by the ptomaines of pus-microbes, putrefying material, and living epi- thelial cells. An entire organ may be destroyed by coagulation necrosis. Pale infarcts after embolism are products of this change. The so-called fibrin wedges, which were formerly regarded as a decolorized blood-clot, consist of such tissues. At first the cells are normal in outline and appearance; later, the nuclei disappear and the cells break up into granular masses. In the internal organs coagulation necrosis is most frequently met with in the kidneys, spleen, typhoid deposits, tubercular lesions, the vicinity of mycotic foci, and in atheroma of the blood- vessels. In the parenchyma of organs it attacks the epithelial cells, while the connective tissue remains intact. On mucous surfaces it is represented by the diphtheritic and croupous exudations. While the chemical processes which take place in coagulation necrosis cannot as yet be explained satisfactorily, there can be no doubt that this form of necrosis is nearly always, if not always, of mycotic origin, and it must be regarded practically in the light of a bacterial necrosis. Klebs describes the same condition askaryolysis, karyorhexis, and vacuolar degeneration. He claims that early disappearance of the nucleus is not an essential, but an accidental, condition. In a case of pseudo-diphtheria Klebs found the bacilli between cells devoid of nuclei, and only in the centre of the necrotic patch did he find bacilli within the cells ; from this he concluded that karyolysis is due to the action of chemical products of the bacilli. In the second group of mycotic necroses the process differs as in typhus. Here the necrotic centre, which contains no cells, is surrounded by a zone, in which both cells and nuclei are also absent, but which contains a large number of chromatin bodies, lying free in the tissues. As these bodies PATHOLOGICAL AND CLINICAL VARIETIES OF NECROSIS. 177 are found in a location where the cells and nuclei have been destroyed, it can hardly be doubted that they represent remnants of these. Accord- ing to Wolmkom and Grassle, these bodies are liberated by rupture of the nuclear envelope. This method of cell destruction is called karyo- rhexis. A third form of cell necrosis is vacuolar degeneration, in which the change is initiated in the protoplasm itself. This must not be mis- taken for cell oedema. In vacuolar degeneration the protoplasm ruptures, and the nuclei of epithelial cells, which line a hollow viscus,are liberated, as Langhans observed in this form of cell necrosis in the kidney. The cell ruptures on account of increased intra-cellular pressure, and the process well deserves the name plasma rhexis. This form of cell destruction was formerly considered a post-mortem change. For the sake of simplicity it is advisable to substitute for the different forms of cell necrosis described by Klebs the general term, coagulation necrosis, devised by Weigert. Necrobiosis.—This is a term applied by Virchow to the spontaneous wearing out of living parts. Death of isolated cells is a physiological process as long as they are replaced by new cells of the same tissue type. Necrobiosis occurring on a more extensive scale is a pathological con- dition, and is etiologically identical with coagulation necrosis. The term can be used to signify circumscribed cell necrosis without reference to its etiology or minute morbid anatomy. Progressive Gangrene.—This form of gangrene is always of bacterial origin. The microbe most frequently found in the tissues is the strep- tococcus pyogenes. It occurs most frequently after wounds which open up a large surface of loose connective tissue, as in compound fractures, compound dislocations, excision of the breast, with removal of axillary glands and extirpation of large, fatty tumors. The streptococcus in- vades the connective-tissue spaces rapidly, somewhat after the manner of diffusion of the streptococcus through the lymphatic vessels. Much of the connective-tissue necrosis results from the direct action of the pus-microbes and its ptomaines on the cells. The necrosis of the skin is no indication of the extent of the disease in the deeper tissues. The infection is initiated by a chill, and the fever which follow resembles severe sepsis from other causes. If infection occur during the operation, or at the time of accident, the first symptoms may be looked for within forty-eight to seventy-two hours. If suppuration has occurred it is diminished with the appearance of septic infection, and the discharge becomes thinner and sanious. Lymphangitis frequently accompanies the deep-seated phlegmonous inflammation. Gangrene appears in the tissues first affected, and spreads rapidly along the connective tissue, Not only the gangrene is progressive, but also the attending septicaemia. 12 178 PRINCIPLES OF SURGERY. The larger the area of necrosis, the more extensive the field for the growth of pus-microbes and putrefactive bacteria. Progressive gangrene is an exceedingly dangerous form of infection, and unless treated by heroic measures at an early stage is sure to lead to a speedy fatal termination. Progressive Gangrene, with Emphysema.—Etiologically this form of gangrene is identical with the preceding plus secondary infection with gasogenic bacteria. The necrosed tissue answers the purpose of a nutrient medium for saprophytic micro-organisms, which not only generate gas which is diffused through the dead tissues, but the soluble toxic substances which they elaborate in the necrotic area are absorbed into the circulation,—an occurrence which gives rise to toxaemia. Em- physema almost always extends far beyond the limits of the visible gangrene, but its presence is a sure indication of the extent of the in- fection in the deep-seated tissues. Progressive gangrene, with emphy- sema, is the most fatal form of gangrene, and only in exceptional cases will the surgeon succeed in warding off a certain fatal termination by early operative interference. In both kinds of progressive gangrene the part is swollen, oedematous, the skin presenting first a livid, bluish color, which afterward shades into a greenish or reddish-black hue. Bullae, containing a reddish serum, form at points where the gangrene is spread- ing. Besides sulphuretted hydrogen, butyric and valerianic acid, am- monia sulphur, etc., are some of the many chemical products of putre- faction. The rapidity with which progressive gangrene, with and without emphysema, spreads, has led the French authors to apply to them the term gangrene foudroyante. Moist Gangrene.—Progressive gangrene is necessarily a moist gan- grene, as bacteria cannot germinate without moisture. All forms of mycotic gangrene are forms of moist gangrene. All necrosis in the interior of the body belong to this variety. The moisture of the dead tissue is due to imbibition of the oedema-fluid, and consequently moist gangrene is apt to follow vascular conditions, in which there is some im- pediment to the return of venous blood, as in cases of obstruction in a large artery, and more especialby when a large vein has become obliterated by a thrombus. Moist gangrene is attended by all the dangers incident to putrefaction. In this form of gangrene the line of demarcation is the seat of suppurative inflammation. Dry Gangrene.—In dry gangrene the dead tissue undergoes mum- mification, and on this account the soil is unfitted for the germination of putrefactive bacteria. Dry gangrene is usually the result of a trauma, the action of a chemical substance, or it follows a diminished blood- supply. In senile gangrene it follows in consequence of a gradual diminution of blood-supply, owing to atheromatous degeneration of the PATHOLOGICAL AND CLINICAL VARIETIES OF NECROSIS. 179 arteries, while the return of venous blood remains unimpaired. Dry gangrene is often an aseptic gangrene. If no infection take place with pus-microbes the line of demarcation is formed by granulation tissue, and the gangrenous part, if small, is absorbed, or if this is impossible on account of its size it is separated by the granulations. If suppuration take place this occurs at the junction of the dead with the living tissues. Dry gangrene is usually not attended by any general symptoms, and all attempts to remove the dead tissue should be postponed until the line of demarcation has formed. Senile Gangrene.—This is the gangrene of the aged, or, rather, it is the gangrene which is caused by atheromatous degeneration of the arteries. Senile marasmus, in the form of atheromatous degeneration of the arteries, may occur in persons less than 40 years of age, and is often absent in octogenarians. Senile gangrene always occurs in parts where the circulation is feeblest; consequently it usually commences in one of the toes. If the necrosed tissue remain aseptic the rapidity of the extension of the gangrene depends on the condition of the blood- vessels. It may remain limited to one toe, or it may extend from toe to toe, and then creep along the dorsum or plantar surface of the foot, or on both sides simultaneously, and extend quite rapidly to the leg as far as the knee. Usually the disease extends along the course of one of the principal arteries, and extends later to other parts of the foot in con- sequence of greater embarrassment of the arterial and venous circula- tion. If infection in the vicinity of the necrosed tissue with pus- microbes take place, a suppurative inflammation may follow senile gan- grene, which will give rise to a progressive and rapidly-fatal form of the disease. In the dry form of senile gangrene the tissues mummify, are firm, and perfectly black in color. In the moist variety the parts present the same appearances as in progressive gangrene. If a line of demarca- tion form, the separation of the dead from the living tissues requires an unusually long time, as the circulation is enfeebled to such an extent that tissue proliferation takes place very slowly. Diabetic Gangrene.—It is a well-known clinical fact that persons suffering from diabetes are very prone to be attacked by gangrene. The reasons for this are as yet unknown. Gangrene occurring from trivial causes in persons presenting the appearances of usual health, and in whom no evidences of atheromatous degeneration of the arteries can be detected, should awaken the suspicion of the existence of diabetes, and no time should be lost in making a careful examination of the urine. A strictly antidiabetic diet has often resulted in arresting further extension of the gangrene. Konig has found that after amputation for gangrene in diabetics the quantity of sugar in the urine is diminished. 180 PRINCIPLES OF SURGERY. Decubitus.—Gangraena per decubitum literally means gangrene from pressure. It occurs in consequence of pressure from splints, bandages, and the prolonged recumbent position in bed, especially in persons suffering from fracture of the spine, or acute infectious diseases attended by great impairment of the circulation. Pressure without infection is productive of dry aseptic gangrene, but usually gangrene from this source is complicated by infection with pyogenic or putrefactive bacteria, or both. If gangrene from pressure is inevitable, it is apparent that its occurrence should be met by timely precautions for the purpose of pre- venting accidental infection. Gangrene from splint pressure can be prevented by interposing between the splint and bony prominences a thick cushion of salicylized cotton. Bed-sores should be prevented by changing the position of patient frequently and protecting the parts most exposed to the ill effects of pressure with fenestrated rubber cushions, by enforcing absolute cleanliness, and by keeping the skin in a healthy condition by applications of spirituous lotions. Both in gangraena per decubitum and senile gangrene the necrosis is caused by impairment or complete suspension of the capillary circulation. Noma.—Noma, cancer aquaticus, is characterized by rapid, gan- grenous destruction of the cheek, which usually commences some distance from the lips. This disease is exceedingly rare in this country, but quite prevalent in the large cities of Europe. It attacks exclusively children, occurring most frequently between the ages of 3 and 8 years. Healthy children seldom suffer from this disease; it either appears in badly- nourished, cachectic subjects, or it occurs as a complication of some of the eruptive fevers or typhus. In reference to the etiology of noma, little is known. The almost constant occurrence of the disease in a dis- tinct part of the cheek and its limitation to one side of the face would indicate that it might be the result of some nervous disturbance. It is, however, more probable that it is a form of nicotic necrosis. A few observations on the bacterial origin of noma have been made. Lingard found in the tissues a long bacillus, which he believed was the cause of the disease. In gangrenous stomatitis in the calf, which affects this animal at particular seasons of the year, he found bacilli which are very similar in appearance to those present in noma in man. On cultivation they present characters which render them easily distinguishable from other bacteria, and on inoculation of these micro-organisms into the calf a gangrenous stomatitis is again produced. Ranke's investigations on noma led to the following conclusions: Different forms of gangrene resulting from noma can unquestionably occur spontaneously in children who have a tendency to disease of this character; that is, without infection from contact. The frequent occur. PATHOLOGICAL AND CLINICAL VARIETIES OF NECROSIS. 181 rence of noma in public institutions, and the apparent preference of the disease for localization upon the mucous membrane of the different openings of the body, suggest that the origin of it may be referred to the invasion from without of micro-organisms. In the zone of tissue contiguous to that which has undergone necrosis may be found cocci which in number appear like a pure culture. At the periphery of the necrotic zone which has been invaded by cocci the connective tissue is found in a state of active proliferation. The entire condition is suggest- ive of the tissue necrosis in field-mice, which is caused by a chain coccus, described by Koch. Up to the present time the specific nature of the cocci which Ranke found in noma tissues has not been shown. Undoubt- edly, further bacteriological research will prove that noma is a mycotic necrosis, and that the dead tissue, like in other forms of necrosis, is subsequently invaded with putrefactive bacilli. The disease commences as a circumscribed livid spot upon the surface of the mucous membrane of the mouth, and a corresponding portion of the cheek in its entirety is indurated. Soon the color of the affected mucous membrane becomes darker, and the skin, which at first presented a dusky appearance, is turned nearly black, and the epidermis is elevated in a blister, which afterward is turned into a black eschar. With the separation of the gangrenous part an opening in the cheek is left without any sign of a line of demarcation. The gangrene spreads in all directions, and, if not arrested spontaneously or by the use of energetic measures, often destroys the entire cheek. The disease is not limited to the soft tissues, but attacks the maxillary bones, often causing extensive necrosis and loss of teeth. The gangrene seldom extends beyond the median line in the lips, and the tongue usually remains free. In the majority of cases the disease is fatal. Death is preceded by symptoms of intense sepsis, with secondary septic inflammation of some of the internal organs, especially the intestines and lungs. In some cases a gangrenous affec- tion of the genital organs occurs, which in every respect resembles the affection of the cheek. In case recovery takes place, the defect caused by the necrosis has to be restored by a plastic operation. Hospital Gangrene.— Gangraena nosocomialis, ulcerative-wound diph- theritis, only occurs as an infection of wounds, and, as the name hospital gangrene indicates, is seldom met with outside of large unsanitary hos- pitals. Before wounds were treated antiseptically, it occurred as a fre- quent complication after operations or open injuries in most of the Euro- pean hospitals. It was prevalent among the wounded during the War of the Rebellion. Thanks to the labors of Lister and his followers, it has now disappeared almost completely among civilized nations. The simple fact that this dreadful disease has been almost completely expunged from the 182 PRINCIPLES OF SURGERY. oldest and most infected hospitals by the antiseptic treatment of wounds furnishes conclusive proof of its mycotic origin. Unfortunately, prac- tical bacteriology was born too late to take advantage of the numerous opportunities to study the etiology of this form of wound infection. A feature of this disease of unusual bacteriological interest is the fact that it attacks not only recent wounds, but also wounds covered by healthy granulations. A healthy granulating surface is considered as a good, if not an absolute, protection against the ordinary pathogenic bacteria which infect wounds, but the microbe of hospital gangrene manifests no such discretion. The first evidence of the appearance of hospital gangrene is the formation of a yellowish, pultaceous mass upon the surface of a recent wound or upon a granulating surface. This mass can be readily wiped away, with the exception of the lowest layers, which are firmly attached to the surface. The skin in the immediate vicinity of this deposit becomes red and inflamed, and is soon displaced by the same material. The original wound assumes a yellowish-gray appearance, and is rapidly enlarged by the extension of the destructive process. Within three days to a week the wound is enlarged to double its original size. In this the pulpous form of the disease, extension toward the depth of the wound is slow, as fascia and muscles offer considerable resistance to its progress in this direction. In the ulcerative form of hospital gangrene the wound or granulation surface becomes the seat of an ichorous discharge, and the tissues undergo rapid destruction by molecular disintegration. The ulcerative form of hospital gangrene makes more rapid progress than the pulpous. Although these two forms occur as distinct affections throughout, combinations of the two have been observed. Hospital gangrene, in preference, attacks small wounds, as punctures, the bites of leeches, abrasions, blistered surfaces, etc. Many authors have been inclined to believe that diphtheritic inflamma- tion of a wound and hospital gangrene are identical, but so far no positive proof of such identity has-been furnished. The clinical course of both of these processes is nearly the same, but etiologically and pathologically the differences are apparent. Heine claimed that he observed hospital gangrene where the wounds were infected with virus from patients suffering from genuine diphtheria, and again he saw genu- ine diphtheritic lesions of mucous membranes in patients who were exposed to the contagium of hospital gangrene. The general symptoms in the beginning of an attack of hospital gangrene are not severe. The patient complains of a loss of appetite and a general feeling of malaise. In old persons, children, and debilitated subjects, it may prove fatal with- out the occurrence of special complications. One of the great dangers which attend hospital gangrene, especially the ulcerative form, is second- PATHOLOGICAL AND CLINICAL VARIETIES OF NECROSIS. 183 ary haemorrhage. During the pulpy degeneration or molecular disinte- gration of the tissues vessels are implicated, and a sudden haemorrhage from a large vessel frequently leads to a rapidly fatal termination. The large vessels show an unusual resistance to the destructive effect of hospital gangrene, but not infrequently they give way, especially if the disease attack a stump after amputation. Septic intoxication is never so well marked in hospital gangrene as in diphtheritic affections of mucous membranes. Billroth believes that hospital gangrene is caused by a specific micro-organism which is only reproduced under certain atmospheric conditions ; hence the appearance of the disease formerly in an epidemic form. Clinical observations leave no doubt that the disease is carried from one patient to another by means of sponges, instruments, hands, etc. Perforating Ulcer of Stomach and Duodenum.—These ulcers follow circumscribed necrosis of the wall of the stomach or duodenum, caused by a diminished arterial blood-supply of a limited vascular district. That these ulcers are of vascular origin is shown by their shape and direct relation to an artery. The defect is in the form of a cone, the base being directed toward the lumen of the viscus, and the apex cor- responds with a small artery which must have been partially or com- pletely obstructed before the necrosis occurred. These ulcers are sometimes multiple, and in the stomach they are found in preference along the lesser curvature. After interruption of the arterial circula- tion the wedge-shaped ischaemic, necrosed portion is removed by the action of the gastric juice, and the ulcer is made. As perforating ulcer of the stomach or duodenum never occurs in cases of ulcerative endocar- ditis, but selects in preference young females, the causes of vascular obstruction must be of a local nature. The sphacelus shows molecular decay, but no trace of inflammation. Perforating ulcers of the stomach and intestines are of interest to the surgeon, because in case of perfora- tion their treatment has been brought within the legitimate sphere of abdominal surgery. The more frequent occurrence of perforation is prevented by circumscribed plastic peritonitis, which seals the defect or establishes an adhesion between the affected portion of the organ and some other organ. Perforating Ulcer of Foot.—This ulcer follows a localized necrosis of the foot, which is supposed to be in part, at least, the consequence of vasomotor disturbances, to which are added impediments to the circula- tion and frequently infection with pathogenic micro-organisms. This ulcer is remarkable for the regularity of its outline, looking as though a piece had been cut out with a punch. The defect corresponds to the shape of the detached necrosed tissue. The necrosis affects all of the 184 PRINCIPLES OF SURGERY. tissues of the part in which it occurs, not even sparing the bones and articulations of the foot. The dissections of Duplay, Morat, Fischer, and others leave no doubt that this strange ulcer originates from necro- sis following degeneration of the nerves of the affected region. Infec- tion with pus-microbes follows the necrosis,—an occurrence which renders the treatment more intractable. Ergotine.—One of the effects of chronic ergot intoxication is symmetrical dry gangrene. Bread made of flour containing ergot has not infrequently occasioned, in Europe, fatal epidemics, usually attended with dry gangrene. As before stated, the gangrene following the pro- longed administration of this drug is either the result of a chronic angiospasm, or of a paralytic effect of the drug on the peripheral nerves. Prognosis.—The prognosis in a case of gangrene should be based on the etiology, location, and extent of the disease which caused the gan- grene. The existence of complications must also be taken into careful consideration. Acute, rapidly-spreading gangrene, irrespective of the causes which may produce it, must always be considered as an exceed- ingly grave condition. Mycotic progressive gangrene, with and without emphysema, unless treated early and heroically, proves fatal almost with- out exception, death resulting from septicaemia. Gangrene following obliteration of the principal artery of a limb would result in death, in the majority of cases, unless a fatal sepsis is prevented by early amputa- tion. Necrosis of the entire or greater part of important internal organs is incompatible with life from the greatly diminished or com- pletely suspended function of important organs. The prognosis, so far as life is concerned, in cases of senile gangrene, is rendered exceedingly grave when the gangrene spreads rapidly, in consequence of an ascending arterial thrombosis, or thrombo-phlebitis, and life is in imminent danger when the gangrene due to diminished blood-supply is complicated by a rapidly-spreading suppurative inflammation, or if septic intoxication arise from invasion of the moist necrosed tissue with putrefactive bac- teria. The general condition and age of the patient play an important part in arriving at correct prognostic conclusions. Patients debilitated from antecedent, acute, and chronic disease are in greater peril of life than robust, healthy persons whose circulation and tissue resistance has not been impaired. Infants and the aged succumb to gangrene more readily than young adults and persons in middle life, although the gan- grene may have resulted from the same causes, reached the same extent, and inoculated the same parts. Gangrene of some important organ, as the lungs or intestines, is more dangerous to life than peripheral gan- grene. The co-existence of complications, such as diabetes, Bright's PATHOLOGICAL AND CLINICAL VARIETIES OF NECROSIS. 185 disease, tuberculosis, valvular disease of the heart, and cirrhosis of the liver will influence the prognosis correspondingly. Treatment.—The prophylactic treatment includes such measures, medicinal, dietetic, and otherwise, that are calculated to improve the blood-supply of the part threatened with gangrene, and if this has occurred, or is inevitable, to prevent putrefaction of the dead tissues. In threatened gangrene from obstruction of the main artery of a limb, the establishment of collateral circulation must be aided by placing the limb in a horizontal or slightly-elevated position, and by the external application of dry heat. In the aged suffering from premonitory periph- eral symptoms of gangrene, its actual occurrence can often be postponed by massage, rubbing the limb from the toes toward the body for ten or fifteen minutes twice daily, and by the avoidance of all causes which would bring about stasis in the enfeebled blood-vessels. The minutest lesions of the skin, as abrasions, corns, bunions, ulcers, etc., should receive careful attention in all persons the subjects of a feeble circulation, as they frequently are the starting-point of a gangrenous inflammation. Diabetic persons are exceedingly liable to be attacked with gangrene after the slightest operation or the most insignificant injury, and on this account it is advisable to examine the urine before undertaking an operation in persons presenting the faintest evidences of this disease. As most forms of gangrene are of mycotic origin, all infective atria should be protected against infection from without by thorough antiseptic precautions. The prevention of decubitus has already been referred to, and here will be only mentioned the necessity of securing for the necrosed tissues an aseptic condition by rigid cleanliness and antiseptic measures in cases where the necrosis has occurred, or where it cannot be prevented. In moist gangrene the prevention of putrefaction is a most difficult task. Where gangrene of this type has occurred, or is antici- pated, the whole surface far beyond the area involved or threatened should be rendered aseptic in the same manner as in the preparation for an operation, and the parts protected as far as possible against invasion with putrefactive bacteria by an absorbent antiseptic dressing. A few layers of gauze and a thick compress of salicylized cotton answer an excellent purpose in meeting this indication. If gangrene with putre- faction has occurred, the etiological indications for local treatment are best met by multiple incisions through the necrosed tissues and under- mined skin and the application of a compress wrung out of a 1-per- cent, solution of acetate of aluminum. If the foetor is intense, Labar- raque's solution of chlorinated soda, properly diluted, answers an admirable purpose. In gangrene with partial separation of the slough and considerable undermining, permanent irrigation with either of these 186 PRINCIPLES OF SURGERY. preparations answers the best purpose. All patients suffering from gangrene are debilitated from antecedent or concomitant causes, and consequently are badly affected by any form of the so-called antiphlo- gistic or sedative treatment. Fever is always the result of the entrance of septic material, and should therefore not be treated by antipyretics, but by local measures directed toward the primary cause. Quinine in sedative doses does more harm than good. Veratrum viride, tartar emetic, and the innumerable chemical substances which have recently been so much lauded as anti-fever remedies should never be prescribed in the treatment of fever attending necrosis. The patient's strength must be supported from the beginning by a liberal diet and the use of stimulants. If the heart's action is feeble, digitalis can be given with benefit. Quinine in tonic doses is indicated. Anorexia not dependent on high fever calls for some one or a combination of bitter tonics. The part affected must be placed at rest and in a position most favorable for the passage of the blood through the capillaries. The question of removal of gangrenous tissue and the amputation of a gangrenous limb should receive thoughtful, conscientious consider- ation before an operation is undertaken. The favorable results which have followed the operative removal of a gangrenous part after the line of demarcation had formed, and the great mortality of operations under- taken without such a positive indication, have led many good surgeons to advise postponement of all operative procedure until nature has indi- cated the site of operation. This conservative rule, however, is incom- patible with the teachings of modern surgery. We know that death in cases of rapidly-spreading gangrene is caused by septic intoxication. We also know that the cause of the septic intoxication inhabits the dead tissue, and we are also aware that the extension of the immediate cause of gangrene (vessel-obstruction), ascending thrombosis in the arteries, and ascending thrombo-phlebitis in the veins proceed from the gangre- nous part. In view of these facts, the delay of operative measures in the treatment of gangrene until the line of demarcation has been estab- lished would be to wait for something which, in the most urgent cases, never occurs. In the absence of symptoms indicating danger from septicaemia it is not only advisable, but absolutely necessary, to postpone the operative removal of the gangrenous part until nature locates the site for the operation by the formation of the line of demarcation. In aseptic dry gangrene involving parts where no formal operation is neces- sary to secure a favorable healing, later spontaneous elimination should be waited for, and after separation of the necrosed tissue the granulating surface is treated in the usual manner. In moist gangrene the dead tissue is removed as soon as partial separation has taken place bv divid- PATHOLOGICAL AND CLINICAL VARIETIES OF NECROSIS. 187 ing with scissors the more resistant structures, as fascia and tendons, after which the resulting wound is treated upon antiseptic principles. In gangrene of the extremities amputation can be done safely, and with good prospects of success, as soon as the line of demarcation has formed. In such cases it is necessary to remove as little as possible of the healthy tissue by carrying the incisions in such a manner as to leave flaps composed of healthy tissue simply long enough to cover the bone. No typical operation should be adopted, as the flaps must be made not in conformity with any text-book rules, but the condition of the limb. If the patient is febrile, and the character of the fever indicates as its origin the gangrenous part, delay, to say the least, is attended by in- creased danger of extension of the gangrene, and death from septicaemia. Such cases fare best at the hands of prudent but courageous surgeons. Procrastination in such cases is a sign of timidity or ignorance. What is to be done must be done at once. The patient and friends must be made acquainted with the dangers incident to delay, and the only pros- pect of recovery by early amputation. Consultation with one or more of the neighboring physicians is an absolute necessity in such cases. Fortified by a fair understanding with the patient and his friends, sup- ported by the advice and counsel of one or more of his colleagues, no surgeon need fear to follow the dictates of his conscience, even in the most unpromising cases. The distinguished Hueter related several cases where early amputation saved the life of patients who were in stupor from the effects of septic intoxication to such an extent that an anaes- thetic was unnecessary. Early amputation should be urged and done in all cases where life is placed in jeopardy from absorption of septic material from the gangrenous part. The results after amputation under such circumstances will always remain uncertain, because in many in- stances fatal general infection occurs soon after the development of the first general symptoms, and the local infection frequently extends to the site of operation, rendering a recurrence of gangrene in the stump a great probability. Amputation should be done, as near as possible, through healthy tissue. Much good judgment is necessary to determine this location. It is safe to maintain that the more acute the attack, the more distant should the amputation be made from the apparent boundary- line of the gangrene. In gangrene from obstruction of a large blood- vessel and in gangrene attended by ascending thrombo-phlebitis, arterial thrombosis, or both of these conditions, the line of amputation should fall through a point where the vessels are patent, otherwise a recurrence of the disease is almost sure to take place. Before the amputation is made the part to be removed should be enveloped in towels wrung out in an antiseptic solution for the purpose of preventing contamination of 188 PRINCIPLES OF SURGERY. the wound with septic material from the dead tissue. It is almost need- less to mention that Esmarch's elastic bandage should never be used, as by its application septic material might be forced into the circulation. The limb should be rendered as nearly as possible bloodless by holding it for a few minutes in a perpendicular position, when an elastic con- strictor is applied some distance above the point selected for the ampu- tation. In septic patients the parenchymatous oozing sometimes is difficult to control, but is managed most successfully by keeping the limb in the elevated position, and by making surface-pressure with a large, flat sponge or gauze compress wrung out in hot water. As most of these patients are prostrated from the effects of the disease, they are liable to suffer from shock, and measures should be resorted to to prevent this complication, or, at least, diminish its severity. For this purpose a subcutaneous injection of T^ to T|7 grain of atropia with £ grain of morphia is administered hypodermatically before the anaesthetic is dimin- ished. Two ounces of whisky or the same amount of brandy is given at the same time perorem, or, preferably, per rectum. Ether is preferable to chloroform in these cases as an anaesthetic. After the operation the most careful after-treatment is required to meet possible emergencies. Shock is treated by alcoholic stimulants, camphorated oil, musk, and coffee. If the stomach is irritable, brandy, whisky, or coffee is admin- istered by the rectum. Camphorated oil or musk is given hypoder- matically every half-hour until the patient reacts. External heat is use- ful in relieving congestions of internal organs and in stimulating the action of the heart. Amputation wounds made through tissues that are not positively known to be aseptic should always be drained; this is the more necessary if the soft tissues are oedematous. Should the tissues at the seat of amputation not present a satisfactory appearance, it is advis- able to go up higher, more especially if the vessels are obstructed by a thrombus. The fate of the patient is decided within a few days after the amputation. The most favorable symptom is a reduction of the temperature to normal within a few hours after the operation, which will be the case if the fever has been caused by a septic intoxication. With the removal of the tissues which furnished the toxic substances and the elimination of these through the secretory organs the septic symptoms subside, and if the patient has sufficient strength left to carry him over the immediate effects of the operation the prospects of recovery are good. If the patient is the subject of a progressive sepsis, the amputa- tion, in all probability, will prove powerless as a life-saving measure, as the microbes which have reached the circulation reproduce themselves with great rapidity, and death from this cause results within a few hours to several days. Prompt improvement soon after the operation, with PATHOLOGICAL AND CLINICAL VARIETIES OF NECROSIS. 189 recurrence of febrile symptoms in a few days, indicates the occurrence of gangrene in the stump. Such symptoms demand a change of dressing. If gangrene is present, all sutures are removed, a thorough local disin- fection practiced, after which the stump should be treated by constant irrigation. Reamputation at this time would, in all probability, prove fatal, and reliance on local disinfection, combined with the use of stimu- lants and tonics, is advised, with a feeble hope that these measures may become the means of limiting the extension of the disease, and of sup- porting the heart's action until the line of demarcation is established, when the surgeon's services are again required to assist nature's efforts in the elimination of the dead tissues. In noma and hospital gangrene, the infected tissues are removed with the sharp spoon, and after thorough antiseptic irrigation the actual cauter}' is applied, and the further man- agement of the wound is the same as in case of infected wounds from other causes. Chlorinated water or a solution of bromine are excellent preparations after the primary disinfection and cauterization in the treatment of these diseases. • CHAPTER VIII. Suppuration. bacteriological causes and histogenesis of suppuration. Suppuration is the most frequent termination of acute inflammation. Inflammation terminating in the formation of pus is called suppurative, both on account of its etiology and the nature of the inflammatory product. Suppuration is the process by which the morphological elements of the inflammatory product, the leucocytes, and embryonal cells are converted into pus-corpuscles. Suppurative inflammation is caused by the action upon the tissues of specific micro-organisms, the pus-microbes, and the transformation of leucocytes and embryonal cells into pus-corpuscles is accomplished by the same cause. The brilliant results which have been obtained by the antiseptic treatment of wounds made it exceedingly probable that all wound-infective diseases are caused by living micro-organisms. The probability was increased when Koch, in 1879, showed the direct connection existing between certain traumatic infective diseases in animals and the never-absent definite micro-organ- isms. It requires no longer any arguments to show, at this time, that all inflammatory wound complications, among them suppuration, are, without exception, caused by the introduction into the tissues of specific pathogenic microbes. Etiologically, most of the purulent processes constitute more of a unity than was formerly believed, and the clinical varieties are mostly determined by the intensity of the infection, the manner of localization, and the degree of resistance possessed by the tissues. The most conclusive evidence of the correctness of this asser- tion is furnished by the fact that the same streptococcus which produces a simple abscess is likewise the most frequent cause of progressive gan- grene, and of that most grave form of suppuration—pyaemia. I. HISTORY OF MICROBIC ORIGIN OF SUPPURATION. As in the case of nearly all infective diseases, years before the specific pus-microbes were discovered, living organisms were found and described in pus, and were believed to be the essential cause of suppura- tion. Twenty-five years ago Klebs discovered, in the tubuli uriniferi in cases of pyelo-nephritis following suppurative cystitis, between the (191) 192 PRINCIPLES OF SURGERY. pus-cells, small, round cocci, which he believed produced the infection. In 1872 the same author published the result of his researches, during the Franco-Prussian war, on septic-wound diseases. In this work he again referred to the micro-organisms which he had previously described, and showed that they existed in the tissues and organs—the seat of suppu- rative inflammation—before pus had formed. He also showed how these micro-organisms enter the circulation and become the direct cause of pathological conditions in distant organs. Even at that time he placed great stress on the fact that, as long as the cocci remained only in the tissues at the point of infection, they produce only local inflammation or necrosis, but as soon as they enter the circulation fever and other symp- toms of general septic infection follow. Ogston, the discoverer of pus-microbes, published the results of his observations and researches in 1881. This patient investigator examined the pus of 69 abscesses for micro-organisms, and found in 17 of them a chain coccus (streptococcus), in 31 cocci which arranged themselves in groups which resemble a bunch of grapes (staphylococcus), and in 16 both of these forms were present. In cold abscess he was unable to find either of these micro-organisms. He also ascertained that these two forms of microbes differed in their manner of diffusion in and action on the tissues, as the streptococcus, following the lymph-channels and con- nective-tissue spaces, was seen to be the cause of diffuse suppurative processes, while the staphylococcus was found by him only in abscesses which were circumscribed. Rosenbach took up the work where Ogston left it, and, as the fruit of a number of years of patient study and research, published his classical work in 1884 (" Microorganismen bei den Wundinfections Krankheiten des Meuschen," Wiesbaden, 1884). This work must serve as a basis for all future research on suppurative inflammation. Rosen- bach availed himself of the advantages offered by an improved technique in bacteriological research, cultivated the different pus-microbes upon solid nutrient media, and pointed out the difference in the macroscop- ical appearances of the cultures of the different kinds of pus-microbes, which enabled him to differentiate between them by the naked-eye appearances of the cultures upon the different nutrient substances. He discovered the staphylococcus pyogenes aureus, the micrococcus pyo- genes tenuis, and three kinds of bacillus saprogenes. Passet should be mentioned next in the long list of distinguished names of original investigators who have made the bacteriology of suppuration a special study. He discovered and described the staphy- lococcus citreus and the staphylococcus cereus albus and flavus, and from a perirectal abscess he cultivated the bacillus pyogenes foetidus. The INDIRECT CAUSES OF SUPPURATION. 193 streptococcus which he found he maintained was different from the one described by Rosenbach, as it resembled more closely the streptococcus of erysipelas, but this claim has not been substantiated by subsequent investigations. The bacillus pyocj^aneus was described "by Gessard and Charrin. The gonococcus, the specific microbe of gonorrhoea, was dis- covered by Neisser in 1879. In our own country the micro-organisms of pus have been studied by such men as Sternberg, Osier, Councilman, Ernst, and Park. II. INDIRECT CAUSES OF SUPPURATION. Inflammation produces in the tissues conditions which must be regarded as indirect causes of suppuration. These conditions favor the suppurative process by bringing the histological elements of the inflam- matory product in a position or relation to the blood-vessels which impairs or suspends their nutrient supply. In acute inflammation the connective-tissue spaces become crowded, in a short time, with the corpuscular elements of the blood, which, by their presence in such great number, cause dilatation of these spaces and pressure upon the adjacent capillary vessels, which often result in complete stasis and consequently arrest of blood-supply. In consequence of suspended nutrition arising from vascular obstruction, the leucocytes undergo coagulation necrosis and lose their power of resistance to the action of pathogenic micro- organisms. If inflammation attack the fixed tissue-cells with an in- tensity short of producing necrosis, the cells proliferate and the embryonal cells thus produced constitute another source of histological elements of the inflammatory product. If the cells are produced in excess of the capacity of the inflamed part to supply them with new blood-vessels, the local anaemia thus created places them in the same unfavorable condition as the leucocytes in the crowded connective-tissue spaces, and they are exposed to the same risk of death from malnutrition. If, as the result of rapid tissue proliferation and local ischaemia, the embryonal cell become completely detached from the matrix which produced it, it is placed in the worst condition, so far as its vitality and vegetative capacities are concerned, and it readily succumbs to the deleterious action of the pus-microbes. It can be set down as a rule that all conditions, local or general, which impair cell nutri- tion favor the suppurative process. Suppuration in inflammatory foci is always observed first where cell nutrition is most impaired, hence in the primary inflammatory product among the leucocytes most distant from capillary vessels, and among embryonal cells that have become isolated or occupy a place most remote from the vascular supply. 13 194 PRINCIPLES OF SURGERY. III. DIRECT CAUSES OF SUPPURATION. Clinical suppuration is caused by the action of pus-microbes on the leucocytes and embryonal cells, by which these cells, the morphological elements of the inflammatory product, are converted into pus-corpuscles. A number of investigators maintain that suppuration can be produced artificially in animals by injecting into the tissues certain Chemical Pyogenic Substances.—The substances which have been found to possess the property of exciting suppurative inflammation are metallic mercury, turpentine, and croton-oil. Councilman introduced turpentine and croton-oil in aseptic glass capsules into the subcutaneous connective tissue of animals under strict antiseptic precautions, and, after the wound had healed and the capsules had become encysted, rup- tured them subcutaneously. He found that both of these substances caused a circumscribed suppuration. Uskoff claimed that a consider- able quantity of indifferent substances, such as milk, olive-oil, etc., if injected subcutaneously in animals, either at once or by repeating the injection from time to time, caused suppuration, and that turpentine administered in the same manner always acted as a pyogenic agent. Orthmann, under Rosenbach's supervision, repeated UskofFs experi- ments, and, by resorting to more strict antiseptic precautions, could not verify the correctness of his conclusions in reference to the pus-pro- ducing properties of indifferent substances. His experiments with croton- oil, turpentine, and metallic mercury always resulted in inflammation and suppuration. Grawitz and de Bary ascertained that croton-oil, when injected in small quantities into the subcutaneous tissues of rabbits, caused a serous transudation or a fibrinous exudation, while larger doses acted as a caustic, and were only occasionally followed by suppuration. If they injected a mixture of pus-microbes and croton-oil it always was followed by the formation of pus. They maintained that certain chemi- cal substances, used in a definite degree of concentration, injected into the subcutaneous tissues of animals, prepared the tissues for the growth of the pus-microbes. From a later series of experiments Grawitz became more firmly convinced that aseptic turpentine, used in sufficient quantities, always causes a suppurative inflammation in the connective tissue. Inoculations of different nutrient media with pus produced by turpentine showed that it contained no pus-microbes. He also deter- mined that such chemical pus had a destructive effect on pus-microbes. This action of sterile pus he attributes not to the presence of ptomaines, but to the action of its albuminous constituents. His experiments also lead to the important observation that when gelatin cultures are over- saturated with albumen, or peptone, pus-microbes cease to multiply. Very recently Rosenbach has made a series of experiments which has DIRECT CAUSES OF SUPPURATION. 195 convinced him that the chemical pyogenic substances which have been mentioned, when injected into the tissues of animals, cause suppuration independently of the presence of pus-microbes. Among those who, from their own experimental work, have come to diametrically opposite conclusions, can be mentioned Scheuerlen, Ruigs, Nathan, and Biondi. If we consider for a moment how difficult it is, in experimenting on animals with indifferent substances and chemical irritants, to procure for the seat of injection a perfectly aseptic condition, it is not difficult to conceive that opinions still differ in regard to the immediate and essen- tial cause of suppuration. Taking it for granted that certain chemical pyogenic substances, when injected in sufficient quantities into the tissues of animals, have the power to produce suppuration, inflammation and suppuration produced in such a manner represent clinically suppurative affections. Neither the inflammation nor the suppuration following it are progressive in their character. The chemical substance produces inflammation over an area which corresponds with the extent of its diffusion, and the cellular elements of the inflammatory product are converted into pus-corpuscles by the destructive action of the substance or their protoplasm. The whole course of the artificial affection remains aseptic throughout, and the pus which is produced is aseptic and sterile, —not clinical, but chemical, pus. In suppuration, as we observe it at the bedside, the direct cause which produced it multiplies in the tissues, hence its tendency to become progressive, and from the pus which is produced the immediate and essential cause—the pus-microbes—can be cultivated. Practically, in man, the .occurrence of suppuration from the action of pyogenic chemical substances would be possible only on the surface of the body. Pus-Microbes.—That the pus-microbes are the immediate and essen- tial cause of suppurative inflammation and pus formation has been well established by clinical observation and experimentation. Clinical experi- ence during the last twenty years has shown be}ond all doubt that sup- puration in wounds can be prevented by measures which are calculated to remove, destroy, and exclude pathogenic micro-organisms from with- out. Rosenbach found that in dogs and rabbits a small quantity of a pure culture of the staphylococcus pyogenes aureus injected under the skin produced a most violent suppurative inflammation ; cultures of the staphylococcus pyogenes albus had the same effect. Cultures of the streptococcus pyogenes produced only slight inflammation in rabbits, while they proved very fatal in mice. Passet took a pure culture of the staphylococcus pyogenes aureus the size of a pea, grown upon potato, and mixed it with 1 cubic centimetre of distilled water. Of this mixture he injected under the skin of a mouse 0.1 cubic centimetre; the animal 196 PRINCIPLES OF SURGERY. recovered. Another mouse was treated in the same manner, but 0.04 cubic centimetre of a liquefied-gelatin culture was used, and this animal died in eighteen hours. Cocci were found in the blood. In rabbits and dogs a subcutaneous injection of 1 cubic centimetre of liquid-gela- tin culture of the aureus usually produced an abscess at the point of inoculation. If the dose was increased to 5 cubic centimetres of the same culture the animals died in from eighteen to twenty hours. At the same time a local inflammation was found at the site of inoculation. In all of the fatal cases the pus-microbe was found in the blood. Of the culture of the streptococcus pyogenes it was found necessary to inject a considerable quantity in order to produce suppuration. Liquefied-gela- tin cultures of the staphylococcus pyogenes aureus and albus, in doses of 1 cubic centimetre, injected into the abdominal cavity of rabbits, were well tolerated, and death was produced only when the dose was increased to from 4 to 6 cubic centimetres. Injection of cultures of the strepto- coccus pj^ogenes into the peritoneal cavity was even better tolerated, and usually had to be repeated several times before the animal died of septic peritonitis. A needle dipped into a culture of pus-microbes he could insert into points without causing suppuration; but the injection of from 0.3 to 0.5 cubic centimetre of a mixture of pus-microbes, sus- pended in distilled water, into the hip-joint of rabbits, was followed by suppurative arthritis, rupture of the capsule, and diffuse para-articular phlegmonous inflammation and suppuration, and often death of the animal. Injection of 1 or 2 drops of a liquefied-gelatin culture of the staphylococcus pyogenes aureus, or. albus, into a vein of a rabbit did not produce any serious disturbance, but if the dose was increased to from 0.5 to 1 cubic centimetre, it, as a rule, caused fatal disease. In such cases, multiple suppurating foci were found in the kidneys, liver, spleen, and lungs, with pleuritis and peritoneal effusions, pericarditis, and myocarditis ; also serous and purulent effusions into joints and muscular abscesses. The effect of inoculation with pus-microbes in man is the same as in animals. Garre made a superficial abrasion on one of his fingers, and applied a pure culture of the stapl^lococcus pyogenes aureus; the only symptom observed was a slight redness eighteen to twenty-four hours after the inoculation. He then made three small incisions, and inocu- lated himself with a larger quantity of the culture, which was followed by superficial suppuration. Fehleissen repeated the same experiments upon himself with cultures of different kinds of pus-microbes, and, if he succeeded in causing suppuration, this was alwaj^s slight. He also found minute doses, administered subcutaneously, harmless ; while larger doses, suspended in water, almost without exception caused abscesses, and, in DIRECT CAUSES OF SUPPURATION. 197 animals, very large doses produced death from sepsis before suppuration could take place. Brockhardt introduced a trace of a mixed culture of staphylococcus aureus and albus into the cutis of his left fore-finger; after forty-eight hours a small abscess had formed, which was opened, and in the pus the same microbes were demonstrated. Bumm injected a pure culture of the yellow staphylococcus into the subcutaneous tissue of his own arm, and into the arms of two other persons. In each in- stance an abscess developed, which varied from the size of a pigeon's egg to that of a man's fist, according to the time which elapsed before they were opened. In the pus of these abscesses the same pus-microbe which had been injected was found. The above observations are con- clusive in showing that pus-microbes can be cultivated from the pus of every acute abscess, and that, in man and animals, the injection of a sufficient quantity of a pure culture into the tissues is followed by sup- puration ; and thus far positive proof has been furnished of the direct etiological relationship Avhich exists between pus-microbes and suppura- tion. Rhine has recently published an account of his experiments, and his results are somewhat in conflict with the authorities quoted above. He frequently failed to produce suppurative inflammation, even when he injected a large quantity of a pure culture, and by repeating the injec- tion from time to time. He is of the opinion that, when the absorptive capacity of the tissues is not diminished, the pus-microbes are removed too rapidly to produce their pathogenic effect. The effect of inoculation with pus-microbes will, of course, always vary, according to the quantity of the microbes and the local and general susceptibility of the animal experimented on. Watson Cheyne has shown most conclusively that the number of bacteria introduced greatly modifies not only the intensity of the symptoms, but also the character of the disease. His experiments were made with cultivations of Hauser's proteus vulgaris. He estimated that -^ cubic centimetre of an undiluted culture of this microbe con- tains 225,000,000 bacteria, and when this quantity was injected into the muscular tissue of a rabbit it produced speedy death. A quantity of the same culture corresponding with ^ cubic centimetre, administered in the same manner, caused an extensive abscess at the point of injection, and death of the animal in six or eight weeks. Doses of less than 5^ cubic centimetre produced no effect,—in fact, doses of less than ^ to T^ cubic centimetre, or, in other words, fewer than about 18,000,000 bac- teria, seldom caused any positive result. The same author found that in the case of the staphylococcus pyogenes aureus it was necessary to inject something like 1,000,000,000 cocci into the muscles of rabbits, in order to cause a rapidly-fatal result, while 250,000,000 produced a small abscess. In the case of the tetanus bacillus, death did not occur in 198 PRINCIPLES OF SURGERY. rabbits when fewer than 1000 bacilli were introduced. He believes, as does Rinne, that the action of the preformed ptomaines on the tissues modifies the result. It is, therefore, probable that, in the experiments in which injection of pus-microbes did not produce suppuration, an insufficient number of active microbes were used, and that where indif- ferent substances and chemical irritants caused suppuration the implanted or injected material was contaminated, or that infection at the point of injection occurred through the wound, or subsequently through the cir- culation. The latter method of injection should always be borne in mind in cases w.here the presence of an aseptic substance in the tissues has apparently been the cause of suppuration. The tissues altered by the action of chemical irritants constitute a foreign substance, which may determine localization of microbes floating in the circulation, while, at the same time, the chemical alterations which they have caused in the tissues have prepared a favorable soil for their reproduction. Of late a number of pathologists have gone one step farther, and maintain that pus-microbes are not the direct cause of suppuration, but that their presence is essential for the production of ptomaines, to which they attribute pyogenic properties. If certain pyogenic, aseptic, chemical substances can convert living cellular elements into pus-corpuscles, as has been asserted upon good authority, we should naturally expect that chemical substances produced by pus-microbes in inflamed tissue might possess the same pathogenic property, and we will briefly consider what is known in reference to Ptomaines of Pus-Microbes as a Cause of Suppuration.—Grawitz and de Bary, after detailing the results of their experiments with injections of chemical irritants in their investigations on pus formation, give an account of their experiments with the ptomaines of pus-microbes. They maintain that these ptomaines, like chemical irritants,prepare the tissues for the growth and reproduction of pus-microbes. The action of these substances can be studied by injecting sterilized cultures of pus-microbes, in which the only active agents could be the preformed toxines. These observers injected 4 cubic centimetres of a sterilized culture of the staphylococcus pyogenes aureus under the skin of a dog, with the effect of causing suppuration. The pus was examined for microbes, but none were found. They assert that the presence of oxygen is of the greatest importance in the production of ptomaines. Grawitz experimented also with a pure preparation of cadaverin, prepared by Brieger from bacteria. Cadaverin is a colorless fluid, the chemical formula of which is identical with pentamethylendiomin; a 2^-per-cent. solution of this substance destroyed the staphylococcus pyogenes aureus in an hour, and a small quantity added to a culture of pus-microbes arrested further growth. DIRECT CAUSES OF SUPPURATION. 199 A solution absolutely free from microbes, injected under the skin of animals, according to strength and quantity used, produced cauterization or inflammation, terminating in suppuration or inflammatory oedema, followed by resolution and absorption. The pus produced by cadaverin contained no bacteria as long as the skin remained intact. The injection of a mixture of a solution of cadaverin and pus-microbes was always followed by a progressive phlegmonous inflammation. Schenerlen was the first to study the local action of ptomaines on the tissues. He intro- duced into the subcutaneous connective tissue of rabbits aseptic glass capsules containing sterilized infusion of meat. The wounds healed by primary union. As soon as the capsules had become encysted, he broke off both ends of the capsule, so as to saturate the tissues in its imme- diate vicinity with the fluid it contained. Three to six weeks after implantation of the capsule an incision was made down to it, and the parts submitted to a thorough examination. The ends of the capsule were always found to contain a few drops of thin, yellow pus, which, under the microscope, showed all the characteristic appearances of that fluid. No inflammation of the surrounding tissues. Cultivation experi- ments with the pus yielded negative results. It is evident that suppura- tion in these instances was caused by the action of the preformed ptomaines on the leucocytes and embryonal cells, and that its extension did not occur because the cause did not multiply in the tissues. In about twenty experiments the pus was found only inside of the cap- sule. Weigert has repeatedly shown that the difference between a purulent and fibrinous exudation can be readily demonstrated, as the former does not coagulate, although white corpuscles and plasma may be present. Klemperer believes that this difference is due to previous destruction of fibrogen in the pus by the pus-microbes. The putrid-meat infusion used by Schenerlen caused limited suppuration, and on that account it must also have possessed the property to prevent coagulation. To prove this he made the following experiment: The abdomen of a rabbit was opened while the animal was under the influence of chloroform, and blood was drawn directly from the aorta into a glass tube containing putrid extract of meat. As the fluids gradually became mixed the blood assumed a brownish-red color; coagulation did not occur for hours and days, while in the control experiments, with solution of salt, the blood coagulated firmly after the lapse of a few minutes. He next made thirty cultures of the staphylococcus pyogenes aureus upon agar-agar gelatin, and the same number of cultures of the albus, and after completion of their growth, fourteen days later, he sterilized them with boiling water, and, after shaking the fluid, removed the cultures and boiled them for a 200 PRINCIPLES OF SURGERY. few minutes, and finally filtered them; he thus obtained about 150 cubic centimetres of a light-yellow fluid. This was reduced to 8 cubic centi- metres by boiling; before using, the fluid was again filtered. The filtrate was put in capsules, and after sealing their ends hermetically they were inserted into the subcutaneous connective tissue of animals with the same care as in the preceding experiments. The suppuration which followed the breaking of the glass capsule in these cases was again found to be limited to the space with the capsule, being caused by action of the preformed ptomaines on leucocytes and embryonal cells, which found their way into the interior of the glass capsule. The cadaverin and putrescin, two ptomaines prepared by Brieger, were next experimented with in the same manner. In preventing coagu- lation the results were even more striking than with the former sub- stances. These experiments leave no doubt that ptomaines derived from pyogenic bacteria produce a chemical action on leucocytes and embryonal cells by which they are converted into pus-corpuscles. The suppuration thus produced, however, never extends beyond the tissues which are brought in contact with them, and, therefore, always remains circum- scribed. In this respect the results of the experiments just cited do not correspond with suppuration as we observe it in practice, as here from the same causes, and apparently often under the same conditions, the process presents the greatest possible variations in reference to its intensity and extent. In one case the suppuration remains circumscribed, result- ing in a furuncle ; in others the regional infection is more extensive, and a diffuse, phlegmonous inflammation is the result; while in the third class the local infection leads to general systemic invasion, and the patient dies of sepsis or pyaemia. The clinical form of suppuration is noted for the progressive character of the infection, which is due to the reproduction of pus-microbes in the tissues and the production of ptomaines pro- portionate in amount to the number of microbes present, and, perhaps, also modified to a certain extent by the character of the soil. Practi- cally, the matter remains the same as before it was known that the ptomaines produced in the tissues by the pyogenic micro-organisms could cause suppuration, as pus-microbes must be introduced into the organism, where they must also find an appropriate soil for their repro- duction, before ptomaines can be produced in sufficient quantity to account for the occurrence of the clinical forms of suppuration. To the practical surgeon it is immaterial to know whether the transformation of leucocytes and embryonal cells is brought about by the direct action of pus-microbes or by the ptomaines which they produce in the tissues. Description and Specific Action of the Different Pus-Microbes.—The microbes which, when present in sufficient number in the tissues, excite DIRECT CAUSES OF SUPPURATION. 201 suppurative inflammation are called pus-microbes. Their effect on the cellular elements of the inflammatory product is a specific one, convert- ing them into pus-corpuscles. Only such microbes will be described here which have been cultivated from pus, and the specific action of which has been demonstrated experimentally. I. Staphylococcus Pyogenes Aureus.—The yellow staphylococcus is the microbe most frequently present in acute abscesses. Under the microscope it cannot be distinguished from the staphylococcus pyogenes albus. It is easily cultivated upon gelatin, agar-agar, coagulated blood- serum, and potato. The culture liquefies gelatin. It grows best at a temperature approaching that of the blood, but can be cultivated at 30° C. It peptonizes albumen and coagulates milk. The culture grows in the track of the needle and upon the surface of the nutrient medium. The gold-yellow color of the culture appears only if the colony is ex- posed to atmospheric air. Cultures upon gelatin or agar-agar retain their virulence for a year or more. This coccus is met | with frequently in acute circumscribed abscesses, osteo- '$t§l!>°& 2 myelitis, pyaemia, and ulcerative endocarditis. $> jty 2. Staphylococcus Pyogenes Albus.—This pus- :°&|§s»* .3r the action of a ferment, and that the chemical changes brought about in this manner occasion rise in temperature, while the products of oxidation are eliminated through the kidne37s. Riedel found, in many cases of simple subcutaneous fracture, albumen in the urine during the first three or four days, and the urine alwa3's contained brown masses, which he regarded as products of the red blood-corpuscles. Worm Miiller found invariabty, after transfusion of blood, a considerable increase of urates in the urine. The occurrence of fever after the introduction of foreign aseptic substances into the cir- culation, can only be explained upon the supposition that they destroy red and white corpuscles in the blood, and that in this manner fibrin ferment, the cause of the fever, is generated, 314 PRINCIPLES OF SURGERY. Symptoms and Diagnosis.—Fermentation fever is prone to follow an operation or injury if antiseptic solutions are allowed to remain in the wound, thereby causing necrosis of the superficial tissues, or where, after closure of the wound, parenhymatous oozing gives rise to tension,—a local condition which forces the products of coagulation necrosis into the circulation. As not all extravasations of blood give rise to fever, we must take it for granted that when fever is not produced its absence is owing either to an absence of fibrin ferment or the existence of local conditions which prevent its absorption. From my own observations I am convinced that the amount of extravasated blood holds no relation whatever to the frequency of its occurrence or its intensity. A small extravasation under high pressure is more frequently the cause of fermen- tation than a large blood-clot in a location less favorable to the absorp- tion of fibrin ferment. Fermentation fever makes its appearance within a few hours after an injury or operation, and, as a rule, it is not preceded by a chill. The temperature rapidly reaches its maximum, which varies from 100° to 104° F., and remains, without much variation, in the vicinity of the maximum height, to drop suddenly to normal at the end of the first to the third day. The pulse is correspondingly increased in frequency during the febrile attack. The sensorium remains intact, the appetite is not much disturbed, and none of the subjective symptoms are proportionate to the severity of the febrile disturbance. Patients with a high temperature feel so well that, if their wounds permit it, they will insist in walking around and will attend to their business, contrary to the advice of the attending surgeon. The most important diagnostic features of fermentation fever are its early onset after an injury or operation, and its spontaneous subsidence in from one to three days. As the disease is caused by the introduction of phlogistic substances from a local focus, and propagated by intra-vascular chemical changes, it is uninfluenced by any form of medication. The fever subsides sponta- neously upon cessation of the primary cause, and with the elimination through the kidneys of the products of intra-vascular chemical changes. As the remaining forms of sepsis usually appear at a time when fermen- tation fever has run its course, the differential diagnosis presents no great difficulties. The treatment of fermentation fever is entirely of a prophylactic nature. The prophylactic measures consist in a careful haemostasis, and in cases where parenchymatous oozing, from the nature of a wound or the anatomical structure of the tissues, is to be expected, the prevention of the accumulation of the primary wound-secretion by efficient drainage. Fermentation fever must be included among the septic diseases, as the fibrin ferment acts as a toxic substance in the same manner as the toxines CLINICAL FORMS OF SEPTICAEMIA. 315 elaborated by septic micro-organisms. Future research may yet demon- strate that even this, the most harmless form of septicaemia, is not an aseptic fever, but that it is caused by pathogenic micro-organisms, either too few in number or not of sufficient potency to produce the graver forms of the disease. (b) Sapraemia.—This word was devised by Mathews Duncan to include a form of septicaemia resulting from the absorption of the products of putrefaction. Sapraemia is the typical form of septic intoxication, as it is always caused by the introduction into the circulation of preformed toxines or ptomaines elaborated in dead tissues by putrefactive bacteria. It is closeby allied to fermentation fever, as the symptoms are never in- tensified after the removal of the primary cause, but, as a rule, subside promptly after this has been accomplished. As sapraemia never occurs without putrefaction of necrosed tissue, and as putrefaction never takes place without infection with putrefactive bacteria, it becomes necessary 1 to consider briefly the micro-organisms which are known to cause the clinical forms of putrefaction. 8sl %SJ l§/,j% 3 Fig. 72. Fig. 73. Fig. 74. Figs. 72, 73, and 74.—Bacillus Saprogenes 1, 2, 3. 962 :1. (Rosenbach.) Bacilli of Putrefaction.—The bacilli of putrefaction exercise their pathogenic qualities only in dead tissue exposed to the atmospheric air. Clinically they are therefore present in the products of coagulation necrosis, or as a secondary infection in tissues destined by other micro- organisms. Most of them possess gasogenic properties. Rosenbach discovered, in different fetid secretions, three forms of bacilli which he designated respectively bacillus saprogenes 1, 2, 3. Bacillus Saprogenes 1.—A comparatively large bacillus, which mul- tiplies by end spores, which, however, grow only from one end of the bacillus. On nutrient agar-agar the bacillus grows in the form of an irregular sinuous streak, with a mucilaginous appearance. The bacilli grow readily also in blood-serum, and all cultures emit the odor of decom- posing kitchen refuse. Albumen or meat acted upon by a culture of this bacillus undergoes rapid putrefaction if exposed to atmospheric air, but if air is excluded the action of the microbes upon these substances is very slight. Cultures injected into healthy tissues and joints are harmless. 316 PRINCIPLES OF SURGERY. Bacillus Saprogenes 2.—This bacillus was isolated by Rosenbach from fetid sweat. The rods are shorter and thinner than the preceding ones. This bacillus develops very rapidly on agar-agar, forming transparent drops, which become gray. The culture yields a characteristic fetid odor, similar to the last. Cultures of this bacillus injected into the knee-joint and pleural cavity of rabbits caused acute suppurative inflammation and death. Bacillus Saprogenes 3.—This bacillus was discovered by Rosenbach in the pus of 2 cases of osteomyelitis with septic manifestations complicating compound fracture. Cultivated on nutrient agar-agar, an ash-gray, almost liquid culture is developed, with a strong, characteristic odor of putrefaction. Injected Fig. 75.—Proteus Vulgaris. 285:1. Swarming Islets. (Hauser.) into the knee-joint or abdomen of a rabbit, an opaque, yellowish-green infiltration resulted. Proteus Vulgaris.—This and the following species have been recently described by Hauser as present in putrefying meat-infusions, and as being intimately connected with the process of putrefaction. As the name indicates, these bacteria are capable of changing their form during their development. The different species of proteus have been described as coccoid, bacteroid, spindle-shaped, and spiralinar, on account of the ever-changing form they assume during their growth. In proteus vul- garis the bacteria vary greatly in size. Many of the rods are actively motile, and cultivated upon nutrient gelatin they convert it into a turbid, grayish-white liquid. If cultivated in a capsule containing 5 per cent, of nutrient gelatin, a few hours after inoculation, the most characteristic movements of the individual bacilli CLINICAL FORMS OF SEPTICEMIA. 317 are observed on the surface of the gelatin, although at this early stage no liquefaction can be detected. The movements are not observed if the nutrient medium contains 10 per cent, of gelatin. Spore formation was never observed. Injected subcutaneously in small doses, no results were obtained; larger doses sometimes caused circumscribed abscess at the point of injection. Intra-venous injection of a large dose produced toxic symptoms in rabbits and guinea-pigs, and these were not modified by using the filtrate of a liquefied culture, showing that the toxic sub- stance was held in solution. Proteus Mirabilis.—Rods varying greatly in length, sometimes so short that they appear like cocci, at others of considerable length. The rods occur singly and in zoogloea, and sometimes in tetrads, pairs, chains, or as short rods in twos, resembling bacterium termo,—in fact, in all conceivable transition forms. Cultivated on nutrient gelatin they form a thick, whitish layer, in concentric circles, which in time lique- fies the medium. Similar movements are observed in capsule-cultivations as with proteus vulgaris. The patho- genic properties of the mirabilis are the same as those of vulgaris. Proteus Zenkeri.—Rods about four times as long as wide, in two, like bacterium termo. Cultivated on nutrient gelatin no liquefaction re- sults, but a thick, whitish-gray la37er is formed, with sloping margins. The bacilli are motile, and the same phe- nomena are observed on the solid medium as in the other forms. Spirilli and spiralinar forms are seldom seen. Gelatin and blood-serum cultures emit no fetid odor, but meat-infusion undergoes rapid putrefaction and yields the usual fetid odor. The pathogenic qualities are the same as those of the other species of proteus. As the microbes of putrefaction, which have first been described, possess limited or no pathogenic qualities when introduced into healthy tissue, it is evident that their toxic effect is caused by a soluble substance which they produce when they find their wa37 into dead tissue exposed to atmospheric air. This leads us to a consideration of the Ptomaines.—Ptomaine is a term used to designate certain toxic substances (resembling alkaloids) which are produced during the process Fig. 76.—Proteus Mirabilis. 285:1. Swarming Islets. (Hauser.) 318 PRINCIPLES OF SURGERY. of putrefaction. Gautier has shown that in dead animal tissues proc- esses of putrefactive decomposition set in, by which certain alkaloids are elaborated from albuminous substances, which have been called ptomaines by Selmi. In the latter part of the seventeenth century Kircher and Leuwenhoek claimed that putrid substances contained minute microscopical worms, which caused the putrefaction. In 1820 Kerner pointed out the resemblance between the symptoms of poisoning by sausages and by atropine. He was thus the first to raise the sus- picion that toxic alkaloids were formed through the decomposition of albumen. In 1856 Panum showed that the inflammatory change which occurs in the intestinal mucous membrane of animals fed on putrid infusions is due to a chemical poison, which remained unaffected by boiling for a long time ; and his conclusion that the toxic substance contained in putrid fluids was of a chemical nature was confirmed by Weber, Hemmer, Schweninger, Stich, and Thiersch. In 1875 W. B. Fig. 77.—Involution Forms of Proteus Mirabilis. 524:1. (Hauser.) Richardson isolated a toxic substance, which he called " septine," from the inflammatory transudation in the peritoneal cavity of a person that had died of pyaemia. With this substance he successfully infected animals. He also found that this substance could be made to combine with acids, so as to form salts, without losing its toxic qualities. Berg- mann and Schmiedeberg isolated a crystalline poison from decomposing yeast, to which they gave the name of "sepsin." This substance, when injected into the subcutaneous tissue or venous circulation in animals, produced well-marked symptoms of septic intoxication ; the intensity of the S3^mptoms were found to vary with the amount of the substance in- jected. Zuelzer and Sonnenschein obtained, from macerated dead bodies and from putrid meat-infusions, small quantities of a crystallizable sub- stance which exhibited the reactions of an alkaloid, and had a physio- logical action like atropine, dilating the pupil, paralyzing the muscular fibres of the intestine, and increasing the rapidity of the pulse. In 1857, Pasteur made the important discovery that specific micro-organisms CLINICAL FORMS OF SEPTICEMIA. 319 are the cause of the various forms of fermentation and putrefaction. No discovery, perhaps, attracted such universal attention as Pasteur's theory of fermentation. This theory was strengthened somewhat later by Lemaire's observation, that all fermentative changes in fluids are sus- pended on the addition to the fluids of phenic acid, from which he concluded that fermentation must be due to living organisms. Next came the carefully-conducted experiments of Lister, who showed that air is deprived of its action in causing putrefaction of organic substances if it is passed through a filter, or if the fluids are placed in an open vessel with the mouth of the vessel so arranged that dust cannot reach the fluid by gravitation. Lister's great life-work, antiseptic surgery, that has created a new epoch in the history of medicine and surgery, is based upon what then was still a theory, that inflammation, suppuration, and septic infection of wounds are caused by living specific micro-organisms. Selmi discov- ered ptomaines in an exhumed body, in 1872. The ptomaines isolated by him were volatile alkaloids. Gautier, independently of Selmi, and about the same time, made the same observations, but believed that the toxic substances were volatile, and that in their action they resembled the narcotics, morphia and atropia, and were more nearly allied to the alkaloid extracted from poisonous mushrooms. Semmer gives an account of the action of septic substances as studied experimentally b37 Guttmann, of Dorpat. The experiments were made with putrid substances, products of inflammation, septic blood, and cultivations of septic bacteria. These researches showed that a chemical poison is formed in putrefying substances, and that a certain quantity of such poison produces symptoms of sepsis and death in animals. The blood of animals killed with such putrid poisons was found to possess no infective qualities, and the usual putrefactive bac- teria were destroyed in the blood, and onty appear again after the death of the animal. It was claimed, even at that time, that the bacteria elaborate the poison, as experiments made with cultures grown outside the bod3r produced the same effect. Another conclusion arrived at was that putrid substances administered subcutaneousby may produce gangrene, phlegmonous inflammation, or erysipelas, according to the stage of putrefaction, temperature, culture-soil, etc. The infective material was never found in the blood, but alwa37s in the products of inflammation. It was clearly stated that true septicaemia is alwa37s preceded by a stage of incubation, and that its contagium is destroyed by boiling, putrefaction, and germicides. Bergmann and Augerer produced a condition in animals resembling septicaemia, by injecting into the circulation pepsin, pancreatin, and 320 PRINCIPLES OF SURGERY. trypsin. When death occurred after intra-vascular injections of these ferments, fibrinous deposits were found in the heart and pulmonary vessels. These experiments were, therefore, confirmatory of the obser- vations previously made by Edelberg and Birck, who had shown that the injection of putrid substances into the circulation materially increased the free fibrin ferment in the circulating blood. Blumberg concluded, from his numerous experiments on animals, that the s3Tmptoms which follow an injection of putrescent material into the circulation are not always constant; that, in fact, extreme prostra- tion, high temperature, rapid pulse and respiration are the only constant symptoms found. The same author also confirmed the statement that the blood of patients dying from putrid intoxication contained no micro-organisms. Samuel maintains that putrid fluids, from the second day until the eighth month of putrefaction, act differently, and divides their action according to this supposition into three stages : 1. Phlogo- genie, in which they produce only inflammation. 2. Septogenic, in which they produce in the living organism putrefactive processes. 3. Pyogenic, in which they cause only suppuration, having lost in the meantime their other pathogenic qualities. Mikulicz found that putrid fluids, according as they are free from bacteria or contain more or less of putrefactive microbes, will produce a slight inflammation, a suppurative inflammation, or a progressive phleg- monous inflammation. Frankel detected but few micrococci in the blood of septicaemic patients, and observed that the3r greatty increased after death ; but, after the lapse of some further time, altogether disappeared, thus also confirming a fact previousby known, that putrefaction destined septic microbes. These observations may tend to harmonize the dis- crepancy of opinion, growing out of the different results obtained by different experimenters, by injections of putrid substances, as some of the fluids may have contained an abundance of living micro-organisms, while others may have been rendered sterile by age, owing to advanced putrefactive changes. Brieger and Maas have rendered valuable service in the chemical isolation of ptomaines, or, as Brieger calls them, toxines, from putrid substances, and the results of their inoculation experiments established more firmly the fact of putrid intoxication by these soluble alkaloid substances. The number of bacteria in rabbits killed b3r septic infection is so great that death may ensue from simple mechanical causes, while in fatal cases of sepsis in man the number is often so small that it seems natural to suppose that the micro-organisms are capable of pro- ducing some poisonous substance, which destroys the patient before they have time to multiply to the extent observed in septicaemia in rabbits and mice. CLINICAL FORMS OF SEPTICAEMIA. 321 Rinne asserts that the chemical products of pus-microbes alone, as well as sterilized putrid fluids, never produce metastasis. He sterilized fluid cultures of the staphylococcus pyogenes aureus after filtration, and injected directly into the blood-vessels of rabbits as much as 4 grammes of this fluid, and in dogs increased the dose to 14 grammes. Many of the animals showed slight symptoms of septic intoxication, somnolence, diarrhoea, and collapse. By using still larger doses the symptoms were intensified and the animals died from well-marked symptoms of septic intoxication. Metastatic abscesses were never found in these cases. The same author has recentby published some very interesting observa- tions on the immediate cause of death in rabbits inoculated with a pure culture of Koch-Gaffky's bacillus. The animals were inoculated at the base of the ear, and immediately after death the ptomaines were isolated from the tissues by Brieger's method. In every instance he obtained a substance called metli37lguanidin, which on chemical analysis was shown to consist of the formula C2H7N3. When this substance was injected into rabbits it produced symptoms of septic intoxication which resembled, in every particular, those produced by the injection of pure cultures obtained from septicaemic rabbits. As methylguanidin could not be produced from the cadavers by the same method, Hoffa naturally came to the conclusion that it was a product of the bacilli, and that death was to be attributed to the production of this toxic substance in the tissues of the infected animals by the specific action of the bacilli. The source of methylguanidin in the body is kreatin, and the bacteria must possess the property of oxidation, as kreatin is transformed into methylguanidin only by oxidation. Brieger has isolated from human corpses a different set of toxic alkaloids, one of which he calls " cadav- erin" and the other " putrescin," which are but feeble poisons ; while two others, " madeleine " and " sepsin," which are produced later on in the decomposition, are much more powerful poisons, causing paralysis and death. From decomposing albuminous substances he has obtained many other well-defined chemical bodies, as well as some substances to which no names have 37et been given. Bourget isolated several toxic bases from the viscera of a woman who had died of puerperal sepsis. He also obtained from the urine from patients suffering from the same disease similar toxic bases, which killed frogs and guinea-pigs, when administered by injection, showing that the toxic substances formed during life, and that they are elimi- nated through the kidne3'S. The experimental and clinical researches to which I have referred above show conclusively that septic intoxication is caused by the presence of dead tissue in the body in a state of putrefaction, from the presence 21 322 PRINCIPLES OF SURGERY. of putrefactive bacilli, and that the immediate cause of the intoxication is the absorption of preformed ptomaines from such a local focus of putrefaction. Symptoms and Diagnosis.—Septic intoxication sufficient in severity to give rise to grave general disturbances is usually initiated by a chill, or at least b3r a sensation of chilliness, followed by a continued form of fever, the temperature rapidly increasing to 102° to 104° F., with slight morning remissions. The character of the pulse furnishes the most reli- able information in regard to the intensity of the intoxication. All ptomaines of putrefactive bacteria exert a depressing influence on the heart; hence the force and frequency of the pulse furnish important diagnostic and prognostic evidences. The pulse is always soft and com- pressible,—qualities which indicate diminished intra-vascular pressure, resulting from an enfeebled vis a tergo. Complete loss of appetite, vomiting, and diarrhoea are almost constant symptoms in grave cases. The tongue is usually furred, dry, and, in severe cases, presents the "dried-beef" appearance. The urine is scanty and heavily loaded with urates. Headache is often complained of in the beginning of the attack. Delirium, restlessness, insomnia, are symptoms which denote approach- ing danger. Subsultus, dilatation of pupils, clammy perspiration, livid appearance of visible mucous membranes, low-muttering delirium, invol- untary discharges, coldness of the extremities, fluttering, and feeble pulse precede death from septic intoxication. One of the most important elements in the diagnosis is the detection of a local focus of putrefaction. As the putrefaction always occurs in parts of the bod3r exposed to the atmospheric air, its existence can readily be ascertained by the sense of smell. The intensity of the foetor of the gases produced by the putrefac- tive bacteria varies greatly, but the smell is always suggestive of decom- posing meat or kitchen refuse. The impression is quite prevalent, not only among the laity, but also in the profession, that the local lesions which cause septicaemia always emit a fetid odor. This is a grave mis- take. Foetor is associatad with putrefaction, and as such is suggestive of sapraemia, and not true progressive sepsis. The latter may be combined with sapraemia, but when it occurs independently of this no bad smell can be detected, and yet it is the most fatal form of sepsis. In reference to the differential diagnosis between sapraemia, fermentation fever, and septic infection, it must be remembered that septic intoxication can only occur from putrefaction, and therefore three conditions must invariably be present in the etiology of this form of sepsis : 1. Dead tissue. 2. Infection of this dead tissue with putrefactive bacteria. 3. A sufficient length of time must have elapsed since the injur37 or operation for the putrefactive bacteria to produce a toxic quantity of ptomaines to cause CLINICAL FORMS OF SEPTICEMIA. 323 symptoms of intoxication. The dead tissue may be a blood-clot in a wound, around the fragments of a compound fracture, or in the interior of the uterus; it may be tissue devitalized by a trauma, heat or cold, the action of chemical substances, or the action of bacteria other than putrefactive; or it may be detached, retained fragments of placental tissue. That such dead tissue has become the seat of infection with putrefactive bacteria can be ascertained by the presence of foetor and bubbles of gas. At the temperature of the body putrefaction progresses very rapidly ; but a differential diagnosis can generally be made without much difficulty, between sapraemia and fermentation fever, by the time which has elapsed between the injury or operation and the manifesta- tion of the first symptoms of septic intoxication. Fermentation fever appears within a few hours, certainly always before the end of the first day, while septic intoxication from putrefaction seldom begins before the expiration of twenty-four hours. If septic infection begin during this time it is not attended by an37 evidences of putrefaction. Prognosis.—Uncomplicated sapraemia proves fatal b3r the absorption of a deadly dose of ptomaines from a local depot of putrefaction, and the prognosis will therefore depend upon the stage of intoxication and the feasibility of the removal of the infected dead tissue b37 surgical treatment. If an efficient, radical treatment can be instituted at a time before a fatal dose of toxic substances has reached the general circula- tion, the prognosis is favorable. A decomposing blood-clot or detached fragment of a placenta can be readily removed and the field of operation sterilized. The prognosis in sapraemia complicating progressive gan- grene is alwa3Ts grave,as the dead tissue is increased by other microbes; hence the conditions created by both kinds of microbes are of a pro- gressive character. Treatment.—The prophylactic treatment of sapraemia consists in the removal of dead tissue, prevention of subsequent extravasation and ac- cumulation of blood by careful haemostasis,—if necessary, by drainage, —and finally sterilization, by antiseptic measures, of dead tissue that cannot be removed. Iodoformization of dead tissue is an excellent means of preservation. In the extra-peritoneal treatment of the stump after supra-vaginal extirpation of the uterus, the same object is accom- plished by touching the raw surface with a solution of perchloride or persulphate of iron or pure carbolic acid. Wounds in which dead tissue is unavoidably retained should always be treated by drainage. After symptoms of septic intoxication have developed early, radical treatment must be pursued. This treatment comprises the removal or sterilization of the dead tissue. A decomposing blood-clot is to be removed and the parts are thoroughly irrigated with a solution of corrosive sublimate, and 324 PRINCIPLES OF SURGERY. re-accumulation prevented by efficient drainage. In cases of gangrene complicated by putrid intoxication, where it is impossible to remove the infected tissues by mechanical measures, and complete disinfection with- out such a procedure cannot be effected, the best results are obtained by permanent irrigation with a saturated solution of acetate of aluminum. Under this treatment the soluble toxic substances are washed away as fast as they are formed, and sterilization of the soil for the putrefactive bacteria is gradually accomplished by the saturation of the dead tissue with this safe and efficient antiseptic solution. If a suppurating cavity is the seat of putrefactive changes, it becomes necessary to remove the nutrient medium for putrefactive bacteria by first washing out the cavity with a strong antiseptic solution, to be followed by the mechanical re- moval of dead tissue, shreds of connective tissue, dead granulations, etc., by means of a sharp spoon or dull curette, and subsequently by another antiseptic irrigation. The surgical treatment of sapraemia will soon decide the fate of the patient. If a fatal dose of ptomaines has reached the general circulation before an effort is made to procure sterilization of a local depot of putrefaction the local treatment will, of course, prove unsuccessful in preventing a fatal result, and the disease will continue its relentless course uninfluenced by the treatment. If, however, the in- toxication has not progressed to this extent, efficient local treatment is followed b37 the most brilliant results. Within a few hours after the sterilization of the local focus of putrefaction the temperature falls to normal, the pulse becomes slower and fuller. If the tongue has been dry it soon becomes moist; if the patient has been delirious consciousness returns, and the patient is convalescent in a few days. The results of the antiseptic local treatment in these cases are the strong contrast with the useless and often dangerous internal administration of antipyretics. The treatment directed toward the disinfection of the local focus of putrefaction removes the cause of the intoxication, while the antipyretics may effect a temporary reduction of the temperature, but at the same time, by diminishing the contractile power of the heart, only add to the danger by diminishing the resistance to the action of a depressing poison. The use of antipyretics in the treatment of sapraemia is strongly contra- indicated. All debilitating treatment must be carefully avoided as being unscientific and as adding to the existing dangers. The best results are obtained by such local treatment by which the further production of ptomaines is prevented, consequently by measures which meet the etio- logical indications. The debilitating effects of the ptomaines on the heart are met by the timeby and judicious administration of stimulants. In urgent cases such diffusible stimulants as sulphuric ether, camphor, and musk can be administered with advantage subcutaneously, in order CLINICAL FORMS OF SEPTICAEMIA. 325 to gain time for the action of remedies which will have a more permanent effect on the heart. Digitalis, strophantus, strychnia, and atropia in small doses are excellent cardiac tonics and stimulants, and are indicated in cases where the pulse is very rapid and soft, denoting a feeble peripheral circulation from a weakened heart. Where life is threatened from syncope the patient is not allowed to assume a sitting postion, for fear that the increased intra-cardiac pressure might result in sudden death from heart-failure. Alcoholic stimulants are to be given in doses sufficiently large to improve the character of the pulse, and at sufficiently short intervals to maintain this effect without interruption. Brandy or whisky, in doses of an ounce every two hours, diluted with water, are most to be relied upon, but champagne, Greek sherry, or Reich's Tokayer are excellent substitutes. If the stomach is irritable or the symptoms are less urgent, concentrated liquid food, like beef-tea, milk, and eggnogg, must be given at regular intervals to assist the action of stimulants in sustaining the heart's action until sufficient time has been gained for the elimination of the ptomaines. (c) Progressive Septicaemia.—This is the septic infection of modern authors, and differs from septic intoxication in that it is caused not by putrefactive bacteria, but b3r microbes which enter the circulation from some local septic focus, and which retain their capacity of reproduction in the blood. It is called progressive sepsis, because, only too often, it is not followed by any abatement of the symptoms, as the essential cause has passed beyond the reach of any local treatment, and goes on increasing in the blood until it destroys the patient. The intoxication in this form of sepsis is not only caused by ptomaines which are produced at the primary seat of infection, but ptomaines are also produced in the blood by the microbes which it contains. True progressive sepsis is caused b3' the introduction of septic micro-organisms into the tissues, where they multiply and, later, reach the blood, where mural implantation and capillar thrombosis take place, which directly interfere with the proper nutrition and function of important organs, and where the septic intoxication is caused by the formation of ptomaines, both in the blood and living tissues. For this form of sepsis Neelsen has suggested the name of " acute m37cosis of the blood," to distinguish it from putrid intoxication, which we have just described, and which Neelsen calls " toxic mycosis of the blood," in which few or no microbes are found in the blood, and in which death is due exclusively to the absorption of preformed toxic substances from a putrefying depot. Causes.—Klebs discovered and described a microbe, the mikrosporon 326 PRINCIPLES OF SURGERY. septicum, which he believed was the specific cause of septic processes, but recent researches seem to prove that the pus-microbes are the most frequent cause of progressive sepsis. The pus-microbes either reach the circulation directly by permeating the vessel-wall, or they enter by a more indirect route, through the lymphatic channels. The latter mode of infection gives rise to the most acute and fatal form of sepsis. In man37 cases of septic infection the presence of lymphangitis can be demonstrated during life, and by examination after death. A few 37ears ago Bergmann advanced the theory that in septicaemia micro-organisms enter the colorless blood-corpuscles, and by multiplication within them cause their dissolution, a process during which the fibrin-generators are elaborated,—an occurrence ending in intra-vascular coagulation and capillary embolism. In Koch's septicaemia in mice such a chain of pathological conditions can be readily demonstrated, but in many cases of fatal sepsis in man the mfcrobes found in the blood are few, no de- struction of leucocytes can be shown to have occurred, and extravasations and capillary embolism are absent; hence death cannot be attributed to fibrin intoxication. In such instances we can only assume the presence of a soluble ptomaine which is diffused throughout the entire body and destroys life by its toxic properties. The formation of pus at the primary seat of infection is not necessary in the causation of septicaemia by pus- microbes. Septic infection is as liable to take place from wounds that do not suppurate as from suppurating wounds. Why a wound infected with pus-microbes should give rise to progressive sepsis in one individual, and suppuration or suppuration and pyaemia in another, does not admit of a satisfactory explanation at the present time. Rinne has shown that diminution of the absorptive capacity of the tissues at the seat of infection plays an important part in the develop- ment of septic processes. If the pus-microbes are rapidly absorbed, destroyed in the blood, or removed by elimination, septic inflammation is prevented. If, on the other hand, the local conditions are such that the microbes remain in the tissues, and by their rapid multiplication produce a large amount of soluble toxines, which, when they reach the blood, not only produce intoxication, but prepare the blood and tissues for the localization and reproduction of the microbes at points distant from the primary seat of the infection, the pathogenic effect of the microbes on the tissues at the primaiy seat of infection diminishes their power of resistance, and the microbes either enter the blood-vessels directly or through the lymphatics. Experimentally it has been shown that if a large quantity of pus-microbes is introduced into the peritoneal cavity, or directly into the circulation, death results from sepsis before a sufficient length of time has elapsed for the pus-microbes to produce CLINICAL FORMS OF SEPTICEMIA. 327 the histological changes which are necessary for the production of pus. These experiments are strongly suggestive of the fact that, in man, infec- tion with pus-microbes causes progressive sepsis, if a large quantity of pus-microbes is introduced into+tissues debilitated by a trauma, antecedent pathological conditions, or the action of preformed ptomaines. Under such circumstances the pus-microbes are reproduced with great rapidity at the primary focus of infection, enter the circulation before suppu- ration has had time to develop, and produce a complexus of symptoms and a series of pathological changes characteristic of progressive sepsis. Symptoms and Diagnosis.—The most typical clinical picture of progressive sepsis is produced in cases of septic peritonitis, dissection wounds, puerperal septicaemia, and acute multiple osteomyelitis. In septic peritonitis, after laparotomy or penetrating wounds of the abdomen, the septic inflammation, as a rule, develops within the first forty-eight hours, and with it the characteristic symptoms of septicaemia appear. In puerperal sepsis and the gravest form of acute suppurative osteomyelitis, the septic S37mptoms often overshadow the primary disease to such an extent that this is entirely overlooked. Dissection wounds often prove fatal from septic infection, which spreads from the wound along the course of the lymphatic'vessels, and finally becomes general through the medium of the circulation. Septic infection from an accidental or operative wound can take place within twenty-four hours, and seldom occurs later than the third or fourth day, unless the infection has taken place after the first dressing. Like all other acute infectious processes, septicaemia is ushered in by a more or less pronounced chill, or at least a subjective sensation of chilliness, which may be repeated during the first twenty-four hours. The chill is never so pronounced as in p37aemia, and does not return with the same regularity and intensity as in that affection. The chill announces the termination of the period of incuba- tion, and is promptly followed by symptoms of reaction which, in their severity, are proportionate to the intensity and gravity of the attack. One of the most prominent features of the disease is a profound pros- tration, which may be well marked a few hours after the beginning of the attack. If septicaemia follow an operation, or a severe accident, it is sometimes almost impossible to decide whether the pronounced loss of strength should be attributed to shock, the use of an anaesthetic, or the beginning of an attack of septicaemia. One of the most delusive symptoms is the utter indifference of the patient, not only as to his own grave condition, but to all of his surroundings. This apathy is a char- acteristic symptom of profound septic intoxication. The patient com- plains of no pain, assures the physician and friends that he is feeling 328 PRINCIPLES OF SURGERY. well, shows absolutely no anxiety concerning his own fate, and does not comprehend the anxiety of those around him. Drowsiness, border- ing almost on stupor, is frequently observed. The face presents a pale or ashy-gray color, and in advanced cases*it presents a yellowish, icteric tint, but the sclerotica always retains its white color. In the beginning of the attack the pulse ranges between 80 and 90 degrees, but becomes rapid, small, and compressible as the intoxication and capillary obstruc- tion progress. The character of the pulse is of great diagnostic and prognostic importance. If the pulse within a short time reach a fre- quency of 140, and imparts the sensation as though the artery were only half filled with blood, it is a symptom which forebodes immediate danger. The temperature is variable. A subnormal temperature, with a rapid, feeble pulse, indicates a grave and probably fatal form of sepsis. If the temperature is at first only slightly increased, but gradually rises to 103° or 104° F., it denotes progressive sepsis. A high temperature and a firm pulse, not exceeding 120 beats to the minute, are indications of less serious import than a low temperature with a rapid, feeble pulse. The eyes are sunken, often suffused with an abundant secretion from the conjunctiva. The features present a stolid appearance, without any expression of intelligence. Capillary oozing at the primary seat of infection is a common occurrence, and capillary haemorrhage underneath the skin and visible mucous membranes is frequently observed. Vom- iting and diarrhoea are often present from the beginning, and in rapidly fatal cases remain as persistent symptoms, in spite of measures that may be employed to subdue them. The discharges from the bowels are often stained with blood. The urine, as a rule, is scanty and loaded with urates. Billroth places great importance upon the appearance of the tongue. The tongue is always coated; in grave cases it is pointed at the tip, its margins are red, while the dorsal surface is dry and covered with a dry, often almost black, crust. Return of moisture is always a favorable omen. Great thirst and complete loss of appetite are always present. Delirium is a frequent, but not a constant, symptom. If the case progress to a fatal termination, the pulse becomes more and more frequent, respira- tions become shallow and labored, the face presents a c37anotic hue, the surface is bathed with a clammy perspiration, the extremities become cold, and death finally is caused from heart-failure. In the differential diagnosis it is important to remember fermentation fever, septic intoxi- cation, typhoid fever, internal sepsis, and acute multiple suppurative osteomyelitis. Progressive septicaemia always has a stage of incubation ; that is, a certain length of time intervenes between the time infection occurred and the appearance of the disease. This period of incubation CLINICAL FORMS OF SEPTICAEMIA. 329 may terminate at the end of a few hours and it may be prolonged to four days, according to the number of pus-microbes introduced and the anatomical structure and physiological properties of the tissues primarily infected. Fermentation fever follows an injury or operation within a few hours, and never occurs after the expiration of twenty-four hours. In fermentation fever the maximum symptoms appear at once, and the force of the pulse and strength of the patient remain unimpaired. Fermenta- tion fever seldom lasts for more than one or two days, while in progres- sive sepsis the symptoms become aggravated as the infection increases. In putrid intoxication the maximum symptoms are produced b3~ the in- troduction into the blood of preformed soluble toxic substances from a depot of putrefaction. Evidences of putrefaction in aii37 part of the body would speak in favor of septic intoxication, while, if septic infec- tion exist at the same time, it must be regarded not in the light of a cause, but as a complication. Typhoid fever is preceded by a well- marked prodromal stage which is absent in septic infection. The erup- tion in typhoid fever is characteristic, while the eruption which is sometimes seen in progressive sepsis closely resembles the rash of scar- latina, and is caused by the presence of pus-microbes in the superficial lymphatic vessels. Internal sepsis is usually preceded by a septic phar- yngitis, and frequently attended by ulcerative endocarditis. Acute mul- tiple osteon^-elitis, the cause of fatal septic infection, can be recognized bA' searching for points of tenderness in the localities attacked most fre- quently by this disease. The final diagnosis of septic infection must be based upon the existence of an infection-atrium, through which pus- microbes have entered the tissues, and from which they have reached the general circulation. Prognosis.—The prognosis of progressive septicaemia is always grave. In cases where pus-microbes exist in large numbers at the pri- mary seat of infection, and reach the general circulation with great rapidity, and meet with conditions favorable for their reproduction, death is inevitable in spite of the most energetic local and general treat- ment. The prognosis is more favorable if infection has taken place from a locality amenable to thorough local disinfection, if this is practiced upon the first appearance of symptoms, as this treatment prevents fur- ther ingress of pus-microbes into the circulation. The existence of mul- tiple points of metastatic inflammation renders a recovery improbable. Delirium, rapid and feeble pulse, subnormal temperature, dry tongue, persistent vomiting and diarrhoea are all unfavorable symptoms from a prognostic stand-point. Capillary haemorrhages distant from the primary infection-atrium are infallible indications of progressive sepsis, and their existence warrants a most unfavorable prognosis. Progressive 330 PRINCIPLES OF SURGERY. sepsis may cause death in twelve hours, and in fatal cases life is seldom prolonged for more than one week. Pathology and Morbid Anatomy.—In rapidly-fatal cases of progres- sive septic infection, the absence of gross macroscopical pathological changes is a characteristic feature of this disease. In such instances even the most careful search for tangible lesions will result negatively. Cloudy swelling of the parenchyma of internal organs indicates the existence of coagulation necrosis, caused by the action of the ptomaines of the pus-microbes. Pus-microbes have been frequently found in septic blood. Haemorrhagic extravasations into organs, and more par- ticularly underneath serous and mucous membranes and the skin, are frequently present. The blood presents almost a black color, and shows little or no tendency to coagulate. The tymphatics interposed between the primary seat of infection and the blood-vessels are frequently found in a state of septic inflammation. The wound through which infection has taken place may present but slight or no gross anatomical changes. The spleen is enlarged and the pulpa softened to the consistency of a blood-clot. Thrombosis and embolism are absent. Under the micro- scope the capillary vessels eveiywhere present all the evidences of a septic inflammation. The soluble ptomaines in the blood produce coagu- lation necrosis of the intima, which determines mural implantation of the pus-microbes and the colorless corpuscles and results in capillary hyperaemia and congestion. In some places alteration of the capillary wall has taken place to such an extent as to give rise to rhexis. The most important microscopical changes in the tissues and organs, in patients who have died of sepsis, are the pathological conditions within and in the immediate vicinity of capillary vessels that indicate the exist- ence of multiple foci of metastatic inflammation, which characterize clinically and pathologically progressive sepsis. If life is prolonged for a sufficient length of time, these foci become the centre of a suppura- tive inflammation. Slight effusions into the large serous cavities are frequently found. Treatment.—The antiseptic measures which have been described in the treatment of wounds are the best and only known means of effective prophylaxis against septic infection. Any method or methods of treat- ment which can be relied upon in the prevention of suppuration will be found efficient in preventing septic infection. As retention of wound-secretion is one of the important etiological conditions in the causation of septic infection in wounds that are not completely aseptic, drainage should be emplo37ed in all cases where an accumulation of the primary wound-secretion is to be feared. As septic infection is just as liable to occur through a small as a large wound, the most insignificant CLINICAL FORMS OF SEPTICAEMIA. 331 injury should be treated upon the strictest and most pedantic antiseptic precautions. If, in spite of the greatest care, symptoms of septic infection appear after an injury or operation, no time should be lost by the useless administration of antipyretics, in the vain hope that by reducing the temperature the condition of the patient will be improved, but the first and essential object of treatment should be to remove the cause of the fever by resorting to secondary disinfection. All sutures must be removed and every portion of the wound rendered accessible to local treatment. Extravasated blood and necrosed shreds of tissue must be removed, when the wound is to be irrigated with a l-to-1000 solu- tion of corrosive sublimate, after which it is dried and the whole surface brushed with a 10-per-cent. solution of chloride of zinc. After another irrigation and after drying the surface again, a thin film of iodoform is applied, and then the wound is tamponed with iodoform gauze and dressed antiseptically. Such a wound should never be re-sutured until the local and general sj'mptoms indicate that it has been rendered completely aseptic. If this secondary disinfection prove unsuccessful, recourse should be had to permanent irrigation with a saturated solution of acetate of aluminum. Secondary disinfection of the peritoneal cavity, in cases of septic peritonitis after laparotomy, has so far not proved ver3r satisfactory, but as it is the only recourse in dealing with such desperate cases, that without it would surely run a fatal course in a short time, it should never be neglected. A number of the sutures near the lower angle of the wound are removed with blunt instruments, the margins of the wound are separated, and the abdominal cavity is flushed with warm salicylated water until the fluid returns perfectly clear. The end of the rubber tube attached to the irrigator must be inserted in such a manner that the stream will reach the most depend- ent portions of the abdominal cavity; hence it is inserted into the deep- est portion of the pelvis, and when this portion of the abdominal cavity has been thoroughly washed out the lumbar regions are dealt with in a similar manner. After the irrigation has been completed, the patient is turned upon the face, so as to permit the escape of fluid by gravita- tion. A large glass drain is then inserted and its opening closed with salic37lated cotton, after which the antiseptic dressing is applied in such a manner that the end of the tube remains accessible to the removal of fluid by aspiration as often as circumstances may require. In progres- sive sepsis, following in the course of progressive gangrene of a limb, amputation will become necessary if secondary disinfection and perma- nent irrigation have proved of no avail in arresting the septic infection. The general treatment of septic infection is the same as has been advised in cases of septic intoxication. CHAPTER XIII. Pyaemia. Pyemia, or pyohaemia, is a general disease caused by the entrance into the circulation of pus or some of its component parts, characterized by recurring chills, an intermittent form of fever, and the occurrence of metastatic abscesses. Although this disease was known a long time before Piorry applied to it the name it still bears, its intimate relation- ship to suppurative processes was first pointed out by this surgeon. Piorry maintained that, as the name implies, pyaemia is caused by the entrance of pus into the blood. Virchow, on the other hand, contended that no pus is found in the blood of pyaemic patients, and that the sec- ondary or metastatic abscesses are not true abscesses resulting from the accumulation of pus derived from the blood, but that they are the result of embolic processes, puriform softening, inflammation, and suppuration around the blocked vessel. Recent bacteriological investigations have shown that Piorry's views are so far correct in that pus is produced within blood-vessels by the entrance of pus-microbes into the circula- tion. As a wound complication pyaemia can only occur after suppura- tion has taken place in a wound, and, as a complication of non-traumatic lesions, it can onty develop in the course of suppurative affections. The great prevalence of p37aemia in overcrowded and badly-ventilated hos- pitals, during the time before the antiseptic treatment of wounds came into use, gave rise to a general belief that the disease was due to a spe- cific cause, and ever since bacteriology became a science diligent search has been made to discover the specific microbe. Since the discovery of the microbes of suppuration, new light has been shed upon the etiology and pathology of this disease. Bacteriological examinations of p3'aemic products have shown that one or more kinds of pus-microbes are always present, thus establishing the direct relationship which exists between a suppurating process in some part of the bod3r and the development of metastatic or pyaemic abscesses. Clinical experience has only corrobo- rated the scientific investigations of this subject, inasmuch as it has shown that the frequencj' of p37aemia has been diminished in proportion to the lesser frequency of suppurative inflammation under the antiseptic treatment of wounds and suppurating lesions. We are justified, upon the basis of well-established facts, in claiming that pyaemia is not a (333) 334 PRINCIPLES OF SURGERY. disease per se, but that its occurrence depends upon an extension of a suppurative process from the primary seat of infection, and suppuration in distant organs by the transportation of emboli infected with pus- microbes through the systemic circulation. The distant, or metastatic, abscesses contain the same microbes which are found in the wound- secretions, or in the abscess from which the general purulent infection took place. Experiments have shown that a culture of pus-microbes from a furuncle may produce p37aemia in animals, and that the microbes cultivated from a pyaemic abscess, when injected under the skin of an ani- mal, may cause only a localized suppurative inflammation without any general symptoms. BACTERIOLOGICAL AND EXPERIMENTAL RESEARCHES. While the direct relationship existing between suppuration and py- aemia was well understood clinically for a long time, it was left for Klebs to demonstrate for the first time the direct connection of the p3raemic processes with the presence of specific microbes. In his researches into the nature of this disease during the Franco-Prussian war in 1870, he discovered in the pyaemic products certain micro-organisms which he called micrococci of pyaemia. He found that these microbes always arranged themselves in the form of colonies or groups which he termed zoogloea. He found this microbe invariabby present, notably at the pri- mary seat of infection, but also in the most distant organs,—wherever, indeed, pathological changes occurred during the course of the disease. Pasteur, in studying the puerperal form of pyaemia, discovered a chain coccus which undoubtedly was identical with the streptococcus pyogenes, but which he called microbe enchapelet. Hueter and Vogt found a micro-organism in pyaemic products which they include among the mo- nads. Burdon-Sanderson supposed that he had discovered the essential microbic cause of pyaemia in the shape of a " dumbbell shaped germ," which in all probability was a staphylococcus. Schiiller examined the contents of metastatic joint affections in 12 cases of puerperal pyaemia, and invariably found pus-microbes. Rosen- bach investigated 6 cases of typical pyaemia with a view to determine the nature of the microbes present in the pyaemic products. He found the streptococcus pyogenes present in the blood, and metastatic deposits in 5 of them; in 2 of these cases staphylococci were also present, although fewer in number. In only 1 of them he found staphylococci alone, and this case recovered. Pawlowsky made a bacteriological ex- amination of the pus of metastatic abscesses in 5 cases of pyaemia. In 4 cases he found the staphylococcus pyogenes aureus, and in the fifth case, which was remarkable for the extent of the joint complications, he BACTERIOLOGICAL AND EXPERIMENTAL RESEARCHES. 335 found the streptococcus pyogenes. He believes that the staphylococcus pyogenes aureus is the usual cause of pyaemia, and especially of that form characterized by multiple abscesses in the internal organs. Large cultures of this coccus suspended in water and injected subcutaneously in rabbits caused death, and at the necropsy multiple abscesses were found. He maintains that pyaemia in man occurs when disturbances in the circulation are present, so that floating cocci find favorable points for localization within the blood-vessels. He created such disturbances artificial^7 in animals by making intra-venous injections of cinnabar, with the result that the glandular material determined localization of the microbes which were introduced into the circulation. Besser examined bacteriologically blood, pus, and parenchymatous fluid from organs in 23 cases of pyaemia. In 8 cases the staphylococci albi and aurei were found ; in 14, streptococci; and in 1, streptococci and staphylococci simultaneous^. The microbes were discovered during the patient's life in pus in ever3r one of 20 cases examined ; in blood, in 11 of 12; and in parenchymatous serum, in 1. After death, in pus, in 17 of 17 ; in blood, 4 of 9 ; and in organs, 9 of 14. Besser's predecessors described 23 additional cases of P3raemia, in 14 of which staphylococci were found ; in 7, streptococci. Total, 46 cases : in 22, staphylococci; in 21, streptococci; in 3. both. Besser was unable to detect the slightest morphological or pathogenic difference between the microbes of suppu- ration and those of p3Taemia. Okinschitz made the relationship which exists between the pus- microbes and pyaemia the subject of bacteriological investigation. He found that pyaemic blood invariabby contained either the streptococcus pyogenes or the staphylococcus p3'ogenes aureus, demonstrated by cultivation and ordinary microscopical examination. As the haemic microbes seldom show any signs of fission, as compared with the bacteria at the primary focus, it is reasonable to infer that reproduction takes place mainly in the pus, and not in the blood; hence the great impor- tance of thorough disinfection and destruction of primary foci. The number of microbes in the circulating blood bears a direct relation to the gravity of the disease. If they are abundant, even in the absence of metastases in internal organs, the prognosis is grave, and if scanty, even if metastatic foci are present, the prospects of a favorable termi- nation are better. Pyaemia in Rabbits.—Koch produced pyaemia artificially in rabbits by injecting putrid fluids. A piece of a mouse's skin, about a square centimetre in size, was macerated for two days in 30 grammes of dis- tilled water, and a syringeful of this fluid was injected subcutaneously into the back of a rabbit. Two days the animal remained apparently 336 PRINCIPLES OF SURGERY. B—----- A—- well, then it began to eat less, became gradually weaker, and died one hundred and five hours after the injection. An extensive subcutaneous abscess was found at the seat of injection. In the abdominal wall the yellowish infiltration extended in parts through the muscles and even to the peritoneum. The peritoneal surface presented evidences of inflam- mation. The intestines were adherent, and the peritoneal cavity con- tained a small quantity of turbid fluid. The liver showed on section gray, wedge-shaped patches. In the lungs infarcts the size of a pea were found. A syringeful of blood taken from the heart of this animal was now injected un- der the skin of the back of a second rabbit. The second animal died in forty hours, and at the necrops3' nearly the same pathological con- ditions were found, only that the peritonitis was less advanced. Further experiments showed that TV drop of pyaemic blood proved fatal in rabbits in one hundred and twenty-five hours. All subsequent experiments proved that the less the quantity of blood injected the longer the time which elapsed before death occurred, but where the quantity was reduced to the one-thousandth part of a drop no result followed. On microscopic examination cocci were found in great numbers everywhere throughout the body, and more especially in the parts which had undergone alterations visible to the naked eye. The description of the microbe found cor- responds with the stapli37lococcus. The rela- tion of the microbes to the blood-vessels could be seen best in the renal capillaries (Fig. 78). In the interior of the vessel, at C, is a dense deposit of micrococci adherent to the wall, and inclosing in its substance a number of red blood-corpuscles. The capillary stasis is either due to the power of the microbes of Causing the red blood- corpuscles, to which they adhere, to stick together, or their property of pro- ducing in their immediate vicinity coagulation of the blood, and thus cause thrombosis. The microbes were found so arranged that they inclosed red blood-corpuscles in the capillary vessels of all the organs examined, m Fig. 78.—Vessel from the Cortex of the Kidney of a Pyemic Rabbit. X 700. (Koch.)* A, nuclei of the vascular wall; B, small group of micrococci between blood- corpuscles ; C, dense masses of micro- cocci adherent to the wall and inclosing blood-corpuscles; D, pairs of micrococci at the border of the large mass. * Copied from "Traumatic Infective Diseases," by permission of the New Sydenham Society, London. BACTERIOLOGICAL AND EXPERIMENTAL RESEARCHES. 337 as, for example, in the spleen and in the lungs. Koch believes that the large metastatic deposits in the liver and in the lungs do not arise by gradual growth of a mass of micrococci, as in Fig 78, but by the arrest of large groups and of the clots associated with them; in other words, by true embolism. In the metastatic deposits an extensive development of micrococci occurs, and these are not confined to the vessels, but invade the neighboring tissues. In the peritoneal cavity the micrococci were not found in large masses, but isolated, in pairs or in small groups. In the vicinity of the abscess he detected the microbes in the walls of veins, and their passage through these into the interior of the vessels could be readily discerned in mai^ places. As Koch has pointed out, the microbe of pyaemia in rabbits, which is a pus-microbe, when brought in contact with the red blood-corpuscles, increases their viscosity and the3r form larger or small coagula in the blood. They can thus no longer pass through the minute capillary net-work, but are arrested in the smaller vessels. From the point of infection fresh micrococci pass constantby into the blood, and also individual micrococci will become detached from these small thrombi and emboli, and mix with the blood- stream. As the microbes are constantly being deposited b37 mural im- plantation, their number in the circulating blood always remains relatively small. Klein described a micrococcus of p37aemia in mice. Certain cocci which were present in pork proved fatal to mice in about a week, producing both purulent inflammation at the point of injection and metastatic abscesses in the lungs. Inoculations in the same species of animal with pyaemic products reproduced the disease in a typical manner. Pawlowsky found that by simultaneous injection of sterilized cinnabar, and of cultivation of staphylococcus pyogenes aureus into the circula- tion, he produced abscesses in various organs—in fact, the typical picture of pyaemia. The presence of particles of foreign bodies rendered material aid in the development of metastatic abscesses, as the mere arrest of pus-microbes in the circulation without them, as a rule, was not found sufficient of itself to lead to the production of true pyemia. In rabbits, even, the introduction of a large quantity of a culture of pus-microbes into the circulation did not produce pyaemia. Twenty-four hours after the injection he found the microbes in large numbers in the pulmonary and other capillaries, but after forty-eight hours they had all disappeared from the blood. If the cocci are incorporated in, or are attached to, an embolus, this latter, by producing alterations in the endothelia of the blood-vessels at the point of impaction, create a locus minoris resistentiae favorable to the growth of the microbes. In the experiments of Pawlowsky, the particles of cinnabar acted upon the 22 338 PRINCIPLES OF SURGERY. endothelial lining of the capillary vessels in the same manner as the fragments of a thrombus, by impairing the local nutrition of the tissues with which the37 were brought in contact. ETIOLOGY. If pyaemia can be artificially produced in rabbits, mice, and guinea- pigs with pus, or with a pure cultivation of the same with or without the presence of foreign bodies, the same local conditions are first pro- duced at the point of inoculation which invariably precede the develop- ment of p37asmia in man. Some of the veins at the seat of primary in- fection are invaded by pus-microbes, and become blocked by a thrombus; this thrombus undergoes puriform softening; small fragments containing pus-microbes become detached and are washed away and enter the general circulation as emboli, which, when they become arrested, establish independent centres of suppuration. In such cases the same microbes can be found in the wound, in the blood, in the tissues around the abscess, and in all distant p37aemic products. Although the strep- tococcus pyogenes has been found most frequently in the pus at the primary seat of infection and in the metastatic abscesses of pyaemic patients, there can be but little doubt that any of the pus-microbes, when present in sufficient quantity in the blood, can produce the disease. The occurrence of pyaemia from suppurating wounds or abscesses does not depend so much upon the kind of pus-microbes which have caused the primary suppuration as upon surrounding circumstances. The location and anatomical structure of the tissues, in which the primary infection has taken place, exert an important influence in the production of the disease. It is an exceedingly familiar clinical fact that suppurative inflamma- tion of the medullary tissue in bone is frequently the cause of pyaemia. Acute suppurative osteomyelitis, without direct infection through a wound, is always due to intra-vascular infection—localization of pus- microbes in the capillary vessels of the medullary tissue. The microbes come first in contact with the endothelial cells when mural implantation has taken place, and the coagulation necrosis which follows leads to thrombosis. The products of the intra-vascular coagulation necrosis furnish a most favorable nutrient substance for the growth and multipli- cation of the pus-microbes; consequentby the area of intra-vascular in- fection is rapidly increased. The growth of the thrombus in a proximal direction soon leads to extensive thrombo-phlebitis, and, as softening of the thrombus takes place, to embolism and metastatic suppuration. Pyaemia following a suppurative inflammation in a wound, or in the course of a phlegmonous inflammation of the connective tissue, is the ETIOLOGY. 339 result of an infection with pns-microbes which penetrate the veins from without. The pus-microbes, coining first in contact with the outer coats of the veins, give rise to phlebitis, which progresses from without in- ward, and which is followed by thrombosis as soon as the intima is reached. The intra-vascular dissemination of the pus-microbes then takes place in the same manner as in cases of primary thrombo-phlebitis. Ordinary pyogenic microbes may and do cause pyaemia, if they enter the blood incorporated in, or attached to, fragments of an infected blood-clot, or other solid materials, which, after they have become impacted in blood- vessels as emboli, prepare the soil in distant organs for their localization and reproduction. The importance of thrombosis and embolism, as essential factors in the causation of pyaemia, has been clearly established by clinical obser- vation and experimental research. Emboli may originate in the Em- phatic vessels when these are the seat of invasion by pyogenic microbes, which, however, is ver3r seldom the case. In chronic pyaemia, in which multiple metastatic abscesses are formed, embolism takes no essential part in the process ; the microbes enter the blood-current without such a vehicle, and are brought in direct contact by mural implantation with the interior lining of vessels weakened by injury, or other local and general debilitating influences. Experimental research has shown con- clusively that the mere introduction of pus-microbes into the circulation is not necessarily, or even usually, followed by pyaemia, and their acci- dental entrance in the course of a suppurative inflammation is not always followed by serious consequences. There can be no doubt that some pus- microbes reach the circulation in nearly every case of suppuration, but their pathogenic action is prevented, or neutralized, by an adequate resist- ance on the part of the tissues with which they are brought in contact and their rapid elimination through healthy excretory organs. A limited number of pus-microbes injected into the circulation of a healthy animal, or accidentally introduced into the blood of an otherwise healthy person, are effectively disposed of by the white blood-corpuscles. If, however, the same number of microbes are present in combination with fragments of a blood-clot, the infected foreign particles produce such nutritive changes in the tissues surrounding them as to transform them into a favorable soil for the pathogenic action of the microbes. The same happens if free pus-microbes localize in a part the vitality of which has been previously diminished by trauma, or antecedent pathological changes, which constitute a locus minoris resistentiae for the growth and multiplication of the pus-microbes. Pyaemia, therefore, must be looked upon rather as a serious and fatal complication of suppurative lesions than an independent specific disease. The immediate causes of pyaemia 340 PRINCIPLES OF SURGERY. are the formation of an infected thrombus at the primary seat of infec- tion and disintegration of this thrombus to such an extent that frag- ments become detached and are conveyed by the blood-current to distant organs, where they are arrested in the smaller arteries as emboli. Thrombosis.—A thrombus is an intra-vascular blood-clot locally formed within the heart or a blood-vessel, and the process by which it is formed is called " thrombosis." A thrombus is called venous if it occur in a vein, arterial if it form in an artery. A red thrombus is produced if the blood coagulate in its entirety, while a white thrombus is com- posed of fibrin exclusive^ or the fibrin and the colorless and third cor- puscles of the blood. A mural thrombus is a thrombus which is attached to the inner surface of a vessel-wall without occluding the entire lumen of the vessel. Notwithstanding the numerous and ingenious experi- ments which have been made for the purpose of ascertaining the imme- diate cause of intra-vascular coagulation of the blood, this subject awaits a more satisfactory explanation than can be given at the present time. Richardson, Bruecke, and Lister have shown that the mere mechanical interruption to the flow of blood in a vessel is not a sufficient cause of coagulation. Blood has been kept in a fluid condition in a vessel between two ligatures for an indefinite period of time in the living tissues. Virchow, Cohnheim, Baumgarten, and Zahn maintain that the color- less corpuscles are in the closest manner related to thrombus formation. Zahn, from observations on the living mesentery of the frog, found that when the wall of a vessel was injured the colorless corpuscles accumu- late around the injured part, constituting what he calls a white throm- bus. The corpuscles subsequently, in great part, disintegrate and give rise to a granular accumulation, which, by its action upon the fibrinogen of the blood, causes a precipitation of fibrin. Since the discovery of the third corpuscle, or haematoblast, by Hayem and Bizzozero, the part taken by this element of the blood in the process of coagulation has been carefully studied by Eberth and Schimmelbusch. The third corpuscle possesses a peculiar property to adhere to any foreign body or irregularity of surface of the intima of the blood-vessels. The authors just quoted found that when a vessel is injured, as b3' tying a ligature around it and removing this in a quarter of an hour afterward, these minute blood-disks manifest a peculiar ten- dency to adhere to the injured part of the tunica intima and to each other, forming a white mural thrombus. The process by which mural implantation of the third corpuscle takes place these authors call conglu- tination, the mass thus formed being composed primarily and exclusively of this morphological element of the blood. If an aseptic thread is ETIOLOGY. 341 drawn across the lumen of a vessel in which the blood-current is moving, the third corpuscle is arrested in its course and becomes deposited upon the thread, which in time becomes the centre of a white thrombus. Con- glutination, under such circumstances, is a purely mechanical process. Eberth and Schimmelbusch demonstrated by their experiments that conglutination is most liable to occur where irregularities of the tunica intima are present. If by a trauma inflammatory or degenerative changes take place, the endothelial lining of a blood-vessel is rendered rough and uneven ; conglutination takes place first at the points which project farthest into the lumen of the vessel, because here the projecting body encroaches upon the axial current, which conveys the third cor- puscle. In thrombosis from pathological causes, mural implantation of the third corpuscle takes place upon an intima roughened by inflamma- tory or degenerative changes. Thrombus formation, as we observe it in pyaemia, always takes place upon a vessel-wall altered by the action of pus- microbes. The form of thrombosis intimately associated with the etiology and pathological anatomy of pyaemia occurs in a vein within or in close proximity to the primary suppurative lesion. The close relationship of phlebitis to pyaemia was well understood b37 John Hunter, who believed that the former alwa37s preceded the latter. He taught that the phlebitis resulted in intra-venous production of pus and the formation of metas- tatic abscesses. Cruveilhier, on the other hand, regarded thrombosis as the first link in the chain of pathological conditions in pyaemia. The idea of primary thrombosis as a cause of disease was carried by his pupils so far that nearly all inflammatory processes were by them attrib- uted to thrombotic changes in small veins ; not only inflammatory lesions, but even tumors were supposed to originate in this manner. A new as- pect was given to the pathology of this disease by the careful experi- mental investigations of Virchow on thrombosis and embolism. He showed that the metastatic deposits always occurred at points where vessels had been blocked by an embolus derived from a disintegrating thrombus. In the light of recent research phlebitis precedes thrombus formation at the primary seat of the infection. The pus-microbes which are present in the infected tissues permeate the vein-wall, and induce inflam- matory changes characteristic of this form of infection. As soon as the infection has reached the intima this structure is roughened, and upon the projecting points conglutination takes place, and the foundation for thrombus is laid by a pavement composed of the third corpuscles of the blood. Upon this surface aggregation of the colorless corpuscles takes place, and, as these structures undergo coagulation necrosis, fibrin is formed and a mural thrombus is established. The pus-microbes, which have reached the interior of the vein through 342 PRINCIPLES OF SURGERY. the inflamed vein-wall, multiply in the thrombus, and produce here, as elsewhere under similar favorable circumstances, their specific patho- genic effect. The thrombus thus formed is an infected thrombus which precludes the possibility of its removal by absorption. With an in- crease of the intra-venous infection coagulation is hastened, and a red thrombus soon fills the entire lumen of the vein, surrounded by a zone composed exclusively of blood-disks, colorless corpuscles, and fibrin, which compose its mural portion. As soon as the lumen of the vein has been completely obstructed the conditions for coagulation are improved, and the thrombus increases in size in both directions. The contact of Fig. 79.—Laminated Thrombus in a Vein. The Dark Granular Lay- ers are Composed of Colorless Blood-corpuscles and Fibrin ; the Central. Lighter Portion, of Red Corpuscles. 1:97. (Birch- Hirschfeld. ) the blood with the dead, infected thrombus results in coagulation, and in this manner layer after layer is added to the thrombus. If thrombus formation take place in advance of the primary phlebitis, inflammation of the vein-wall follows as an inevitable consequence from the presence of the infected thrombus, the inflammatory process spreading like the infection from within outward. The growth of a thrombus is seldom arrested in a central direction until some large vein-trunk is reached, into which the apex of the thrombus projects. The blood-current in a vein into which the apex of a thrombus from an adjacent vein projects frequently arrests its proximal extension, but ETIOLOGY. 343 if the venous circulation is impeded, or the thrombus continues to grow b3 the addition of new layers, in spite of the obstacles presented, one portion after another of a vein becomes involved, and the thrombus rapidly increases in length in a proximal direction. A venous thrombus in a pyaemic patient is only loosely attached to the vein-wall, as the pus-microbes transform the white corpuscles, which remain after coagu- lation has occurred, into pus-corpuscles, and in this manner softening and disintegration of the thrombus are accomplished. If a thrombus, at the point where it is in contact with the venous circulation on the proxi- mal side, become sufficiently softened, fragments become detached and are carried away by the venous current as emboli. Embolism.—An embolus is a detached thrombus, part of a thrombus, or any foreign substance transported by the arterial blood-current to its place of impaction. The process or act by which this is accomplished is called embolism. An aseptic embolus produces disturbances at the seat of impaction, which result exclusively from the sudden interruption of the blood-supply to the tissues fed by the obstructed vessel. The effect on the tis- sues is the same as though the vessel had been tied with an aseptic ligature. Virchow found that aseptic caoutchouc emboli, introduced into the right side of the circulation through the jugular vein, produced no serious trouble after their impaction in the branches of the pulmonary artery. Panum ascertained, by his experiments, that small, simple emboli in the pulmonary artery become encysted. The emboli of foetal cartilage which Maas introduced into the jugular vein in dogs did no damage to the pulmonary tissue, and not only retained their vitality but became the nucleus of a temporary tumor. An aseptic embolus, derived from plastic intra- vascular exudations or an aseptic thrombus, affects the tissues at the seat of impaction in the same manner as the aseptic substances which have been used to produce embolism artificially in animals. An embolus consisting of a fragment of an infected thrombus, as is the case in pyaemia, is a culture medium which contains the same microbes as caused the primary infection, and which at the seat of impaction estab- lishes an independent centre of infection, which etiologically and patho- logically is identical with the primary invasion. The embolic origin of metastatic abscesses was first pointed out by Virchow, who, at the same time, showed that the emboli are always Fig. 80.—Thrombo- phlebitis. (Billroth.) A, central end of venous thrombus projecting into a larger vein-trunk; B, vein- branch not closed by a thrombus. 344 PRINCIPLES OF SURGERY. derived from venous thrombi undergoing puriform softening. The closure of a vessel by thrombosis is always a slow, gradual process, while the obliteration of an artery by an embolus is the work of a moment. The gradual closure of a vessel by the slow growth of a thrombus is not attended by the same degree of disturbance of nutrition as when a vessel of similar size is suddenly blocked by the impaction of an embolus. Septic thrombo-phlebitis does not lead at once to embolism, as new layers are constantly being added to the proximal end of the thrombus, from where the fragments which constitute the emboli are alwa3rs derived. Embolism only occurs if the proximal end of the thrombus has become sufficiently softened that fragments separate spon- taneously and enter the venous circulation, or if the fragments are washed away by the venous current from a projecting thrombus. As the infected thrombus is always located in a vein within, or in close proximity to, the seat of primary infection, the detached fragments or emboli reach the right side of the heart with the venous blood, and, as they are usualby too large to pass through the pulmonary capillaries, the3' become impacted in the branches of the pulmonary artety. The lung acts as a filter, and is therefore the most frequent seat of embolism and metastatic abscesses. The circulatory disturbances at the seat of impaction give rise to pathological conditions which are characteristic of embolism, and can be readily recognized in the examination of organs after death. The area of tissue affected by the sudden closure of a vessel by the impaction of an embolus is called an infarct, and the process which produced the pathological changes infarction. Infarcts are always wedge-shaped, the apex of the triangle corresponding to the location of the embolus, and the base to the ultimate branches of the obliterated vessel. Cohnheim has described what he calls a terminal artery, by which is meant one whose branches inosculate only with those of the corre- sponding vein, one which is devoid of collateral anastomosis. Such are the renal and splenic arteries, and, in a less complete manner, those of the brain, heart, stomach, and lungs. If a terminal artery in the kidney or spleen is obstructed collateral circulation cannot be established, and necrosis of the tissues which depend on the closed artery for their blood- supply is an inevitable consequence. The same result follows embolism of a terminal artery in the spleen. In the other organs which have been enumerated the terminal arrangement of the arteries is not as absolute, and embolism is not followed by necrosis with the same degree of certainty, as circulation cannot be restored, under favorable circum- stances, by collateral branches. The first effect of the closure of an artery, by an embolus in any of these organs, is the appearance of a wedge-shaped area of ischaemia, which in size corresponds to the size of ETIOLOGY. 345 the vessel obstructed. It may be so small that it can hardly be detected by the naked eye, or the base of the wedge may be l£ inches in length. The border of this wedge-shaped space becomes the seat of active hyper- aemia, the surrounding vessels undergoing rapid dilatation. The hyper- aemia is usually so intense that rhexis takes place and the parts become infiltrated with blood ; hence the expression haemorrhagic infarct. Hamilton is of the opinion that the haemorrhagic infarcts in the lung are not caused b37 embolism, but by rupture of small vessels and haemor- rhage into the alveoli, the distribution of the fine branches of the bronchi determining the shape of the infarct. Although the ultimate branches of the pulmonary artery cannot be called terminal arteries, in the strictest sense implied by this term, if they become suddenly blocked by an embolus, collateral hyperaemia is so intense that haemorrhage into the Fig. 81.—Embolus of Branch of Pulmonary Artery. Hemorrhagic Infarction of Alveoli. Chromic-Acid Specimen. 1:100. (Birch-Hirschfeld.) parenchyma of the organ frequently takes place,—a condition well represented in Fig. 81. In haemorrhagic infarcts of the lung resulting from embolism the tissues involved are firmer than normal, and, on section, present pneu- matic appearances, which are due to infiltration with leucocytes and extravasation of blood, as well as transudation of blood-plasma through the walls of the hyperaemic blood-vessels surrounding the ischemic area. As the emboli usually lodge in the peripheral branches of the pulmonary artery, the infarcts are most frequently located near the surface of the lung. Immediately after embolism has occurred the district supplied by the obstructed vessel presents an anaemic appearance, which soon gives place to a reddish color, resulting from the haemorrhagic infiltration. As in pyaemia the embolus conveys from the primary seat of infection the 346 PRINCIPLES OF SURGERY. specific microbes of suppuration, it becomes the centre of a suppurative inflammation. The pus-microbes multiply in their new location and at once induce a suppurative arteritis, and, after their passage through the inflamed vessel-wall, they attack the histological elements contained in Fig 82—Pyemic Abscess of Lung. X 360. (Hamilton.) A, walls of alveoli: B, effused, small, round cells ; C, fibrin lying in alveolar spaces; D, cell entangled in meshes of same; E, E, E, masses of micrococcus (staphylococcus) lying in exudation. the exudation, which breaks down, becomes purulent, and is converted into an abscess. In the lung the leucocytes which are present in the infarct are converted into pus-corpuscles, and the interstitial connective tissue undergoes necrosis and can be found as detached shreds in the abscess. ETIOLOGY. 347 Embolism and metastatic abscesses, although more frequently found in the lungs in pyaemia, are not limited to this organ. To explain the occurrence of embolism in more remote organs, as the kidneys, spleen, liver, brain, etc., we must assume either that an embolus in the pulmonary artery becomes the nucleus of a thrombus, which, by its growth, reaches across the pulmonary capillaries and projects into the pulmonary vein, where fragments again become detached and enter the systemic circula- tion, or zoogloea of pus-microbes, passing the first filter (the lungs), are arrested in the capillaries of distant organs, or, finally, leucocytes im- pregnated with pus-microbes serve as minute emboli, and, after their localization in distant organs, become the cause of metastatic suppura- Fig. 83.—Coagulation Necrosis from a Kidney Infarct. X300. (Birch-Hirschfeld.) A, zone of reactive inflammation; B, loss of nuclei in the necrosed epithelia. (The nuclei of connective- tissue cells are in part preserved.) tion. In the kidney the infarctions appear as sharply circumscribed areas of a pale, cream-yellow color. When cut into, the infarct has a wedge shape, the narrow end pointing to the hilus. The red zone is not so marked as in infarctions of the spleen, and the greatest vascularity is in the direction of the embolus. As in infarcts of the lung, the hy- peraemic zone corresponds to the vessels nearest the ischaemic area. Extravasation of blood, although present, is never so marked as in the lung. The epithelial cells within the hyperaemic zone are destroyed by coagulation necrosis, and if the embolus is aseptic this portion of the kidney is removed by molecular degeneration and absorption, leaving a cicatrix behind. 348 PRINCIPLES OF SURGERY. Infarcts of the kidney occurring in pyaemia are converted into abscesses in the same manner as in the lungs, by the escape of pus- microbes from the embolus through the inflamed arterial wall into the tissues starved by defective blood-supply. SYMPTOMS AND DIAGNOSIS. As a wound complication pyaemia never occurs before suppuration has taken place, seldom before the seventh, usually about the ninth to eleventh, day after the accident or operation, if it is the result of a primary infection of the wound. In patients threatened with p37aemia, an ill-defined train of premonitory symptoms precede the actual develop- ment of the disease. These symptoms apply to the appearance of the wound and the general condition of the patient. The onset of the disease may be suspected at any time after suppuration has occurred, when evidences of serious capillary stasis manifest themselves at the seat of inj ury or operation. The thrombo-phlebitis gives rise to oedema; the margins of the wound appear puffed and elevated, the granulations pale and flabby; suppuration, which may have been profuse, becomes scanty ; the pus changes its character, and, instead of a yellowish, cream- colored fluid, it becomes sanious, serous, or sero-sanguinolent. Careful inspection of the parts at this time may reveal the existence of thrombosis in one or more of the veins leading from the focus of primary infection. The general premonitory S3'mptoms are indicated by a slight degree of intoxication, the result of the introduction into the circulation of pus-microbes and their ptomaines, from the primary focus of suppuration, causing a slight rise in the temperature and a general feeling of malaise, thirst, and loss of appetite. The actual development of the disease is initiated by a well-marked severe chill or rigor, which lasts from a few minutes to an hour or more. The chill resembles a malarial chill, and has often been mistaken and treated as such. Such a chill in a patient suffering from a suppurating wound or abscess is always an alarming symptom. It is an entirely subjective S3rmptom, as the ther- mometer placed in the axilla during the algid stage indicates a rise in the temperature, which often reaches 104° to 105° F. before the patient ceases shivering. Chills have been artificially produced in animals by^ the introduction of foreign substances into the circulation, and in pyaemia it is an indica- tion that fragments of an infected thrombus, and with them a large quantity of pus-microbes, have entered the circulation. The chill may recur at regular intervals daily or every other day,—a feature which may still further add to the difficulty in making a differential diagnosis between pyaemia and malaria. Usually, however, the chill recurs at SYMPTOMS AND DIAGNOSIS. 349 irregular intervals, one, two, or three times a day, as a rule, increasing in frequenc37, and often in intensity, as the disease progresses. If, for instance, during the first few days the patient has one chill daily, and, after a few days two or more during the same time, every additional chill indicates a more advanced stage of intoxication, and an increase in the number of metastatic foci. After the chill the fever continues for several hours, with a temperature of 103° to 104° F., until the appear- ance of profuse perspiration, when the temperature falls to normal, or even a little below that. The chill, fever, and sweating coming in the same order and of about the same duration as in malaria, the clinical picture resembles the latter almost to perfection, and on this account many cases of P37aemia have been mistaken in the beginning for malaria, and vice versa. The fever which attends p3raemia always is of an intermittent or re- mittent ty-pe. In acute pyaemia the chills may return several times during twenty-four hours, the temperature between them showing re- missions, but seldom returning to normal. In subacute and chronic cases the remissions are well marked between the chills, the temperature often sinking below normal. Vomiting and diarrhoea are less constant symptoms than in septicaemia. The pulse in its frequency corresponds to the temperature; its force is always reduced by the depressing effect of the ptomaines upon the heart. Delirium is occasionally present, but, as a rule, the mind is clear until the end. The yellowish color of the skin, almost constantly present in p3'aemia, has been attributed to icterus, resulting from metastatic processes in the liver; but in the majority of cases it is not the result of retention and absorption of bile, but is caused by destruction of red blood-corpuscles and pigmentation of the tissues with the coloring material thus liberated. It is an icterus, which, on account of its origin, is called " hasmatogenous icterus" The metastatic deposits in the kidne37s are indicated by the appearance of albumen and sometimes pus in the urine. Metastatic Suppuration.—Infarcts in one or more of the internal organs are present in every case of pyaemia, and suppuration in some of the large cavities is of frequent occurrence. In reference to the number of secondar37 metastatic foci of suppuration, a great deal depends on the clinical form which the disease assumes. In the acute form, which proves fatal within one to three weeks, the infarcts are numerous and the abscesses quite small, while in some of the infarcts the existence of suppuration cannot be demonstrated macroscopically. In chronic P37aemia, in which life is prolonged for months, and sometimes even a year, the number of secondary foci are few, but they have resulted in the formation of large abscesses. The presence of infarcts of the lung 350 PRINCIPLES OF SURGERY. are indicated by symptoms and signs which point to circumscribed foci of inflammation in this organ. If the infarct is immediately underneath the pleura, it gives rise to circumscribed pleuritis and sharp, lancinating pain at a point corresponding to the location of the infarct, always aggra- vated b3r the respiratory movements. In such cases friction-sounds can often be heard over the infarct. The consolidation of the tissues in- volved by the infarct by inflammatory infiltration from the vessels sur- rounding it is attended by crepitant rales, bronchial breathing, and dullness on percussion, over an area corresponding to the size of the infarct. A pulmonary abscess which takes the place of an infarct in- creases in size by encroaching upon the surrounding tissues, and in chronic cases may empty itself into a bronchial tube. A subpleural infarct, infected with pus-microbes, not infrequently leads to suppurative pleuritis and empyema by the extension of the infection from the lung- tissues to the adjacent pleura. In the same manner a suppurating infarct of the lung may become a direct cause of suppurative pericar- ditis, and pyocardium if its location is adjacent to the pericardium. The onset of metastatic foci in the lungs is often insidious, and even large infarcts often occasion only slight subjective symptoms and ob- jective signs. Embarrassed breathing should admonish the attendant to search for evidences of multiple infarcts of the lung. Abscesses in the liver, caused by septic emboli, vary in size from that of a pea to an orange, but occasion no symptoms unless they are located immediately underneath the serous covering, when they cause localized pain. Embolic infarcts in the kidneys may be suspected if the urine contains albumen, or pus, or both. The spleen is always enlarged in pyaemia, but, as this is the case in all acute infective processes, the presence of an infarct or abscess is only to be suspected if the symptoms, especialby pain and cir- cumscribed tenderness, point to the existence of perisplenitis. Enormous P37aemic abscesses often develop insidiously and without pain, or the ordinary symptoms of acute inflammation between muscles and in the subcutaneous connective tissue. Metastatic suppuration in p37aemia takes place not only where infarction has occurred, but also in localities where the existence of embolism cannot be demonstrated anatomically, this being notably the case in joints and the large serous cavities. Sup- purative pericarditis, pleuritis, and peritonitis frequently complicate acute, rapidly-fatal pyaemia. Suppurative synovitis, multiple or limited to one joint, is a frequent complication, both in acute and chronic pyaemia. Metastatic suppuration in these localities develops without demonstrable infarcts, and occurs, in all probability, in consequence of mural implantation of pus-microbes or infected leucocytes upon the wall of capillary vessels, the intima of which has been damaged by ptomaines SYMPTOMS AND DIAGNOSIS. 351 held in solution by the circulating blood. As in all cases of pyaemia pus-microbes and their ptomaines necessarily constantly enter the cir- culation from the primary focus of infection, they prepare the soil for the reception and pathogenic action of pus-microbes in the vessels and tissues of certain organs, more especially the synovial membrane of joints and the serous membranes lining the large cavities. Pyaemic abscesses, when well-developed, always contain yellow pus of the con- sistence of cream. Examined under the microscope, such pus contains corpuscles in which no sign of a nucleus can be found. The pus-microbes are always present in great numbers, both within the pus-corpuscles and in the pus-serum. While some doubt may remain after the first chill as to the nature of the disease, this doubt is dispelled with the recurrence of the chills. In acute cases the chill returns once or twice daily, but, unlike in cases of malaria, if the chill is of daily occurrence, it does not come at a fixed time, as is the case in malaria. If the disease does not culminate into a daily chill, the temperature "" . ~^!%. then shows an irregular remittent :--''■"■ :'4$stx** ».. '° %.'■*. C^ ■ • 'X ^Br type of fever. The patient loses •.?*"*''\./°-> '-"^'V ..'•'•: •"*"*'•* strength and flesh rapidly, and the £■■:; .' «>.',' gp^v.V./;.«,'.v 7'*V- •'••■ face presents the color of a mixture 1W '^LS'.'.■-.'.»•; ."/-**;* .-'"'"'""*..«,'" of the hectic flush with the icteric „ ^P<'ls »■*.'•■.■'''"/gift**"j *'"' . ^Ei^' hue. While the pulse at first rises 'x.- .*-'* .*«!'"/-'". .,\ ^Hp*'\\ only to 100 to 120 beats per minute t|y| " ,,') . ''"'"''* " .- during the febrile exacerbations, it FlG "JT-py^ic pus. showing com- soon remains at from 120 to 150 per Ks^KI an T^nSe of minute. Great thirst and complete JSKS^^TiS^^)^1™* loss of appetite remain constant symptoms. The tongue and lips are dry, diarrhoea is more common as septic intoxication advances, and the stools are frequently stained with blood. As the fatal termination approaches, delirium and sopor come on, and under increasing symptoms of depression death takes place gradually from heart-failure, or suddenly from embolism of the pulmonary artery. In chronic cases the duration of the disease is sometimes prolonged for months, and Billroth relates a case where the patient lived for a year. In chronic cases the chills recur at long intervals, and the fever assumes a remittent type between them. In still another class of chronic P3raemia the chills ultimately disappear, and the fever assumes a mild, continuous type, while the patient gradu- ally succumbs to decubitus, amyloid degeneration of internal organs, or a slow form of septic intoxication. 352 PRINCIPLES OF SURGERY. PROGNOSIS. The prognosis of p3y ligation, for the purpose of preventing mechanically the entrance of detached fragments of a thrombus into the circulation; but this procedure has not answered the expectations, as the emboli will reach the general circulation through collateral branches. Removal of the infected thrombi by amputation or resection of the affected portion of a vein are more reliable prophylactic measures than ligation in the continuity of a principal vein-trunk on the proximal side of the primary seat of infection. Detachment of fragments of a disintegrating throm- bus must be prevented as far as possible b3^ securing absolute rest for the infected part, as all sudden movements, active and passive, and sudden disturbances of the circulation may become the means of separation of fragments, and their transportation as emboli into the circulation. The curative treatment of pyaemia, medical and surgical, is unsatisfactory. Quinine, natrum benzoicum, and the different preparations of salicylic acid have been used quite extensiveby in the treatment of the fever which attends the disease. Antifebrin, antipyrin, and other drugs of the same class of remedies are worse than useless, as the favorable effects from their antipyretic action are more than overbalanced by the harm they do in depressing the action of the heart. External heat and the internal ad- ministration of diffusible stimulants should be used to shorten the dura- tion of the rigors. Alcoholic stimulants are indicated in the acute and chronic forms of the disease. In chronic pyaemia a daily7 tepid bath is of the greatest value. In the same class of cases it is of the utmost importance to support the patient's strength by systematic feeding and the use of the malt bever- ages, such as beer, ale, and porter, with a view of prolonging life until the primar3r cause is eliminated from the primary and secondary depots of infection, spontaneoush7 or by surgical treatment. In acute cases of P3Taemia, originating from a wound of one of the extremities, or from acute suppurative osteomyelitis of the long bones, the question of removal of the primary focus of infection by amputation will present itself. If, from a study of the symptoms, it become apparent that multiple infarcts exist in the lung, or lungs, and other organs, amputation is not permissible, as it would only result in shortening the life of the patient. The propriety of an amputation should only be considered in the begin- ning of the disease, and before extensive dissemination of the purulent infection by embolism has taken place. In a suppurating, compound fracture, amputation may be indicated for other reasons than those of a 356 PRINCIPLES OF SURGERY. threatened or developed attack of pyaemia. Secondary disinfection of a suppurating wound with excision of thrombo-phlebitic veins, where this is possible, should be practiced in all cases of pyaemia for the purpose of preventing or limiting general dissemination by embolism. In chronic cases the secondary metastatic processes should receive early and careful attention. As in these cases the metastatic suppuration, as a rule, is not caused by embolic infarcts, life is threatened by the secondary lesions, from which ptomaine intoxication is maintained, and from which new places ma3r become infected by localization of pus-microbes in capillary vessels weakened by the action of ptomaines. Suppurating joints are incised, drained, and irrigated under strict antiseptic precautions, and if the metastatic suppuration is limited to a single joint this can be done with a fair prospect of a favorable result. Purulent collections in the serous cavities or connective tissue are dealt with in a similar manner. Careful attention to diet and the sanitary surroundings of the patient, combined with energetic surgical treatment of the suppurating foci, will, at least occasionally, be rewarded by an ultimate recovery. SEPTICOPYEMIA. In the absence of more accurate knowledge concerning the microbic cause of septicaemia, we must, at least for the present, assign to septi- caemia and pyaemia the same bacteriological cause. That pus-microbes can produce septicaemia, when introduced into the circulation in sufficient quantity, has already been shown, and that pus-microbes have been frequently cultivated from septic products is a matter of demonstration ; hence the disease, if not identical with pyaemia, from a bacteriological stand-point, is at any rate closely allied to it. It has also been shown that, in case the life of septic patients is prolonged for a sufficient length of time, the metastatic foci of inflammation are the seat of incipient suppu- ration ; hence such cases resemble pyaemia upon a pathological basis. In pyaemia, after cessation of the rigors, which are the most character- istic clinical symptom of this disease, the fever resembles septicaemia, and, as the clinical picture thus developed rests upon pathological con- ditions typical of p37aemia, it would be proper to apply to such cases the term septico-pysemia. For the same etiological and pathological reasons we apply the same term to septicaemia in which post-mortem examination reveals the presence of minute, multiple, suppurating foci. Septico-pyaemia may be defined as a condition in which the symp- toms indicate the presence of both septicaemia and pyaemia, and in which the post-mortem appearances point to septic and purulent infection. Leube described such a combination of the two diseases, which as yet are SEPTICO-PYEMIA. 357 considered as distinct, occurring in patients in whom lie was unable to trace the source of infection from without; hence he called the affection spontaneous septico-pyasmia. Litten, on the other hand, in similar cases, was always able to locate the infection-atrium, but the primary infection at the time acute symptoms set in had either disappeared or its location could only be ascertained by most careful examination. Jiirgensen applied to these cases the lengthy compound word " kryptogenetic- septico-pyaemia," as he was unable to find a tangible infection-atrium. In a recent article on the subject he gives an account of 100 cases that came under his own personal observation. The patients were usually attacked first with acute pharyngitis, and, as this stage was generally attended by a chill and a general feeling of malaise, the patients generally attributed the onset of the disease to exposure to cold. In most cases the general infection was announced by a severe chill. Rapid loss of strength was one of the most prominent symptoms; the patients in a few hours after the chill became utterly prostrated. The symptoms which pointed to local processes during life were referred most frequently to the lungs, liver, spleen, pleura, heart, and the long bones. Whether the primary infection occurred through the pharynx, where the first symptoms were manifested, could not be definitely ascertained. In the acute cases, the symptoms were grave from the beginning and increased in intensity as the infection progressed, while, in the chronic cases, infection is kept up from some suppurating focus, and the disease may continue for several years. Subcutaneous and retinal haemorrhagic extravasations were frequently observed. Post-mortem examinations revealed suppuration in some of the internal organs, and vascular changes which are characteristic of sepsis. These cases may be compared with acute suppurative osteomyelitis, where, after the most careful inquiry and the most scrutinizing examina- tion, we often fail in furnishing reliable evidence for locating the primary source of infection. It is possible that the pus-microbes enter through an intact or inflamed mucous membrane, or through the appendages of the skin, and that they remain in a latent, inactive condition until a weak point is created somewhere in the body, where they localize in a soil prepared for their reproduction and pathogenic action, or, what is more likely the case, the37 entered through an abrasion or slight lesion, which may have been so insignificant that the patient himself failed to notice it, and produced no symptoms until, by accident or disease, a proper soil was prepared for the initiation of an acute attack in one or more of the internal organs. The remote dangers which may follow infection through an insignificant wound, or from a small, suppurating focus, should remind the surgeon of the importance of treating these little 358 PRINCIPLES OF SURGERY. ailments with the necessary care and attention, and by so doing he will often be the means of preventing fatal complications. In 2 cases of kryptogenetic septico-pyaemia that have come under my own observa- tion the disease was complicated by ulcerative endocarditis. In 1 of these cases the immediate cause of death was gangrene from embolism of the popliteal artery. CHAPTER XIV. Erysipelas. Erysipelas is a self-limited, acute, non-suppurative inflammation of the lymphatic vessels of the skin or mucous membrane, attended by red- ness and a continued type of fever. As a wound complication it occurs independently of suppuration, and in its uncomplicated pure form remains as a superficial affection, the inflammation never passing beyond the structures of the skin or mucous membrane. HISTORY OF ITS MICROBIC ORIGIN. The contagiousness of erysipelas has been recognized for centuries, and on this account early attempts were made to include it among microbic diseases. In 1868 Hueter maintained that erysipelas and hos- pital gangrene were identical diseases and caused by the same micro- organism. Its microbic nature was again made the subject of investi- gation in 1872, when Napveau discovered micrococci in the blood of erysipelatous patients. Wilde detected the same microbes in the blood, but asserted that similar micro-organisms could be found in the pus in wounds from which the erysipelas developed. In 1874 Recklinghausen found masses of micrococci in the lym- phatic channels in the inflamed skin at the border of an erysipelatous inflammation. Nearly the same time similar observations were made by Billroth, Ehrlich, Tillmanns, and Koch. Tillmanns produced the disease artificially in animals by injecting subcutaneously the serum con- tained in the bullae of erysipelatous skin. Koch attempted to produce the disease artificially in rabbits with injections of different putrid fluids, but failed until he made inoculations with mouse-dung softened in distilled water. He injected the material under the skin of the ear, and produced an inflammation which in its course resembled erysipelas. The swelling and redness spread slowly downward from the point of inoculation. On the fifth day it had extended as far as the root of the ear. The ear became exceedingly vascular, so that the separate vessels could no longer be identified, while the tissues were softened and oedematous. The animal died on the seventh day. Blood taken from the heart of this animal produced no effect in other rabbits. No microbes could be found in the blood or in any other (359) 360 PRINCIPLES OF SURGERY. organ except the affected ear. In transverse sections of the ear the blood-vessels were seen to be markedly dilated, full of red corpuscles, and surrounded by the nuclei of white corpuscles. Between these and the cartilage-cells bacilli were found. The bacilli were present close to the cartilage only. Here they were Fig.85—Section of Ear of Rabbit Parallel to Surface of Cartilage The Morbid Process Resembled Erysipelas, x 700. (Koch.)* A, ball-like accumulation of bacilli; B, accumulation of nuclei above the layer of bacilli • C nuclei of flat cells connected with the cartilage below the layer of bacilli; D, bacilli arranged Darallel to each other. ° r found in large clusters, from which the bacilli radiate in all directions. This net-work of bacilli extended over the whole cartilage of the ear on both surfaces. Inflammation was most marked in the vicinity of the bacilli, and, consequently, in the absence of other causes, there could be no doubt that the erysipelatous inflammation was caused by these * Copied from " Traumatic Infective Diseases," by permission of the New Sydenham Society, London. DESCRIPTION OF STREPTOCOCCUS ERYSIPELATOSUS. 361 microbes. Orth found micrococci in the contents of the bullae of erysip- elas. Recklinghausen and Lukowsky found them in the lymphatic ves- sels and the connective-tissue spaces in the structures affected by erysipelas. Billroth and Ehrlich found bacteria not only in the lym- phatic vessels, but also in the blood-vessels of the inflamed skin. Till- manns found microbes in erysipelatous skin, and Letzerich, in cases of erysipelas attacking vaccination wounds, found them in the wound itself, in the blood-vessels, muscles, liver, spleen, and kidneys. The essential specific cause of erysipelas was finally discovered by Fehleisen in 1883. He cultivated the microbe from erysipelatous products, and demon- strated its essential etiological relationship to erysipelas by producing the disease artificially, in animals and man, by inoculations with pure cultures. From the morphological appearance of the microbe and its direct etiological bearing to erj'sipelas he called it the streptococcus of erysipelas. With pure cultures of this microbe he produced by inocula- tions not only er37sipelas in animals, to prove its specific pathogenic qualities, but successful inoculations were also made in man for thera- peutic purposes. DESCRIPTION OF STREPTOCOCCUS ERYSIPELATOSUS. The streptococcus erysipelatosus, discovered by Fehleisen, when examined under the microscope appears in the - form of chains, the links of which are minute cocci, 3 to 4 micromillimetres in diameter. The streptococcus of erj-sipelas invades the superficial lymphatic channels of the skin or mucous membrane exclusively, but it can also be found in the serum contained in bullae. Each coccus, when it is about to divide, becomes larger FEiYsiraL™TO™PHKE and oval, and soon appears made up of two hemi- at^c^^staine^with spherical masses, the two new cocci resulting from gartm )N' X 95°' (Baum~ fission of the old one. Morphologically, the strep- tococcus of erysipelas and the streptococcus pyogenes are nearly iden- tical, only that the cocci of erysipelas are somewhat larger, while both are somewhat smaller than the staphylococci. CULTIVATION. This microbe can be readily cultivated in bouillon at ordinary room- temperature ; also upon gelatin, agar-agar, and solidified blood-serum. Upon solid nutrient media the appearances of the cultures resemble very strongly those of streptococcus pyogenes. There is less tendency, however, to the formation of terraces the margin is thicker and more 362 PRINCIPLES OF SURGERY. irregular in outline, and the appearance of the growth is more opaque and whiter. Rosenbach mentions, as another distinguishing feature between the two, that the culture of the streptococcus of er37sipelas represents the shape of a fern, while the outlines of the cultures of the pus-strepto- coccus describe the shape of an acacia-leaf. The culture appears as a very delicate grayish-white film. The growth is very slow, and the individual colonies remain small. The streptococcus of erysipelas does not liquefy gelatin. The microbe of erysipelas grows equally well when ox3'gen is excluded. If gelatin is inoculated by puncturing with a needle charged with a pure culture, microscopical colonies can be seen the whole length of the track of the needle at the end of twenty-four hours. In four days the culture has reached the height of development, and colonies the size of a grain of sand to that of a pin's head occupy the whole length of the needle-track. In cultures the microbe retains its pathogenic qualities for about four months. INOCULATION EXPERIMENTS. Fehleisen produced, artificially, typical erysipe- las in rabbits by injecting pure cultures under the skin of the ear. Koch and Gaff ky used cultures grown upon solidified blood-serum and inoculated 9 rabbits. In 8 of these typical erysipelas de- veloped, the attack lasting from six to twelve days. Krause obtained positive results by inoculat- ing gray mice. In all cases where the inoculation proved successful the erysipelatous inflammation started at the point of inoculation, and extended rapidly, always following the lymphatic channels. In Krause's experiments the animals died after three or four days, even when only a minute quantity of the culture was injected under the skin of the back. Examination of the infected tissues after death showed that inflammation followed the invasion of the microbes, and consequently the principal pathological changes were found within and in the immediate vicinity of the lymphatic channels. INOCULATION FOR THERAPEUTIC PURPOSES. As soon as it was demonstrated experimentally that simple, uncom- plicated erysipelas is a disease attended by but little danger to life, the suggestion was near that, if the disease could be artificially produced in Fig. 87.—Stale Cul- ture of Streptococ- cus of Erysipelas in Gelatin at Ordi- nary Temperature of Room, Four Days Old, Natural Size. (Baumgarten.) INOCULATION FOR THERAPEUTIC PURPOSES. 363 man by inoculation with pure cultures, the local and general conditions thus produced might prove useful in the cure or amelioration of some diseases not amenable to operative treatment and internal medication. Of 1 persons the subjects of incurable tumors, inoculated by Fehleisen with pure cultures, 6 developed typical erysipelas ; in the seventh case the patient had passed through an attack of erysipelas only a few weeks previously, and was, in all probability, still protected against a new attack. This patient was inoculated a second time with a negative result. In other instances a second inoculation failed after a successful inoculation. The period of incubation was fixed at from fifteen to sixty- one hours. The microbe was found only in the lymphatic vessels and con- nective-tissue spaces, and when the culture was pure suppuration was never produced. Fehleisen has seen, by this treatment, a cancer of the breast become smaller, a lupus disappear almost completely, while a case of fibro-sarcoma and another of sarcoma were not materially affected by this method of treatment. Janicke and Neisser have recorded a death from erysipelas thus intentionally produced in a case of cancer of the breast beyond the reach of an operation. At the necropsy it was proved that the tumor had almost completely disappeared, and the microscopical examination of portions that had remained appeared to show that the tumor-cells had been destroyed through the direct action of the microbes. Biedert saw, in a child suffering from a sarcoma involving the posterior part of the cavity of the mouth and pharynx, the left half of the tongue, the naso-phar37ngeal space, and the right orbit, the tumor disappear almost completely during an attack of erysipelas. Cases, on the other hand, have been reported in which, after an accidental or intentional attack of erysipelas, the tumor commenced to grow more rapidly. Neelsen reports a case of carcinoma of the breast, in which, after two severe attacks of erysipelas, the tumor not only commenced to grow faster, but at the same time the regional infection progressed also more rapidly. Babtchinsky made the accidental discovery that the microbe of erysipelas is a direct antagonist to the virus of diphtheria. His son, while suffering from a most severe attack of diphtheria, was suddenly attacked by erysipelas. This complication, grave of itself, seemed to hasten the fatal termination of the case, and during the first few hours of the eruption the patient was much worse. But the next day the symptoms had much improved, and the patient made a rapid recovery. Following this indication Babtchinsky inoculated a second case of diphtheria with a culture of the microbe of erysipelas grown on agar- agar, and with an equally happy result. Since this time, of 14 cases of diphtheria treated with these inoculations, 12 resulted in recovery, and, 364 PRINCIPLES OF SURGERY. as in the 2 cases resulting fatally the inoculation produced no effect, these negative results only tend to confirm the efficacy of the curative inoculations. It is remarkable that in all of the cases where er37sipelas was produced artificially this disease pursued a mild course, and the patients recovered rapidly from both diseases. Schwimmer gives an account of 11 cases of lupus, in all of which no improvement was observed after an intercurrent attack of erysipelas. In a case of keloid an attack of erysipelas was followed by marked improvement, and a lipoma underwent a similar favorable change from the same cause. S^^philitic lesions he saw temporarily benefited, while the erysipelas had no effect in permanently influencing the course of the disease. Bruess gives an account of the effect of erysipelas on tumors in 22 patients. Among these 3 cases of sarcoma were permanently cured. Two cases of multiple keloid after burns were also cured. In 4 cases of lymphoma of the neck some of the glands became smaller and some disappeared. In 5 cases the erysipelas was artificially produced by inoculation with a pure culture. In 3 cases of carcinoma of the mamma 1 was not influenced by the disease, 1 became one-half smaller, and 1 was reduced to a small induration in the scar the size of a pea. A multiple fibro-sarcoma was greatly benefited, while an orbital sarcoma was not improved. In view of the uncertainty of the result, and the not inconsiderable danger which attends the intentional form of erysipelas in patients debilitated by antecedent disease, it is safe to predict that no further inoculations will be made in man until, perhaps, future research will demonstrate a certain specific antagonistic action of the streptococcus of erysipelas against some other pathogenic microbes, the cause of grave diseases not amenable to successful treatment b37 less heroic measures. MANNER OF INFECTION. An intact skin or mucous membrane furnishes absolute protection against infection with the streptococcus of erysipelas. This microbe cannot reach the lymphatic vessels without an infection-atrium, which may be a small abrasion, a wound, blister, ulcer,—in fact, any breach of continuity in the skin or mucous membrane. Before antiseptic surgery was practiced, infection frequently occurred through accidental or inten- tional wounds. Antiseptic surgery has greatly diminished the frequency of traumatic erysipelas, but has not completely eradicated it, as an occasional case will occur in the hands of the most careful antiseptic surgeons. Even before the microbic cause of erysipelas was known, Trousseau, one of the closest of clinical observers, claimed that infection MANNER OF INFECTION. 365 with the virus of erysipelas is only possible through some wound or abrasion of the skin ; the latter ma37 be so insignificant as to be unnotice- able and entirely overlooked by both patient and physician. Idiopathic or spontaneous erysipelas, so called, does not exist; every case of ery- sipelas is traumatic, in so far that by injury or disease the necessary infection-atrium must be created through which the streptococcus can reach the lymphatic vessels. In erysipelas without a tangible infection- atrium, infection occurs through a minute puncture or abrasion, which may, perhaps, never have attracted the patient's attention, and which has become invisible at the time the disease is first noticed. Infection, however, ma3T also take place through a mucous membrane, through which the microbes enter the tissues in the same manner and under the same conditions as when infection takes place through the skin. One of the severest cases of erysipelas that ever came under my observation Fig. 88.—Section through Skin near the Margin of the Erysipelatous Zone. X "00. (Koch.) 1, 1, each a lymphatic vessel filled with streptococci in chains. commenced in the pharynx, or tonsils, and, as the symptoms subsided here, a typical and severe facial erysipelas developed. As the patient was suffering at the same time from secondary syphilis, it is probable that the streptococcus of erysipelas entered the tissues through the secondary syphilitic lesions in the pharynx. In the tissues the strepto- coccus of erysipelas invades the lymphatic channels exclusively, and manifests here its specific pathogenic qualities. The erysipelatous inflammation is, in reality, a specific, progressive lymphangitis, the para-lymphatic tissues becoming affected by contiguity. Within the lymphatic channels the microbe multiplies, and diffusion of the infection takes place in the course of the lymphatic vessels, but does not always follow in the course of the lymph-stream. The lymphatic vessels are often found crowded with the microbe, which is destroyed in a short time, as with the subsidence of the inflammation the microbe disappears. According to Koch, and Fehleisen, the microbe is always 366 PRINCIPLES OF SURGERY. found most numerous in the portion of the skin corresponding to the border of the inflamed area. At this point the lymphatics frequently appear completely blocked by dense colonies of this microbe, so that no lymph-corpuscles can be seen among them. As the inflammation extends to the surrounding connective tissue, some of the microbes leave the lymphatics and enter the connective-tissue spaces, where they come in contact with the inflammatory exudation. Within the lymphatic vessels the streptococci are found between the lymph and colorless blood-cor- puscles ; in the connective tissue they are found also within the proto- plasm of leucocytes. Metschnikoff maintains, in opposition to most of the modern au- thors, that the arrest of the extension of the erysipelatous inflammation is accomplished by phagoc37tosis. The accumulation of leucocytes in the inflamed tissues has, undoubtedly, a salutary effect in mechani- cally blocking the avenues through which infection takes place; but as most of the microbes are outside of, and not within, the leucocytes and lymph-corpuscles, it is difficult to conceive how limitation of the extension of the infection could be accomplished solely by phagoc37tosis. The microbes have a very short existence in the tissues ; the inflammation which they initiate continues for some time after all microbes have dis- appeared. The ptomaines which microbes secrete produce protoplasmic alteration of the connective-tissue cells and the capillary blood-vessels, which prolong the inflammation be3rond the period when the tissues are in a sterile condition. Others have claimed that self-limitation of ery- sipelas is due to destruction of the microbes by the high temperature which attends the disease. De Simone has recently shown that pure cultures of the streptococcus of erysipelas lose their power of reproduc- tion if they are exposed for two days consecutively to a temperature of 39.5° to 41° C. Clinical experience, however, has demonstrated conclu- sively that erysipelas is not arrested in its course by a temperature of 40° C, or more. It appears that the streptococcus exhausts the soil of the nutrient material which it requires for its growth and reproduction in a short time. In the blood-vessels of the inflamed skin no strepto- cocci can be found, but that they occasionally enter the blood-vessels is sufficiently evident from the occurrence of metastatic erysipelas, and the direct transmission of erysipelas from mother to foetus by infection through the placental circulation. As the streptococcus of erysipelas produces its pathogenic effects in the lymphatic vessels, and diffuses itself through these channels in the tissues, it becomes obvious that in all cases infection takes place as soon as localization is effected in the superficial lymphatic structures, or in the spaces contributory to them, and in direct connection with an infection-atrium. RELATION OF ERYSIPELAS TO PUERPERAL FEVER. 367 RELATION OF ERYSIPELAS TO PUERPERAL FEVER. Obstetricians recognized the danger of exposing puerperal women to the infection which might emanate from erysipelatous patients long before the microbe of erysipelas was known. Since the discovery of the microbe by Fehleisen, this subject has attracted renewed attention, and positive knowledge has accumulated both from accurate clinical obser- vation and from the fertile and more positive field of experimentation. Gusserow asserted, upon the basis of an extensive experience, that no direct etiological relations exist between the contagium of erysipelas and puerperal fever. He had under his care puerperal women suffering from erysipelas of the skin without any serious disturbances following in the genital tract. In 10 other cases, one of them occurring during an epi- demic of puerperal fever, the eiysipelas was observed as a complication of septic affections of the genital organs. Gusserow claims that in this case it cannot be claimed that erysipelas could have caused the puerperal affection, as the latter preceded the former. But another point could be raised, as it might be claimed that the septic processes should be made answerable for the occurrence of eiysipelas. This author has studied this subject also by way of experiment. A pure culture of the strepto- coccus erysipelatosus, which had been tested and found reliable in pro- ducing erysipelas b37 the usual methods of inoculation, was injected into the peritoneal cavity of 2 rabbits ; in 2 others it was applied to an open wound of the abdomen, and in the last 2 animals it was injected into the subserous connective tissue of the peritoneum. In all of these animals no effect was produced, and no pathological changes were detected at the point of injection when the animals were killed, some time after the inoculation. Gusserow looks upon the results of these experiments, if not as positive proof, nevertheless as strong evidence against the claim that er3Tsipelas can cause puerperal sepsis. Winckel, an equally reliable and able observer, has come to entirety opposite conclusions. He culti- vated from a parametritic abscess, which had developed after childbed, Fehleisen's streptococcus. Injections of this culture into rabbits pro- duced typical erysipelas. The same author also observed er3rsipelas fol- lowing in a puerperal woman suffering from suppurative perimetritis, pleuritis, and metro-lymphangitis. The patient died on the thirteenth da}r. The starting-point of the erysipelas could be traced to an ulcer of the vulva. Blood taken from the right side of the heart soon after death was inoculated upon a solid nutrient medium, and produced a culture of the streptococcus of erysipelas. The same culture was obtained by in- oculations with fluids taken from the peritoneal and pleural cavities, the uterus, kidne37s, and the liver. In 3 cases a culture thus obtained was injected into the peritoneal cavity of rabbits, and no peritonitis followed. 368 PRINCIPLES OF SURGERY. In 1 experiment the injection produced suppurative peritonitis. Guinea- pigs proved less susceptible to infection than rabbits. In white mice the inoculations were invariably productive of a fatal disease. From the results of these experiments the author claims that the virus of ery- sipelas is one of the most virulent puerperal poisons, and believes that they prove the casual relations of eiysipelas to puerperal sepsis. Doyen also found, both in mild and severe cases of puerperal fever, a streptococcus similar to the one described by Rosenbach and Fehleisen. He made some inoculations to determine the relationship between puer- peral sepsis and erysipelas. The streptococcus found in the infected tissues of puerperal-fever patients caused erysipelas, and the streptococ- cus found in eiysipelas developed puerperal fever. From his own obser- vations and experiments the author arrived at the conclusion that the microbe of puerperal sepsis is the same as that of erysipelas. From a clinical and bacteriological stand-point it is evident that puerperal sepsis from infection with the streptococcus of erysipelas can only occur when the streptococcus is brought in contact with an absorbing surface in the genital tract; but when this takes place, and the microbes reach the en- larged lymphatic vessels of the puerperal uterus, the most violent and fatal form of puerperal sepsis is almost certain to follow. RELATION OF ERYSIPELAS TO PHLEGMONOUS INFLAMMATION AND SUPPURATION. Some difference of opinion still exists, among bacteriologists, with regard to the question whether the streptococcus of erysipelas possesses pyogenic properties. The majority of those who have studied this subject experimental^ do not consider the streptococcus of erysipelas as a pus-microbe, and assert that when suppuration takes place in erysipelas it is the result of a secondary infection with pus-microbes, and, on this account, look upon phlegmonous inflammation as a complication, and not as a condition belonging to the erysipelatous process. Hajeck made careful investigations to show that the streptococcus of erysipelas is neither in form nor culture materially different from the streptococcus pyogenes, but he showed, also, that in 51 cutaneous or subcutaneous in- oculations with a pure culture of the streptococcus of erysipelas in rabbits the result was alwa37s a superficial migrating dermatitis which resembled to perfection erysipelas in man, while similar injections with the strepto- coccus of pus produced a more intense and deeply-seated inflammation, which in almost every instance terminated in suppuration. The differ- ence in the action of the two microbes on the tissues plainly demon- strated their non-identity. Microscopical examination of the inflamed tissue showed a still more important difference as far as the localization PHLEGMONOUS INFLAMMATION AND SUPPURATION. 369 and local diffusion of the microbes were concerned. The microbe of erysipelas was always found with the products of inflammation within the lymphatic vessels, and only exceptionally in the connective-tissue spaces, which anatomically are only a part of the lymphatic system. The pus streptococcus penetrates the tissues more deeply ; it is not only found in the lymphatic vessels and connective-tissue spaces, but it mi- grates beyond the lymphatic channels and infects different kinds of tissue. thus giving rise to a more deeply-seated and more intense inflammation. The streptococcus of erysipelas is found only exceptionally in the im- mediate vicinity of blood-vessels ; while the microbe of pus can always be seen arranged in radiate lines around vessels entering the adventitia, the muscular coat, and often even in the lumen of the vessel. In man the same histological differences can be seen in the tissues the seat of erysipelatous and phlegmonous inflammation as in the artificial conditions in animals subjected to experiment, and the same pathological differences are also constantly found. The author asserts that Fehleisen was in error when he claimed that the formation of abscesses occurred independently of the eiysipelatous infection. He affirms that in rabbits inoculated with the virus of erysipelas after the acute inflammation has subsided circum- scribed small nodules which remain may suppurate, but suppuration never becomes diffuse, while after injection with cultures of the strepto- coccus p37ogenes the inflammation assumes a phlegmonous type and the suppuration is always more diffuse. Hajeck maintains that under certain circumstances a circumscribed superficial suppuration can also take place in erysipelatous inflammation in man. When suppuration in a joint takes place, however, it is not caused by the erysipelatous infec- tion, but is due to the presence of pus-microbes. Eiselsberg, Bonone, Bordini, Passet, and Simone are of the opinion that the streptococcus of eiysipelas and the streptococcus of suppuration do not differ in their pathogenic effects. Smirnoff found in 1 case of erysipelas the specific microbe in the metacarpophalangeal joint of the left hand, which was the seat of the disease. In the case of a man who had died of erysipelas, enormous col- onies of the streptococcus were found in the right shoulder and knee joints. The synovial fluid injected into rabbits occasioned erysipelas migrans. Rheiner found Fehleisen's streptococcus in all cases of traumatic erysipelas which he examined, but was unable to find it in 2 cases of gangrenous erysipelas following typhus. In these cases he found bacilli which he believed were identical with Klebs-Eberth's bacillus of typhus. Kahlden, after a careful study of the recent literature on erysipelas, and the difference in opinion on the pathogenic properties of the strepto- 24 370 PRINCIPLES OF SURGERY. coccus erysipelatosus, remarks that the subtility in the differences between the morphology and the cultures of the microbe of erysipelas and the streptococcus of suppuration is undoubtedly the reason why no uniformity of opinion exists in regard to their specific pathogenic effects, especially as to the possibility of Fehleisen's streptococcus producing suppuration. To this I might add that not every superficial diffuse inflammation of the skin is erysipelas, and not every abscess occurring during, or soon after, an attack of erysipelas should be considered as a product of the erysipelatous infection. The surgeon will do well to adhere to the teachings of Fehleisen, who is positive in his assertion that the streptococcus of erysipelas never produces suppuration, until more convincing proof shall have been furnished of the pathogenic identity of the streptococcus of erysipelas and the streptococcus of suppuration. SYMPTOMS AND DIAGNOSIS. Erysipelas, like most of the acute infectious diseases, has no well- marked premonitory stage, the attack being sudden and followed by all the symptoms which usher in an acute febrile affection. The period of incubation in man has been fixed at from fifteen to sixty-one hours by the inoculations which have been made to produce the disease artificially for therapeutic purposes. Inoculations prove successful if the skin is punctured with a needle the point of which had been dipped into a pure culture of the streptococcus. Such punctures have no visible lesion after a few hours,—a fact which readily explains the disappearance of a visible infection-atrium at the time the disease appears, in cases of erysipelas developing without a demonstrable breach of continuity in the skin. In the adult the disease commences, almost without exception, with a chill which sometimes amounts to a severe rigor. Nausea and vomitino- are often present during the first few hours. The chill is followed by a rise in the temperature, which in a few hours increases to 104° F. or more. The fever assumes a continuous type, and in uncomplicated cases the difference between the morning and evening temperature is slight. Headache, thirst, and complete loss of appetite are constant and promi- nent symptoms. The pulse is at first full and bounding and seldom exceeds 100 beats per minute. In severe cases delirium is present almost from the beginning, and continues until the fever subsides. Almost simultaneously with the appearance of the general symptoms, the skin in the immediate vicinity of the infection-atrium shows evidences of the existence of a superficial inflammation. The patient complains of a sense of tightness in the part, which is accompanied by a burning and itching sensation. SYMPTOMS AND DIAGNOSIS. 371 In traumatic erysipelas the wound presents no changes in its appear- ance ; if suppuration is present the purulent discharge becomes some- what diminished in quantity and the pus is rendered more serous. The skin around the seat of infection is firmer to the touch, and if the erysipelas has started from a wound infection has occurred from a certain portion of the wound, while the remainder shows no evidences which point to erysipelatous inflammation. The skin which is involved by the erj'sipelatous inflammation presents, almost from the beginning, a characteristic rose or crimson color. With the appearance of the typical discoloration the inflammatory exudation has reached its height. The color disappears under pressure, but upon the removal of the press- ure no depression is left, showing that little or no oedema is present. The induration of the skin is most marked at the border of the erysipe- latous zone, and disappears with the absorption of the inflammatory product and the return of the natural color of the skin. The margin of the zone is abrupt and distinct on the side of the healthy skin. The border of the erysipelatous zone is not straight, but irregular, and often fan-like projections can be felt which project into the healthy skin, and, when present, they are characteristic, almost pathognomonic, of this form of dermatitis. The degree of swelling varies according to the intensity of the infection and the anatomical structure of the part involved. If the infection is intense and parts are implicated which are abundantly supplied with loose connective tissue, the swelling is greater than in cases where the infection is mild or the skin is stretched over firm, resisting parts. In facial erysipelas, for instance, the swelling is much greater around the orbits than in the scalp, because in the former locality the loose, cellular, connective tissue underneath the skin becomes swollen and oedematous from the escape into it of the inflammatory transudation. The specific inflammation, starting from the point of infection, spreads continuously and uninterruptedly along the course of the super- ficial lymphatics, but is not limited to the direction of the lymph-current. The intra-lymphatic diffusion of the streptococcus is not a passive, but an active, process. As this microbe is non-motile, its transportation in a direction opposite to the lymph-stream can only occur b3r its reproduc- tion. The lymph-current in most, if not all, of the inflamed lymphatic vessels is temporarily arrested by the blocking of the interior of the lym- phatic vessels with colonies of the streptococcus and the accumulation of lymph-corpuscles; consequently the colonies become fixed points from which new tissues are infected by their increase in size in all directions, owing to rapid reproduction of the microbe. The fever continues until the infection comes to a stand-still. The intensity of the subjective 372 PRINCIPLES OF SURGERY. symptoms does not always correspond with the temperature, as patients may feel quite well when the temperature registers 104° to 105° F., while others show evidences of serious disturbance with a much lower temperature. Small vesicles and large bullae usually result from conflu- ence of a number of vesicles. The contents of these blisters are first serous, but suppuration may follow later from the entrance of pus- microbes. Bullae with haemorrhagic contents denote a grave attack. The duration of erysipelas is extremely variable. Genuine erysipelas may run a typical course and terminate in recovery in two days, or the disease may extend over a period of two weeks or more. The extent of surface successively invaded determines its duration. If it start from a wound of the hand it may extend along the forearm and arm to the shoulder, from here along the back to one or both of the lower extremi- ties, and before such a large territory of skin has passed through all the stages of the disease more than four weeks may elapse. As soon as the disease ceases to migrate the general symptoms subside, and within a few days the skin returns to its normal condition, and the patient recovers his usual health in a remarkably short time,—a fact which tends to prove that er37sipelas, in its uncomplicated form, does not impair the function of any of the internal organs to any considerable extent. Exfoliation of the skin is a usual occurrence. In the differential diagnosis we have to consider lymphangitis, er3-thema, phlegmonous inflammation, and thrombo-phlebitis. In lymphangitis from other causes than the streptococcus of erysipelas the inflammation follows larger lymphatic channels, which appear as red lines, and seldom, if ever, is the skin proper inoculated in the inflammatory process, while erysipelas is a combination of bymphangitis with dermatitis. Erythema appears as circumscribed points of inflammation in the skin with healthy tissue between, while, on the other hand, erysipelas shows no such interruptions, the inflammation being a continuous, uninterrupted process followed by speedy repair. Phlegmonous inflammation is accompanied by inflamma- tion of the skin, which, in its external appearances, closely resembles erysipelas; but the differential diagnosis rests on the location of the primary inflammation, which is alwa37s the superficial lymphatics of the skin in erysipelas, and the subcutaneous tissue in phlegmonous inflam- mation. In phlegmonous inflammation the deep-seated inflammatory exudation is the primary pathological condition, and the lymphangitis follows as a secondary result, while in erysipelas the primary specific lymphangitis and dermatitis are primary conditions, and if the subcu- taneous tissue become involved later on it must be regarded as a com- plication, and not as an integral part of the disease. Patients suffering from erysipelas complain of a smarting, burning, or itching sensation in CLINICAL FORMS OF ERYSIPELAS. 373 the affected skin; phlegmonous inflammation is attended by severe pain, which is of a throbbing character. Thrombo-phlebitis, starting from a chronic ulcer of the leg, has often been mistaken for erysipelas, not only by laymen, but also by physicians. Thrombo-phlebitis is often attended by inflammation of the tissues around the inflamed vein and of the superimposed skin, but the inflammation follows in the course of the vein, and not in the course of lymphatics; at the same time the vein can be felt as a solid, tender cord. CLINICAL FORMS OF ERYSIPELAS. The clinical forms of erysipelas are identical in so far that they are all caused by the same microbe, and that the disease primarily consists of a specific lymphangitis and dermatitis; but they vary greatly, accord- ing to the location and structure of the part affected, the intensity of the infection, and the existence of complications. Erysipelas Erythematosum.—This is the mildest form of erysipelas. It is described as erythematic because the affected skin shows but little swelling, and the affection appears more as an efflorescence than an inflammation. No bullae form, and only slight exfoliation takes place during convalescence. Erysipelas Bullosum.—In this form the inflammation of the skin is more intense and the swelling more marked, in consequence of which blisters or bullae form underneath the cuticle. The pathological condi- tion resembles a burn in the second degree. Removal of the cuticle leaves the papillary layer of the skin exposed. The bullae often become the seat of secondary infection with pus-microbes, which transform the serous contents into pus. From such superficial foci of suppurative inflammation ma3r develop what has been termed— Phlegmonous Inflammation.—As we are not in possession of con- clusive proof that the streptococcus of erysipelas possesses pyogenic properties, we can only explain the occurrence of phlegmonous inflam- mation of the tissues underneath the skin affected by erysipelatous inflammation by taking it for granted that the deep-seated phlegmonous inflammation is caused not only by the streptococcus of erysipelas, but by the accidental entrance into the tissues of microbes of suppuration. As soon as secondary infection with pus-microbes takes place the clinical picture of erysipelas is overshadowed or obscured by the suppurative inflammation. The typical general and local symptoms which char- acterize the erysipelatous inflammation give way to symptoms which indicate the existence of a diffuse suppurative inflammation. The tem- perature shows greater remissions, and the pulse becomes more rapid and feeble. The tongue is often red and dry, while all of the remaining 374 PRINCIPLES OF SURGERY. symptoms point to intoxication from absorption of ptomaines- produced in the tissues by the pus-microbes. The swelling of the part affected is no longer limited to exudation into the substance of the skin, but affects mainly the deep-seated tissues. We have reason to believe that in most, if not in all, cases of phlegmonous erysipelas the secondary infection with pus-microbes takes place from a superficial suppurating focus as from a suppurating bulla, and that the microbes from here invade the subcutaneous connective tissue. The phlegmonous inflammation spreads with great rapidity, so that in a few days the skin of an entire extremity may become under- mined with pus, the patient, in the meantime, having complained but little of pain. Such an extremity on palpation imparts the sensation of a partially filled diffuse abscess-cavity. The external appearances furnish, often, no reliable indications of the extent of the deep-seated destruction. If incisions are made at this time a large quantity of pus escapes, mixed with shreds of necrosed connective tissue, and examina- tion reveals extensive destruction of the subcutaneous connective tissue and intermuscular septa. Phlegmonous inflammation, as a rule, does not attack tissues the seat of an erysipelatous inflammation, but the tissues weakened by this disease and infected with pus-microbes. A sudden increase in the temperature of patients suffering from erysipelas is often the first symptom which commences this complication, and such an occurrence should admonish the attendant to detect it early in order to subject it to timely and efficient treatment. Erysipelas Gangrenosum.—This is an exceedingly grave form of er}rsipelas. Most of the authors are of the opinion that if the strepto- coccus of erysipelas multiplies with sufficient rapidity, in the interior of the lymphatic vessels and the connective-tissue spaces, so as to com- pletely block these channels by its growth, a sufficient amount of ptomaines is produced to cause necrosis of the tissues, and under such circumstances the erysipelatous inflammation terminates in gangrene of the skin. This gangrene may take in circumscribed multiple patches, so that after separation and elimination of the dead tissue the skin presents a cribriform appearance, or it may involve a large district of the skin, and then give rise to extensive loss of this structure in case the patient survives the disease. As the gangrene often commences in the portion of skin covered by bullae, it still remains an open question whether it results from the action of the streptococcus of erysipelas, or whether it is the result of a secondary infection with pus-microbes. Isolated patches of gangrene of the skin are met with in many cases that termi- nate in recovery, but extensive gangrene of the skin is always a serious complication, as it inay result in death from septicaemia, or, if life is not CLINICAL FORMS OF ERYSIPELAS. 375 destroyed, it at least greatly protracts the recovery, and often calls for a tedious treatment to restore the lost tissue by skin-grafting. Erysipelas Metastaticum.—By metastatic erysipelas is meant the occurrence of an erysipelatous inflammation in an organ or a part where the process developed separately from the primary field of infection. If, for instance, er37sipelas should appear in an extremity opposite to the one primarily affected, without extension of the disease across the skin of the trunk, it would furnish a good example of what is meant by metastatic erysipelas. Again, if during an attack of erysipelas of one of the extremities the patient should be attacked with symptoms of men- ingitis, and at the necropsy the streptococcus of erysipelas could be demonstrated in the inflamed envelopes of the brain, this would furnish another illustration of metastatic erysipelas. Two possibilities present themselves in explaining the occurrence of metastatic erysipelas. In the first place, colonies of the streptococcus in an active condition might reach a part distant from the erysipelatous inflammation with the lymph- current, and, meeting with favorable conditions, might establish an addi- tional focus of erysipelatous inflammation, which, of course, would have to be necessarily in a part between the primary field of infection and the termination of the lymphatic vessels leading from the infected dis- trict. If no such connection can be established, then the metastatic process results from the entrance of streptococci in an active condition into the circulation and their localization in distant parts or organs by mural implantation upon the wall of capillar vessels prepared for their localization and reproduction. In most instances metastatic erysipelas is of such an embolic origin. Erysipelas Migrans.—Migration of the inflammatory process is one of the characteristic clinical features of er37sipelas. In ordinary cases migration is limited to the anatomical region affected. In cases of facial erysipelas the disease seldom spreads be37ond the scalp, and in erysipelas of the extremities the disease usually subsides after it has extended over an extremity. Migrating erysipelas is that form of the disease where the erysipelatous inflammation extends from place to place, and from limb to limb. I have seen this form most frequentby in infants, starting from the umbilicus or the external genital organs. I have seen it start from these points, ascend in an upward direction along the anterior aspect of the body, and, after reaching both shoulders, spread to the upper extremities, later to descend down the back, and finally terminate in the toes after traveling nearly over the whole surface of the bod37. Ei-37sipelas of the extremities or trunk never extends to the face or scalp, while, in exceptional cases, erysipelas of the face assumes the migrating form. Migrating erysipelas is usually attended by only moderate swelling 376 PRINCIPLES OF SURGERY. and slight constitutional disturbances. One peculiarity of this form of erysipelas is that the same regions may become involved a second time. Erysipelas Facialis.—This is the so-called spontaneous or idiopathic form of erysipelas, as in most cases even close inspection does not reveal the existence of an infection-atrium. The disease usually commences in one of the alae, or at the root of the nose,—localities where minute skin lesions are frequently produced, and localities which more than any other part of the face are exposed to infection by contact. As far as its extension is concerned, facial erysipelas pursues the most typical course. The inflammation spreads toward the cheek and orbit on the side first affected, and then creeps across the bridge of the nose to the opposite side, to follow a similar course here. About the second or third day it reaches the forehead, and from here and the outer margins of the orbits it invades the scalp, to terminate usually about the end of a week at the nape of the neck. The chin and anterior aspect of the neck never become affected in facial erysipelas. Facial erysipelas is attended by considerable swelling, the eyes being often completely closed by the oedematous lids. Bullae form frequently about the centre of the cheeks and the forehead. One^f the dangers of facial erysipelas consists in the direct extension of the erysipelatous inflammation from the skin along the blood-vessels to the meninges of the brain. The meningitis under these circumstances is not a metastatic process, but the result of a direct extension of the inflammation from the skin to the meninges, along structures which connect them through the intervening skull. Patients who have suffered from facial erysipelas are not protected against subsequent attacks ; in fact, experience has shown that they are more prone to infection in the future than persons who have never suffered from this disease. If the bullae suppurate, there is always danger arising from suppurative thrombo-phlebitis, suppurative lepto-menin- gitis, and suppurative encephalitis,—fatal complications plainly attribu- table to secondary infection with pus-microbes. Traumatic Erysipelas.—We have seen that, in the strict sense of the word, all cases of erysipelas are traumatic in their origin, in so far that infection never takes place through an intact skin or mucous membrane; consequently the disease never occurs without an infection-atrium, which may be a wound or a lesion of the surface through which the strepto- coccus gains entrance into the lymphatic channels. The expression " traumatic erysipelas" is still retained for the purpose of designating erysipelas as one of the numerous forms of wound complications. If a recent wound is infected with the microbe of erysipelas the disease de- velops within fifteen to sixty-one hours after the accident or operation. PROGNOSIS. 377 The disease ma37 occur in consequence of later infection at any time before cicatrization is completed, as granulations furnish no absolute protection against infection. I have seen the disease originate more frequentby in granulating than in recent wounds,—a strong argument in support of the advice that full antiseptic precautions should not be relin- quished until the healing process is completed, if the patient is to be pro- tected against an attack of erysipelas. Another important fact should alwaj's be remembered : that small wounds are more frequently attacked by erysipelas than large wounds, because the latter receive more careful attention, and are, as a rule, subjected to more rigid antiseptic treatment. PROGNOSIS. Simple uncomplicated erysipelas is not a fatal disease unless it attacks infants or persons debilitated by age or antecedent diseases. Death is caused more frequentby b3' complications. The most common fatal complications are suppurative inflammation at the seat of er37sipe- latous inflammation, or metastatic suppuration in distant parts or organs, resulting from secondaiy inflammation with pus-microbes, or, finalby, ex- tension of the eiysipelatous inflammation to important organs, as the brain or its envelopes, in cases of facial erysipelas, or the occurrence of metastatic er3'sipelas in vital organs from embolic processes. The prog- nosis is, therefore, based large^7 upon the absence or presence of com- plications, which must be carefully sought for in all cases where general or local sN'mptoms point to their existence. The temperature, pulse, and condition of nervous and digestive organs furnish important and valuable prognostic indications. TREATMENT. The number of specifics which at different times have been recom- mended in the local and general treatment of erysipelas must throw doubt upon the efficacy of any local applications or internal remedies in arresting the further progress of eiysipelas. At the same time it must not be forgotten that uncomplicated erysipelas is a disease which tends to spontaneous recovery, and seldom proves fatal, even if it is al- lowed to pursue its own course, unaided by any local application or in- ternal medication. The erysipelatous inflammation is of short duration, and passes through its different stages uninfluenced by local or general treatment. Since its microbic origin has been suspected different meth- ods of treatment have been recommended to arrest the further progress of the disease by destroying or rendering inert the primary cause. Hueter aimed at the destruction of the specific microbe by injecting at different points at the border of the er37sipelatous zone 5 to 6 cubic 378 PRINCIPLES OF SURGERY. centimetres of 3-per-cent. solution of carbolic acid. This method of treat- ment in the hands of others has been followed almost without exception by negative results. It is possible that subcutaneous injections of a l-to-1000 solution of corrosive sublimate in non-toxic doses would yield better results. The continued application of cold, even of an ice-bag, has been found useless in arresting the disease. As it has been found that a temperature of over 40° C. continued for two days has at least an inhibitory effect on the growth of the streptococcus of erysipelas in artificial nutrient media, it would appear rational to resort to hot anti- septic compresses in the local treatment of erysipelas. If the area involved is limited, a compress, saturated with a weak hot solution of corrosive sublimate, would answer a most admirable purpose. If a large surface is affected some of the weaker germicidal solutions could be used in the same manner. Moisture and heat relieve also the burning, smart- ing sensation more promptly and efficiently than the different filthy oils and salves which have been employed. Application of tincture of iodine, muriated tincture of iron, and solutions of nitrate of silver are worse than useless, because they destroy the skin, which should be carefully preserved in order to protect the patient against secondary infection with pus-microbes. Recently Kraske recommended multiple minute incisions or, rather, scarifications in the skin, at the peripheral zone of the er3Tsipelatous inflammation, for the purpose of preventing further extension of the disease. If the skin is first rendered aseptic, and subsequent secondary infection is guarded against by the application of a reliable anti- septic, this treatment may prove valuable in modifying the progress of the disease. After scarification a hot, moist, sublimated compress should be applied, to be immediately replaced by another when removed. The external use of ichtli3rol, so highly recommended b37 Nussbaum, has proved useless in ny hands, both in relieving suffering and in prevent- ing the extension of the disease. Wolfler has recently called attention to the value of the mechanical treatment of erysipelas. He has published 18 additional cases of ery- sipelas treated by pressure of strongly adhesive plasters. After the plaster is applied the disease extends into the compressed parts of the skin, which swell considerably and remain swollen for several days, and then both the swelling and the fever diminish. He recommends that by way of precaution a second line should be commenced several centi- metres distant from the first. The part must be carefully inspected once or twice daily in order to detect any loosening of the plaster. Occa- sionally the erysipelatous inflammation extends in diminished intensity for a short distance beyond the first line of plaster, but this does not TREATMENT. 379 last long. This method of treatment is at least harmless, and if future experience should prove, as it probably will, that it will not succeed in arresting the local extension of the disease, it will at least provide an efficient protection for the inflamed skin. Phlegmonous inflammation and metastatic suppuration should be prevented, as far as possible, by the employment of such measures as will guard against the formation of suppurating foci in the inflamed skin. Bullae should be evacuated as soon as they form by puncturing with an aseptic needle, carefully preserving the cuticle as a protection against the entrance of pyogenic microbes. Infiltrated air should not reach the inflamed skin, and for this purpose it should be covered either with an antiseptic, moist compress, or a thick layer of antiseptic cotton. The skin is disinfected in advance of the extension of the disease, and is sub- sequently protected against additional infection by applying a hot, moist, antiseptic compress, or by covering it with antiseptic absorbent cotton. If suppuration take place in the interior of bullae the cuticle should be removed, after which the surface is carefully disinfected by irrigation with a germicidal solution, followed by an application with a 10-per-cent. solution of chloride of zinc, and further infection prevented by an anti- septic dressing. If phlegmonous inflammation develop in spite of these prophylactic measures, early and free incisions are made, free drainage established, and a subsequent treatment followed out appropriate for phlegmonous inflammation not complicated by erysipelas. Gangrene of the skin is to be treated by applying a hot antiseptic compress until the dead tissue is eliminated, when the defect is replaced by skin-grafting. Internal medication has even been less satisfactory than the local meas- ures in the treatment of eiysipelas. During the febrile stage the admin- istration of the tincture of ferric chloride and the mineral acids does more harm than good. If the temperature is high, a daily antipyretic dose of quinine is indicated, and exerts a favorable influence upon the local process and the general condition of the patient. If the patient is restless a full dose of Dover's powder should be given at bed-time. Symptoms of prostration are met early by the use of a substantial wine or some other alcoholic stimulant. Symptoms of collapse are treated by administering internally 1^ grains of camphor every hour, or the same amount of the drug is dissolved in oil of sweet almonds and injected subcutaneously every half-hour or hour until symptoms of intoxication, delirium, and reduc- tion of the pulse to 50 or 55 beats per minute are produced. The cam- phor treatment in grave cases of erysipelas was introduced b37 Pirogoff, and has yielded excellent results when the threatening symptoms point to an enfeebled heart. 380 PRINCIPLES OF SURGERY. ERYSIPELOID. A new form of infective dermatitis, which in many respects resembles erysipelas, has been recently described by Rosenbach under the name of " erysipeloid." It attacks usually the fingers and exposed portion of the hand, and is most frequently met with in persons who handle game or dead animals, as cooks, butchers, fish-dealers, and tanners. The affec- tion starts from some minute abrasion of the skin as a bluish-red infiltra- tion, which slowly advances in an upward direction. The inflamed parts are the seat of a burning, smarting sensation. While the skin at the point of infection returns to its natural condition and color, the zone of infiltration becomes larger, as it continues to spread until the disease appears to exhaust itself in the course of from one to three weeks. The infectious material which produces this disease is contained in decom- posing animal substances. Infection may take in any abraded part of the body which comes in contact with material containing the virus. The temperature remains normal, and the general health is not affected. The inflammation travels very slowly, so that if infection take place in the tip of a finger it reaches the metacarpo-phalangeal joint in about eight days, and during the second week it spreads over the back of the hand, from where an adjacent finger may become affected, the extension then taking a direction opposite to the lymph-current. Repeated experiments to obtain a pure culture of the microbe failed, until in November, 1886, the author succeeded in cultivating it upon gelatin from a case in which the disease could be traced to infection from old cheese. The author injected a pure culture under the skin of his own arm at three different points. After forty-eight hours he experienced a smarting, burning sensation at the points of injection; at the same time a circumscribed redness appeared around each puncture, which soon be- "came confluent. On the fifth day each puncture was surrounded by a zone of inflammation the size of a silver dollar, somewhat elevated above the niveau of the surrounding skin. While the centre of this red patch became pale, the zone of inflammation continued to enlarge. In the in- flamed skin the capillary vessels could be seen dilated,—a condition of the circulation which imparted to the tissues an arterial hue with a slight tinge of brown, while inside of the zone the color was a livid brown. In the skin which had returned to its normal pale color slight suggillations appeared, as though some of the red blood-corpuscles in the tissues had been destroyed during the progress of the disease. The in- flammation appeared to have completely subsided on the eighth day, when the smarting sensation returned, and a new zone appeared around the old one. On the tenth day the area measured in its transverse diameter 24 centimetres, and in the parallel direction of the arm 18 centimetres. ERYSIPELOID. 381 After this the affection disappeared permanently. During all this time the general health remained unimpaired, and the temperature varied from 36.8° to 37.2° C. A microscopical examination of the pure culture showed that it was composed of swarms and heaps of irregular, round, and elongated bodies somewhat larger in size than the staphylo- coccus. The author first believed that these bodies were cocci, but later he saw a net-work of intertwining threads, and decided that thej7 were thread-forming microbes. In old cultures the threads were veiy abun- dant, and arranged in ever37 possible way and direction. These threads appeared as though branches were given off, but on closer examination it could be seen that no organic connection existed between them. Ter- minal spores at the tips of the threads were numerous and could not be stained. Neither the microbes nor the threads manifested motile power in the culture, or when suspended in water; a gelatin culture became visible on the fourth day as a delicate cloud, which increased in size very slowly at a temperature of 20° C. The older cultures change into a brownish-gray color, and then resemble the culture of the bacillus of septicaemia in mice. In cultures 4 months old the growth was not entirely suspended. The author, as 3ret, has not given a name to this microbe, but believes, on botanical grounds, that it belongs to the " claclo- thrix " variety of micro-organisms. He wished to ascertain the action of this microbe on lupus, but in several cases in which it was tried the inoculations failed. Erysipeloid is a harmless form of infection, and subsides spontaneously in the course of two or three weeks. I have seen a number of cases in persons handling fish and game, where the affection started in one of the fingers, extended slowly as far as the dor- sum of the hand, and then gradually invaded an adjacent finger and the back of the hand as far as the wrist. In the cases that have come under my observation the inflammation never extended be37ond the wrist. The disease is self-limited, and its local extension is not arrested by any topical applications. CHAPTER XV. Tetanus. The wound-infective diseases in which the microbes or their pto- maines act upon the central nervous system are represented by tetanus and hydrophobia. The specific microbes which are the cause of these diseases produce no gross pathological changes in the brain or spinal cord, but the minute tissue changes cause a central irritation, which is manifested by spasm of certain definite muscular groups. Tetanus is an infective disease in which the specific microbic cause exerts its patho- genic action on the central nervous system, and which is clinically char- acterized by spasm and rigidity of definite muscular groups. BACTERIOLOGICAL STUDIES. The classification of tetanus with the infectious diseases is of recent date, but the infectious nature of the disease was well known and estab- lished before the discovery of the bacillus tetani. In 1859Betoli related the case of a bull that died of tetanus after castration. Several slaves ate some of the flesh of the dead animal, and of these 3 were (in a few days) seized with tetanus and 2 of them died. He adds, further, that in Brazil, where this occurred, the flesh of animals dead of tetanus is generally regarded as capable of transmitting the disease. In 1870 Auger reported a case in which a horse had spontaneous tetanus, after which 3 puppies which had been in the same stable were also affected. Larger, in 1853, saw a woman who had a fall while cleaning a farm-yard, causing a slight wound of the elbow. Four weeks later she was seized with tetanus, and on investigation it was found that a horse affected with that disease had been in a stable opening into the yard where she fell. He also mentions another circumstance which strongly points to the infectious nature of tetanus. In a small village, where tetanus was previously unknown, 5 cases appeared in eighteen months under quite different climatic conditions. Of these, 1 had been taken to a hospital, after which 2 others in the same ward became affected with the disease. In 1884 Carle and Rattone produced the disease artificially in animals by inoculations with pus from tetanic patients. Nearly at the same time the real microbic cause of tetanus was discovered by Nicolaier and Rosenbach. Nicolaier showed the exogenous origin of the disease by (383) 384 PRINCIPLES OF SURGERY. finding a bacillus in earth, which produced tetanus in animals when injected into the tissues. Rosenbach found the same bacillus in the pus of a patient suffering from traumatic tetanus. The identity of the bacillus of tetanus with Nicolaier's bacillus of earth tetanus was demon- strated in Koch's laboratory, April 10, 1887. Bacillus Tetani.—Rosenbach describes the bacillus as an anaerobic micro-organism which presents a bristby appearance, with a spore at one of its extremities which gives it the resemblance to a pin, or drum-stick. According to Kitasato the bacilli produce spores in thirty hours in cultures kept at a temperature of the body. The37 possess great resistance to heat, as they have been found active after an exposure of one hour to 80° C. of moist heat, but they are destined by placing them in a steril- Fig. 89.—Tetanus Bacilli. Spore-bearing Rods from an Agar Culture. Mounted Preparations, Stained with Fuchsin. X 1000. (Frankel-Pfeiffer.) izer heated to 100° C. for five minutes. The bacillus has been found in different kinds of surface soil and in street-dust. In man it has been found in tetanic patients in the wound-secretions, in the nerves leading from the seat of infection, and in the spinal cord. Cultivation.—Rosenbach found it impossible to obtain a pure culture ; although he resorted to fractional cultivation, it was found that the last cul- ture was still contaminated by one or more additional microbes. Fluegge claimed to have obtained a pure cultivation by heating for five minutes the mixed culture to 100° C, but after this procedure the bacillus was incapable of further propagation. After many trials it was found that sterilized solid blood-serum was the best soil for the propagation of the bacillus outside of the body. Both Nicolaier and Rosenbach observed BACTERIOLOGICAL STUDIES. 385 the anaerobic nature of the bacillus, as it was found impossible to obtain a culture by streak inoculations, or in any other manner b3r which oxygen could not be excluded. The culture appeared slowly, as a delicate, whitish-gray film, in the track of the stab inoculation, below the surface of the culture substance. By a long series of cultures, Rosenbach finally succeeded in eliminating all other microbes, with the exception of a bacillus of putrefaction. The growth of the bacillus takes place most readily at an equable temperature of 37° C. (98.6° F.), and becomes first visible about the third day in the depth of the culture media. Kitasato has finally succeeded in obtaining a pure culture of the bacillus of tetanus from pus taken from a patient suffering from this disease. As the bacillus will onby grow where atmospheric air can be excluded, he exposed his cultures to hydrogen gas with complete exclusion of oxygen. Mixed cultures, which had been kept for several days in the incubator, were then exposed for half an hour to a temperature of 80° C. Further growth was then obtained upon plate cultures in closed glass vessels filled with lydrogen gas. B37 heating the mixed culture to 80° C. he destined all microbes with the exception of the bacillus of tetanus, which, later, was cultivated upon solid nutrient media in an atmos- phere of hydrogen gas. At a temperature of 18° to 20° C, a visible culture appeared at the end of a week. If the temperature was increased to blood-heat the bacilli and spores developed more rapidly. Inoculation Experiments.—Nicolaier produced tetanus in rabbits and mice, experimentally, by inoculations with different kinds of surface soil. Out of 140 experiments, in 69 a disease was produced identical with tetanus in man. In the pus, at the point of inoculation, bacilli and micrococci were constant^7 found. Among the bacilli one form was constantly present; this bacillus resembled in appearance and culture the bacillus of septicaemia in mice, but was more slender. This bacillus was found in isolated places in the connective tissue, but could not be found in the muscles, nerves, and blood. Earth sterilized b3'exposing it to a high temperature for an hour proved harmless, showing conclusive^7 that the contagium of tetanus had been destnyed. Inoculations with pus taken from tetanic animals were most successful. Inoculations with mixed cultures grown in solidified blood-serum yielded positive results. Rosenbach made his experiments with mixed cultures grown from pus, taken from the line of demarcation of a case of frost gangrene, in a patient who had died of tetanus. The inoculations proved successful. Bonone reports the case of a man suffering from paraplegia, the result of disease of the spine in the dorsal region, complicated b37 an exten- sive sacral decubitus, the seat of phlegmonous inflammation, who was 25 386 PRINCIPLES OF SURGERY. suddenly attacked by tetanus, which proved fatal in two days. One hour after death a small portion of the infiltrated tissue around the gangre- nous part was removed, and after reducing it to a fine pulp by tritura- tion he injected it under the skin of a rabbit. Twenty-two hours after inoculation the animal died with well-marked symptoms of tetanus. The products of inflammation from the point of injection thrown into the subcutaneous tissue of other animals produced the disease, while intra- venous injections proved harmless. The gravity of symptoms following subcutaneous injections was commensurate with the quantity of fluid injected. Guinea-pigs proved less susceptible to infection than rabbits. In the pus taken from the dead tissue he found, besides the usual pus-microbes, a bacillus which resembled in every respect the one de- scribed by Nicolaier and Rosenbach. Hochsinger made his observations on a case of tetanus which proved fatal on the fifth day. The day before the patient died blood was abstracted from a vein, under strict antiseptic precautions, for microscopical and bacteriological study. No micro- organisms could be found in it. With the greatest care sterilized, solid blood-serum was inoculated with the blood, by making, with the needle, both superficial streaks and deep punctures. The nutrient medium was kept at a temperature of 37° C. (98.6° F.). On the third day a white, cloiKby streak marked the direction of the deep punctures, while the superficial plant remained sterile. On the third day a portion of the culture was removed and stained with aniline gentian, and the character- istic bacillus was found. A large rabbit was infected by injecting blood obtained from the patient during life. The blood was diluted with sterilized water, and a S37ringeful of this mixture was injected under the skin in the iliac region, and half of this quantity under the skin of the left thigh. The next da3T the animal was quite ill and unable to use the left hind-leg, which was dragged along in walking. At this time great nervous excitability was observed, the exaggerated reflex symptoms being especially well marked in the posterior extremities, which, on the slightest touch, were thrown into clonic spasm. On the following da>7 the animal was found dead. A few hours before death well-marked S3rmp- toms of tetanus developed. Injections of blood from this animal pro- duced no results in other rabbits, and culture experiments were equally fruitless. A S3rringeful of inspissated blood of the patient, kept for three weeks, thrown under the skin of a white mouse, was followed by a fatal attack of tetanus, while a second animal inoculated in a similar manner with one-half of this quantity remained perfectly well. Fluegge had before observed that by injecting blood from animals rendered tetanic by inoculation it was necessary to use a large quantity in order to reproduce the disease in other animals, and even by doing so BACTERIOLOGICAL STUDIES. 387 the result was not always satisfactoiy. It appears that the blood of tet- anic patients possesses greater toxic properties than the blood of animals suffering from the same disease. Hochsinger also made inoculations with the mixed cultures. A syringeful of a liquid culture was injected into the subcutaneous tissue of a medium-sized rabbit. Tie next day the reflexes were increased, respiration more rapid, and the animal appeared otherwise quite sick. On the third da37 the poste fior extremi- ties were stiff, the animal dragging them in walking; reflex irritability enormously exaggerated. On the fifth da3r the animal duid, with well- marked s37mptoms of tetanus: A number of similar successful experi- ments are reported b3' the same author. In rabbits, Fluegge estimated the stage of incubation at from three to five da37s, and the duration of of the disease, from the time the first S37mptoms were noticed to the fatal termination, from five to seven days. Beumer gives an accurate and able description of his studies in 2 cases of tetanus. The first case occurred in a mechanic, who injured himself under the nail of the right middle finger with a splinter of wood. Eight da3rs after the injuiy,the patient having had but slight pain in the finger, pains appeared in the neck and muscles of the back. The next morning spasms of the muscles of the chest, abdomen, and jaw developed. These attacks occurred at intervals of an hour and a half. Four da37s later the lower extremities were affected, also the upper, but in a less degree. An incision was made and the foreign bod37 removed, which was followed b3r the escape of a drop of pus; death on the fourth day. The second case was a boy 6^ years old, who was brought into the clinic with well-marked symptoms of tetanus, and who lived only a few hours after his admission. The author obtained some of the dust and splinters of wood from the place where the mechanic had injured himself, and in- serted small particles under the skin of mice and rabbits. In all experi- ments the animals were attacked with tetanus in from two to three days after inoculation, and during the third or fourth. The spasms were always noticed first in the muscles nearest the point of inoculation. A fragment of tissue from the sole of the foot was taken from the boy, and small particles of it inserted into the subcutaneous tissue of 6 mice. In all of these s3rmptoms of tetanus appeared after two days, developing gradually into general convulsions and death. The same results were obtained in mice and rabbits b37 inoculations of particles of dust taken from the spot where the boy sustained the injury. The same author also made numerous experiments with different kinds of earth. Of 10 experiments with soil taken from the ocean- beach, tetanus followed in only 2. On the other hand, of 10 inocu- lations with garden-earth and street-dust, all proved successful but 1. 388 PRINCIPLES OF SURGERY. Of the greatest scientific and practical interest are the observations made by Bonone, in reference to the causation of tetanus by infection with earth containing the bacillus discovered by Nicolaier. He had an opportunity to observe a number of cases of tetanus after the earth- quake at Bajardo. Of the 70 persons injured in the ruins of the church, 7 were attacked by tetanus. From bacteriological investi- gations in connection with these cases, he came to the same conclusions in regard to the cause of the disease as Nicolaier, Rosenbach, Fluegge, and Beumer before him. Of special importance is the observation made by him, that the secretions from the wounds and the exudation from the part, the seat of tetanic convulsions, when dried and preserved between two sterilized watch-glasses, retained their virulent properties for at least four months. All animals inoculated with dust from the debris in the interior of the church were attacked with tetanus. Control experiments with dust from the ruins at Diano-Marina were always followed by nega- tive results. Of the many persons injured during the same earthquake at this place, not one was attacked by tetanus. Ohlmiiller and Goldschmidt made a thorough bacteriological inves- tigation of a case of tetanus following complicated fracture of the right thumb. The disease appeared the day following the injury, and proved fatal in seventeen hours. Soon after death inoculation experiments were made with blood taken from the heart and spleen, and pus from the seat of fracture. The cultures were grown in solid blood-serum kept at a temperature of 38° C, (100.7° F.). The tubes containing blood from the heart and spleen remained sterile, but the nutrient media infected with pus showed signs of growth. The bacilli which were detected re- sembled those of mouse-septicaemia, only somewhat larger in size. In addition to these microbes streptococci and a thick bacillus were found. Two mice were inoculated with this mixed culture. Twelve hours after infection tetanus developed, followed by death in seventeen hours. The spasms commenced in the tail, extended to the posterior extremities, and then gradually advanced in a forward direction. From these animals blood-serum was taken, with which other mice were infected. Aoain tetanus was produced, and successful cultivations were made of 2 mice of equal size and age; 1, which received one portion of a culture, died of tetanus on the ninth day, while the other, which received a dose three times as large, died on the third day. Of 3 cases of tetanus which recently came under the observation of Lumniczer, he was able to demonstrate the microbic origin in 1. In this case the attack followed a gunshot injury. After the disease had developed fragments of hemp were removed from the canal made by the bullet, and in them the char- acteristic bacillus was found. Cultures were made to the tenth genera- BACTERIOLOGICAL STUDIES. 389 tion, and with them animals were inoculated, and tetanus was invariably produced. Pus taken from abscesses produced at the point of inocula- tion contained the bacillus, and inoculation experiments made with it yielded positive results. Cultures made from the blood or organs of the tetanic animals remained sterile. Inoculations with blood from these animals proved harmless. Kitasato experimented with a pure culture of the bacillus of tetanus on mice, rats, guinea-pigs, and rabbits, and never failed in producing the disease, provided a sufficiently large dose of the culture was adminis- tered. In mice the disease appeared, without exception, twenty-four hours after the inoculation, and proved fatal in two to three days. The tetanic convulsions were first always local, appearing first in the muscles nearest the point of inoculation, and becoming gradualty more diffuse. He was unable to find the bacillus at the seat of inoculation, the blood, or in any of the internal organs. He is of the opinion that if tetanus is produced b37 inoculation with a pure culture the bacilli do not remain in the bod3' for any length of time, but are rapidly eliminated. The ex- periments and clinical observations which have just been quoted furnish conclusive proof that tetanus is a microbic disease, and that the bacillus of tetanus discovered by Nicolaier and Rosenbach is its essential cause. Whether cultivations from chronic cases of tetanus can produce an acute and rapidl37-fatal attack in animals remains to be determined. In this direction I have recently made an observation which, if not convincing, is at least very suggestive. A boy 15 years of age, previously in good health, was attacked with acute osteonyelitis in the lower extremity of the femur. The surgeon in attendance trephined the bone just above the external condyle during the first few da3rs,and before an abscess had formed in the soft parts. A few da37s after the operation trismus set in, followed by typical chronic tetanus. Six weeks later the patient entered the Milwaukee Hospital, and was placed under my charge. At this time the patient had become emaciated to a skeleton. Trismus and opisthotonus were well marked, and the lower ex- tremities were rigid and fixed in the extended position. The slightest touch, or a draught of air in the room, would bring on intense convul- sive attacks for several minutes, attended by excruciating pain. Pro- fuse fetid discharge at the site of operation ; pulse, 140; temperature, from 99° to 101° F. (37.3° to 38.8° C). Believing that the primary infection had taken place through the operation wound, and that the osteonyelitic products served the purpose of a nutrient medium for the bacillus tetani, I determined to operate in spite of the grave S37mptoms. As the spinal cord at this stage of the disease was necessarily the seat of the intense congestion, I resorted to chloroform as an anaesthetic in preference to 390 PRINCIPLES OF SURGERY. ether. The usual operation for necrosis of the lower end of the femur was made, and a large triangular sequestrum removed from the lower and posterior aspect of the bone. The involucrum was defective, and its inner surface was found lined with a thick layer of flabby granulations. Gelatin tubes were inoculated with blood, pus, and granulation tissue. The tube inoculated with blood remained sterile, while the two remaining tubes showed a copious growth of staphylococcus pyogenes albus, which rapidly liquefied the gelatin. A portion of the granulation tissue was disinfected with a weak solution of carbolic acid, dried between layers of antiseptic gauze, and inserted under the skin of a full-grown, large rabbit. No suppuration followed, and the animal remained perfectly well for six weeks, when both posterior extremities became rigid and could not be used in walking. The next day tetanic convulsions affect- ing the muscles of the back and all the limbs appeared, and on the fourth day death supervened. The interesting features in this case are that the patient recovered from the tetanus after a long illness, extending over three months; that marked improvement followed the operation, which had for its object thorough disinfection of the infection-atrium; and that the inoculation with granulation tissue in the rabbit was followed by an acute attack of tetanus after an incubation stage extending over six weeks. In the ex- periments related above the animals were inoculated with cultures, earth, other infected foreign substances, fragments of diseased tissue, or with wound-secretions from tetanic patients; the stage of incubation rprely extended over two or three da37s, and often the spasms appeared in eighteen to twenty-four hours, and the disease produced death in from two hours to three days. The same question has been raised in connection with the pathogenic action of the bacillus of tetanus as with pus-microbes : Is the disease of which it is the specific cause due to the presence of the microbe, or the ptomaines which it elaborates in the tissues ? Ptomaines of the Bacillus Tetani.—Brieger, by his indefatigable labors, has demonstrated beyond all doubt that the ptomaines of the bacillus of tetanus cause tetanic convulsions. St^chnia in toxic doses produces a condition which, so far as the muscular spasms are concerned, closely resembles tetanus. If this and other drugs belonging to the same group can act upon the spinal cord in such a manner as to cause spasms and muscular rigidity, we should, a priori, expect that if the microbe of tetanus produce ptomaines in the tissues these might produce the same effect on the cord, and that the symptoms are produced by them and not by the direct action of the microbe. Nearly all authorities are agreed that the bacilli present in the blood of tetanic patients are BACTERIOLOGICAL STUDIES. 391 few, and in animals in which the disease was produced artificially the blood was often found sterile. More microbes have been found at the seat of primary infection, and in the tissues between it and the spinal cord, than in the blood itself,—another proof that the direct cause of the disease is the product of the microbes, and not the microbes themselves. Brieger has succeeded in isolating four toxic substances from mixed cultures of the tetanus bacillus in sterilized emulsion of meat. The first, tetanin, in doses of a few milligrammes, administered subcutaneously in mice, produced the characteristic symptoms of tetanus. The second, tetanotoxin, causes, first, tremors; later, paralysis and convulsions. The third, muriate of toxin, has not been designated b3T a special name; it produces also well-marked S37mptoms of tetanus, but, besides, excites the salivaiy and lachrymal glands to increased functional activity. The last, spasmotoxin, produces severe clonic and tonic spasms, which prostrate the animal at once. Besides meat-emulsion, the contused brain-substance from horses and cattle was used ; also cows' milk mixed with carbonate of lime. It seems that the culture substance determined, to a certain extent, the kind of toxin which was produced; thus, in cultures grown in brain-substance, besides the tetanin, tetanotoxin was found in greatest abundance; old cultures, in which the tetanus bacilli were dead, produced none of these toxic substances. The same author has veiy recently been successful in isolating tetanin from the amputated arm of a patient the subject of tetanus. The disease had developed a few days after a severe crushing injury of the hand and forearm. The first symptoms manifested themselves in the morning, and at 12 o'clock (noon) the operation was performed; at 5 o'clock on the same da37 the patient expired suddenly during one of the tetanic convulsions. The bacilli of tetanus were found in the serum taken from the ©edematous portion of the forearm, in connection with other bacilli of different length,—staphylococci and streptococci. Serum containing these microbes injected under the skin of mice, guinea-pigs, and rabbits invariably produced tetanus. On the other hand, a dog treated in the same manner, as well as after injections of tetanin, remained well. A horse inoculated with a culture of bacilli in meat-emulsion showed no symptoms of tetanus, but an abscess formed at the point of inoculation. The infiltrated tissues of the amputated arm planted on sterilized meat-emulsion, solid blood-serum, and emulsion made of the flesh of fish, yielded, besides ammonia, only tetanin; no trace of tetanotoxin, spasmotoxin, nor the unnamed toxin which could be obtained from Rosenbach's bacillus. A moderate dose of tetanin injected into the subcutaneous tissue of a horse produced muscular contractions which lasted for a considerable length of time, but the 392 PRINCIPLES OF SURGERY. characteristic symptoms of tetanus, as witnessed in horses suffering from tetanus, did not appear. ETIOLOGY. The clinical and experimental researches just quoted demonstrate that the bacillus tetani is found in the wound-secretions, the tissues, and, in some instances, in the blood of tetanic patients, and that tetanus in animals can be produced artificially by injections of wound-secretions of tetanic patients, or by using mixed or pure cultures,—facts which have firmly established the microbic nature of the disease. The essen- tial cause of tetanus is the bacillus first discovered by Nicolaier in earth, and by Rosenbach in the wound-secretion of a tetanic patient. Period of Incubation.—The period of incubation, both in man and animals, appears to be extremeby variable, in some instances lasting only twenty-four hours, while in others weeks imiy elapse between the time of infection and the first manifestations of the disease. This may depend on one of three things: 1. The number of bacilli introduced may be so small that a much longer time is necessary before active symptoms are produced than if a larger quantity had been introduced, as Watson- Cheyne has shown that in animals the injection of a limited number of the bacilli of tetanus produced no S3rmptoms. 2. The location of the infection-atrium and anatomical characteristics of the tissues surround- ing it may influence the time which is necessary to develop the disease. 3. Brieger's investigations have shown that tetanic convulsions in animals are produced by injections of tetanin,—one of the toxic ptomaines derived from cultures of the bacillus of tetanus ; and it is more than probable that the active symptoms of tetanus in man are due not to the presence in the tissues of the bacillus, but to the toxic action of the ptomaines on the spinal cord; so that the duration of the period of incubation is further modified by the capacity of the infected tissues to yield the different ptomaines. The degree of virulence of the bacillus of tetanus must certainly play an important part, not only in determining the duration of the incubation stage, but also the gravity of the disease. Specific Microbic Cause.—There can be no doubt that both the acute and chronic forms of tetanus are caused by the same microbe, and that the clinical difference depends upon the degree of virulence of the primary cause, on the one hand, and the degree of susceptibility of the individuals to tetanic infection, on the other. In reference to the susceptibility to infection with the bacillus of tetanus, it has been shown by reliable statistics that the colored races, under the same conditions, are attacked more frequently by tetanus than the Caucasians. Inoculation experiments have shown that the greatest ETIOLOGY. 393 difference exists among different kinds of animals in this respect, and there is no reason why the same difference of susceptibility to this dis- ease should not exist in the human species. As the natural habitat of the bacillus of tetanus is the soil, we can readily understand that the disease should occur more frequently in some localities than in others, and wly it is more prevalent in southern than northern climates. The excretions and cadavers of tetanic animals ma37 infect the soil, where, under favorable conditions, the bacillus may multiply, and in this manner a greater or less portion of the surface soil becomes a nutrient medium, in which an immense culture is developed from which new cases can become infected. A warm climate is more favorable for the unlimited reproduction of the bacillus in the soil than northern countries; hence the greater prevalence of this disease in the tropics. Infection-Atrium.—As the bacillus of tetanus is the essential cause of the disease, the remaining causes are accidental conditions, which result in the formation of an infection-atrium. We have no evi- dence that the bacillus can enter the tissues through an intact mucous membrane or unbroken skin. Idiopathic tetanus, so called, is a clinical form of tetanus where even the most thorough examination reveals no infection-atrium. As in cases of erysipelas, under similar circumstances, the local lesion may have been so insignificant as not to have attracted the patient's attention, or if he was cognizant of it at the time it may have completely disappeared at the time the first S37mptoms developed themselves. In trismus sive tetanus neonatorum infection undoubtedly takes place through the umbilicus. In a case of this kind Beumer found the tetanus bacillus in the tissues. There is hardly an operation, capital and minor, which has not furnished its quota to the long list of tetanic patients. It has been observed most frequently after amputation, castra- tion, and extirpation of the tlyroid gland. Weiss reported 13 cases of tetanus occurring after extirpation of the thyroid gland. He attributes the frequency with which this disease follows the removal of this organ to irritation of peripheral nerves induced by the numerous ligatures. Middeldorpf observed paralysis of the facial nerve in some of these cases,—a circumstance which would indicate a central origin of the disease. In 53 total extirpations of the thyroid gland for goitte made by Billroth, tetanus followed in 12 cases, while no cases occurred in 109 partial operations. Two cases became chronic, in which the disease, at the time von Eiselsberg made the report, had lasted for six and nine years. In 7 cases there was, besides the ordinary characteristic symptoms, an involvement of the muscles of the face, neck, larynx, diaphragm, and abdomen ; so that dyspnoea and even 394 PRINCIPLES OF SURGERY. loss of consciousness occurred. In the fatal cases death occurred in from three to thirty da37s, and in 1 case after seven months. Quite a number of cases have been reported during the last few years where it occurred after abdominal section. Tetanus occurring after an operation must be the result of infection through the operation wound with the specific bacillus, which, without exception, takes place by contact. As the bacillus of tetanus is not a pyogenic microbe, it is not necessar37 that a wound through which infection has occurred should suppurate. When suppuration takes place it is in consequence of a mixed infection. It is a well-known clinical fact that punctured, lacer- ated, and gunshot wounds of the hands and feet are most liable to be followed by tetanus. Before it was known that tetanus is a microbic disease, the frequency with which this disease complicated such injuries was explained upon the ground that the part injured was abundantly supplied with sensitive nerves, and that the irritation caused by the injury provoked the disease. As thousands of operations upon the hands and feet performed under antiseptic precautions have not resulted in a single instance in tetanus, this explanation is no longer tenable. The antiseptic treatment of wounds has greatly diminished the fre- quency of tetanus as a complication of operation wounds. Expe- rience has shown that the same treatment which prevents suppuration and other wound-infective diseases has also diminished the frequency of tetanus. Wounds of the hands and feet are so often followed by tetanus, because, in the first place, the implement or substance which inflicts the wound is frequently contaminated with infected earth or dust, and, in the second place, such wounds are often neglected and exposed to subsequent infection from the same sources; and, lastly, infected foreign bodies are often allowed to remain in the wound. In a number of instances animals were successfully infected by inserting under the skin particles of foreign bodies removed from tetanic patients. Wounds of the hands and feet are no more liable to cause tetanus than wounds in any other part of the body, provided they are not exposed to greater risk of infection. Infection through the uterus after abortion and during childbed has been repeatedly observed. Gautier has collected 74 cases of tetanus, 36 following abortion and 38 following confinement. Autopsies were made in 15 cases ; 3 pre- sented, on microscopical examination of the brain and cord, no appreci- able lesion ; in 1 case a retained putrefied placenta was found in the uterus; in 5 suppurative metritis or salpingitis; in 1 ovarian cyst. The other autopsies showed hyperaemia of brain, cord, and meningitis ; in 1 haemorrhage into the lateral ventricles. Ten patients recovered,—5 after abortion, 5 after labor. SYMPTOMS AND DIAGNOSIS. 395 Frost gangrene is especially prone to be followed by tetanus. Of 375 cases of tetanus collected by Thamhayn, the disease followed wounds of the fingers and hand in 27 per cent.; of the thigh and leg, 25 per cent.; of the toes and foot, 22 per cent.; of the head, face, and neck, 11 per cent.; of the arm and forearm, 8 per cent.; and of the trunk, 6 per cent. Of 700 cases collected by the same author, the disease was known to have fol- lowed a trauma in 603. As males are more frequent^7 exposed to injury than females, the disease is correspondingly more frequent in that sex. The largest number of tetanic patients are found among persons from 10 to 30 years of age, although no age is entirely exempt. According to Larrey, Cullen, and Dupuytren, the disease can be caused, and is alwa3's aggravated, b37 drafts of cold air. That the disease is never caused b3r exposure to cold requires no argument; that drafts of cold air aggravate the disease when it exists is unquestionable, as every peripheral irritation cannot fail in aggravating the muscular spasms. SYMPTOMS AND DIAGNOSIS. The ptomaines of the bacillus of tetanus act upon the brain and spinal cord in a somewhat similar manner as strychnia. If the spinal cord is injured strychnia acts only upon the parts supplied with nerves from the intact portion of the cord. If the posterior roots of the spinal nerves are divided it produces no spasms in toxic doses. If in an animal the brain and medulla oblongata are removed the effect of strychnia upon the muscles is not impaired. Injection of hydrate of chloral arrests the spasm produced by strychnia, and, consequently, chloral must be con- sidered as the most efficient antidote to strychnia. Even the most acute cases of tetanus begin insidiously. The patient, perhaps, complains of a sensation of chilliness and a feeling of soreness about the region of the neck, and shooting pains and stiffness in particular muscular groups. The first symptom which announces the onset of this dreadful disease is difficulty in mastication. The patient discovers, accidentally, that he is unable to open the mouth sufficiently to drink or grasp the food. On inspection nothing abnormal is found, but on trying to separate the teeth the*masseter muscle on each side becomes rigid and prominent. This spasm of the muscles of mastication is called trismus. It is the first group of muscles affected by the central lesion produced by the ptomaines of the tetanus bacillus. If other causes of this condition, such as inflammatory lesions in the pharynx and the alveoli of the maxillary bones, can be excluded, the existence of trismus is almost a pathogno- monic symptom of tetanus. The patient next complains of difficulty in swallowing, as the muscles of deglutition become affected. The next muscular groups to become involved are the muscles back of the neck 396 PRINCIPLES OF SURGERY. and the extensors of the spine, giving rise to retraction and fixation of the head and overextension of the spine,—conditions which, when well developed, produce what is called opisthotonus. In well-marked opis- thotonus the body rests on the occiput and heels when the patient is in the dorsal position. If the body is bent in an opposite direction, from contraction and rigidity of the anterior pectoral and abdominal muscles, the condition is called emprosthotonus. Contraction of muscles on the side of the chest and abdomen gives rise to pleurosthotonus. Orthotonus means tonic spasm and rigidity of all the voluntary muscles,—a con- dition frequently present in advanced cases of tetanus. The face of tetanic patients presents a characteristic mask-like appearance from the contraction and rigidity of the facial muscles. The muscular spasms are clonic, and are always aggravated by the slightest causes, as walking in the room ; touching the bed-clothes or the body of the patient; drafts of air ; sudden, unexpected noises. The affected muscles are rigid from tonic contraction, but this state of rigidity is increased by the paroxysmal clonic spasms. In acute cases the temperature soon rises to 40° to 41° C, and the pulse is correspondingly increased in frequency. The temperature curve shows but little change during twenty-four hours. The sensorium usu- ally remains unaffected throughout the entire course of the disease. As the patient finds it difficult to clear the mouth, the profuse salivary se- cretion escapes from the mouth. Respiration is impeded in proportion to the number of the respiratory muscles affected. In severe cases early dyspnoea and cyanosis are present. Special senses remain intact. The pain is mostly excruciating, extending from the neck and back in the direction of the nerves, leading to the affected muscular groups. The pain is always aggravated with the increased convulsive movements, resulting from the action of external irritants. In consequence of deficient food-supply, the intense pain, and loss of sleep, rapid emaciation and loss of strength appear as early and con- stant symptoms. Approaching exhaustion is announced by profuse clammy perspiration, coldness of the extremities, and a rapid, feeble, and intermittent pulse. As soon as the intercostal muscles are affected res- piration becomes more and more embarrassed, and when finally the diaphragm is thrown into a tonic spasm respirations and pulse cease, general cyanosis follows, and death may ensue during the first spasm of the diaphragm. Should, however, the patient rally from this attack, he will be almost certain to succumb to the second or third attack. Wunderlich has seen the temperature shortly before death rise to 42° or 43° C, and the same has been observed in animals dying from tetanus by Billroth, Fick, and Leyden. A post-mortem rise in tempera- • CLINICAL FORMS OF TETANUS. 397 ture to 44.7° C. has been recorded by Wunderlich, and he attributed this strange phenomenon to paralysis of the central heat-moderators. In chronic tetanus the disease commences very insidiously, and the graver symptoms, such as a very high temperature, feeble and intermittent pulse, spasm of the intercostal muscle and diaphragm, are absent. The tem- perature is normal or only slightly elevated. Trismus is always present, to which may be added spasm and rigidity of the muscles of the back of the neck and the extensors of the spine. The trismus makes it diffi- cult to administer food in sufficient quantity, and, on this account, pro- gressive emaciation is one of the prominent features of this form of tetanus, as the disease, as a rule, lasts from six to ten weeks. The dis- appearance of symptoms is as gradual as their onset. In the differential diagnosis it is important to distinguish between tetanus and strychnia poisoning, lysteria, cataleps37, hydrophobia, cerebro-spinal meningitis, and basilar meningitis. With few exceptions it is possible in tetanus to establish the fact of infection, and the clinical history shows that differ- ent muscular groups become involved successively in regular order, first trismus, then rigidity of the muscles at the back of the neck, and, finalty, opisthotonus. In acute cases the disease is attended by a continuously high temperature. In str37chnia poisoning the maximum symptoms, opisthotonus or orthotonus, are developed suddenby, as soon as a toxic dose of the drug has been absorbed. The convulsive movements in hysteria are not limited to any definite muscular groups, and the pulse and temperature are normal. The same can be said of catalepsy. In hydrophobia, as we shall see subsequently, the spasms are limited to the muscles of deglutition, the stage of incubation is longer than in tetanus, and infection is always caused by the bite of a rabid animal, usually a dog. In cerebro-spinal meningitis muscular spasm and rigidity are limited to the extensor muscles of the spine ; so that, even if the disease has caused well-marked opisthotonus, trismus is absent. Tubercular meningitis is usually ushered in by intense headache, vomiting, and photophobia, and if tonic muscular spasms set in they affect the muscles at the back of the neck almost exclusively. Trismus is never present. CLINICAL FORMS OF TETANUS. Acute Tetanus.—The stage of incubation, as a rule, is shorter than is the chronic form of the disease. Trismus develops gradually, but after it has once been established the extension of the disease to other muscular groups is rapid. A high temperature and rapid, feeble pulse are always present. Respiration is mechanically embarrassed by the successive implication of the different muscular groups which are con- cerned in the function of respiration, the last one to become affected 398 PRINCIPLES OF SURGERY. being the diaphragm. The disease may prove fatal in twenty-four hours, and the duration is seldom prolonged for more than a week. Chronic Tetanus.—The disease not only commences insidiously, but the symptoms appear gradually and never develop to the same extent as in acute tetanus. The most marked feature is trismus, which may be fol- lowed by a mild degree of opisthotonus. The muscles of respiration are not implicated, and if death result it is from marasmus and exhaustion and not from apnoea. The duration of the disease is seldom less than six, nor more than ten, weeks. Trismus.—Tetanus in which only the muscles of mastication are affected is called trismus. With the exception of the infantile form, trismus is a chronic and comparatively benign affection. Tetanus Neonatorum.—Tetanus occurring in infants during the first week after birth is clinically characterized as trismus, and proves fatal almost without exception in a few days. Infection takes place through the umbilicus before or after separation of the cord. It is a disease that occurs much more frequently in tropical than northern climates, for reasons which have been heretofore explained. Tetanus Hydrophobicus, or Head Tetanus.—This is a form of tetanus which was first described by E. Rose, in 1870. In the cases which have been reported, it followed head injuries, especially wounds of the face. Besides trismus, it is characterized by paralysis of the facial nerve on the injured side. During deglutition, the muscles which are concerned in this act are thrown into spasm, and on this account the disease bears a strong resemblance to hydrophobia. Klemm has collected up to date 24 reported cases of this disease. Most of them recovered, and in those that died the disease passed into the typhoid form of tetanus. PROGNOSIS. The most important element in prognosis is the type of the disease. The more acute the onset and the more intense the symptoms, the greater the immediate danger to life. If death does not occur within two weeks the prospects of an ultimate recovery are good. Of 280 cases which comprise the Calcutta statistics of this disease 75 per cent, proved fatal. This list represents about the average mortality of this disease. The greater the excitability of the motor centres of the spinal cord, and the more rapid the successive involvement of different muscular groups, the greater the danger of an early dissolution. In acute cases death is always preceded by great dyspnoea, and death usually occurs during an attack of convulsions, in which the intercostal muscles and the diaphragm take part. Chronic cases terminate, as a rule, in recovery after an illness lasting from six to ten weeks. PATHOLOGY AND MORBID ANATOMY. 399 PATHOLOGY AND MORBID ANATOMY. The absence of gross pathological changes is characteristic of tetanus. The only constant lesion found is a lyperaemic condition of the medulla oblongata and the spinal cord, to which special attention has been called by Leyden, Joffre37, Ranvier, and Robin. As all of the peripheral manifestations of the central lesion point to an increased excitability of the nervous centre, we would expect that the principal lesions are to be found in the gray substance of the cord. In 1857 Rokitansky described tetanus as an ascending neuritis. He found a connective-tissue proliferation, in the form of a semi-fluid, adhesive, grayish substance, between the medullary elements of the nerves leading from the infected district. In some cases he found extensive destruction of the nerve-tubes, and their space occupied by the products of granular degeneration,—colloid and amyloid corpuscles. Lockhart-Clark and Dickinson found, as the most constant patho- logical lesion, inflammatory softening of the gray substance of the cord and dilatation of the vessels. Michaud and Benedict found cell prolifera- tion into the anterior cornua of the cord and great vascularity. Elischer regarded the central lesion as a nyelitis with vacuolation in the ganglia- cells. Tyson found in 2 cases destruction of the central canal of the cord, with disintegration of the posterior cornua. Aufrecht narrowed the morbid anatomy of tetanus down to atrophy of the anterior horns, in the cervical portion of the spinal cord. Schultze was never able to discover any evidences of myelitis. The hyperaemia of the cord, which is so constantby found, may be the result of a passive congestion ; at present this cannot be accepted as proof of inflammation, because in most cases the anatomical and clinical evidences do not sustain this supposition. The view that tetanus is essentialby an ascending neuritis, as was claimed by Rokitansky, is no longer tenable, since it is not supported by the results of recent investigations. It is left for future research to furnish more reliable information concerning the pathology and morbid anatomy of tetanus. At present we can onty surmise that the ptomaines of the bacillus act upon the gray matter of the cord, where minute lesions are produced, which must account for the clinical mani- festations of the disease. TREATMENT. The prophylactic treatment of tetanus has in view the prevention of infection by the usual antiseptic precautions in the treatment of wounds and local lesions which might become the necessary infection-atrium. As tetanus follows more frequently injuries insignificant in themselves than large wounds or major operations, it behooves the surgeon to treat the minutest lesions with the greatest care, and in strict accordance with 400 PRINCIPLES OF SURGERY. antiseptic principles. Foreign bodies should be carefully searched for and removed. Even the most recent accidental wounds should be treated as infected wounds, and should be rendered aseptic by a thorough primary disinfection. The antiseptic treatment must be continued until the wound is completely healed, and during this time the injured part must be kept at rest. Wounds of the lower extremities must be treated by confining the patient to bed, and wounds of the upper extremities demand, in their treatment, fixation of the limb upon some kind of a splint or, at least, suspension in a sling. In acute cases of tetanus the most that can be expected from treat- ment is palliation. The excruciating pain is often only relieved by inhalation of chloroform. The administration of chloroform should be conducted by the physician in attendance or a reliable assistant, and should only be carried to the extent of relaxing the contracted muscles, and repeated as often as necessary to procure rest. Morphia in doses of £ to £ grain, with ?hif grain of atropia, should be given hypodermati- cally every three or four hours until the desired effect is reached. In less severe cases the internal use of hydrate of chloral and potassic bromide, each in doses of from 15 to 20 grains, can be given every three or four hours with excellent effect. Woorara, which has been quite extensiveby used in the treatment of the disease, is absolutely contra- indicated, as its paralytic effect on the heart cannot fail in producing an37thing but a deleterious effect. All patients suffering from tetanus should be kept in a quiet, dark room, and all kinds of excitement must be careful^7 avoided, as bodily and mental rest are important elements in the treatment. As mastica- tion is impossible, the patient must be nourished with liquid food, which he can sip through an elastic tube. If swallowing is impossible, a small elastic tube is introduced through one of the nostrils into the stomach, and food is administered at regular intervals by this method. In chronic tetanus warm baths are grateful to the patient, and exercise a decided influence in ameliorating the symptoms. The surgical treatment of tetanus has yielded no better results than the internal use of drugs. In all cases the infection-atrium should be carefully examined, and, if neces- sary, the wound or local lesion should be thoroughly disinfected, as this treatment may be the means of preventing further infection from this source. Scars should be excised and foreign bodies removed. Under the belief that tetanus is an ascending neuritis, nerve-section, or neurotomy, has been practiced for the purpose of preventing further extension of the inflammation b37 interrupting the continuity of the nerve; but the results, as could be expected, were disappointing, and the operation has fallen into well-deserved desuetude. When nerve-stretching TREATMENT. 401 was the rage in the treatment of all kinds of nerve affections it was also applied in the treatment of tetanus, but the results were no better than after neurotonry. Nocht reported 24 cases of tetanus treated ly this method, and of this number onby 4 recovered,—the average percentage of recoveries in all cases of tetanus not treated b37 surgical resources. Amputation is onby indicated in cases where the local conditions which gave rise to tetanus make it necessary to resort to this operation. 26 CHAPTER XVI. Hydrophobia. Hydrophobia, lyssa, canine madness, and rabies are synonymous terms used to designate a nervous disease caused by the bite of a rabid dog or other animal, attended with violent spasms if the patient attempts to swallow water or other liquids, and b3r embarrassment of respiration from spasm of the laiyngeal muscles. This disease never occurs spon- taneously in man, but is alwa37s the result of inoculations with the virus of a rabid animal. Although this disease never originates elsewhere than in the dog and animals belonging to the same species, the wolf, fox, and jackal, the virus of rabies is capable of being communicated to all warm-blooded animals. It has been estimated that in man the disease is derived in nine out of ten cases from dogs ; sometimes it is contracted from cats, and sometimes, but ver37 rarety, from foxes or wolves. The specific virus of hydrophobia appears to be generated in the glandular appendages of the mucous membrane of the mouth and throat, and is transmitted by the saliva of the rabid animal. For this reason it has been observed that inoculation is more apt to take place from a bite on an uncovered part of the bod3r, as, for example, on the hands or face, than from a bite inflicted through the clothes, as in the latter case the greater portion of the saliva is deposited in the clothing. Not every person bitten by a rabid dog necessarily contracts the disease, as statistics have shown that about one-third of the animals and human beings bitten by mad dogs escape all danger. This partial immunity is explained in part by the virus being diluted, and being wiped from the teeth of the rabid animal b37 clothing; and also by well-ascertained facts proving the absence of susceptibility to its action in certain individuals, both in animals and in man. Renault's careful experiments proved that one-fourth of the inocu- lated creatures escaped the effects of the inoculations, which were mortal in the other three-fourths. As in civilized countries the disease is con- tracted almost exclusively from rabid dogs, it is necessary to call atten- tion to the symptoms which characterize the disease in this animal, in order that it ma37 be recognized in time, so that the infected animal can be isolated and kept in close confinement until the result shall prove or disprove the correctness of the diagnosis. It is a great mistake to kill (403) 404 PRINCIPLES OF SURGERY. an animal suspected to be rabid, until by careful observation continued for some length of time, or from the result of the disease, a positive diagnosis can be made, and thus a great deal of unnecessary fear may be avoided. HYDROPHOBIA IN THE DOG. The name " hydrophobia," meaning literally a dread of fluids, is a proper designation for the disease as it occurs in man, because a peculiar dread of fluids is the most characteristic symptom of this disease in the human being. This symptom does not exist in the dog; hence, in this animal we should speak of the disease as rabies, in man as hydrophobia. Fleming, who is an acknowledged authority on everything that pertains to hydrophobia, makes the following statement in reference to the ability of rabid animals to take fluids: " The many hundreds of rabid dogs seen by Blaine, Youatt, and others did not evince any marked aversion to fluids. On the contrary, the rabid animal is generally thirsty, and if water be offered will lap it up with avidity, and, at the commencement of the disease, will always swallow it. When, at a later period, the con- striction about the throat, which is symptomatic of the malady, renders swallowing difficult, the animal does not the less endeavor to drink, and lappings are as frequent and prolonged as deglutition is retarded. Even then we see the suffering creature, in despair, plunge its entire muzzle into the vessel, and gulp at the water as if determined to overcome the spasmodic closure of the throat by forcing down the fluid. Tantalus did not experience a greater torment with regard to water than does the unlucky dog." The excessive sensibility to pain and the action of the mildest external irritants so characteristic of hydrophobia in the human being are absent in the rabid dog. The animal is almost insen- sible to pain; he will dash himself against the bars of his kennel, tear them when his mouth is lacerated and bleeding, and he has been known to seize a red-hot poker in his mouth and hold on to it, apparently unconscious of suffering. Rabies in the dog must be suspected when the animal becomes dull, morose, mopes, and avoids his master and companions. During the commencement of the disease the animal is exceedingly restless, and is always on the move, prowling, snapping, and barking at imaginary objects. During the first two or three da3rs there is rarel37 any tendency on the part of the animal to bite, nor to paroxysms of uncontrollable fury. The danger in this stage to man and other animals comes from lick- ing rather than biting, for there is a propensity to extraordinary demon- strations of affection. After a time, however, a paroxysm of maniacal fury comes on, generally provoked by the sight of another dog. When this has subsided the animal again becomes controllable, but manifests HYDROPHOBIA A MICROBIC DISEASE. 405 a strange disposition to wander from place to place. He is now most dangerous. With a slinking and troubled aspect, his head and tail down, his e37es suffused, and foam at his mouth, he walks or trots along, snapping and biting at real and imaginary objects. He is only aggressive when attacked, and then his fury seems unbounded. When tired out from inadequate nourishment and the ceaseless wanderings, he drops exhausted in some out-of-the-way, solitary corner, and, after a rest, starts off again on his lonely journey, seemingly impelled by some irresistible force, and is finally killed or dies of exhaustion. The duration of the disease in the dog never exceeds ten days, and in the majority of cases the animal dies on the fourth or the sixth day after the appearance of the first symptoms. From a study of the symptoms in this animal we can readily distinguish three stages: 1. Prodromal. 2. Irritation. 3. Paratytic. During the prodromal stage the most noticeable changes refer to the altered habits of the animal, while the stage of irritation culminates in attacks of ungovernable rage, provoked by real or fancied causes. The last, or paralytic, stage precedes death, which takes place from exhaustion. The period of incubation in the dog is variable; it is usually from six to twelve weeks, but may extend to a much longer period. Frank, from a study of 200 observed cases of rabies in the dog, found that the aver- age period of incubation was three months ; the extremes, six and seven days, and eleven months. HYDROPHOBIA A MICROBIC DISEASE. Raynaud and Lannelongue discovered that rabbits could be success- fully inoculated with saliva from rabid animals. Pasteur corroborated these observations by his own experiments, and cultivated from the blood of the infected rabbits in veal-bouillon a micro-organism which in its shape resembled the figure " 8 "; this microbe was surrounded by an envelope of a gelatinous substance. In the cultures these rods are said to have become converted into chain cocci. Fowls and guinea-pigs were not found susceptible to inoculations with cultures of this microbe. After Pasteur had regarded these micro-organisms as the cause of hydro- phobia, he produced the same disease in rabbits by inoculations with saliva from healthy persons. Vulpian also succeeded in producing, by inoculations of normal saliva in rabbits, a disease which proved fatal in two days; and with a small quantity of blood taken from the dead animals the disease could be communicated to other rabbits. The dis- ease thus produced was probably the same as that described by Stern- berg This observer caused marked septicaemia in rabbits by injecting subcutaneously his own saliva in small doses. Injections of 1.25 to 1.75 406 PRINCIPLES OF SURGERY. cubic centimetres, with few exceptions, caused death, usually within forty-eight hours. The constant and characteristic lesion found was a diffuse cellulitis, or inflammatory oedema, extending in all directions from the point of injection, attended with an abundant exudation of bloody serum, swarming with micrococci. Haemorrhagic extravasations in the connective tissue, and in various organs, were of frequent occur- rence, and changes in the liver and spleen, such as are common in rapidly- fatal septic diseases, were generally found. The disease could be com- municated by dipping a hypodermic needle into the blood of a rabbit just dead from the result of an injection of saliva; inoculating a healthy rabbit, a rapidly-fatal septicaemia was produced. Gibier found, in the brain of hydrophobic animals, round, shining granules, which stained slowly and imperfectly in aniline dyes. Fol stained the brain-substance, according to Weigert's method, and discovered in the hollow spaces of the neuroglia groups of micrococci. The same microbe he found also in the nerve-fibres, between the sheath and axis-cylinder. Babes stained the specimens according to Gram's method, and found cocci in the cells, especially those of the surface of the brain. The cocci looked like diplococci, and were alwa3rs found aggregated in flat clusters. Fol and Babes claim to have succeeded in obtaining a culture of the microbes found in the brain. The former used for nutrient medium a filtrate of triturated brain and parenchyma of salivar37 gland. Of 8 dogs, rats, and rabbits inoculated with the first culture, 5 died of well-marked hydrophobia; of 8 dogs inoculated with the second culture, four died. The inoculations were always made by infecting the brain through an opening in the skull. The microbes in the cultures corresponded in shape and size with those found in the brain of hydrophobic animals. The third series of cultures produced only negative results. The microbes in these cultures were more readily stained than most of the first two cultures. Babes cultivated the microbe upon gelatin and coagulated blood-serum, to which was added brain-substance obtained from rabbits. The cultures grew slowly, and appeared as gray spots. Successful inoculations were made with the second and third generations. The microbe of hydrophobia exists, but so far it has not been discov- ered. That hydrophobia is a microbic disease can no longer be doubted. At the present time we can safely assert, without fear of contradiction, that the essential cause of this disease is a specific virus, which can only be reproduced within the living organism. As a small quantity of this virus introduced into the tissues can result in the most serious conse- quences, there exists no doubt that it possesses the properties pertaining to living organisms, more especial^- the capacity of reproduction after CAUSES. 407 its entrance into the body. That the disease is not caused by preformed ptomaines, communicated from the saliva of rabid animals, is shown by the variable and, on the whole, long stage of incubation which precedes all true infective processes. Another convincing proof of its microbic origin is the well-established fact that the disease can be artificially pro- duced by implanting fragments of brain- or cord- tissue, taken from animals dead of rabies, into healthy animals. Furthermore, the blood and secretions of a rabid animal, its flesh and viscera, even the cooked flesh of a rabid ox, when eaten, would seem to be capable of conveying the disease. A pupil at the veterinary school of Copenhagen inoculated himself with the virus by cutting his finger slightly, while examining the body of a dog that had died of rabies on the evening before; the student died of hydrophobia in six weeks. The clinical symptoms, as well as the pathological conditions found in the brain and spinal cord of hydrophobic patients, bear such a strong resemblance to tetanus that it appears probable that the microbe possesses analogous pathogenic prop- erties, and that the actual development of the disease follows the action of its ptomaines upon the central nervous S37stem. The latent stage of the disease, or the long duration of the period of incubation, depends either upon the slow growth of the microbes or that these reach the place slowly from where they exert their specific pathogenic properties. CAUSES. The microbe of hydrophobia does not penetrate the intact skin or healtly mucous membrane; hence its entrance into the tissues takes place through an infection-atrium, usually a punctured wound made by the bite of a rabid animal. As the microbe pre-exists in the saliva of the rabid animal, inoculation takes place at the time the wound is inflicted. Infection, however, can take place by the deposition of the infected saliva upon a surface from which absorption can take place. This can occur from the licking of a wound or abraded surface by an infected dog, as happened in one of my cases. A lady of rank and fashion had a pimple on her face, from which she had scratched off the head. Hydrophobia was thus contracted, and she perished by this terrible disease. SYMPTOMS AND DIAGNOSIS. Great diversity of opinion exists as to the length of the period of incubation in man. In the 2 cases of hydrophobia that have come under my own observation, the time of infection and the onset of the disease could be accurately fixed, and in both of them the stage of incu- bation lasted forty-two days. In 106 cases of hydrophobia in human beings of all ages, collected by Bonley, 23 occurred within two months 408 PRINCIPLES OF SURGERY. after infection, and the remainder came in at varying periods, the longest time noted being eight months. The cases reported where it was sup- posed the disease developed some years after the persons were bitten by a dog lack accurac3r of observation, and either the diagnosis was not correct or infection occurred more recently, as we have the authority of Fleming that the disease never occurs later than eight months after inoculation. Age appears to have some influence in modifying the dura- tion of the stage of incubation. In the cases where the length of this stage could be accurately ascertained, in patients under 20 years of age the mean period of incubation was six weeks; from 20 up to 72 it was two months and a half. Before the actual development of the disease in man, there is usually a period of a few days during which ill-defined premonitory symptoms can be detected. The wound through which the virus entered is the seat of a sensation of uneasiness and itching, and sometimes of actual pain, which radiates along the course of the nerves of a limb. The cicatrix often presents a congested appearance, and is tender on pressure. The patient is melancholic and irritable, and sleep is disturbed. The first characteristic symptom of hydrophobia in man is a sense of tightness and choking about the pharynx, attended by a hesitation in swallowing, especially of liquids. In one of my cases this early disturbance of the function of the muscles of deglutition made it possible for me to recognize the disease a few hours after the attack commenced. The patient was a sailor, about 30 years of age, who sent for me to treat him for a supposed cold. The only thing he complained of was a sense of constriction in the throat and difficulty in swallowing. In examining the cavity of the mouth and pharynx for evidences which would explain the existing symptoms, I found a profuse salivary secretion; the mucous membrane of the pharynx was congested, but no signs of deep-seated inflammation could be found in the region of the tonsils. My suspicions were awakened at once. I ascertained that six weeks before a small pet dog owned by the family had died after a few days of illness, and that one day during this time, when the patient was lying on his back on the floor, the dog had licked a small sore on the anterior surface of the lobe of the left ear. Requesting the patient to drink water from a glass which I handed him, I noticed a hesitation on his part to comply with my wish ; but finally he grasped the glass with both hands, which trembled considerably, and, after waiting for the proper moment to come, applied it rapidly to his lips and made a desperate but futile effort to swallow; the attempt was repeated several times, but only a very small amount was swallowed. The next group of muscles to become affected with convulsive spasms are the muscles of respiration about the larynx. The symptoms of a SYMPTOMS AND DIAGNOSIS. 409 well-developed case of hydrophobia are so well depicted by Fleming that I will give his own description. "The difficulty in swallowing rap- idly increases, and it is not long before the act becomes impossible, unless it is attempted with determination, though even then it excites the most painful spasms in the back of the throat, with other indescriba- ble sensations, all of which appal the patient and cause him to dread the very thought of liquids. Singular nervous paroxysms or tremblings become manifest, and sensations of stricture and oppression are felt about the throat and chest. The breathing is painful and embarrassed, and interrupted with frequent sighs or a peculiar kind of sobbing move- ment, or catching of the breath ; there is a sensation of impending suffo- cation and of necessity for fresh air. Indeed, the most marked symptoms consist in a horribly violent convulsion or spasm of the muscles of the larynx and phar3rnx, or gullet, b3^ which swallowing is prevented, and at the same time the entrance of air into the windpipe is greatly retarded. Shuddering tremors, sometimes amounting to general convulsions, run through the whole frame, and a fearful expression of anxiety, terror, and despair is depicted on the countenance." Frothing at the mouth is rarely observed, but the viscid, tenacious mucus in the fauces and the profuse salivary secretion are frequentby for- cibby ejected by hawking and spitting. Shortly before death the patient's mouth is often full of this mucus or froth, which in some cases is tinged with blood. The pulse at first is not much changed in force and fre- quency, but as the disease advances it becomes feeble and rapid, and often intermittent. The temperature is always increased. In both of my cases the thermometer registered from 101° to 103° F. at different times in the axilla. A post-mortem temperature of 106.2° F., taken in the rectum immediately after death, has been recorded. Occasionally the patient has hallucinations of sight and hearing, but usually the mental faculties are not much impaired. One patient, al- luded to by Trousseau, heard the ringing of bells, and some mice run about on his bed. To the by-stander the most distressing phenomenon presented by hydrophobic patients is the fear of impending death, which is usually manifested soon after the attack, and remains throughout the whole course of the disease. No kinds of assurances or consolation are able to dispel it. Death occurs from complete exhaustion, in most cases attended by well-marked evidences of asphyxia from spasm of the glottis ; sometimes a convulsion is the final symptom, as in tetanus. The differential diagnosis between hydrophobia and tetanus is not always easy. In both diseases the stage of incubation is variable, and both are characterized by excessive excitability of the cerebro-spinal centre as is evident from the muscular spasms and great hyperaesthesia 410 PRINCIPLES OF SURGERY. of the entire surface of the body during the stage of irritation. In hydrophobia infection always takes place from the bite of a rabid animal, and the difficulty in swallowing is not caused by spasm of the pharyn- geal muscles, but by tonic contraction of the muscles of mastication, notably the masseters. In tetanus respiration is impaired by rigidity of the respiratory muscles of the chest; in hydrophobia by spasmodic con- tractions of the respiratory muscles of the laiynx. Acute softening of the brain, and meningitis affecting the base of the brain and upper por- tion of the spinal cord, may give rise to symptoms that bear a faint re- semblance to the clinical picture of hydrophobia, but a careful study of the s3rmptoms, individually and collectively, will disclose the real nature of the case under consideration. A purely neurotic affection has been described as lyssa nervosa falsa, which, it has been said, resembles genu- ine hydrophobia closely. Such cases are undoubtedly one of the mani- fold manifestations of lysteria ; and, if so, it can be differentiated from true hydrophobia by the absence of fever and by the fact that the mus- cular spasms are not limited to the muscles of deglutition and the mus- cles of the laiynx. Trousseau speaks of lyssa nervosa falsa as a mental hydrophobia. Fayrer describes a case of this kind in a young Scotchman in India, and Bollinger quotes a case of a bo37 who was twice frightened into simulated hydrophobia. In making a positive final diagnosis of hydrophobia, it is necessary to establish, in the first place, the fact that infection occurred from a rabid animal within eight months from the development of the disease ; and, in the second place, it is necessary to prove the existence of spasms of the muscles of deglutition in attempts to swallow liquids ; and if at the same time spasms of the muscles of the larynx interfere with the function of respiration, all doubt as to the nature of the difficulty has been removed. PROGNOSIS. If any doubt existed as to the nature of the case during life, an early fatal termination will corroborate the suspicions that may have been en- tertained. De'croix reports 9 cases of spontaneous recovery in dogs. In man this terrible disease is invariably fatal; there is no authentic instance on record of recovery from genuine hydrophobia. Death results unexpectedly, suddenly, or from apoplexy, asphyxia, or exhaustion, in from twelve hours to six days from the appearance of the first symptoms. The mean duration of the disease is about four days. One of my patients died on the fourth and the other on the fifth day after the attack. In 90 cases collected by Bonley, death occurred in 74 during the first four days, the largest proportion of these being on the second and third days. In only 16 was life prolonged beyond the fourth day. PATHOLOGY AND MORBID ANATOMY. 411 PATHOLOGY AND MORBID ANATOMY. Hydrophobia, like tetanus, to which disease it is so closely allied in many respects, is characterized b3r the absence of gross pathological changes in the nervous centres and at the primary seat of infection. The scar which marks the wound or lesions through which infection occurred may be red and slightly swollen, but these changes are not present in all cases. H3drophobia is a disease in which there is eveiy indication of irritation of certain nerve-centres and of a greatly increased reflex irritability. The centres irritated here are less those of the cerebral hemispheres than of the spinal cord and medulla oblongata. The symp- Fig. 90.—A Bloodvessel from Medulla Oblongata in a Case of Hydrophobia. Large Numbers of Round Cells are .Seen in its Sheath. X350. (Coates.) toms point mainly to the medulla oblongata, and after death well-defined vascular lesions can be detected in this structure by means of the microscope. Similar lesions, but less marked, can be found in the spinal cord, and still to a lesser degree in the other parts of the nervous system. The most prominent condition is an accumulation of leucocytes around the vessels in the substance of the cord and medulla oblongata. Where the local lesion is most advnnced the vessels are surrounded by several layers of leucocytes, which would indicate that the microbe of hydro- 412 PRINCIPLES OF SURGERY. phobia or its ptomaines produce an alteration of the capillary wall of sufficient intensity to entitle the process to be called inflammation. An increase of leucocytes is evident everywhere, so much so that the collec- tions which can be found in different parts have been called miliary abscesses. As the leucocytes show no evidences of even approaching transformation into pus-corpuscles, these aggregations of leucocytes do not deserve the name of abscesses. Klebs is of the opinion that the mi- crobe of hydrophobia does not enter the circulation directly, but invades in preference the lymphatic vessels, as he found general lymphatic en- gorgement in a recent case. The same author also discovered, particu- larly in the submaxillary gland, deposits of finely granular, strongly re- fractive corpuscles of a faint, brownish color, closely packed together in Fig. 91.—From the Salivary Gland in a Case of Hydrophobia. In the Middle is the Portion of a Duct ; abundant Round Cells around it as well as the Glandular Structures shown in Outline, x 350. (Coates.) clusters and rows, which he regards as possibly the vehicles for the transportation of the specific virus. Well-marked evidences of leuco- cytes have been found by many in the salivaiy glands. There is lyperaemia and oedema of the substance of the brain, medulla oblongata and cord, and of their membranes ; deep-red injection of the mucous membrane of the pharynx and epiglotis, and sometimes recent swelling of the tonsils, follicular glands of the tongue, pharyngeal follicles, and of the lymphatic .glands in the neighborhood of the jaw. The stomach and intestines show decided injection, and often haemor- rhagic extravasations. The lungs are charged with blood, with frequent points of capillary haemorrhage, and sometimes emphysema as a result of the d37spnoea. In the kidneys, also, there are signs of irritation in the form of dilatation of vessels and haemorrhage. According to Bol- TREATMENT. 413 linger, the anatomical picture bears the strongest resemblance to that seen in cases of death from asphyxia or thirst. The conditions found, post-mortem, furnish an illustration that here an intense irritant is cir- culating in the blood, and the intensity of it may be judged from the fact that all these very marked appearances, although nearly all of them recognized only by the use of the microscope, occur in the short space of three or four days. TREATMENT. As hydrophobia is an absoluteby fatal disease, the treatment resolves itself into prophylactic measures to prevent the disease, and means of palliation after it has developed. Prophylactic Treatment.—The most effective proplylactic measures consist in preventing the spread of the disease, among animals, by the killing or strict isolation of animals which present S3Tmptoms of rabies. If animals, which are suspected of being rabid, are known to have bitten persons, they should not be killed at once, but should be kept in close confinement unknown to the injured person, until, by observation or the course of the disease, a positive diagnosis can be made. As soon as a positive diagnosis of rabies can be made, then the animal should be killed to prevent any further possibility of infecting other animals or persons. If a person is bitten by an animal which presents suspicious s37mptoms, no time should be lost to prevent infection by removing or destroying the A'irus. (a) Excision of Wound.—As the virus of hydrophobia appears to be slowly diffused in the tissues, thorough local treatment of the wound may prove successful in preventing infection, even if resorted to several hours or da3's after inoculation has occurred. As soon as possible after the bite has been inflicted, a constrictor should be applied on the proxi- mal side of the wound and medical aid summoned without delay. In the meantime an attempt should be made to remove the virus from the wound by suction. In recent cases the simplest and safest treatment consists in excising the tissues in the immediate vicinity of the puncture, and after thorough disinfection close the wound with sutures. (b) Cauterization of Wound.—The same object is accomplished, but with a lesser degree of certainty, by cauterization. The most efficient caustic is the actual cautery. With the knife-point of a Paquelin cautery the wound is deeply cauterized, and the resulting eschar is protected against infection with pus-microbes by an antiseptic dressing. Of the chemical caustics the most valuable are caustic potassa, nitric acid, sul- phuric acid, and nitrate of silver, their efficienc37 being estimated in the order named. The authority for excision and thorough cauterization, as prophylactic measures, is to be found in the fact that, of 134 collected 414 PRINCIPLES OF SURGERY. cases, in which bites of mad dogs were cauterized, 68 escaped and 42 died,—a degree of immunity far above the average, which is 33 per cent. (Bonley.) (c) Prophylactic Inoculations.—Pasteur has shown, by a long series of inoculations, made first in monkeys, rabbits, and guinea-pigs, and later exclusively in rabbits, that if the virus of hydrophobia is introduced into the brain of these animals the disease is invariabl37 produced after a fixed period of incubation. As the period of incubation in successive inoculations in the same animal is shortened, we must take it for granted that the virulence of the material is increased. In the rabbit the first inoculation under the dura mater is followed b37 a period of incubation of fourteen da3's' duration, which, in successive inoculations in the same animal, is reduced to seven days. Back inoculations in dogs produce in these animals fatal rabies in the same length of time. Pasteur made an additional important discovery, as he found that the spinal cord of the inoculation rabbits, increased in virulence by successive inoculations, is again diminished in its virulence b37 preserving it in dry air, guarding at the same time against contamination with other micro-organisms. This discovery led to a method by which the virulent action of such prepa- rations can be accurately graded, inasmuch as the action of the spinal cord, in the drying-room, in 7 to 8 days is reduced from its highest degree of virulence to nil. By using the spinal cord of rabbits treated in this manner in different strengths, at first weak and then gradually stronger preparations, it was found possible to render animals immune to the action of inoculation material of the highest potemy. By this method Pasteur succeeded in creating absolute immunity against the strongest hydrophobic virus in 50 dogs. The success of these prophylactic inocu- lations in animals enabled Pasteur to resort to the same method of treatment in persons bitten by rabid animals, as the long stage of incu- bation made it possible to carry out this treatment before the actual development of the disease was expected. The first human being sub- jected to this treatment was on July 5, 1885, and from that time until the close of the year 1889 2682 persons bitten by rabid animals, or animals that were suspected of being mad, with the result that of this large number only 31 died, equivalent to 1.15 per cent., while the general mortality in persons under similar circumstances without such prophy- lactic inoculations has been at least 16 per cent. The danger is always greatest when the bite is inflicted by rabid wolves. Pasteur collected 100 cases of persons bitten by rabid wolves, and of this number not less than 82 died. Pasteur had an opportunity to submit to his treatment 38 persons bitten by rabid wolves, and of this number only 3 died,—a mortality of 7.89 per cent. TREATMENT. 415 The following tables represent Pasteur's work for fo ur 3rears :- Table A. Table B. Table C Total. Years. 52 •6 3 IS 5 li c"3 »2 ■6 3 si 00 ej •a 5 5S Hhh Sft P-H sS. PnfH w 0) fcFH ^5 1886 . . 231 3 1.30 1926 19 0.99 514 3 0.58 2671 25 0.94 1887 . . 357 2 0.56 1156 10 0.86 257 1 0.39 1770 13 0.73 1888 . . 402 6 1.49 972 2 0.21 248 1 0.40 1622 9 0.55 1889 . . 346 2 0.58 1187 2 0.17 297 2 0.67 1830 6 0.33 Total . . 1336 13 0.97 5241 33 0.63 1316 7 0.53 7893 53 0.67 The bites have been divided into three categories,— 1. Those of the head and face; 2. Those of the hands ; 3. Those of the limbs and trunk,—with the following result:— Tables A and B. Table C. Total. c"3' 5 « Ph£ 5 &2 c ^ 2ft e'f3 g C3 ■6 3 « ® 213 S <° g ci ? " PhH 13 5 *\3 is a 3 u u o ». 3. Limbs and trunk .... 593 3768 2216 14 26 6 2.36 0.69 0.27 79 619 618 l 3 3 1.27 0.48 0.48 672 4387 2834 15 29 9 2.23 0.66 0.32 Total........ 6577 .46 0.70 1316 7 0.53 7893 53 0.67 Table A comprises those persons bitten by animals determined to be rabid by experiments in rabbits, made in the laboratory, or by the death of other animals, or persons, bitten by the same animal. Table B comprises those persons bitten by animals demonstrated to be rabid by the examination of a veterinary surgeon, or by the clinical signs shown during life. Table C comprises those persons bitten by animals suspected to be rabid. These results must convince the most skeptical of the practical utility of Pasteur's prophylactic treatment against hydrophobia, and, although the method will not be perfect until the microbe of this disease is discovered and mitigated (pure cultures are employed), this crude method must be viewed as a great boon to a class of patients otherwise exposed to the risks of contracting the most terrible and hopeless of all 416 PRINCIPLES OF SURGERY. diseases. Pasteur institutes have sprung up in different parts of the civilized world, and the accumulated experience of all those engaged in this kind of work bears strong testimony in favor of the prophylactic inoculations against hydrophobia as taught and practiced by Pasteur. At the bacteriological laboratory in Cuba 306 persons have been treated by the " double intensive" plan. Of these only 2 died after going through the full course,—a mortality of 1.63 per cent. All these cases were bitten by dogs proved experimentally and clinically to be rabid, or, at any rate, suspected. That the inoculations were conducted with due conservatism is indicated by the fact that only 306 persons were treated out of 700 applicants. Some of the failures Pasteur attributes to the long intervals between the prophylactic inoculations, and in grave cases he now advises that successive inoculations should be made with cord- substance twelve, ten, and eight days old, during the first twenty-four hours; on the second day with material six, four, and two days old ; on the eighth day with material one day old, to be followed by two similar series of inoculations. By following this energetic plan of prophylactic treatment he has been able to secure protection even in the most urgent cases; that is, in cases where the stage of incubation had nearly terminated. Palliative Treatment.—The nature of the disease should, under no circumstances, be disclosed to the patient, as the people, high and low, educated and ignorant, are only too familiar with the terrible suffering caused by this affection and its absolute certainty of a fatal termination in a few days. In one of my cases the patient had been made acquainted with the character of the ailment, and begged piteously that his life might be terminated by the administration of chloroform, knowing well that the intense suffering would continue to the last moment. As light, draughts of air, and noise of every kind increase the suffering by exag- gerating convulsive spasms, these aggravating causes should be elimi- nated from the patient's room, and only a limited number of persons should be admitted to render the necessary assistance and cany out the directions of the attending physician. As the saliva of hydrophobic patients contains the specific virus, those placed in charge of the patient should protect themselves against inoculation by preventing the contact of the saliva with abraded surfaces, or, still better, by covering any abrasions which may exist with a collodium dressing. Thirst is quenched by administering water per rectum. Medicines by the mouth should not be given, as every attempt at swallowing brings on violent spasms of the muscles of deglutition and the respiratory muscles of the lar37nx. Mor- phia combined with small doses of atropia should be given subcutaneously in such doses and at such intervals as will procure rest. The subcu- TREATMENT. 417 taneous administration of quinine and woorara has been advised, but both of these remedies are more harmful than useful, and neither of them either add anything to the duration of life or alleviation of suffer- ing. The only remedy which can be relied upon to afford prompt relief is chloroform by inhalation. Ether should never be used, as the hyper- aemic condition of the brain and spinal cord which is present in every case of hydrophobia sufficiently contra-indicates its use. The inhalation of chloroform must be conducted by an assistant or a competent, re- liable nurse, and should never be carried beyond the point where relief is afforded, and it should be repeated as often as the paroxysms return. 27 CHAPTER XVII. Surgical Tuberculosis. Tubercular lesions furnish a most excellent illustration, clinically and under the microscope, of the origin, course, termination, and tissue changes of what is known as chronic inflammation. A histological description of a tubercular nodule is a description of the patholog3r of chronic inflammation. Tuberculosis in all its forms is caused by a specific microbe, the action of which upon the tissues produces his- tological and vascular changes which are characteristic of chronic inflammation. Of all the microbic diseases, with the exception of sup- puration, tuberculosis is of the greatest interest and importance to the surgeon. Of the greatest interest because the tubercular lesions which come under his care are more clearly understood from a bacteriological stand-point than most of the other surgical diseases, and of the greatest importance on account of their great frequency. That large class of ill-defined lesions which were grouped under that indefinite and vague term scrofula, in the text-books of but a few 3-ears ago, have been shown by recent research to be identical with the recognized forms of tuber- culosis, etiologically, clinically, and anatomicalby. In this chapter I shall aim to give a brief description, from a bacteriological and clinical stand-point, of such localized tubercular lesions which, by general consent, are regarded as surgical affections and requiring surgical procedures in their successful treatment. HISTORY OF THE MICROBIC ORIGIN OF TUBERCULOSIS. The first inoculation experiments with tubercular products were made by Kortum in 1789, and Cruveilhier in 1826. In 1834 Erdt suc- ceeded in producing numerous nodules in the lungs of horses by inocu- lating them with tubercular pus, and Klencke, in 1843, produced tuberculosis in rabbits by intra-venous injections of tubercular matter. The results obtained from the crude inoculation experiments which were made years ago by Villemin pointed strongly toward the infec- tiousness of tuberculosis. Villemin's experiments consisted in the subcutaneous insertion, behind the ear of rabbits, of fragments of tubercular tissue or fluid taken from the cavity of a tubercular lung, recently removed from a patient who had died of pulmonary phthisis, (419) 420 PRINCIPLES OF SURGERY. The first animal thus infected was killed three and a half months after inoculation. The lungs and most of the internal organs were found diffusely infiltrated with miliary tubercle. His numerous later experi- ments yielded similar results, and led him to the following conclusions: " Phthisis of the lungs (like tubercular diseases in general) is a specific infection. Its etiology depends on an inoculable agent. It can be readily communicated from man to animal by inoculation." Yogel repeated the experiments of Yillemin on horses without success. Biffi, Yerga, and Sangalli experimented on mules, cows, sheep, dogs, cats, mice, and chickens with negative results. The experiments of Langhans led hire to the conclusion that tubercle could not be com- municated in the manner described by Yillemin. He claimed that the inoculation material acted only the part of a foreign body, the inflam- mation following its insertion into the tissues differing in no way from the ordinary forms of inflammation. Among those who made successful inoculation experiments, and adopted the doctrines advanced by Yillemin, may be mentioned Hevard and Cornil, Hoffmann, Cohn, Bchier, Empis, Mantagazza, Bizzozero, Lebert and Wyss, Klebs, Koester, Waldenburg, Bijuen, Simon, Sanderson, W. Fox, Papillon, Nicol, and Laveran. Hevard and Cornil were able to propagate them. They inocu- lated with genuine tubercular material, but failed with cheesy products. Marcet inoculated 11 guinea-pigs with the sputa of phthisical patients, and in 10 of them the experiment proved successful. Cohnheim injected tubercular material into the anterior chamber of the e37e in rabbits, and succeeded in producing the disease artificially in this manner. Hueter produced tuberculosis of the iris by inserting into the anterior chamber of the eye in rabbits fragments of tubercular tissue. Toussaint showed that true tubercle, both in man and animals, reproduces itself indefinitely with absolutely constant and identical properties, and that it is quite capable of being transmitted from animal to animal without losing its virulence. Krishaber and Dieulefoy experimented on monkeys, and the results obtained led to the conclusions: 1. That human tubercle, when inocu- lated, kills a monkey in nine out of ten cases, with lesions analogous to those met in man. 2. The effect of the inoculation varies according to the substance emplo3Ted; the gray granulation is most, and the pulmonary parenclyma least, infectious. Schiiller and Lentz made successful inoculations with blood taken from tuberculous rabbits. Lippl, Schwenniger, Tappeiner, and Weichselbaum succeeded in pro- ducing the disease in animals by inhalation. Successful feeding experi- ments were made by Chaveau, Aufrecht, and Bollinger. Since Yillemin announced the inoculability of tuberculosis, diligent search was made HISTORY OF THE MICROBIC ORIGIN OF TUBERCULOSIS. 421 to discover and isolate a specific micro-organism which should be characteristic of this disease. The first cultivation experiments were made by Klebs in 1877. He found, by examining fresh specimens of tubercle of human beings, that they invariably contained bacteria. He cultivated them in egg-albumen and Bergmann's culture fluid, and found, by experiment, that the cultures produced the same effect in causing disease by inoculation as the tissues from which they were grown. Injections of the culture under the skin, into the muscles, lungs, pleural and peritoneal cavities, caused death of the animals from tuberculosis. Cultures made in a similar manner from scrofulous glands and lupus-tissue produced the same effect in animals. Max Schiiller repeated the experiments of Klebs with the same results. He described the specific microbe as round and rod-shaped bacteria, the rods bulbous at both ends, composed of two, seldom more, spherical bodies. He found these microbes in great abundance in tubercular joints and tubercular foci in bone. He produced the disease artificially in animals which were previously inoculated by making contusions of joints. Other workers in the same field advanced theories, found and described microbes, which were supposed to bear a direct etiological relationship to tuberculosis, but nothing definite was known on the subject until the father of modern bacteriology, Robert Koch, in 1882, announced to the profession his great discove^7. He had found and demonstrated the true and essential cause of tuberculosis, the bacillus of tuberculosis, and, in his first publication, brought such convincing proof of the correctness of his claim that, with few exceptions, it brought conviction even to the minds of the most skeptical. He had not ony found the bacillus, but showed that it was present in all tuber- cular lesions. He had isolated and cultivated the bacillus from tuber- cular tissue ; and, finally, he had furnished the crucial test—had produced tuberculosis, artificially, in animals by inoculation with pure cultures. A number of pathologists who inoculated animals with non-tubercu- lar material claimed that they had produced pathological conditions analogous to those found in animals which had been infected with the virus of tuberculosis. Fragments of sponge implanted in the abdominal cavity produce a condition which resembles tubercular inflammation, and it has been asserted that powdered glass has a similar property. Schot- telins, Wargunin, Wcichselbaum, and Martin have emplo37ed various substances by way of experiment, such as powdered cheese, brain- substance, lycopodium-seed, Ca37enne pepper, and pulverized cantharides. They caused these to be inhaled in the form of a fine spray, with the result that the3' were almost invariabty able to produce, in different ani- mals, an eruption of nodules in the lung and sometimes in other organs. 422 PRINCIPLES OF SURGERY. With Limburger cheese Weichselbaum produced an eruption in the lungs and kidneys of dogs, after fifteen inhalations during seventeen days, which, histologically, could not be distinguished from the products of genuine tuberculosis. Further experimentation soon showed that these were instances of pseudo-tuberculosis ; that, while the gross appearances of the lesions resembled true tuberculosis, inoculations with this material never reproduced the disease, while inoculations with tubercular tissue could be done through a series of animals without impairing the potency of the virus or varying the constancy of the results. Koch's discovery did not lead to such energetic search for the bacillus of tuberculosis among surgeons as physicians, because, as Konig asserts, the symptoms and signs of the tuberculous affections coming under the observation of surgeons are so characteristic that, for practical purposes, a correct diag- nosis could be made in the majority of cases without a knowledge of their microbic nature and the improved methods for making a positive diagnosis derived therefrom. Koch himself, in the publication above referred to, demonstrated the presence of the bacillus in lupus, the so- called scrofulous glands, tubercular joints, etc. He called attention to the fact that in these affections the bacillus can be constantly found in giant cells and between the epithelioid cells, while it is more difficult to find it in cheesy products, unless caseation has taken place quite rapidly. Koch examined 19 cases of miliary tuberculosis, in which bacilli were found in every nodule; 29 cases of phthisis, in every one of which bacilli were found most numerous, with the exception of the sputum, in recent caseous foci and in the walls of cavities undergoing speedy de- struction. He also found them constantly in tuberculous ulcers of the tongue, tuberculous pyelo-nephritis, and tuberculosis of the uterus and testicles ; also in 21 cases of tuberculosis of lymphatic glands. Further, in 13 cases of tuberculosis of joints and in 10 cases of tuberculosis of bone ; in 4 cases of lupus, in which only a single bacillus could be seen in the giant cells ; in 17 cases of Perlsucht in cattle. Finally, in animals inoculated with tubercular virus: 273 guinea-pigs, 105 rabbits, 44 field- mice, 28 white mice, 19 rats, 13 cats, besides dogs, chickens, pigeons, etc. Examinations of sputa and organs in various other non-tubercular affections for bacilli resulted, without exception, negatively. Weichselbaum, Meisels, and Lustig found tubercle bacilli in the blood in cases of acute miliary tuberculosis, both during life and after death. Schuchardt and Krause examined 40 cases of tuberculosis of bones, joints, tendon-sheaths, and the skin in Yolkmann's clinic, and never failed in finding bacilli, although in some specimens careful and prolonged search had to be made. Schlegtendal examined 520 specimens of pus from tuberculous sup- DESCRIPTION OF BACILLUS TUBERCULOSIS. 423 / purations, and found bacilli present in about 75 per cent, of the cases. Mogling found the bacillus never absent in tuberculous pus from 53 patients. The literature on the etiological relation existing between the bacillus of tuberculosis and the affections of the skin, glands, bones, and joints, which have heretofore been grouped under the head of scrofula, is immense; but the foregoing quotations will suffice to show the regu- larity with which the bacillus can be found in the tissues of the so-called scrofulous affections, as well as in all recognized clinical forms of tuberculosis. DESCRIPTION OF BACILLUS TUBERCULOSIS. The tubercle bacillus, with the exception of the bacillus of septi- caemia in mice, is the smallest of the known bacilli. The length of each rod varies from one-fourth to three-fourths of the diameter of a red blood-corpuscle. The thickness corresponds to that of the bacillus of sepsis in mice. The rods are either straight or, what is more common, bent or curved near the centre. In cultures and in the tissues they occur singly, in pairs, or in bundles. In a state of fructification the bacilli contain from two to six spores. In stained rods the spores appear as clear, minute, ovate spaces, as the3T are not affected by the coloring material, bacilli^n^aining In some bacilli the spores form slight projections on ^J^f^f Zelss' A0,4- the sides of the rod. Reproduction by spore for- mation also takes place in the tissues within the animal body. In badby-stained specimens, and on superficial examination, the spores im- part to the bacillus the appearance of a chain coccus; but, examined closely, it is seen that the protoplasm of the bacillus is continuous, and the apparent interruptions are due to the presence of the spores. The bacilli of tuberculosis are non-motile, and consequently possess no power of locomotion, and cannot penetrate into the tissues without assistance. In the tissues they are found in the interior of giant cells and within and between epithelioid cells. They are constantly found in places where the tuberculous process is commencing or actively progressing. In the beginning they are isolated and in the interior of cells ; later, they be- come more abundant and form groups. In cheesy deposits they are either entirely absent or few in number. The virulence of caseous material is due mostly to the presence of spores, which may remain in a latent condition and yet retain their power of reproduction under more favorable conditions for an indefinite period of time. As soon as giant cells appear, they contain bacilli in their interior, as a rule. In some giant cells only one bacillus can be found, and then it occupies a part of the cell which contains no nuclei. 424 PRINCIPLES OF SURGERY. In giant cells with numerous bacilli the latter arrange themselves around the periphery in the interior of the cell, while the centre contains few or none. The first ingress of bacilli into the diseased tissues probably takes Fig 93 —Giant Cell with One Tubercle Bacillus. Section from Lupus of Skin. 700:1. (Fluegge.) place by wandering cells, which transport the non-motile microbe. In many inoculation experiments such bacilli-containing cells have been found in the blood and tissues. Fig. 94.—Giant Cell. Miliary Tuberculosis. 700:1. (Fluegge.) Staining.—The peculiar behavior of the bacillus of tuberculosis to different staining material enabled Koch not only to discover this microbe, but also to differentiate it from all other microbes. While the aniline dyes and other nuclear staining material showed no micro-organ- DESCRIPTION OF BACILLUS TUBERCULOSIS. 425 isms in tubercular products, the bacillus came plainly into view if a small quantity of alkali was added to the aniline solution. Later experience proved that the same effect is produced if, instead of an alkali, anilin, tolnidin, turpentine, carbolic acid, or ammonia is added. All of these substances aid the penetration of the staining fluid into the bacillus. Of especial advantage is the discovery, also made by Koch, that the staining fluid is fixed more permanentby b37 treating the sections stained with alkaline aniline dyes with nitric or muriatic acid, a procedure which removed the staining from the cells, nuclei, and all other bacteria, while the tubercle bacillus alone remains stained. The preparation is further \V«^^^ \ if/^*" completed by staining once with one V ^Mlf \\ a. of the ordinary aniline dyes, which « J \?*~- iJMifi stains the cells and nuclei and other ■/' bacteria, so that the tubercle bacil- l^p lus, for instance, appears red, the "VW nuclei and other bacteria blue. Most of the bacilli in Fig. 95 VJ^J '/" /x —£- nnntiin onnrps Hip mnirmfv r>f tlipm Fig. 95.—COVER-GLASS PREPARATION from contain spoies,tne majont3 01 tnem phthisical sputum, double stain- slightly curved or bent; they lie (^a^Tarten?KLICH'S Method' x 150a free,—that is, outside the cells. Where they appear to be within the cells, a close examination shows them to be either upon or underneath the cells. For section-staining Ehrlich's method is the best:— Saturated alcoholic solution of methyl-violet or fuchsin, . . 11 parts. Aniline water,..........100 " Absolute alcohol,..........10 " Sections are left for twelve hours in this solution. Treat the speci- mens with l-to-3 solution of nitric acid a few seconds; wash in alcohol (60 per cent.) for a few minutes; after-stain with diluted solution of vesuvin or methylene-blue for a few minutes ; wash again in 60-per-cent. alcohol; dehydrate in absolute alcohol; clear with cedar-oil; mount in Canada balsam. The examination of fluids for bacilli can be done rapidly and most satisfactorily by Gibbes' method :— gibbes' magenta solution. Magenta,...........2 parts. Aniline oil,...........3 " Alcohol (specific gravity 0.830),.......20 " Distiller! water,..........20 " Stain cover-glass preparations in this solution for fifteen or twenty minutes ; wash in l-to-3 solution of nitric acid until the color is removed ; 426 PRINCIPLES OF SURGERY. rinse in distilled water; after-stain with methylene-blue, meth3'l-green, iodine-green, or a watery solution of cr3rsoidin, five minutes; wash in distilled water until no more color comes awa37; transfer to absolute alcohol for five minutes; di'37, and preserve in Canada balsam. Cultivation.—The best culture medium for the bacillus of tubercu- losis is solid, sterilized blood-serum of the cow or sheep, with or without the addition of gelatin, at a temperature of 37° to 38° C. (98.6° to 100.4° F.). The bacillus grows very slowly, and onby between the tem- peratures of 30° and 41° C. (86° and 105.8° F.). In about a week or ten da3rs the culture appears as little, whitish or 37ellowish scales and grains. Cultivations can also be made in a glass capsule or solid blood- serum, and the appearance of the growth studied under the microscope. The scales or pellicles are then seen to be made up of colonies of a perfectly characteristic appearance. The growth ceases after three or four weeks. The blood-serum is not liquefied unless putrefactive bacteria contaminate the culture. Frankel figures, in his " Atlas der Bacterien- kunde," a luxuriant culture of the bacillus of tuberculosis upon glycerin- agar. Nocard and Roux have found that coagulated blood-serum is improved for the growth of the bacillus by adding peptone, soda, and sugar. A further addition of 6 to 8 per cent, of glycerin favors the growth of the bacillus still more, while, at the same time, it prevents the formation of a dry crust upon the culture medium, which otherwise forms by evaporation. They also made successful cultivations upon agar-agar bouillon, to which was added 6 to 8 per cent, of gbycerin, kept at a temperature of 39° C. (102.2° P.). Koch has cultures 3 years old which have passed through 40 genera- tions and still retain their virulence, showing plainly the longevity and tenacity of the bacillus of tuberculosis. INOCULATION EXPERIMENTS. Long before the discovery of the bacillus of tuberculosis by Koch, genuine tuberculosis was produced artificially in animals by inoculation with the products of tubercular inflammation. Hueter inoculated the anterior chamber of the eye in rabbits with lupus-tissue, and produced typical tuberculosis of the iris. Schiiller introduced fragments of lupus- tissue directly into the veins of animals, and in this way caused pulmo- nary tuberculosis. Koch produced tuberculosis in animals susceptible to this disease by implantation of tubercular tissue in various localities and by inoculation with pure cultures, the experiments yielding, almost without exception, positive results. The same author inoculated the anterior chamber of the eyes in 18 rabbits from 5 cases of lupus, and in INOCULATION EXPERIMENTS. 427 all of them tuberculosis of the iris was produced, and, if life was pro- longed for a sufficient length of time, was followed by tuberculosis of the lymphatic glands of the neck, lungs, kidneys, liver, and spleen. Similar results were also obtained in 5 guinea-pigs. Cornet has made numerous experiments, in Koch's laboratory, on animals, to ascertain the inoculability of tuberculosis through abrasions of the skin, or a pure culture of tubercle bacilli is applied to a cutaneous abrasion; the result in most, if not all, cases is a local tuberculosis in the adjacent lymphatic glands, and, later, a general miliary tuberculosis. The same author made, more recently, a long series of experiments on dogs, to ascertain the different avenues through which tubercular in- fection is known to take place. Tubercular sputum and pure cultures inserted into the lower conjunctival sac in healthy dogs produced tissue hyperplasia at the seat of inoculation, and was followed by infection of the cervical glands on the corresponding side. Some of the glands underwent caseation, and the presence of bacilli could be demonstrated in all of the pathological products. In other animals the tubercular material was introduced into the nasal cavity. The cervical glands, especialby those on the corresponding side, became enlarged and caseated. Infection through the mouth, by depositing the tubercular material in a depression made with a blunt instrument between the canine teeth, re- sulted also in tuberculosis of the glands of the neck. Infection of the external meatus of the ear, without creating an infection-atrium intention- ally, was followed by infection of the Lymphatic glands behind the ear and along the neck on the same side. Cutaneous tuberculosis in the form of an ulcerating lupus was produced by shaving the skin on one side of the nose and face, and scratching it with a finger-nail infected with a pure culture. Injection of pure cultures into the healthy vagina of bitches resulted in local tuberculosis and secondary infection of the inguinal glands. Inoculations of other parts were followed by the same train of symptoms,—local tuberculosis at the seat of infection, followed by dissemination of the process along the course of lymphatic channels. The lungs -were found affected only in two of the animals. These ex- periments show conclusively that the bacillus of tuberculosis, introduced through superficial peripheral infection-atria, seeks the lymphatic chan- nels, through which it is extensively disseminated before general infec- tion takes place. Cornil and Leloir implanted lupus-tissue into the peritoneal cavity of guinea-pigs, and in 5 cases out of 14 experi- ments produced peritoneal and general tuberculosis. Pagenstecher and Pfeiffer took the secretion of the conjunctiva from patients suffering from lupus of this structure, and injected it into the anterior chamber of the eye in rabbits. After five to six weeks nodules could be seen on the 428 PRINCIPLES OF SURGERY. surface of the iris, which, on examination, were found to be in every respect identical with tuberculosis of this organ. Doutrelepont inocu- lated the peritoneal cavity in 50 guinea-pigs, and in 8 rabbits the anterior chamber of the eye with the same material, with the result that in all of the animals local tuberculosis was produced at the point of inoculation, and in 3 of the guinea-pigs and in 1 rabbit the local disease was followed by general tuberculosis. Inoculations with material from so-called scrofulous glands produce the same effect as when lupus-tissue is used, and we are, therefore, forced to conclude that these glands owe their existence to the same cause. Arloing prepared an emulsion from a scrofulous (tubercular) gland, caseous in its centre, which was taken from a boy aged 14. This was injected beneath the skin of 10 rabbits, and the same number of guinea- pigs. Visceral tuberculosis developed in all of the guinea-pigs, but the rabbits remained healthy, except that 2 showed yellow, caseous granula- tions at the seat of inoculation. Some glands excised from the neck of a young woman produced tuberculosis both in rabbits and guinea-pigs. The patient died three weeks after the operation from miliary tubercu- losis. From these experiments he inferred that either scrofula and tu- berculosis were nearly allied affections, but caused by different agents, or they were derived from the same virus, of which the activity was modi- fied in the scrofulous form. That the number of bacilli injected has a great deal to do with the result has recently been satisfactorily demonstrated by Bollinger. He found that infectious milk from a tuberculous cow, which produced local tuberculosis by intra-peritoneal injections, lost its virulence if diluted from 1:40 to 1:100. The sputum of phthisical patients was found much more virulent, and had not lost its power to produce tuberculosis on being diluted 1:100,000, on being injected into the abdominal cavity, or the subcutaneous connective tissue. Feeding experiments with sputum diluted 1:8 yielded negative results. Pure cultures remained virulent when diluted 1:400,000. All the experiments proved that the more con- centrated the material and the greater the number of bacilli, the more rapid and intense was the development of the lesion caused b37 the injec- tion. It was estimated that about 820 bacilli were necessary to produce tuberculosis in guinea-pigs. Intra-peritoneal injections did not always produce peritoneal tuberculosis, and in cases where this did not occur the organs affected were the bymphatic glands, spleen, lungs, liver, kid- neys, and genital organs, in the order of frequency named, showing con- clusively that localization does not invariably take place at the point of primary infection. Direct intra-venous infection by injections of pure cultures, sus- INOCULATION-TUBERCULOSIS IN MAN. 429 pended in distilled water, is the most effective way in which diffuse miliary tuberculosis can be artificially produced in animals with unfail- ing certainty. Koch succeeded also in producing the disease in rabbits, guinea-pigs, rats, and white mice, by inhalation. A pure culture, sus- pended in distilled water, was used with a hand-spray, and the cages in which the animals were kept were filled with the infected spray.° The animals were killed after twenty-eight days, and all of them showed unmistakable signs of pulmonary tuberculosis. INOCULATION-TUBERCULOSIS IN MAN. The opinion that tubercle is capable of inoculation was held by ancient writers, and Laennec, himself, after a nick from a saw while making a necropsy on a phthisical subject, thought that he witnessed an example of inoculation in a small tubercle in the skin, but twenty years afterward this distinguished clinician was in good health, though finally he died of phthisis. Schmidt made a number of experiments to ascertain the effect of inoculations of superficial abrasions of the skin with the virus of tuber- culosis. In guinea-pigs he made abrasions in the skin, to which he applied tubercular material and covered the point of inoculation with collodium. All of his experiments failed in producing tuberculosis, while in the control animals, in which the infectious material was intro- duced into the subcutaneous tissue, or into the peritoneal cavity, tuber- culosis developed without a single exception. He believes that the results of these experiments are only corroborative of the assertion previously made by Bollinger and Koch, that the susceptibility of the cutis for tubercular infection is slight. A sufficient number of authen- ticated cases, however, have been reported during the last few years, to prove that in man tuberculosis is not infrequently contracted by the absorption of tubercular material through small wounds and superficial abrasions of the skin. Volkmann, a number of years ago, made the state- ment that tubercular infection never takes place through a large opera- tion wound, or at the site of severe injuries, but that localization of the bacillus is likely to take place in parts the seat of very slight contusions, or what may appear at the time as an insignificant injury. He explained this b37 assuming that the active tissue changes which take place during the process of regeneration after a severe trauma prevent the infection. In studying the cases of inoculation-tuberculosis, which will be referred to below, it will be seen that the infection-atrium was always caused by a trivial injuty. A very interesting case of inoculation tuber- culosis came under niy own observation during the last year. The patient was a strong, healthy young woman, with a good family history, 430 PRINCIPLES OF SURGERY. who was employed in a rag establishment in sorting rags. Two months before she came under my care she noticed a small sore on the dorsal side of the right index finger, near the metacarpo-phalangeal joint. The place ulcerated, and the granulation tissue which appeared melted rapidly away, forming a deep excavation, which had the extensor tendon for its floor. Two weeks later a nodule appeared in the course of the tymphatic vessels, near the elbow-joint, over the anterior aspect of the arm, which was soon followed by the formation of three other nodules between this point and the primary seat of infection. General health not impaired in the least. Inflamed foci neither painful nor tender on pressure; presented distinct evidences of fluctuation. All the foci were excised and presented the characteristic appearances of tubercular tissue. The primary focus, after excision, left such a large defect that it was found impossible to close the wound by suturing, and consequently the surface was covered with Thiersch's grafts taken from the arm. Primary union of all the sutured wounds and speedy, definitive healing of the defect at the primary seat of infection. There can be no doubt whatever that in this case infection occurred through a small wound of the index finger, by handling contaminated rags, which was followed by dissemination of the bacilli through the lymphatic vessels in direct communication with the primary infection- atrium. I have had also under treatment a well-marked case of exten- sive subcutaneous tuberculosis of the hand, in the person of the mother of several children who had died of pulmonary tuberculosis. The disease originated near the tip of the index finger, at the site of a former abrasion, in which a papillomatous swelling formed. This ulcerated and healed partly, when the disease commenced to spread along the subcu- taneous connective tissue, and when the patient came under my observa- tion it had extended almost over the entire dorsum of the hand. A number of fistulous openings existed, which discharged daily only a few drops of thin, serous pus. The subcutaneous tissue was transformed into a mass of granulation tissue, which was removed with a small spoon through multiple incisions, and the wound surfaces were freely iodo- formized. The process of repair was slow, but satisfactoiy. Martin du Magny has collected the clinical material of cases of inoculation-tuber- culosis, and in his comments upon the cases asserts that the sputum of phthisical patients and animal excretions were the usual carriers of the bacilli; consequent^7 the affection is most frequently met with among physicians, nurses, butchers, and teamsters. The external appearances, manifested at the point of inoculation, consist in the formation of a red nodule in the skin, which increases slowly in size and forms miliary abscesses, in which papillomatous proliferation takes place, and around INOCULATION-TUBERCULOSIS IN MAN. 431 which a new zone of infiltration forms, which in turn again suppurates and becomes papillomatous. The centre heals with the formation of a flat cicatrix, while the destructive process progresses slowly in a peripheral direction. Hanot has collected 6 cases, 1 of which came under his own observa- tion. In this case the patient was in the third stage of phthisis, and died soon after from a tubercular ulcer on the arm of at least two years' standing, while the history of cough only dated from the last two months, which would show that the cutaneous lesion preceded the pul- monary, and was the cause of the phthisis. In the cases which he collected the sources of inoculation were necropsies on tubercular patients, handling old bones, pricking the hand with a fragment of porcelain from the broken spittoon used by a phthisical patient, and in 4 of the cases the tubercular character of the cutaneous lesion was verified by finding the bacilli. Eiselsberg has observed 4 cases of inoculation-tuberculosis dur- ing the last few years. The first case was a girl 16 years old, in whom the disease developed in the track of a perforation of the lobe of the ear made preparatory to the wearing of an ear-ring, and which was kept from closing by the insertion of a thread. The tubercular product appeared in the shape of a hard swelling the size of a hazel-nut. The second case was a young man who injured himself with the point of a knife above the external epicondyle of the humerus. Eighteen days later a swelling, the size of a pea, appeared at the site of injury, with an ulcerated surface covered by pale, flabby granulations. In the axilla of the same side one of the bymphatic glands was found enlarged to the size of a hazel-nut. The third case concerned a woman 50 years of age, who was supposed to have infected herself by washing the clothes of a person the subject of a tubercular abscess of the spine, and who with her fingers scratched an acne pustule on her face. At this point, six to eight days later, a pain- ful swelling, the size of a pea, formed, which subsequent^7 became indu- rated, and opened spontaneously in six weeks. At the end of three months the place of inoculation presented an ulcer with indurated mar- gins. In the fourth case the inoculation followed in the track made by the needle of a hypodermic syringe, in a girl 20 years of age. The swelling which appeared opened after six weeks, and a small quantity of pus was discharged. Four months subsequently the fistulous opening communicated with an abscess-cavity, the size of a silver dollar, lined by a wall of granulation tissue. In all of these cases no evidence of tuber- culosis could be detected in any of the internal organs, and the local dis- ease could be traced in every instance to some antecedent lesion, through which the infection had evidently taken place. The diagnosis in all cases 432 PRINCIPLES OF SURGERY. was based on an examination of the granulation tissue for the bacillus of tuberculosis, which was always found present. Another case of tubercular infection through ear-rings is related from Vienna in a girl, 14 years of age, of a perfectly health37 famil3',who wore ear-rings left to her b37 a friend who had died of pulmonary tuber- culosis. Soon ulcers appeared on the lobes of both ears, the cervical glands became swollen, and percussion and auscultation revealed infil- tration of the apex of the left lung. Tubercle bacilli were found in the ulcers and sputa. This case is 011I37 another instance of inoculation- tuberculosis, where, from the point of infection, the disease extended along the bymphatic system, and, finall37, S3rstemic infection from the entrance of bacilli into the general circulation. In the cases of inoculation-tuberculosis cited above, infection occurred through some slight lesion, puncture, or abrasion, which fur- nished the necessary infection-atrium for the entrance of the bacillus into the tissues, but a number of cases have been reported by reliable observers where infection took place through a larger wound or granula- tion surface. Middeldorpf reports the case of a healthy carpenter, who opened his knee-joint by the cut of an ax, and dressed the wound with a soiled handkerchief. The wound healed kindly, but later the joint be- came swollen, tender, and painful. Resection was performed, and on examining the capsule it was found very much thickened. In the gran- ulation tissue tubercle bacilli were found. Wahl amputated the arm of a boy suffering from gangrene, the result of an injury, and discharged the patient with the wound completely healed, except a small granula- tion surface from which the drainage-tube had been removed. At first the wound was dressed by a girl suffering from tuberculosis. The wound soon showed all the characteristic appearances of fungous disease, and the lymphatic glands became infected from this source. I have seen in numerous instances large wounds made for the removal of tubercular glands become infected a week or two after the operation, after the superficial wound had apparently healed. In such cases the overlying cicatrix is subsequently completely destroyed b37the granulations under- neath. The energetic use of the sharp spoon and free iodoformization are the only resources in finally effecting the healing of such wounds. Konig has seen 16 cases of inoculation-tuberculosis, following operations for tubercular disease of bones and joints, and 2 such cases have been described by Kraske. Czern37 reports 2 cases in which tuberculosis fol- lowed in wounds treated by Reverdin's method of skin-grafting. In both instances the patients were healtli37, and the skin-transplantation was made during the treatment of extensive burns. The skin was taken from limbs amputated for tubercular affections. In both cases HISTOLOGY OF TUBERCLE. 433 tuberculosis of the adjacent joint occurred, and in 1 of them tuberculosis of the granulating surface. A number of cases of inoculation-tubercu- losis following circumcision are on record, in which the infection often occurred in the practice of orthodox Jews, who performed the operation in accordance with the directions laid down in the Mosaic laws. The loose connective tissue of the prepuce, richly supplied with lymphatics, is an admirable surface for absorption, and, when infectious material is brought in contact with it, furnishes the most favorable conditions for the production of local lesions and the transportation of microbes along the bymphatic channels to more distant parts. Lehmann has observed 10 cases of inoculation-tuberculosis in Jewish bo37s, caused by sucking the wound after ritual circumcision by a phthisical person. Ten days after the circumcision the wound became the seat of ulceration, and the inguinal glands began to enlarge. Four of the children died of tubercular meningitis, and 3 died after a prolonged illness caused by multiple tubercular abscesses. Hofmokl has reported a similar case, and Weichselbaum detected the bacillus of tuberculosis in the circumcision wound. Elsenberg has described 3 cases of tubercular infection after circum- cision. All the cases were infants, and the disease appeared primarily in the wound or cicatrix, and, later, in the inguinal glands. Local treat- ment by scraping proved successful. The diagnosis was corroborated by microscopical examinations of the granulation tissue. Willy Meyer re- lates a case in which circumcision was performed according to the rules of the Jewish Church eight da37s after birth by an old man, and in which four weeks after the ceremon37 an induration appeared at the frenulum, and the inguinal glands about the same time began to enlarge. Sy7philis was suspected, and the little patient was put on a specific course of treatment. The inguinal glands suppurated, and another small ab- scess formed in the right gluteal region. The diseased tissue about the glans penis was then excised. Microscopical examination of the granu- lations revealed the presence of miliaiy tubercles and bacilli in great abundance. The above cases furnish abundant and convincing proof of the possibility of the transmission of tuberculosis by cutaneous inocu- lation through superficial abrasions, small wounds, and granulating sur- faces, and this subject is deserving of the most careful attention of surgeons in the matter of prophylaxis, diagnosis, and treatment. HISTOLOGY OF TUBERCLE. A tubercle-nodule is an aggregation of cells primarily invisible to the naked eye, the product of a minute focus of inflammation, caused by the presence of the essential cause of tuberculosis. When the nodule 28 434 PRINCIPLES OF SURGERY. becomes so large that it can be recognized without the aid of the micro- scope, it already consists of a confluence of a number of minute micro- scopic nodules. Lsennec described four varieties of tubercle : 1. Miliary tubercle, where the visible product of tubercular inflammation appears as nodules the size of a millet-seed, of a grayish color, and usually arranged in groups. 2. Crude tubercle, where the miliary nodules have become confluent and have undergone caseous degeneration. 3. Granular tubercle, where the nodules are extremely small, nearly the size of a millet-seed, and scattered uniformly through a whole organ. They are not arranged in groups and have no tendency to become confluent. In the centre they become transformed into yellow tubercle. 4. Encysted tubercles, or such as are constituted of a hard mass of crude tubercle in the centre surrounded by a firm fibrous capsule. These varieties only represent different phases of the same process and different stages of inflammation produced by the same cause. The anatomico-pathological basis of tubercle was created by Virchow, and has been firmly established through the laborious researches of Langhans, Wagner, Klebs, Schuep- pel, Rindfleisch, Koester, Friedlander, Fox, Baumgarten, and many others. The specific-cell theory has had many able advocates, and has been the subject of many animated discussions, but it has at last been abandoned as fallacious and unscientific. There are no specific tubercle-cells. Lebert's tubercle-corpuscle is a thing of the past, and is only re- ferred to as a landmark in the history of tuberculosis. Reinhart showed that these cells, which were regarded by Lebert as characteristic and pathognomonic of tubercle, could be found in all products of chronic inflammation, and their presence was only an evidence that a certain amount of inflammation existed. When we speak of a tubercle, we mean a nodule or granule, which is composed of leucocytes derived from the capillary vessels damaged by the bacillus of tuberculosis, or new cells derived from tissue proliferation of pre-existing cells acted upon by the same cause. The anatomical character of the nodule consists not in the presence of any particular cell-element, but in the peculiar arrange- ment of the cells; and this feature is the only reliable anatomical guide in making a diagnosis by the use of the microscope. The product of tubercular inflammation occurs either in the form of submiliary, micro- scopic granules, visible miliary nodules, or a cheesy infiltration, which may occupy an entire organ, as a lymphatic gland, or large, isolated foci, as in bone. Every tubercular product commences as submiliary nodules, which, when they become confluent, are transformed into visible gray miliary nodules, which again coalesce after they have undergone caseous defeneration from chees37 masses, which may be either small and circum- scribed or large and diffuse. HISTOGENESIS OF TUBERCLE. 435 Virchow defines tubercle as a nodule representing a heterogeneous growth, a product originally necessariby of a cellular nature, taking its starting-point from the connective tissue or from other mesoblastic struc- ture, as marrow, fat, or bone. He asserts that the microscopic or sub- miliary granule contains all of the essential histological elements of tubercle, and by aggregation forms the ordinary miliary nodule of Laennec. When the nodules become confluent the3r may form masses the size of a walnut, surrounded b37 a common zone of embr37onal tissue. The yellow tubercle, the crude tubercle of Laennec, is a more advanced stage of the gray, the histological elements of the latter having under- gone caseation. HISTOGENESIS OF TUBERCLE. Colberg asserts that tubercles in the lungs originate from the nuclei of the capillary vessels and the connective tissue, the epithelial cells lining the alveoli never being primarily affected. Bastian observed tubercle-nodules upon the small vessels in cases of basilar meningitis, but refers their origin not to proliferation of the nuclei of the endo- thelial lining of the vessels, but to new cells springing from the endo- thelial cells of the perivascular lymphatic sheaths which surround the vessels of the meninges of the brain. Knauff demonstrated the lymphoid character of the adventitia by examining the capillary vessels of the visceral pleura in dogs which had been exposed for a long time to an atmosphere impregnated with coal- dust. He found the pigment lodged in small masses close to the walls of small arteries and veins. Examining the same vessels in other dogs not thus treated, he found upon the outer surface of the adventitia opaque, whitish-gray nodules, surrounded by round and oval cells con- taining nuclei, also lymph-corpuscles. The same structures, which he named lymph-nodules, are also found around the same vessels of the pleura in man, and Knauff looks upon these lymphoid structures as the starting-point of tubercular inflammation. Klebs maintains that the endothelial cells of Lymphatic vessels are the most frequent location for the formation of the primary tubercle- nodule. He observed that in cases of tubercular ulceration of the intes- tines the peritoneum is reached through the lymphatic vessels. Silver- stained preparations of inoculation-tuberculosis in rabbits showed that the most recent products occurred in the interior of the lymphatic vessels at points of intersection. In some places the nodules extended into the tissues between the lymphatic vessels, but their centre always corre- sponded to the location of a lymphatic vessel. At some points the nodules were seen to branch out, but these projections, in reality, were within the lymphatic vessels, as the net-work of lymphatic endothelia 436 PRINCIPLES OF SURGERY. could be seen above and underneath the tubercular product. Toward the centre of the nodule no endothelial cells could be distinguished, and this fact led him to the belief that the endothelial cells are directby con- cerned in the production of the new tissue. In the mesentery he saw the tubercles adhere to the outer wall of the capillar7 vessels, and, as the spindle-shaped cells of the outer coat appeared to be pushed apart by the new tissue, he regards the adventitia as a genuine lymphoid struc- ture. Rindfleisch traces the beginning of the process in miliary tuber- culosis of the lungs to a proliferation of the endothelia and the external connective-tissue layer of the capillary lymphatic vessels. Edward Smith believes in the epithelial origin of tubercle. Manz studied the development of tubercle in the choroid in patients suffering from general miliary tuberculosis. So constantly does this disease show itself in this structure that von Graefe, Cohnheim, Frankel, and Bouchut recommend ophthalmoscopic examination as a diagnostic measure in cases of sus- pected pulmonary or general tuberculosis. Manz traces the commence- ment of the disease in the choroid to cell-pullulation in the tunica adven- titia of the small vessels. The process is, however, not limited to this structure ; the non-pigmented stroma-cells may also assist in furnishing material for the new product. Bart, on the other hand, asserts that the vessels, in cases of tuberculosis of the choroid, are not primarily affected ; according to his observations, the process depends exclusively on a degeneration of the stroma-cells, as the remaining tissue did not appear affected. Cohnheim, Ziegler, and others maintain that the leucocytes furnish most of the material in the building up of the tubercle-nodule. Experiments on animals, as well as microscopic examinations of pathological specimens, have sufficiently demonstrated the fact that the tubercle-nodule is nothing more nor less than a circumscribed inflamma- tory product, the histological elements of which are composed of new tissue, formed by proliferation of fixed tissue-cells which have come in contact with the bacillus of tuberculosis or its ptomaines. The specific pathogenic effect of the bacillus consists in its power to cause a chronic inflammation of the tissues in which it has localized or with which it has been brought in contact. The tissues affected are the cells which are nearest the essential microbic cause, irrespective of their embryological origin, their histological structure, or physiological function. In cases of inoculation-tuberculosis the primary nodule develops at the point of insertion of the virus from connective-tissue proliferation, and from here the bacilli enter the lymphatic channels, and the secondary nodules are composed of cells derived from the endothelial, lymphoid, and connective- tissue cells which compose these structures. If the bacilli are injected HISTOLOGICAL STRUCTURE OF TUBERCLE. 437 directly into the circulation or gain entrance into the blood-current from some tubercular focus, they become implanted upon the wall of distant capillary vessels, and the nodule which forms at the seat of implantation consists of cellular elements formed by the tissues of the vessel-wall. As soon, however, as bacilli reach the extra-vascular tissues, they, in turn, furnish their part of the material for the further growth of the nodule. If the tubercle bacillus becomes implanted upon a mucous sur- face, as the bladder, intestines, nose, lai737nx, uterus, etc., if such surface is susceptible to tubercular infection, the epithelial cells take an earl37 and active part in the inflammatory process. From the manner of en- trance into and diffusion through the tissues, it is apparent that the mesoblastic tissues, the connective-tissue and endothelial cells, being the first to become infected, furnish the greatest amount of material in most tubercular lesions; but all tissues, when infected, take part in the process. HISTOLOGICAL STRUCTURE OF TUBERCLE. The essential histological elements which make up a primary tubercle- nodule are: (a) leucocytes; (b) giant cells; (c) epithelioid cells; (d) reticulum. Leucocytes.—One of the convincing proofs of the inflammatory nature of tuberculosis is the presence of leucocytes in the tubercle- nodule. The bacillus of tuberculosis appears to exercise only a mild pathogenic effect on the capillary wall, and the primary inflammatory product is alwa3rs scanty. As the colorless blood-corpuscles can only escape, in considerable number, through inflamed capillary walls which have undergone alteration from the action of some specific microbic cause, it is evident that its migration into the para-vascular tissues, where it forms a part of the tubercular product, can only occur after such alteration has taken place from the action of the bacillus upon the cement-substance of the endothelial lining of the capillary vessels. The leucocytes are found scattered among the other cellular elements, and are found in greatest abundance toward the periphery of the nodule. The leucoc37tes invariably undergo degenerative changes, and are never trans- formed into other forms of cells found in the tubercular product. They have been described as lymphoid corpuscles. Although constantly pres- ent, they are most numerous when the process is acute. Giant Cells.—A great deal has been said and written concerning the origin and diagnostic value of the giant cells in the tubercle-nodule. They resemble the giant cells found in some forms of sarcoma, and appear to be simply certain cells which have outgrown others by taking up a greater amount of nourishment in the shape of leucocytes which have undergone fragmentation. 438 PRINCIPLES OF SURGERY, The giant cells, or, as Klebs calls them, macrocytes, are finely gran- ular, and contain multiple nuclei, which usually occupy the periphery of the cell, or are arranged in a crescent at one end. In tubercular lesions artificially produced in animals the giant cells contain numerous bacilli, which occupy, as a rule, the peripheral zone of the cells. In tuberculosis in man the bacilli in these cells are never so numerous, and as central degeneration of the cells appears they disappear in this portion of the cell, while some may still be found in the periphery. During the progress of the disease the giant cell becomes more and more fibrous toward the periphery, at the expense of the protoplasmic part in the centre. The protoplasm evidently is transformed into or secretes the fibrous margin. Fig. 96.—Giant Cell from Centre of Tubercle of Lung. X450. (Hamilton.) A, granular protoplasmic centre; B, peripheral more-formed part; C, crescent of nuclei; D, endothelium-like cells; E, two vacuoles within the giant cell. If caseation does not take place the bacilli disappear, and the whole cell mass, including the giant cells, is converted into a cicatricial mass. The first evidences of degeneration appear in the centre of the giant cells, and, according to Weigert, they consist of structural and chemical changes which are indicative of coagulation necrosis. In a recent tubercle-nodule the giant cells occup37 the central por- tion, around which the epithelioid cells and leucocytes are arranged. The vacuoles are necrotic foci within the cells. The giant cell found in tubercular tissue has its prototype in normal tissue. Giant cells were first discovered in normal tissue (mar- row of bone) by Robin, who called them myeloplaques. They were sub- sequent^7 accurately described b37 Virchow. In a normal condition they HISTOLOGICAL STRUCTURE OF TUBERCLE. 439 are constantly found in bone and the placenta. Thej7 are also found occasionally in fat-tissue, especially in cases of rapid emaciation. Kun- drat has found them in inflamed serous membranes, and Strieker and Heitzmann in the inflamed cornea. They are always found around for- eign bodies, becoming encysted in the tissues. Friedlander found them present in the aveoli of the lungs in cases of chronic pneumonia. Heubner found giant cells in endarteritis, Baumgarten in gummata, Buhl and Jacobson in granulating wounds, and finalby Johne and Pflug in actinom37cotic foci. The histological source of these cells in tuber- cular affections has been traced to epithelial cells by Zielonko and Weigert; to endothelial cells by Kundrat, Klebs, Herrenkohl, and Zie- lonko ; to connective tissue or endothelial cells b37 Virchow, Fleming, and Ziegler. Schueppel and Rindfleisch believe that they invariably originate within blood-vessels or lymphatics, where these authors regard them as the first step toward the development of tubercle-nodules. Ziegler claims to have seen giant cells develop from white blood-corpus- cles. Hering, Aufrecht, Woodward, Schueller, and Treves are of the opinion that what appears as giant cells in tubercular tissue are not cells, but onby represent spaces which correspond to transverse sections of bymphatic channels, the protoplasm representing the coagulated bymph within these vessels, and what appear as nuclei being enlarged, swollen endothelial cells. Giant cells possess amoeboid movements, and by virtue of these the37 are capable of taking up in their protoplasm fine particles, such as microbes, pigment material, and blood-corpuscles, which have undergone fragmentation. The giant cells in tubercular lesions are hyperplastic, epithelial cells, and consequently are derived from the same histological source as these. Epithelioid Cells.—Cells intermediate in size between the giant cells and the leucoc3'tes are found in evei'37 tubercle-nodule in which the cells have not been destroyed b3r caseation. These cells were first described b3" Rindfleisch, and were called by him epithelioid cells from their struc- tural resemblance to epithelial cells. Klebs calls them platycytes. The37 are about two or three times larger than a white blood- corpuscle, and in shape the37 are either round or somewhat elongated. In structure the3' are finely granular, and contain one large and often a number of small nuclei. The37 form the bulk of all recent nodules, are scattered between the giant cells, and are often arranged in layers around them. The histological source for these cells was supposed to be the leucocyte b}7 Schueppel, Ziegler, and Treves; the endothelial cells of the lymph-spaces by Aufrecht, Hering, and Woodward ; the endothelial cells of the blood-vessels and lymphatics or connective-tissue cells by Rind- fleisch and nearly all of the modern authors. The endothelioid cells 440 PRINCIPLES OF SURGERY. represent the embryonal cells, the product of proliferation from any of the fixed tissue-cells in a tubercular lesion, and they remain as such until they are destroyed by degenerative changes from the continued action upon them of the bacillus of tuberculosis or its ptomaines, or until, on cessation of the primary cause, they are transformed into tissue of greater durability. Reticulum.—Schueppel first called attention to the reticulated structure of tubercle b37 his description of the reticular arrangement within tubercles of lymphatic glands. The reticulum, according to most authors, consists of the pre- existing connective tissue pushed asunder by the new cells. According to Wagner, Schueppel, Brodowski, Thaon, and Ziegler, it is made up of Fig. 97—Section from Mucous Membrane of Pharynx, showing Epithelioid Cells with a few Small Giant Cells. X 350. (Birch-Hirschfeld.) protoplasm. Buhl taught that the giant and epithelioid cells secrete a substance at their periphery which, on becoming firm, is formed into a structure resembling connective tissue. According to his researches only the marginal zone is supplied with loose, ready-formed, connective tissue of the organ. Wahlberg maintained that the principal reticulum consists of protoplasm which is traversed by a net-work of connective tissue. The reticulum is always more marked in the periphery of the tubercle-nodule, where, from pressure, it is condensed into a fibrous capsule (Fig. 98, C). Arrangement of the Cells in a Recent Tubercle-Nodule.—The earliest evidence of the formation of a tubercle-nodule, as witnessed under the microscope, is the appearance of small cells which resemble ordinary HISTOLOGICAL STRUCTURE OF TUBERCLE. 441 embiyonal cells, which are the product of tissue proliferation from a mesoblastic matrix, usually the connective tissue, and its embryological and histological prototype, the endothelial cells of blood-vessels and lymphatics. From these cells the epithelioid and giant cells are, later, developed. Some of the central cells, b37 appropriation of a superabund- ance of food furnished by leucocytes in a state of fragmentation, become hyperplastic, and are transformed into giant cells ; these occupy the Fig. 98.—Fully-Developed Reticular Tubercle of Lung. X 450. (Hamilton.) A, A, A, giant cells; B, vacuole in one of these: C, peripheral capsule of fibrous tissue; D, reticulum of the tubercle ; E, large endothelium-like cells lying on the reticulum and within its meshes ; F, smaller " lymphoid " cells occupying the same situation; G, peripheral fibrous-looking border of the giant cells. centre of the nodule. Around these cells the smaller or epithelioid cells arrange themselves, and between them and in the periphery of the nodule are found the smallest cells,—the leucocytes. Gaule and Tizzoni distinguish three zones in a tubercle: (1) an external, composed of small round cells; (2) a leper, epithelial, or middle zone, containing the reticulum ; (3) a central space containing a giant cell. The structure of a tubercle is not always typical, and hence the division into zones is based more on theoretical grounds than actual 442 PRINCIPLES OF SURGERY. observation. The giant cell is not an essential histological element of tubercle, but an accidental product. In some tubercles giant cells can- not be found, while in others the3T are numerous. Giant cells can only develop from epithelioid cells if the local conditions are favorable for hypernutrition ; that is, if the leucoc37tes in a condition of fragmentation are within their reach. If they are present they always mark the loca- tion of the starting-point of the tubercular infection, as only the older epithelioid cells undergo this change. The number and size of the epithelioid cells are also subject to great variation, and are modified by the nutritive conditions within and in the immediate vicinity of the nodule. If cell proliferation is active the epithelioid cells appear densely packed in the reticulum, nutrition is greatly impaired, and the new cells undergo degenerative changes before they attain their average size. The leucoc3'tes are scattered among the giant and epithelioid cells, and, as they reach the part through the inflamed wall of the capillaries in the immediate vicinity, they are most numerous in the periphery of the nodule and along the course of the affected vessels. GROWTH OF THE TUBERCLE-NODULES. The typical tubercle-nodule is microscopic in size. The growth of the swelling depends on the formation of new tissue, migration of leuco- cytes, and confluence of nodules into larger masses. The bacillus of tuberculosis, when brought in contact with fixed tissue-cells susceptible to its pathogenic action, incites tissue proliferation, which always takes place by karyokinesis. Baumgarten's investigations leave no doubt that phatycytes constitute the entire mass of the forming tubercle. He has also observed karyokinetic figures in tubercular tissue in cells derived from the connective tissue, endothelia, and epithelia. The tubercle bacilli are found in the interior of giant and epithelioid cells and between them. Each tubercle-nodule increases in size by the growth of new cells from pre-existing tissue, and as the primary cause, the bacillus of tuberculosis, multiplies in the tissues, bacilli are conveyed into the surrounding tissues by leucocytes or the plasma-current, and new centres for tubercle formation are established, which, later, become confluent, forming masses of considerable size, the numerous foci of caseation corresponding to the centre of a nodule. The growth of tubercle is favored by local and general conditions which diminish tissue resistance, while retardation takes place in consequence of degenerative changes in the cells of which it is composed, or, if the cells are converted into tissue of a higher type, from disappearance or suspension of activity of the primary cause. PATHOLOGICAL VARIETIES OF TUBERCLE. 443 PATHOLOGICAL VARIETIES OF TUBERCLE. Several varieties of tubercle have been described, according to the histological structure of the tubercle or the structure or condition of the cells of which it is composed. Reticulated Tubercle.—This is the ordinary form of tubercle usually met with, and the most important anatomical feature is the presence of a well-defined reticulum, composed of pre-existing connective tissue and a delicate net-work of branching giant cells, in the meshes of which are found the epithelioid cells and leucocytes. Fibrous Tubercle.— In contradistinction to the reticulated or lymphoid tubercle, a few years ago the fibrous tubercle was described, distinguished by its pearl-like, light-gray appearance, but possessing the same inherent tendency to caseation. It is said to be found most fre- quently in dense, fibrous tissue, and quite often in newly-formed connective tissue. Histologically it is composed of nodules of dense connective tissue, the cells of which have undergone rapid growth, containing, fre- quently, more than one nucleus. A further development only takes place in the interior of the nodule, as here caseation occurs, the caseous focus being surrounded by a firm capsule of connective tissue. The description of fibrous tubercle by Langhans differs materially from the above. According to investigations of this author, the fibrous tubercle has for its favorite location the so-called parenchymatous organs, as the lungs, liver, spleen, kidne37s, testicles, epididymis, and brain. The larger nodules are composed of three zones. The central zone consists of a few connective-tissue fibres, free oil-globules, and cells in a condition of fatty infiltration. The middle zone is composed of connective tissue. As the cells of this zone are not numerous, it presents the appearance of a capsule; in reality, however, it is not a capsule in the proper sense of the word, but a matrix of tissue proliferation, from which the central part of the tubercle is the offspring. Both Langhans and Schueppel, like nearly all of the modern pathologists, regard fibrous tubercle not as a distinct special anatomical form, but as an ordinary tubercle in which the epithelioid cells in the peripheral zone have been converted into con- nective tissue. Fibrous tubercle differs from the ordinary cellular variety only in so far that it contains a larger amount of connective tissue. If in a tubercle-nodule at the time the young cells are yet vigorous the primary microbic cause ceases to act, degenerative changes fail to take place and the embryonal cells are transformed into connec- tive tissue. The cicatricial condition starves out remaining embryonal cells; at the same time an impermeable wall of connective tissue is thrown around the primary depot of infection, which effectually guards against the escape of active bacilli or tlieir spores into the surrounding tissues. 444 PRINCIPLES OF SURGERY. Hyaline Tubercle.—Chiari described another variety of tubercle— the hyaline tubercle. The first specimen in which he found this variety was taken from the liver of a tuberculous child 4 years of age. The nodules in the brain, lungs, and bronchial glands in the same case pre- sented the ordinary structure of lymphoid tubercle. The clear hyaline structure of those found in the liver gave them a very peculiar appear- ance. The change is believed to be due to a hyaline degeneration of the reticulum, and resembles most closely the hyaline degeneration of the capillaries of the brain. Chiari conjectures that it may be regarded as a benign change opposed to caseation, which tends to infection. Hyaline degeneration of any pathological product must now be considered as one of the earliest phases of coagulation necrosis, and, if a considerable area of the nodule undergo this change rapidly and simultaneously, the structures will present a l^aline appearance; but if the hyaline product continue to be acted upon by the same causes, caseation will follow, and the hyaline tubercle becomes a cheesy tubercle. CASEATION. The gray or miliary tubercle is transformed into the yellow, crude, or chees37 tubercle by a process which is called caseation, or ty'rosis. The exact nature of this process remains unknown. The cheesy material is composed of the products of cell necrosis. Earty death of cells is the most characteristic pathological feature of tubercle, which distinguishes it from all other forms of chronic inflammation. Two causes can be advanced to explain this peculiar and almost pathogno- monic form of degeneration, which occurs, almost without exception, in every tubercle if a sufficient length of time has elapsed : 1. Inadequate blood-supply. 2. Specific action of the bacillus of tuberculosis or its ptomaines. Caseation always commences in the centre of a nodule, consequently at a point most remote from the vascular supply, and in cells which have been exposed longest to the deleterious effect of the primary microbic cause. Tubercle is a non-vascular product. From causes which, as yet, are not known, the tubercular product is not supplied with new blood-vessels. The angioblasts are transformed into epithelioid cells that have lost their power of vessel formation. Nodules which have primarily an intra-vascular origin are rendered avascular by closure of the vessel from intra- and peri- vascular cell proliferation. If the primary starting-point is outside of the vessels, the rapidly accumu- lating cells exert pressure upon the surrounding vessels, and thus diminish the blood-supply to the part affected. The new cells require an adequate blood-supply for their further development, and if this fail to take place, as is the case in every tubercular product, they necessariby CASEATION. 445 suffer from malnutrition, and undergo degenerative changes at an early stage of their existence. A deficient blood-supply, in the absence of other causes, would result in fatty degeneration of the new vessels; but caseation is something different from ordinary fatty degeneration, and the bacillus of tuberculosis, or its ptomaines, must be regarded as its immediate and essential cause. Caseation is preceded b37 coagulation necrosis, which is one of the results of the specific action of the bacillus on the tissues. The coagulation necrosis commences in the giant cells, and in the epithelioid cells in the centre of the nodule, and caseation follows as soon as the dead cells have lost their histological identity, and appear under the microscope as a debris in which no distinct cell forms can be identified. Caseation is attended b37 softening, which can be readily recognized in tubercular masses the size of a hazel-nut to that of a walnut, composed of numerous confluent nodules with as many caseating foci. In such masses the small, cheesy cavities become confluent and form spaces of considerable size. Caseation proceeds from the centre of each nodule toward the periphei737, kiyer after la37er of epithelioid cells being destroyed and changed into cheesy material. The part of a tubercle- nodule which has undergone caseation contains few, or no, bacilli, and 37et inoculation experiments show it to be highly infectious. The cheesy material does not furnish the proper nutrient material for the growth and development of the bacillus, which dies from starvation, while the spores, being more durable and possessing greater power of resistance, remain in an active condition for an indefinite period of time in the dead material, and it is due to their presence that infection takes place from chees37 foci, and that successful inoculations can be made with cheesy material. While the disease has become arrested in the centre of a nodule, with the appearance of caseation, its growth in a peripheral direction pursues the same relentless course. The bacilli multiply in recent tubercular tissues, and are carried be37ond the peripheral zone into the surrounding tissues, where new, independent foci of infection are thus established, which, in the course of time, pass through the same series of pathological changes as the primary nodules. It is a well- known clinical fact that acute miliary tuberculosis is not a primary affec- tion, as in all such cases a careful post-mortem examination will reveal the presence of a chees37 focus in a lymphatic gland, the lungs, testicles, a joint, or bone, or some other organ, from which the infection occurred. Weber found cheesy foci in 16 cases of tuberculosis of serous mem- branes. The cheesy mass may lie latent so long as it is solid, but as soon as it liquefies the spores which it contains can be taken up by the blood-vessels and prove a cause of general infection. 446 PRINCIPLES OF SURGERY. CALCIFICATION. One of nature's means in preventing the local extension of tubercle and in guarding against regional and general infection is calcification of the tubercular product. This can only occur as a secondary condition in tubercles that have undergone caseation. Calcification implies the removal of the cheesy material and the substitution for it of inorganic, calcareous material. It is a process which greatly resembles petrifaction. Arrest of the tubercular process by caseation and calcification frequently takes place in the lungs, and, occasionally, in the lymphatic glands. CHAPTER XVIII. Clinical Forms of Surgical Tuberculosis. It is but a few 37ears since it was thought impossible that any other organ than the lungs should be the seat of tuberculosis. The different forms of surgical tuberculosis that will be described below were not cor- rect^7 understood until quite recently, and consequently a rational sur- gical treatment w7as out of question. Most all of the localized tubercular processes were included under the general term scrofula, and were regarded as local manifestations of a general d37scrasia, and treated in accordance with this view of their pathology. The discovery of the bacillus of tuberculosis has rendered the word scrofula obsolete, and has assigned to the tubercular processes in the various organs and tissues of the bod37 their correct etiological and pathological significance, and paved the w7ay for their successful surgical treatment. There is hardly a tissue in the body which ma3r not become the primary seat of tuber- cular infection, or which escapes when diffuse dissemination occurs through the medium of the general circulation. The frequency of tubercular affections is something appalling. At least 1 person out of ever3r 1 dies of some form of tuberculosis. Most of the large hospitals contain from 25 to 50 per cent, of patients afflicted with this disease. The ravages of the disease are to be seen everywhere, in the shape of disfiguring scars of the neck, deformed limbs, and bent spines. Health resorts, frequented for years by tubercular patients, have become infected to such an extent that there is great danger of the w7hole population becoming exterminated by this disease. The sources of infection in such places have become so numerous that it is unsafe to breathe the air, to drink the water, or to eat the food prepared in houses which for years have been hot-beds for the bacillus of tuberculosis, and b37 persons car- rying the microbe upon ever}' square inch of their surface. That whole communities and nations, where this disease has been prevalent for cen- turies, have not been completely depopulated long ago is owing to the fact that many persons possess, from the time of their birth, a degree of resistance to infection that even direct infection by inoculation would prove harmless. The bacillus is not the sole, but the essential, cause of tuberculosis. (447) 448 PRINCIPLES OF SURGERY. HEREDITARY AND ACQUIRED PREDISPOSITION. Almost eveiy author recognizes, as an important element in the etiology of tuberculosis, the existence of a hereditary or acquired pre- disposition. Little is known in reference to the real nature of such a predisposition. A weakness of the lymphatic vessels in scrofulosis was recognized by Sylvius as early as 1695, by Portal in 1690, and still later by Bell, Percival Pott, Hufeland,and Broussais. Fox is of the opinion that a disposition to tuberculosis is created b37 certain anatomical or physiological defects in the lymphatic system. The cause of scrofula was ascribed b37 Virchow to a weakness or imperfection in the arrange- ment of the lymphatic system ; by Hueter to a dilatation of lymph- spaces ; and by Billroth to a constitutional anomaby. Mordhorst regards a sluggish circulation, the consequence of superficial, imperfect respira- tion, by causing capillaiy stasis and favoring inflammatory exudation, a potent factor in producing that peculiar vulnerability of the tissues in scrofulous subjects. Rokitansky placed great stress on the importance of an imperfect circulatory and respiratoiy apparatus as a predisposing cause of tuberculosis. In 1871 Friedlander suggested that in cases of tuberculosis there might be present, and active, a fusion of the scrofu- lous and tubercular diathesis,—a view which was indorsed b37 Charcot in 1877. Aufrecht claims that the disposition to the origin of tubercle may be found in the bymphatic vessels. Riedel defines the hereditary predisposition to tuberculosis as consisting in a peculiar defect in the anatomical arrangement of the tissues, especial^7 of the bymphatic glands, which furnish a favorable soil for infection. Schiiller believes that the noxae of tuberculosis excite a slow form of inflammation, with a tendency to speed37 retrograde metamorphosis of the new material. Quincke recognized a close relationship between scrofula and tubercu- losis, when he says : " Scrofulous persons are especialby predisposed to tu- berculosis; tuberculosis hardby ever occurs except in scrofulous persons." Ziegler was aware that pulmonary phthisis is the most frequent cause of death in scrofulous patients. Whittier, in comparing the etiology of tuberculosis with S37philis, makes use of the following very positive language :— " There is no such a thing as a predisposition to either disease. Either a man has syphilis, or he has it not. One man is not more pre- disposed to either disease than another. Syphilis affects one individual more than another because its virus finds a better lodgment upon mucous membrane. Tuberculosis finds, also, fortuitously, a better nidus in one case than another. The virus of tuberculosis is lodged, in one case, and not coughed up, just as in syphilis the virus is secreted and not washed off." And again: "From any chancre, plaque, gumma, or HEREDITARY AND ACQUIRED PREDISPOSITION. 449 other deposit of syphilis, re-absorption may take place at any time, and re-infection with syphilis; or, better, re-appearance of external signs. So from any caseous nodule, wherein the tuberculous virus is locked up in temporary innocence, absorption may take place under favoring cir- cumstances, and a new outbreak of tuberculous symptoms appear, the quantity of virus thus set free determining, to a great extent, perhaps, the virulence of the symptoms. While the virus is thus locked up, the disease is latent; when set free, it is manifest." Wynne Foot says: " Tubercles are small-celled overgrowths of lymphatic tissue that have preserved such uniformity of size, color, and shape as to have long suggested the probability of their lymphatic origin." Wilson Fox regarded tubercle as an overgrowth or hyperplasia of lymphatic tissue resulting from irritation of the lymphatic elements. Savory, in speaking of the relation of scrofula to tubercle, remarks : " It appears to me that there is nothing sufficient to warrant the patho- logical distinction which it is now the fashion to make between scrofula and tubercle." And further : " Tubercle may be said to be the essential element of scrofula." According to Rokitansky, the most frequent seat of tubercle in children is in the lymphatic glands. Virchow maintained that scrofula constitutes the basis of tubercle, and that in man tubercu- losis depends in general on scrofula. He asserts, further: " On account of the histological identity of the scrofulous and tubercular new growths, it is often impossible, in a given tubercular lesion, to determine how much is inflammatory and how much is tubercular." From the above quotations it becomes apparent that nearby all of the older authors recognized, if not the identity, at least a close relationship between scrofula and tuberculosis. The identity of scrofula and tuberculosis was established not upon anatomical or pathological researches, but was definiteby settled b37 the discovery of the same cause in the local lesions of both. The demonstration of any definite anatomical defect, heredi- tar37 or acquired, which acts as a predisposing cause to tubercular infec- tion, has so far not succeeded. Only a few years ago Formad made some interesting studies concerning the histological structures of tissues that are known to be prone to tubercular infection, and he believed that the changes constantly found were such that favored the arrest of migrating cells. It is more probable that the hereditary or acquired predisposition to tuberculosis, which must now be recognized as an important element in the causation of the disease, must be regarded rather as a diminution of the power of resistance inherent in the tissues to the action of the specific microbic cause than any characteristic anatomical cell defects. From a clinical stand-point, it is important to remember that in the causation of tuberculosis we must recognize a combination 29 450 PRINCIPLES OF SURGERY. of etiological factors, viz.: (1) local or general conditions, resulting from hereditary or acquired causes, which diminish the resisting capacity of the tissues to the action of the bacillus of tuberculosis, which must be regarded as the predisposing cause; and (2) the presence in the tissues of the essential cause of the disease—the bacillus of tuberculosis. The predisposing cause can under no circumstances result in tuber- culosis without action of the essential cause, and the bacillus of tubercu- losis is most certain to produce its specific pathogenic effect in tissues debilitated by hereditary or acquired causes. The different avenues through which infection takes place will be referred to in the further discussion of the subject which heads this chapter. TUBERCULAR ABSCESS. Pathological Anatomy.—The effect of the bacillus of tuberculosis on the tissue is to produce a chronic inflammation, which invariably results in the production of granulation tissue. The embryonal cells furnish, as it were, a wall of protection for the surrounding healthy tissue. The characteristic pathological feature of every tubercular product consists in the tendency of the cells of which it is composed to undergo early degenerative changes, which are caused by local anaemia and the specific chemical action of the ptomaines of the tubercle bacilli, and consist in coagulation necrosis, caseation, and liquefaction of the cheesy material into an emulsion, which has always been regarded as pus, until recent investigations have shown that it is simply the product of retrograde tissue metamorphosis, and not true pus. I believe that it can now be considered as a settled fact that the bacillus of tuberculosis is not a p3ro- genic microbe, and that in the absence of other microbes it produces a specific form of chronic inflammation, which invariably terminates in the formation of granulation tissue; and that when true suppuration takes place in the tubercular product it occurs in consequence of secondary infection with pus-microbes. The so-called tubercular, or cold, abscess contains a fluid which macroscopically resembles pus, but which, when examined under the microscope, shows none of its histological elements. If the bacillus of tuberculosis meets with sufficient resistance on the part of the surrounding tissues, it finally exhausts the nutrient material in the granulations and dies, or remains in a latent condition ; the granu- lation material is converted into cicatricial tissue and the local lesion is cured. The cases in which the tubercular product is removed b37 cica- trization terminate most frequently in spontaneous cure. If, on the other hand, bacilli in sufficient number are present to destroy the granu- lation cells, coagulation necrosis, caseation, and liquefaction of the in- fected tissue take place; a spontaneous cure is still possible if a part TUBERCULAR ABSCESS. 451 of the fluid portion is absorbed and the solid debris becomes encapsu- lated. The same favorable termination is expedited under similar cir- cumstances if the primary lesion has healed, and the inflammatory product is removed by operative interference under the strictest anti- septic precautions, or if, at the same time, the primary focus can be completely removed by extending the operation to the primary lesion. Secondary infection of a tubercular product with pus-microbes without a direct infection-atrium is possible, and if the primary lesion is located in an unimportant organ, and in such a place where the inflammatory product can be early reached or can be discharged spontaneously, a cure is often effected, as the suppurative inflammation may destroy all of the tissues inhabited by the bacillus, and the whole nidus, with the microbes it contains, is eliminated permanently from the body. Such a course is not infrequently observed in cases of tuberculosis of the lymphatic glands of the neck. If, however, the tubercular process affects important organs or parts deeply located with extensive infection of tissue, and secondary infection with pus-microbes takes place, then the patient incurs the danger of septic infection and local and general dissemina- tion of the tubercular process from the breaking down of the protective wall of granulation tissue. That the bacilli do not grow in a tubercular abscess has been definitely settled by Schlegtendal. He examined 520 specimens of fluid from tubercular abscesses, and found bacilli present in only 75 per cent. Garrd has also made an extended series of observa- tions to ascertain the presence of the bacillus in cold abscesses. Accord- ing to this author, many tubercular ulcerations and abscesses are the result of a mixed infection, as has been claimed by Hoffa for some cases of emp3rema complicating pulmonary or pleural tuberculosis. In cold abscesses, and in the liquefied chees37 material of tubercular cavities in bone, no pus-microbes could be found; not even in cases that pursued a rapid course. Cultivations of such material remained sterile, while inoculations produced typical tuberculosis. Such specimens, examined under the microscope, showed none of the morphological elements of pus, but were seen to consist of an emulsion composed of fat-globules and detritus of broken-down tissue suspended in serum. Garre' believes it is possible that, in maii37 cases of suppuration fol- lowing in the course of a tubercular process, pus is the result of a mixed infection, and that the pus-microbes disappear before the examination is made. The walls of the tubercular cavity contain the typical structure of the tubercular lesion and the primary and essential cause of the in- flammation, the bacillus tuberculosis. The infection follows the migra- tion of the abscess in whatever direction that may take place. If an additional infection from without take place, following either a spon- 452 PRINCIPLES OF SURGERY. taneous discharge or after incision, the superficial granulations are destroyed by the suppurative process which is initiated, exposing the patient to the additional risks of septic infection and a more rapid local and general dissemination of the tubercular process. Symptoms and Diagnosis.—The tubercular abscess is called a cold abscess because it lacks the characteristic clinical phenomena which attend the development of an acute or hot abscess. There is but little, if any, rise of the local temperature, and, unless the abscess has reached the skin, looks rather preternaturally pale than red, and the abscess itself is alwa3rs painless and not tender on pressure. The pain, if present, is referred to the primary seat of the tubercular inflammation. Fluctuation is usually well marked, as the tissues around the abscess are not much infiltrated. The most important clinical feature of a cold abscess is its tendenc37 to wander from the place where it originated to distant localities by gravitation; hence the name given to it b3T German writers, senkungs abscess. Thus, in tubercular spondylitis, the abscess may appear in the lumbar region, and is then called lumbar abscess; it may follow the iliac muscle and appear in one of the iliac regions, and is then called iliac abscess ; or, finally, it may follow the psoas muscle and appear above or below Poupart's ligament, when it constitutes a psoas abscess. In tuberculosis of the hip-joint the abscess appears posteriorly underneath the gluteal muscles, if perforation of the capsule in this direction take place ; or it appears anteriorly a considerable distance below the hip-joint, if perforation of the capsule take place in an oppo- site direction. As the contents of the abscess carry the original caHse of the disease, infection of the tissues takes place along the whole course of the abscess, which is always lined with infected granulation tissue. Although the primary cause of a tubercular abscess is most frequently a tuberculosis of a joint or bone, it can also develop in the course of any localized form of tuberculosis, and it is quite frequently met in the course of tuberculosis of the lymphatic glands. The diagnosis must be made with special reference to the nature and location of the primary lesion. In tuberculosis of the spine the fixed pain in the region of the affected vertebrae, radiating from here in the direction of the nerves on each side, is an important symptom, and this symptom is always aggravated by flexion and ameliorated by extension of the spine. In coxitis the pain in the beginning of the disease is usually referred to the inner aspect of the knee-joint, but is always increased by motion in the hip-joint. In cold abscess, caused by glandular tuberculosis, the clinical history will point to a chronic inflammation of the glands which preceded the forma- tion of the abscess. As soon as the abscess reaches the skin that struc- TUBERCULAR ABSCESS. 453 ture becomes inflamed, red, and more and more attenuated by pressure and inflammation, until spontaneous perforation takes place at a point subjected to greatest pressure. If a tubercular product become the seat of a secondaiy infection with pus-microbes, the subsequent S3rmp- toms, local and general, are those of suppurative inflammation. The temperature, which was normal, or nearby so, increases and presents the daily curves indicative of suppuration, while the abscess, which has been painless heretofore, becomes painful and tender on pressure; in fact, a chronic inflammation has been supplanted by an acute one, with a cor- responding change of the clinical picture. If aii37 doubt remain as to the character of the swelling and the nature of its contents, this can be dispelled at once by resorting to an exploratory puncture. In cold abscess the fluid removed presents the appearance of serum in which minute particles of broken-down tissues are suspended, while in an abscess caused by a mixed infection it presents the macroscopical and microscopical appearances of pus. Prognosis.—The danger attending tubercular abscess must be esti- mated exclusively by the extent and location of the primary disease and the presence or absence of tuberculosis in other organs. If the general health remain unimpaired, even an extensive local tubercular disease may be amenable to a spontaneous cure or successful surgical treatment. On the other hand, a tubercular abscess developing in the course of an insignificant and unimportant local lesion occurring in an anaemic person, the subject of incipient multiple foci in different organs, must be regarded as a formidable condition, with little or no prospects of a favorable ter- mination. J have learned to regard pronounced anaemia as an unfavor- able symptom in the different forms of surgical tuberculosis, as it is often an expression that general infection has occurred. Another important matter to be taken into consideration, in making a prognosis in cases where general infection can be excluded, is the possibility of eradicating the primaiy lesion by operative interference. Where this can be done, the chances of successful treatment of the local disease are much better; at the same time, the removal of all the infected tissues is the best guarantee against general infection. Other things being equal, the prognosis is better in patients without a hereditary history of tuber- culosis, and in 37oung persons than those advanced in 3rears. Treatment.—The surgical treatment of large tubercular abscesses is alwa3rs fraught with danger from the fact that, even if conducted under strict antiseptic precautions, it is not always possible to prevent infec- tion with pus-microbes. Large tubercular abscesses were a " note me tangere " to the older surgeons, as it was well known evacuation by incision would be followed within a few days by hectic fever, profuse 454 PRINCIPLES OF SURGERY. sweating, diarrhoea, and other symptoms of septic infection. The early advocates of the antiseptic treatment hoped that the time had come when the surgeon had it in his power to prevent septic infection during the operation by resorting to the necessary antiseptic precautions, and to maintain an aseptic condition throughout the after-treatment under an efficient antiseptic hygroscopic occlusive dressing. If we remember that in cases where the abscess originated from a primary lesion inac- cessible to direct treatment it may require months for the healing process to be completed, it is not surprising that even the strictest antiseptic precautions in the hands of the ablest surgeons have failed in protecting the abscess-cavity against septic infection for such a long time. In a number of tubercular abscesses originating from a tubercular focus in the vertebra, in the hip- and knee-joints, I have succeeded in preventing infection, and the patients were cured after several months of the most careful and watchful treatment; but in a greater number of cases infection occurred at the time of operation, or weeks or months later during change of the dressing, or in consequence of a slipping of the dressing. In abscesses in the gluteal or inguinal regions, especially in children treated by incision and drainage, it is almost next to im- possible to maintain an aseptic condition for weeks and months, and the most careful and laborious efforts in this direction will often result in failure. (a) Evacuation by Aspiration followed by Antiseptic Irrigation and Subcutaneous lodoformization.—The frequency with which failures have occurred after incision and drainage, in the hands of the most enthu- siastic followers of the antiseptic treatment, has again aroused the fear of surgeons in attacking large tubercular abscesses by incision and drainage, and the subcutaneous evacuation with subsequent disinfection of the abscess-cavity has again come into favor. That iodoform exerts an inhibitory effect on the growth of the bacillus of tuberculosis is now generally accepted. Its use in the treatment of tubercular affections is almost universal. It has been extensively used for injection into tuber- cular abscess, after evacuation by aspiration, since Brims advocated this treatment, in 1887. It was first used dissolved in ether in the proportion of 1 part to 20. The ethereal solution has the advantage of bringing the drug in contact with every part of the interior of the cavity by the distention which takes place from the expansion of the ether when exposed to the body-temperature, but the injection is usually followed by considerable pain. Bruns used a suspension of iodoform in glycerin and alcohol. Recently the following formula was suggested by Krause:— TUBERCULAR ABSCESS. 455 Iodoformi subt. pulveris,.........50.0 Mucil. gummi arab.,..........23.0 Glycerini,............83.0 Aquae destillatae,........q. s. ad 500.0 (Ten-per-cent. iodoform mixture.) The evacuation of the abscess is to be done with an ordinary trocar under strict antiseptic precautions. The surface of the abscess is thor- oughly disinfected in the usual manner, and the instruments rendered aseptic by boiling. The trocar is inserted in such a manner that a track, at least an inch in length, is made underneath the skin before the instru- ment is plunged into the abscess-cavity, in order to make the wound, after the removal of the instrument, as nearly as possible subcutaneous. As tubercular abscesses usually contain shreds of dead connective tissue and masses of broken-down granulation tissue, the evacuation is often attended by a considerable difficulty, as these substances block the open- ing of the instrument and thus prevent evacuation. The simplest pro- cedure to overcome these difficulties is to introduce through the canula a small hook made by bending an aseptic wire, and to extract with it any substance which interferes with the escape of the fluid contents. Gentle, uniform pressure is of great value in expediting the escape of the con- tents and in preventing the entrance of air. Iodoformization of the abscess-cavity is not to be done until complete evacuation of solid de- tached particles has been effected by means of irrigation with a 3-per- cent, solution of boracic acid. This can be readily done by inserting the glass tip of an irrigator which holds the solution into the canula. A sufficient quantity of fluid is allowed to flow into the cavity until this is distended as much as before the evacuation of the fluid, when, by gentle pressure, it is forced out through the canula. By filling and emptying the cavity alternately in this manner a requisite number of times, com- plete evacuation of the fluid and loose solid contents is effected, and the cavity is now ready for iodoformization. Whatever formula for the solution is selected, not more than half a drachm of the iodoform should be injected at the first time, and in children even less. If this dose does not produce any unpleasant S3'mptoms, it may be increased the next time the operation is repeated. There seems to be very slight danger of iodoform intoxication, not even a S37mptom of this being observed in 109 cases thus treated by Bruns, of Tubingen. The injection is made with an ordinary but perfectly aseptic syringe, the nozzle of which must fit accurately into the outer end of the canula. If the ethereal solution is used, the iodoform will become diffused over the entire inner surface of the abscess-cavity ; but if a non-evaporating medium for the mixture is used, this must be done by gently kneading and rubbing the parts 456 PRINCIPLES OF SURGERY. over the abscess after the canula is withdrawn. The injection containing the iodoform is, of course, intended to remain in the cavity. The punc- ture in the skin is closed with collodium, and the walls of the abscess are kept in contact b37 compress and bandage. Absolute rest is to be en- forced for some time by splints or confinement in bed, according to the location of the abscess. The operation is to be repeated in the course of a week, or as soon as the abscess-cavity has partially refilled. The treatment of tubercular abscesses by subcutaneous evacuation, with sub- sequent iodoformization, should be adopted and repeated, from time to time, in all cases where the primary lesion is inaccessible to radical surgical treatment, and may yield good results in cases which heretofore had been subjected to heroic surgical treatment from the beginning. It may also prove useful as a preparatory treatment in cases which subse- quent^7 require operative treatment. (b) Incision and Removal of Primary Focus.—In all cases where, from the anatomical location of the primary lesion, it is possible to remove the tubercular product b37 operative interference, and the patient is free from other tubercular affections, a radical operation is absoluteby indicated. In such cases the abscess-cavity is laid freely open in a direction which will secure most ready access to its interior with least injury to surrounding parts. After the abscess has been opened, its con- tents are washed away b37 irrigating with an aqueous solution of iodine, after which the granulations lining the cavity are scraped out with a sharp spoon, and the primary lesion is removed in a similar manner. In dealing with such cavities it is important not to forget that the granula- tions contain tubercle bacilli, and, if the37 are not thoroughly removed, the principal object of the operation—removal of the primary cause—has not been accomplished, and a return of the disease is to be expected. If the abscess communicates with a primary focus in the bone, it is advisable to resort to ignipuncture of the bone after the cavity has been cleared of the granulations with the sharp spoon. The wound is to be closed in the usual manner, leaving onby a small opening at the most dependent point for drainage. The scraped surfaces are now in the same conditions for primary union as a recent aseptic wound, and, if kept in accurate apposition by the antiseptic dressing, which answers at the same time the purpose of a compress, primary union throughout is frequently ob- tained. Abscesses which have opened spontaneously, or during the treatment of which infection has occurred, must be treated on the same principles as acute abscesses. As far as can be done, the suppurating granulations should be removed with the sharp spoon and efficient tubular drainage established, and by frequent antiseptic irrigations an attempt is made to prevent septic infection. Landerer has recently called TUBERCULOSIS OF THE INTERNAL EAR. 457 attention to the value of balsam of Peru in the treatment of tubercular affections. He claims that this drug acts beneficialby by stimulating the tissues to renewed activity, thus neutralizing, at least to a certain degree, the pathogenic effect of the bacilli. Sayre, of New York, has used this remedy for more than thirty years in the treatment of tubercular joints, and his results have certainby been extreme^7 satisfactory. In the treat- ment of open, suppurating, tubercular cavities, the balsam of Peru should be tried as a local application. As a fluid for irrigation under the same circumstances, nothing can surpass the efficacy of a strong aqueous solu- tion of tincture of iodine. (c) General Treatment.—Patients suffering from suppurating tuber- cular cavities require nutritious food, ale, porter, or some of the substantial wines ; out-door air will often prove the best tonic. Change of residence to the sea-shore or some mountain resort has often been known to effect a cure when recovery was despaired of as long as the patients lived in localities less favorably located. In the wa3' of medication the treatment must be purely symptomatic. Appetite is restored 1)37 the use of bitter tonics ; anaemia is treated by the administration of some mild prepara- tion of iron, as the sj'rup of iodide of iron, tincture of chloride of iron, albuminate of iron, or citrate of iron. If codliver-oil is given it should be administered pure, and not in emulsion", and never upon an empty stomach. The pale Norwegian oil is the best. The best time to give the oil, without disturbing the digestion, is an hour or an hour and a half after each meal, in doses of from a teaspoonful to a tablespoonful, according to the condition of the digestion and the age of the patient. TUBERCULOSIS OF THE INTERNAL EAR. That an ordinary otitis media with perforation of the tympanum may occasionally be transformed into a tubercular lesion b37 the entrance of tubercle bacilli there can be no doubt. Habermann has recently investigated this subject by examining, post-mortem, 18 tuberculous subjects, in whom either otorrhoea or deafness, without active discharge, had been observed during life, and in 9 of these he could demonstrate the presence of tubercular lesions in the auditory canal. In 1 case he found, in the left auditory apparatus, tuberculosis of the entire middle ear where the tympanum was intact. In another tubercular subject, a man 38 years of age, in whom tuberculosis of the ear was observed a year and a half before death, the post-mortem revealed extensive tuberculosis of the cochlea, in the internal auditor canal, and in the superior semicircular canal, while the other semicircular canals and the vestibule were destro3red by caries. Infection w7ith the bacillus tuberculosis of granula- tions in the middle ear through a perforation in the tympanum can 458 PRINCIPLES OF SURGERY. occur in persons otherwise in perfect health. The diagnosis in such cases can be readily made by removing fragments of granulation tissue for microscopic examination. If they are found to contain tubercle bacilli a positive diagnosis has been made, and no time should be lost in resorting to a radical operation. The removal of the infected granula- tions with a sharp spoon, followed by irrigation with a warm 3-per-cent. solution of boric acid and iodoformization of the cavity, are the measures to be emplo3red in removing the infected focus and in preventing exten- sion of the disease into other parts of the ear, the mastoid cells, or the meninges of the brain. TUBERCULOSIS OF THE IRIS. Inoculations of the anterior chamber of the eye with tubercular material have shown the extreme susceptibility of the iris to tubercular infection. That this structure should occasionally become the seat of primary infection is evident from a case recently reported by Griffith, The patient Avas a female child 7 months old. The e37e had been affected for one month ; there was an enlarged gland in the neck on the same side, but there were no other physical signs of tubercle ; no history of heredity. A 37ellowish nodule grew from the periphery of the iris of the right e37e, and numerous millet-seed-like bodies from its surface; the pupil was closed, but there was no acute inflammation. The local disease increased rapidly in extent. The eye was enucleated after three weeks' treatment. The disease was found to be confined to the iris and ciliary body. Under the microscope the new growth showed the characteristic structure of tubercle. In 32 recorded cases, in which microscopic and bacteriological tests left no doubt as to the tubercular nature of the disease, only 1 eye was affected in 29. The average age of the patients was 12 years; youngest 4 months, oldest 51 years. In 10 cases bacilli was searched for, but only found in 4; in 1 of the remaining 6 cases, however, the inoculation test was successful. A number of patients recovered completely and permanently after enucleation. If the tubercle is located on the anterior surface of the iris, a diag- nosis can usually be made without much difficulty at an early stage, as the inflammatory product can be seen and carefully examined through the transparent cornea. If some doubt exist at first as to the nature of the swelling, this is soon set aside by the progress of the disease. The primary nodule soon becomes surrounded and covered by an eruption of miliary tubercles. The disease here, as elsewhere, shows its charac- teristic clinical feature,—progressive extension, affecting all the struc- tures contiguous to or continuous with the part primarily affected, irrespective of their anatomical structure. Glandular infection on the TUBERCULOSIS OF THE SKIN. 459 same side is an early and quite constant occurrence. Even if the disease is correctby diagnosticated at an early stage, complete removal by iridec- tomy is impossible, as parts of the iris which present a perfectly normal appearance may already be infected and lead to an almost certain recur- rence of the disease. Enucleation of the affected eye is only justifiable if the disease affect only one e37e, and if the surgeon can satisfy himself that the patient is not suffering at the same time from tuberculosis in other organs inaccessible to successful surgical treatment. TUBERCULOSIS OF THE SKIN. All forms of primary tuberculosis of the skin are the result of direct inoculation with tubercle bacilli. Considering the frequenc37 with which abrasions occur in the exposed portion of the skin, and the innumerable sources of infection with the virus of tuberculosis, it is somewhat strange that primary tubercular lesions of the skin are not of more frequent occurrence. Baumgarten believes that this is due to the slow growth of the bacillus and the dense structure of the deeper portions of the skin,— conditions which enable the superficial wound to heal before the tubercle bacilli have penetrated the tissues to a sufficient depth. Considerable confusion exists at the present time in reference to the nomenclature of primary tubercular affections of the skin. We find descriptions of what is called tuberculosis of the skin, tuberculosis verrucosa cutis, and lupus, all of which affections have been proved to be tubercular in their origin and manifesting the same clinical tendencies. It is time that these imma- terial and unimportant distinctions should be set aside, and these different affections should be included under one head, as primary tuberculosis of the skin, since all of them present the same histological structure, and all of them are caused by direct inoculation with tubercle bacilli. Riehl and Paltauf have described an affection of the skin, under the name of tuberculosis verrucosa cutis, in which the bacillus of tuberculosis is constantly found, and w7hich they attributed to local affection, because all of the patients they examined were persons handling animal products. Riehl has also shown the tubercular nature of papillomatous affections occurring upon the hands of pathological anatomists by finding the bacillus in the tissues. Anatomical and Clinical Proofs of the Tubercular Nature of Lupus. __Lupus vulgaris, and probably the other varieties of this affection of the skin, are nothing more nor less than cases of cutaneous inoculation- tuberculosis. It is well known that lupus occurs most frequently in parts of the body most exposed to injury and infection; that is, in the skin not protected by the hair or clothing. Lupus attacks most fre- quently the nose, face, eyelids, ears, and hands, localities where abrasions 460 PRINCIPLES OF SURGERY. occur most frequently, and parts upon which floating microbes are too liable to become deposited, and where direct inoculation with soiled hands, handkerchiefs, and towels is most likely to occur. I shall quote from a number of reliable authorities at sufficient length to prove that lupus and tuberculosis are identical affections. From a clinical stand- point Hebra brought the different varieties of lupus under one common head. He separated it entirely from syphilis, but otherwise did little to fix its pathological significance. He adopted the classification of Fuchs and the older French and English authors, who taught that it was one of the manifestations of scrofula, and that anatomically it was composed of granulation tissue. Virchow classified it with the granulomata, but denied its identity with scrofula. Rindfleisch described it as a proliferation of epithelial cells,—as a sort of phthisis cutanea. Hueter, who, in his pathological views, was generally far ahead of his time, affirmed that it was a form of fungous inflammation, the specific cause of which, when introduced into the organism, produced miliaiy tuberculosis. Volkmann included it among the affections which anatomically are represented by granulation tissue. Friedlander was the first to take a positive stand in asserting that lupus is a tubercular affection of the skin, and showed its histological identity with other recognized forms of local tuberculosis. He demonstrated the presence of miliary tubercles in it. The absence of caseation in lupus, which was regarded by some authors, among them Baumgarten, as an evidence of its non-tubercular character, has been explained by Schiiller as being due to the soil present in and around the nodules. He also calls attention to the fact that Cohnheim and Thoma have seen caseous foci in lupus, and consequently asserts that the absence of caseation is no proof of the non-tubercular nature of lupus. Neisser accepts fully and pleads strongly in favor of the tubercular nature of lupus. Rassdnitz collected 209 cases of lupus, and found that in 30 per cent, of all the cases it was associated with other evidences of tuberculosis. He placed, also, great importance on the observations that lupus is prone to develop in the scar left after healing of a localized tuberculosis in lymphatic glands, and that lupus is often observed upon the nose or eyelids in cases of chronic nasal or conjunctival ca- tarrh. In 10 to 15 per cent, of his cases lupus could be traced to heredi- tary predisposition. Demme observed miliary tuberculosis in 2 of his cases after scraping lupus. Pontoppindau asserted that, in his expe- rience, in 50 to 75 per cent., patients suffering from lupus manifested ad- ditional evidences of tuberculosis. Quinquaud saw in 3 cases of lupus pulmonary tuberculosis appear as a final cause of death. Of 38 cases that came to the personal knowledge of Bessnier, 8 of them suffered TUBERCULOSIS OF THE SKIN. 461 from pulmonarj7 phthisis. Of 2 patients treated by Aubert, 1 died of acute pulmonary tuberculosis and the other of tubercular pleuritis after scarification. Renoward was able to ascertain the existence of pulmonary phthisis in 50 per cent, of his cases of lupus. Block met with tuberculosis in other organs, before or after the development of lupus, in 114 out of 144 cases. Bender examined 374 cases of lupus. In 159 of these an accurate history could not be obtained. In 99 of the latter number S37mptoms of other antecedent or co-existing tuberculous lesions existed. In 77 of the cases tuberculosis in an etiological or clinical aspect was present. Leloir observed several cases in which, after years, a lupus of the face gave rise to a pseudo-eiysipelatous swelling of the face, which disappeared after a time, to be followed by swelling of the submaxillary lymphatic glands, which remained stationary. Soon after the affection of the lymphatic glands had appeared, febrile disturbances, gastric S3rmp- toms, and evidences of pulmonary infiltration followed. In all of these cases Leloir believes that the virus of tuberculosis had left the primary location, and had migrated through the lymphatic vessels and glands into the lungs. In 10 out of his 17 cases the tubercular nature of lupus was clinically manifest. Sachs ascertained that, of 105 cases of lupus which he collected, in 86 per cent, the patients had co-existing tuberculosis in other parts of the body, or a hereditary predisposition to tuberculosis could be shown to exist. Experimental and Bacteriological Evidences of the Tubercular Nature of Lupus.—If the clinical and anatomical proofs which have been advanced to establish the tubercular nature of lupus point unequivocally in that direction, the crucial test is furnished by the inoculation experi- ments and bacteriological investigations that have been made with the same object in view. Koch, in his paper on the etiology of tuberculosis, states that he produced a pure culture of the bacillus tuberculosis from a case of lupus which resembled in every respect the cultures obtained from recognized tuberculosis, and with the fifteenth generation from this source, one 37ear after the first cultivation, he inoculated 5 guinea-pigs by subcutaneous injection and produced typical tuberculosis in all of them. Doutrelepont found in 7 cases of lupus the bacillus tuberculosis invariably present, in greater or less number, either within the cells or dispersed in small groups between them. He never found them in the interior of giant-cells, but in their immediate vicinity. In a second communication the same author reports 18 additional cases of lupus, in each of which the presence of the bacillus could be demonstrated in the tissues. Demme detected the bacillus in 6 cases of lupus. Pfeiffer found it in a case of lupus of the conjunctiva. Schuchardt and Krause 462 PRINCIPLES OF SURGERY. discovered the bacillus in 3 cases of lupus affecting, respective^7, the face, ears, and leg. In examinations made of 11 cases of lupus by Cornil and Leloir, and 4 by Koch, for the especial purpose of showing the identity of lupus and tuberculosis, the bacillus was found in every instance. In the artificial tuberculosis of animals, produced by implanta- tion of lupus-tissue, the specific microbe was shown to exist by Pagen- stecher, Pfeiffer, Koch, and Doutrelepont. To prove that lupus and tuberculosis are identical, it became necessary to furnish the necessary experimental proof, and to show the uniform presence of the bacillus of tuberculosis in the lupus-tissue, all of which has been done with almost infallible positive results. The inoculation experiments with lupus- tissue have already been referred to, and from them it can be learned that, with few exceptions, the3r were followed by positive results; that is to say, implantation of lupus-tissue into subcutaneous tissue or the peritoneal cavity, in animals susceptible to tuberculosis, gave rise to local tuberculosis at the point of implantation and to dissemination of the process in a manner characteristic of tuberculosis in man. A diffuse tuberculosis of the skin and mucous membranes, occurring as a sort of secondary7 localization in patients suffering from advanced tuberculosis, has been recently described by Pantlen, Bizzozero, Baumgarten, Chiari, Hall, Janisch, Riehl, Vidal, and Finger. As such cases occur in conse- quence of auto-infection in persons debilitated by the ravages of the primary disease in the lungs, it is not surprising that the skin affection should extend more rapidly than in cases of primary tuberculosis of the skin. Pathology and Morbid Anatomy.—As every case of tuberculosis of the skin is caused by the entrance of tubercle bacilli from without through some infection-atrium, the primary pathological changes occur at the point of inoculation. As soon as the bacilli reach the vascular layers of the skin, a nodule forms which contains the histological ele- ments described in the section on the Histology of Tubercle. By the formation of new nodules, a more diffuse cellular infiltration of the tissue between them, the lesion tends to spread, and, by confluence of the infiltrated portions, a dense and more or less extensive area of nodular infiltration may be formed. If the continuity of the epidermic layer of the skin has been restored after infection has occurred, and the cell pro- liferation has been abundant, the swelling ma3r resemble a papillomatous growth, and, on account of the increased vascular suppty, an excessive production and exfoliation of epidermis over the infiltrated area occur. These are the cases of inoculation-tuberculosis which have been described as tuberculosis verrucosa cutis. The nodules undergo disintegration near the centre, and the epidermis at a corresponding point becomes TUBERCULOSIS OF THE SKIN. 463 macerated and detached, leaving at first a minute defect, which secretes a serous fluid. As soon as the underlying granulation tissue has been exposed to infection from without, infection with pus-microbes occurs, and the destruction of tissue is hastened by the suppuration inflammation which follows, as the granulation cells are rapidty destro37ed by the pus-microbes and their ptomaines, and are eliminated as pns-corpuscles. Ulceration now takes the place of the papillomatous growths, and the defect increases in size as rapidly as granulation tissue is produced l^7 the action of the bacillus tuberculosis. New nodules are produced in the immediate vicinity of the ulcer, which are again dissolved by retro- grade tissue metamorphosis of its cellular constituents and purulent liquefaction. It is not uncommon to find, at some places, efforts at repair, and even partial cicatrization and epidermization ; but the disease pursues its relentless course in other directions, and, after what appears as healthy new tissue, becomes again infected and the process of destruction is repeated. In some forms of tuberculosis of the skin the infection remains superficial, and onby the more superficial portions of the skin undergo pathological changes characteristic of tuberculosis; while in other cases the process extends deeper and deeper, until muscles, fascia, and bone are destined by the disease, in the manner of its exten- sion from tissue to tissue resembling the clinical behavior of malignant tumors. In this manner the whole nose, eyelids, and the greater portion of the face are frequently destroyed before the patient is relieved from his sufferings by7 a merciful death. Microscopical examination show's the lesions to consist in the formation of granulation tissue, in which the typical structure and histological elements of tubercle can be readily recognized. Caseation is seldom found, probably on account of the location of the tubercular product so near the surface of the skin, and also because the granulation tissue soon becomes the seat of a secondary infection with microbes which prevent caseation. In most cases a well- marked reticulum is present between the new cells, and these are often grouped in masses around the blood-vessels. Symptoms and Diagnosis.—Tuberculosis of the skin is most fre- quently met with in middle-aged persons, but no age is exempt from it, as I have seen it in children 5 years of age and in persons far advanced in years. It attacks most frequently the nose, eyelids, cheeks, ears, and hands, but it may also develop upon the different parts of the trunk. The disease commences in the form of a small, red, vascular nodule; is not painful nor tender on pressure. In the vicinity of this nodule new foci spring up, and by confluence ma37 form a swelling of considerable size. To the touch these nodules impart rather a sensation of elasticity 464 PRINCIPLES OF SURGERY. than hardness, and if the swelling is large in size an obscure sense of fluctuation may be felt. Before ulceration takes place the surface of the nodules is covered by a thickened epidermis, which can be scraped off in white scales. If no ulceration take place (lupus non-exedens), the nodules ma37 remain stationary in size for an indefinite period of time or undergo a spontaneous cure by cicatrization, during which the epithelioid cells are converted into connective tissue. Ulceration begins over the centre of the nodule, at a point where the nutrition of the tissues is most impaired b37 pressure, and extends from here toward the margins of the nodule, attacking the new nodules almost as fast as they are formed (lupus exedens). Cicatrization and ulceration are often seen side by side. Ulceration is hastened by7 the secondaiy infection with pus-microbes, which invade the granulation tissue in the margins of the ulcer, occupying the tubercular zone. Repair by cicatrization and epi- dermization is more likely to occur if the infection remains superficial, but is usuall37 entirely absent as soon as the tubercular process has ex- tended beyond the limits of the skin. The differential diagnosis as to tuberculosis of the skin, tertiary syphilis, and epithelioma is generally7 very difficult, and sometimes almost impossible. There is very little difference between the histological structure of a tubercle-nodule and a gumma, and the most experienced microscopist is liable to make a mis- take if called upon to make a diagnosis exclusively7 by the use of the microscope. The history of the case is of the greatest importance in making a differential diagnosis between tuberculosis and syphilis. If the patient is positive that he never contracted syphilis, it is still possible that the lesion may be S37philitic, as the disease may have been inherited; if he give a history of primary and secondary S37philis, the affection may still be tubercular; but a straight history of tuberculosis or syphilis will go far in determining the nature of the local affection. If any doubt remain, this can be cleared up by the use of the microscope in the course of five weeks, either by the effect produced by anti-syphilitic treatment or the result of inoculation experiments made by implantation of fragments from the inflammatory product into the subcutaneous tissue in guinea-pigs. The microscopic examination of fragments of tissue removed for this purpose must have in view the detection of the bacillus of tuberculosis, which is constantly present in tubercular tissue. The specimen must be prepared by double staining according to Ehrlich's method, and if the affection is tubercular, the bacillus can be found by making a patient search for it; if it is syphilitic, it will, of course be absent. The bacilli, however, may be so few that even a careful search of stained specimens may result negatively, and in such a case a positive TUBERCULOSIS OF THE SKIN. 465 diagnosis can often be made by observing the effects of a thorough anti- syphilitic treatment. For an adult, ■£■$ grain of sublimate with 15 grains of potassic iodide, dissolved in distilled water, is given four times a day,— after each meal and at bed-time. If the lesion is syphilitic, a decided improvement will be observed in the course of two or three weeks ; if tubercular, this treatment will make no decided impression on the local lesion. The most reliable diagnostic test in differentiating between tuberculosis of the skin and a syphilitic lesion consists in removing, under antiseptic precautions, a fragment of granulation tissue the size of a small pea, and implanting the same into the subcutaneous tissue of a guinea-pig. Tavel has been studying, in a systematic manner, the diagnostic value of implantations of tubercular material in animals, mainly guinea- pigs. He found that fragments of granulation tissue, taken from a tubercular product and implanted into the subcutaneous connective tissue, in the inguinal region in guinea-pigs, invariably produces in this animal local, and later general, miliary tuberculosis, and death in from five to six weeks. The course of the disease thus artificially produced is typical; at the point of inoculation a hard nodule appears first, the result of traumatic response on the part of the tissues around the graft. Next, a lymphatic gland becomes enlarged in the immediate vicinity of the inoculation and in the direction of the lymphatic stream. Often all of the inguinal glands are infected successively. At a later stage the axillary glands become affected At the necropsy it was always observed that, of the internal organs, the spleen becomes affected first, then the liver and luno-.s, but before death is produced almost every organ is the seat of miliary nodules. When the differential diagnosis between tuber- culosis and syphilis cannot be made from a clinical study of the case or by the use of the microscope, inoculation experiments will always furnish the desired information in from three to six weeks. If the lesion is tubercular, the infected guinea-pig contracts the disease, and dies in from five to six weeks ; if it is syphilitic, the implantation will prove harmless and the animal remains well. The differential diagnosis be- tween tuberculosis of the skin and epithelioma must be based on the primary location of the pathological product and the character of the infiltration. Tuberculosis commences in the vascular portion of the skin; hence, the primary nodule is sub-epidermal; while epithelioma starts in the non-vascular epidermis and infiltrates the deeper layers of the skin later. The tubercular nodule is not hard, but somewhat elastic, to the touch. The carcinomatous infiltration feels almost as hard as cartilage, and forms a part of the epithelial layer of the skin from the bernnnino-. A tuberculous ulcer of the skin is covered with flabby granu- 30 466 PRINCIPLES OF SURGERY. lations, and its margins, although infiltrated, do not feel as firm as the borders of an ulcerating epithelioma. Under the microscope the tubercle- nodule shows o-ranulation cells in the meshes of a delicate reticulum, while in a section of an epithelioma a well-marked alveolated reticulum can be seen, the meshes of which are occupied by embryonal epithelial cells arranged in concentric layers. Another microscopic criterion is the absence of blood-vessels in tubercle-nodules, while carcinoma is a vascular structure. Prognosis.—Primary local tuberculosis of the skin may lead to glandular infection, and, after the last lymphatic filter has been passed, to general miliary tuberculosis. The tubercular product in exceptional cases becomes the starting-point of carcinoma. The local extension of the tubercular process is subject to many variations. In some instances the process commences during early life, and remains stationary for twenty or more years, when it suddenly commences to extend very rap- idly, destroying all of the tissues which come in its wa37, irrespective of their anatomical structure. Tuberculosis of the face, manifesting such a tendency to rapid extension, may in a few months destroy nearly all of the soft tissues and a considerable portion of the superficial bones, so that the head looks more like a skull than the head of a living being. In other instances the ulceration keeps extending, while at other points the healing process is progressing with equal speed. In such cases the massive scars are often productive of the most hideous deformities. Recurrence of the disease in the scar-tissue is of common occurrence. The prognosis, as far as life is concerned, is favorable so long as the disease remains local and does not progress rapidly; while life is threat- ened as soon as regional infection through the lymphatic glands takes place, or when ulceration extends rapidly without any tendency to repair by cicatrization and epidermization. Tuberculosis of the skin without ulceration is a more benign form of the disease than when ulceration has occurred, as in the latter case the destructive process is hastened by secondary infection with pus-microbes. Treatment.—About the only medicine that deserves any confidence in the treatment of tuberculosis of the skin is arsenic: This drug can be given in the form of Fowler's solution, in doses of from 3 to 10 drops after each meal, well diluted with water. It is best to commence with the smallest dose and add 1 drop every week until the physiological effect is produced, when the use of the medicine is not suspended, but the dose is diminished. To be of any use, the medicine has to be con- tinued for weeks and months. If the patient is anaemic, it is combined with the tincture of chloride of iron, and, if the patient's appetite is poor, with one or more of the bitter tonics. If the patient is emaciated, pure TUBERCULOSIS OF THE SKIN. 467 codliver-oil can be given with good results an hour and a half after meals, in doses which will be tolerated by the stomach. If digestion is impaired this drug should be withheld. A well-selected, nutritious diet is indicated in all such cases, with plenty of out-door exercise. Salt-water baths invigo- rate the peripheral circulation, and consequently favor the limitation of the disease and the process of repair. The surgical treatment of tuber- culosis of the skin is to be conducted upon the same principles as opera- tion for the removal of malignant tumors. The use of caustics often does more harm than good. The great object of the local treatment is to remove every particle of the infected tissues, for if this is not done a re- currence is almost sure to take place. If the patient object to a radical operation, and the tubercular process has gone on to ulceration, all irri- tating applications should be avoided and the ulcer protected by a piece of lint spread with empl. hydrargyri or unguent, hydrargyri oxyd. albi. Balsam of Peru can also be used with benefit as a local application. If a radical operation is decided upon, this should be done preferably by ex- cision. Excision should be practiced exclusively7 in cases where the extent of the disease is limited. The incision should be made some distance from the visible margins of the infiltration, in order to include tissues which, although presenting macroscopicalby a healthy appearance, may already be infected with bacilli, conve337 making the examination while the patient is fully under the influence of an anaesthetic. If the affection is a neurosis, motion will be found unimpaired ; if it is tubercular, the mobility of the joint will be found lessened by intra-articular adhesions and cicatricial contraction of the capsule of the joint. Prognosis.—Tuberculosis of a joint may terminate in a spontaneous cure in cases in which the intensity of the infection is slight, or the resistance on the part of the patient is so great that the fungous granula- tions do not undergo degenerative changes, but are converted into connective tissue. A partial or complete synechia of the cavity of a joint is often one of the unavoidable results in such cases, leaving the joint in a permanently stiff condition. This endeavor on the part of the organism to limit the extension of the disease is often observed in cases in which the joint affection occurs in connection with osteal tubercu- losis. As soon as perforation of a focus into a joint has occurred a wall of granulation tissue is thrown out around the circumscribed area of infection, and, under favorable circumstances, a partition of cicatricial tissue is formed which isolates the infected from the intact portion of the joint. In such instances we have an illustration how the tubercular process is retarded, and sometimes permanently arrested, by the trans- formation of granulation into connective tissue. For such a favorable TUBERCULOSIS OF JOINTS. 515 termination to take place it is necessary that the tubercular virus should be attenuated by age or want of a proper nutrient medium, or that the pathogenic effect of the bacilli should be neutralized by an adequate resistance on the part of the tissues before degenerative changes have occurred in the granulation tissue. The course of articular tuberculosis is so variable in different cases that it is impossible, during the early stages of an attack, to predict anything certain in reference to the probable outcome. A spontaneous cure is more likely to take place if the patient is young, not anaemic, and, at the same time, well nourished. The hygienic surroundings must also be taken into consideration in rendering a prognosis. The disease shows greater tendencies to limita- tion in children than in persons past the age of puberty. Among the different forms of joint tuberculosis the tubercular hydrops and caries sicca are the most benign, and in these cases a spon- taneous cure is most frequently realized and the same conditions are effected, and which are also amenable to successful surgical treatment. The caries sicca may, according to Konig, terminate in a spontaneous cure in two or three years, with some loss of motion in the joint. It is sometimes difficult to ascertain in a given case when the lesion can be considered as cured. As the most reliable evidences that such favorable termination has taken place must be considered disappearance of swell- ing, pain, tenderness, and restoration of function as far as this can be expected. The patient should not be permitted to use the limb until the active symptoms of inflammation have disappeared. The danger to life arises from the existence of complications, foremost among them being septic infection, pulmonary or general tuberculosis, and amyloid degen- eration of important internal organs. Septic infection is caused either by localization of pus-microbes brought to the tubercular focus through the circulating blood, or, what is more frequently the case, through an infection-atrium, created by a spontaneous opening through an operation wound, or, finally, through a fistulous communication with the joint. Many neglected cases of joint tuberculosis die annually of pulmonary or general tuberculosis. Billroth states that in sixteen 37ears 27 per cent. of bone and joint tuberculosis were lost in this way. Kdnig, from a table of 117 operations for tuberculosis, found that after four years 16 per cent, had died from general tuberculosis. If a patient escape death from septic infection, after secondaiy infection with pus-microbes, he is liable to succumb several years later to auyloid degeneration of the spleen, the liver, and especially the kidneys, with its accompanying anasarca. Treatment.—As spontaneous cure in cases of joint tuberculosis is more frequently the exception than the rule, and if finally it does take 516 PRINCIPLES OF SURGERY. place it does so generally after the limb has become so much deformed that it has become useless and will require a formidable operation to restore partial function, it is evident that timely surgical treatment should be adopted to eradicate the disease, preserve function, and, at the same time, protect the patient as far as can be done against general infection. I. Rest.—As in cases of osteo-tuberculosis, rest is an important ele- ment in the treatment of tubercular joints. It is even more important to secure rest for an inflamed joint than for an inflamed bone, as the inflam- mation is always greatly aggravated by the movements in the joint that necessarily take place as long as the joint is used, which does not apply with equal force to cases of osteo-tuberculosis. The best method to fulfill this indication is to immobilize the limb in a plaster-of-Paris splint, which does not necessarily confine the patient to his room or bed. If one of the lower extremities is to be encased in a plaster splint, I am in the habit of applying the plaster-of-Paris roller over tight-fitting knit drawers, which protect the skin much better than an ordinary roller bandage. All bony prominences should be protected against pressure by careful padding with absorbent cotton. If the hip-joint is the seat of inflammation the splint is applied with the limb in the extended posi- tion, while the patient stands on the sound limb upon a low stool, as in this position autoextension is made by the weight of the suspended limb. In such cases the splint must extend from the toes and embrace the entire limb, the whole pelvis, and abdomen as far as the umbilicus, and the opposite limb as far as the knee-joint. In tuberculosis of the knee- joint the splint should extend from the toes to the groin, and, in ankle- joint affections, from the toes to the knee-joint. Immobilization is to be made with the limb in such a position that in case the joint should be- come permanently stiff the limb can be used to greatest advantage. A slight degree of flexion in the hip- and knee- joint is to be preferred to a perfectly straight position. In inflammation of the shoulder-joint the limb makes the necessaiy counter extension and fixation of the joint by confining the limb, with the forearm flexed, at right angles to the side of the chest, b37 strips of adhesive plaster or a plaster-of-Paris bandage. The hand should be slight^7 extended in immobilizing the forearm in the treatment of tuberculosis of the wrist, while the forearm is flexed at a right angle to the arm in tubercular synovitis of the elbow-joint, with the hand in position half-way between pronation and supination. Early im- mobilization of a tubercular joint not only secures absolute rest for the joint, but, at the same time, this treatment prevents to a great extent subsequent deformities. Treatment by immobilization should be con- tinued until all symptoms of inflammation have subsided, or until more TUBERCULOSIS OF JOINTS. 517 radical measures become necessary. If the arthritis has already resulted in contractures the treatment by extension with weight and pulley is in place, and should be continued until the limb has been brought in proper position for treatment by immobilization. 2. Aspiration.—In tubercular hydrops the intra-articular effusion is often very copious, resulting in enormous distention of the capsule of the joint, which, if continued for any length of time, must necessarity result in great weakening of the joint. Aspiration under these circum- stances relieves the distention and places the vessels in the synovial membrane in a better condition to perform their function in the subse- quent removal of the inflammatory product b37 absorption. After evacua- tion of the contents of the joint the limb should be immobilized and rapid re-accumulation of the fluid prevented by uniform, equable com- pression of the joint b37 strips of adhesive plaster or rubber bandage. 3. Subcutaneous Evacuation of Contents of Joint, followed by Iodoformization.—In tubercular hydrops and abscess of a joint, subcu- taneous evacuation of the fluid contents, followed b37 iodoformization practiced in the same manner as has been described in the treatment of tubercular abscess, yields much more satisfactory results than simple aspiration. In tubercular lydrops irrigation of the joint with a 3-per- cent, solution of boric acid is only necessaiy for the removal of rice- bodies ; if such are not present, the iodoform mixture ma37 be injected at once. Tubercular abscess always requires a preliminaiy irrigation with some mild antiseptic solution, for the purpose of removing detached and disintegrated tubercular products before the iodoform mixture is injected. Krause, in the last eighteen months, treated 43 tubercular joints by means of iodoform injections; cases w7ere treated b37 other means, and where cure without operation seemed impossible, but in which fistulas w7ere not 37et formed. The injections were repeated at intervals of two or three weeks. Pain was greatly relieved by this treatment; the swelling yielded much more slowly, though in six weeks some cases showed a reduction in size and a hardness of the affected parts. The abscess-cavities frequently filled again, rapidly at first, but ultimately re-accumulation ceased. In some cases fistulae formed at the seat of puncture, which first discharged pus, then serum, but ultimately healed entirely. In a fair percentage treated in this way definitive healing was obtained. This treatment promises the best results in cases where granulation tissue is scanty, and where the inflammatory product has not undergone extensive caseation. Its utility is much impaired if suppu- ration has taken place in the joint. Billroth opens the joint, evacuates its contents through the incision, removes (if present) tubercular sequestra, rice-bodies, and tubercular membranes, and then treats the 518 PRINCIPLES OF SURGERY. joint by iodoformization. In general practice, however, it is much safer to follow the subcutaneous method by puncturing the joint with a medium-sized trocar, using the canula for evacuation, irrigation, and iodoformization. 4. Arthrectomy.—Excision of the infected tissues in primary tuber- culosis of the synovial membrane has been practiced for a number of years, and the results of this treatment have been quite encouraging. Primary synovial tuberculosis, without any foci in the articular ends of the bones, should be treated by arthrectomy and not b37 resection, as by the former operation the diseased tissues can be removed effectually without unnecessary loss of healthy tissues that are sacrificed by the latter operation. The success of an operation for tubercular affections depends largely upon the thoroughness with which the operation is done and the absence of suppuration. Arthrectomy should be performed before fistulous openings have formed, and the joint must be opened by an incision that will expose every nook and corner of the capsule. Of the many incisions that have been devised for opening the knee-joint, the one I shall describe here offers the greatest advantages and is open to the least objections. The old-fashioned horseshoe incision, with the convexity directed downward, makes it very difficult to suture the wound, and leaves a scar where it is most exposed to injury. The incision carried directly across the knee-joint, if the patella is divided at the same time, leaves, subsequently, the superficial and deep parts of the wound directly opposite; if the patella is preserved, the scar of the external incision falls upon the most prominent part of the patella, which is again a great disadvantage. The incision, which for several years I have always selected in opening the knee-joint in performing arthrectomy or resection, is slightly curved, but with the convexity directed upward. It is carried from the most dependent portion of the knee-joint, at a point corresponding to the most prominent part of the internal condyle of the femur, in a gentle curve to the upper border of the patella, and from here downward and outward to a point opposite where it was com- menced. The short, semilunar, cutaneous flap is now detached and turned downward. After this an incision is carried directly across the joint, dividing the lateral ligaments and crossing the patella transversely at its centre. The patella, at this step of the operation, is divided with a saw. The upper recesses of the synovial sac are freely opened by making an incision on each side of the upper half of the patella, which is carried as far as the upper recess of the synovial sac. The rectangular flap, composed of the upper end of the patella with its muscular attach- ments, is reflected, which exposes every portion of the upper part of the synovial recess. A somewhat similar flap is made of the lower half of TUBERCULOSIS OF JOINTS. 519 the patella and its tendon, reflected in a downward direction, by which the tissues underneath that portion of the patella and its ligament are fully exposed. With the knee-joint thus exposed it is not difficult to extirpate, with the help of a catch-forceps, a sharp scalpel, and a pair of curved scissors, the entire capsule. The part of the capsule that will be found most difficult to remove is that portion which covers the popliteal vessels, and dips down behind the condyles of the femur and behind the tuberosities of the tibia. During this part of the operation the leg must be forcibly flexed over a small cushion, or the fist of an assistant, in the popliteal space. Arthrectomy is always a tedious operation, as it is absolutely necessaiy to remove all of the infected tissues in order to secure permanent success. If the patella is not diseased it should never be removed. After the capsule has been extirpated the patella is united b3' two chromicized catgut sutures. I have never failed in obtaining bon37 union in four to six weeks after this method of coaptation. After extirpation of the capsule, and before the elastic constrictor is removed, the whole surface should be once more irrigated with a hot solution of corrosive sublimate (1 to 1000), after which it is rubbed off with dry iodoform gauze, in order to remove any detached fragments that have not been washed away. The whole surface is now freely sprinkled with impalpable iodoform, which is rubbed into the surface. Before the con- strictor is removed the wound is packed with aseptic gauze, the flaps are laid over it, and manual compression made for five to ten minutes after the removal of the constrictor, with the limb in an elevated position. This simple procedure serves an admirable purpose in controlling capil- lar haemorrhage, and reduces the necessity of recourse to ligature to a minimum. After all the bleeding has been arrested, the patella is sutured, and the deep parts of the wound are united by buried sutures. Tubular drain- age can usually be dispensed with, as a capillar drain composed of a few threads of catgut will answer an excellent purpose, and will not, like the tubular drain, necessitate an early change of dressing. The external in- cision is closed with silk sutures, the line of suturing being out of the way of the patella, the parts united with the buried sutures being covered throughout by the external flap. A careful haemostasis and rigid anti- septic precautions will make it unnecessary to change the dressing earlier than the end of the second week, and on this account I prefer to immo- bilize the limb in a plaster-of-Paris splint applied over a copious antiseptic dressing. The limb must be kept in an elevated position for at least six hours after the operation, so as to diminish the amount of parenchyma- tous hsemorrhao-e. If all the infected tissues have been removed and the wound remains in an aseptic condition, the external wound will be found 520 PRINCIPLES OF SURGERY. closed in the course of two or three weeks. A fair restoration of func- tion with partial mobility of the joint can be expected in favorable cases. Passive motion must be delayed until the patella has firmly united, which will require from three to four weeks in children and nearly twice this length of time in adults. After the patella has united and the external wound is complete^7 healed, recoveiy is hastened by passive motion, massage, and use of the faradic current. Arthrectomy has a future in the treatment of primaiy synovial tuberculosis of the knee-joint, but for well- known anatomical reasons it is not equally applicable in the treatment of synovial tuberculosis of any other of the larger joints. It is possible that the operation will be modified and sufficiently perfected in the future so as to be applicable in the treatment of s3'novial tuberculosis of the hip- and shoulder- joint. In 2 cases of tuberculosis of the elbow-joint I obtained an excellent result from arthrectomy combined with temporaiy resection of the olecranon process. This process was divided obliquely with a saw at its junction with the shaft of the ulna, and, after the extirpation of all of the infected soft tissues of the joint, the process was fastened in its proper place with an aseptic ivory nail. The functional result was satisfactory. 5. Atypical Resection.—The incision in atypical and typical resec- tion of the knee-joint should be the same as has been described above. The patella is divided transversely, and, if it does not contain a tuber- cular focus, it is not necessary or advisable to remove it, as its conti- nuity, after resection, can be restored by suturing with a durable form of catgut. An atypical resection consists in the removal of tubercular foci in the epiphyseal extremities of the bones that enter into the forma- tion of the joint, without removing the entire articular extremities by a transverse section with the saw. The unnecessary removal of the epiphyseal extremities should especially be avoided in the case of chil- dren, as the removal of one or both centres of growth of bone will result in so much shortening of the limb subsequently as often to render it not only perfectly useless, but it becomes a burdensome appendage. In children atypical resection should be practiced in all cases where all the foci in the articular extremities can be reached and removed by this method. The proper instruments to be used in this operation are the chisel, bone-forceps, and sharp spoon. After the joint has been freely opened, the articular surfaces are carefully inspected for evidences of deeply-seated foci. If perforation into the joint has taken place, the cavity is freely exposed from the articular surface, and all of the infected tissues are removed with chisel and sharp spoon. It is important not only to remove necrosed bone, granulation tissue, and caseous material, but also the surrounding osteoporotic zone of bone that possibly might TUBERCULOSIS OF JOINTS. 521 contain tubercle bacilli. A deep-seated focus may be suspected and searched for if the articular cartilage has become detached over a greater or less extent. Explorations with a small perforator can be made in different directions from the articular surface in searching for deep-- seated foci. If the articular cartilage has become detached over a con- siderable area b3r granulations underneath it, it should be removed, and the exposed bone must be subjected to another careful examination for the purpose of locating and treating deeply seated foci. A circumscribed area of great vascularity is a suspicious indication, and calls for a lim- ited excavation with a small, sharp spoon for diagnostic purposes. It is well for the surgeon to remember that primaiy osteo-tuberculosis with secondaiy involvement of a joint usually consists of more than one focus in one or both epiphyseal extremities. A tubercular infarct is generally recognized ly examining the articular surface, as the cartilage or the exposed portion of the wedge-shaped sequestrum presents ap- pearances of necrosis that cannot be mistaken. After the extraction of the sequestrum the tubercular cavity is submitted to the same treatment as when dealing with a granulating or caseous focus. In primaiy syno- vial tuberculosis, with extension of the disease to the subjacent bone, it becomes necessary to remove the hone37-combed, softened bone over the entire surface with the sharp spoon and chisel. Before the operation is extended to the bone in osteo-tuberculosis, it is always necessary first to extirpate with knife and scissors the infected soft structures of the joint, the S37novial membrane and ligaments, as otherwise the healthy vascular bone may become an infection-atrium for traumatic infection,— a not very infrequent and serious complication after operations on bones and joints for tuberculous affections. Wartmann, after giving a careful account of the results following excision of tubercular joints in the hospital practice of Feurer, gives the statistics of 837 cases of excision of joints for tuberculosis from the practice of different operators. Of this number 225 died. Of the fatal cases, in 26 death followed the operations closely, and resulted from acute tuberculosis, probably induced by the operation. Kdnig observed 16 cases in his own practice in which miliary tuberculosis followed almost immediately after operations on bones and joints for tubercular affections. Kdnig states that the secondaiy infection sets in seven to ten days after operation, which may have been perfectly aseptic, with healing of the wound by primary union. The secondaiy tubercular infection appears either as an acute pulmonary tuberculosis or tuber- cular meningitis, terminating in death three or four weeks after the operation. It is not difficult to conceive the modus operandi of such an occurrence. The resection wound opens numerous veins in the bone, 522 PRINCIPLES OF SURGERY. the lumina of which remain patent, read3r for the introduction of minute fragments of granulation tissue or bacilli, which, on entering the venous circulation, are the direct cause of metastatic tuberculosis in distant organs. We must take it for granted in such cases that a tubercular focus, during the operation, furnished the essential infected fragments of granulation tissue, or free bacilli are aspirated or forced into the openings of wounded vessels, and through them gain entrance into the general circulation. To guard against such an accident, it is necessary to remove from the joint all possible source of infection before operat- ing on the articular extremities. Cartilage that remains firmly attached to the bone may be left. After all foci have been radically eliminated, the field of operation is flushed with an antiseptic solution, and, after drying and iodoformization, the bone-cavities are packed with decalcified antiseptic bone-chips, and the operation is completed in the same manner as in arthrectomy. The treatment of bone-cavities with decalcified bone-packing is of the greatest utility in atypical resection. An atypical resection with subsequent implantation of decalcified bone has for its objects complete removal of the infected tissues in the joint and the surrounding bone, and the partial restoration of the parts destroyed by disease or removed during the operation. In atypical resection of the knee-joint it is not uncommon that nearly an entire condyle of the femur or tuberosity of the tibia must be removed. In such cases the surgeon aims at bony union between the articular ends of the bones, which is accomplished in the most satisfactory manner by placing the parts in a condition to repair the lost bone-tissue, which may be done by filling the defect with decalcified bone-chips. I have repeatedly made excavations in one of the condyles of the femur and in the head of the tibia from the joint surface, the size of a small orange, and obtained bony ankylosis, with the limb in a good position, by filling the cavities with bone-chips. As the bone-chips are always iodoformized before implantation, they serve a useful purpose not only by furnishing a temporary scaffolding for the reparative material, but they constitute a valuable therapeutic measure in the prevention of a local recurrence of the disease in case tubercle bacilli should remain in the cavity or its immediate vicinity. Immobili- zation of the limb after resection should be continued until the process of repair has been completed, which, under the most favorable condi- tions, requires from six weeks to two months. Atypical resections are applicable only to certain joints, as the knee-, elbow-, ankle-, and tarsal joint. The elbow-joint is most accessible through a long, straight in- cision, and after temporary resection of the olecranon prooess. Atypical resection of the ankle-joint can be done through two lateral incisions, TUBERCULOSIS OF JOINTS. 523 with chisel and sharp spoon. In all resections, atypical and typical, ignipuncture is indicated after the excision has been completed, if any portion of the bone is abnormally osteoporotic, as this procedure will stimulate the process of repair, and may prove useful in destroying in- fected tissues, which, from their macroscopical appearance, indicate a healthy condition. 6. Typical Resection.—In typical resection one or both articular extremities are sawn across and removed. In the hip-joint it implies the excision of the head, neck, and part or the whole of the greater trochanter of the femur. A typical resection of the wrist-joint means the removal of the entire carpus, with or without the articular surfaces of the radius, ulna, and metacarpal bones. In a typical resection of the shoulder-joint the head of the humerus is removed. In the knee-joint the operation means excision of the articular surfaces of the femur and tibia ; in the elbow-joint, of the humerus, radius, and ulna; in the ankle, of the tibia, fibula, and astragalus. Typical resections are always made for tubercular affections of the shoulder-, hip-, and wrist-joint. In the re- maining larger joints it is more frequently resorted to in adults than children. In children the operation is limited, with the exception of the shoulder-, hip-, and wrist-joint, to cases where the articular extremities are so extensively diseased that an atypical resection would fail in re- moving all of the infected tissues. Removal of the diseased synovial membrane and ligaments should precede section of the bones with the saw wherever, from the anatomical construction of the joint, this can be done. In the hip- and shoulder- joint the head of the bone must be re- moved first before the soft structures of the joint can be removed. The operation best adapted for resection of the hip-joint is the one devised by Konig, by which the borders of the trochanter major are preserved. In this operation the section of the bone must be made with a chisel. The entire neck and head of the femur are removed b3r dividing the bone transversely with a chisel just below the neck, with the exception of the borders of the greater trochanter, which are split off with the same instrument. The capsular ligament is removed as thoroughly as possible, and the acetabulum is scraped out with a sharp spoon. Pro- vision for drainage must be made in all hip-joint resections. The after- treatment consists of rest in bed upon a smooth mattress, with the limb extended by weight and pulley in an abducted position. After six weeks the patient is allowed to walk on crutches, with a raised sole under the shoe, worn on the opposite side, so that the limb on the resected side makes the necessary autoextension. During the night extension is applied for eight months or a year, in order to prevent unnecessary shortening. Eversion and inversion of the limb while the patient is in 524 PRINCIPLES OF SURGERY. bed are prevented either by a Volkmann railway-splint or by support- ing the limb with sand-bags, applied to each side. Immobilization, after resection of the shoulder-, elbow-, wrist-, knee-, and ankle- joint, is best secured in a plaster-of-Paris dressing, which also serves an excellent purpose in keeping the antiseptic dressing in situ. Temporary resection of the olecranon process in resection of the elbow-joint has yielded excellent results in my hands, as by it the inser- tion of the biceps muscle is not disturbed. The resected olecranon, after the removal of any foci it may contain, is riveted to a denuded surface of the shaft of the ulna with a sterilized ivory or bone nail after the resection has been completed. The forearm is immobilized in a semi- flexed position until bone union between the ulna and olecranon process has taken place, which usually requires about six weeks. After this time passive motion and massage should be made to increase the mobility of the joint. .A straight, single incision upon the dorsal side is best adapted for resection of the wrist-joint, as the extensor tendons of the hand and fingers can be drawn aside sufficiently to afford ample room for the removal of the entire carpus. In the after-treatment of excision of the wrist the forearm and hand as far as the metacarpo-phalangeal joints are encased in a plaster-of-Paris splint, with the hand in a slightly- extended position. Immediate fixation of the resected ends by means of bone or ivory nails, after excision of the knee, is superfluous, as the parts can be kept in accurate position by ordinary fixation dressing. In knee-joint resections the section through the bones must be made in such a manner that when the sawn surfaces are brought in apposition the leg will be slightly flexed, as this position enables the patient to walk more gracefully than with a straight, stiff limb. The artificial support must not be removed until firm bony union has taken place, which will require from two to three months, according to patient's general health and age. 7. Amputation.—Amputation must be reserved for cases presenting special indications. It is the only operation that promises any benefit if the patient suffer from tuberculosis of other organs, provided the general conditions furnish no positive indications. It is also indicated if a tubercular abscess has perforated the capsule of a joint and has extensively infiltrated the surrounding tissues. This condition is to be expected if the limb has become oedematous some distance from the joint. The flaps must be taken from the side of the limb where the skin is in the best condition, and the incision through the deeper tissues must be made through healthy tissue. It is astonishing how rapidly wounds heal, and how quickly patients will recover after amputations for exten- sive local tubercular processes, even in patients greatly emaciated by the disease. CHAPTER XXI. Tuberculosis of Tendon-Sheaths, etc tubercular tendo-vaginitis. Tuberculosis of the tendon-sheaths, or, as Hueter termed this affec- tion, tendo-vaginitis granulosa, has only been recently recognized and described as a primary local tuberculosis. Pathology.—Hueter was of the opinion that this affection is seldom met with as a primary lesion, but that it appears usually as a complica- tion of joint tuberculosis. As a secondary lesion it is a frequent con- comitant of osteal and synovial tuberculosis by direct extension of the inflammation from the primary focus to tendon-sheaths. Volkmann gave an able and accurate description of tendon-sheath tuberculosis in 1875, but at that time he was not aware of its tubercular nature. The first scientific treatise on this affection came from the clinic at Gdttingen by Riedel, who showed that the rice-bodies so commonly found in the so- called fibrinous hydrops of the tendon-sheaths, or hygroma of the flexor tendons of the hand, alwa37s indicated a synovial tuberculosis. Another important paper on the same subject was published by Beger, who re- ports 4 cases that occurred in the clinic at Leipzig. The chronic tendo- vaginitis, or compound ganglia of the old authors, has been shown to be, on careful clinical observation, microscopic examination, and bacterio- logical research, cases of local tuberculosis. The extension of tubercular processes along tendon-sheaths from a tubercular joint after perforation of the capsule has, for a long time, been known to occur, but as a primary lesion it has onby recently been added to the long list of surgical lesions of a tubercular character. As compared with other tubercular affections, primary tendon-sheath tuberculosis is quite rare, as it consti- tutes only 1 or 2 per cent, of the cases in the statistics of local tubercu- lar lesions. When this affection occurs primarily and independently of tuberculosis of an adjacent bone or joint, infection with the bacillus of tuberculosis takes place by localization of floating microbes in some small vessel, and subsequently the pathological processes in the tendon- sheaths resemble those of tubercular joints. In some cases the products of the disease are massive granulations that occupy the inner surface of the tendon-sheaths; in others the granulations are less abundant, but (525) 526 PRINCIPLES OF SURGERY. a copious synovial exudation is thrown out; while in a third class the granulations form hard, white masses, the so-called corpora oryzoidea, which either remain attached to the inner surface of the sheath, or, after their separation, are found as loose bodies. In the form of tendo- vaginitis which corresponds with the fungous variety of tubercular synovitis, the granulations form a layer of from 1 to 4 lines in thickness upon the inner surface of the sheath. The tendon itself is covered with a somewhat thinner layer of granulation tissue, the granulations pene- trating the substance of the tendon between the bundles of connective- tissue fibres, where, by absorption and pressure atrophy, they cause extensive destruction of tissue. In this manner the tendon becomes so much weakened that it ruptures on the slightest traction, or, if the dis- ease has progressed still farther, the loss of continuity becomes complete without a trauma. The intrinsic tendency of the disease consists in progressive extension by continuity of structure along the course of the tendon primarily affected, and when this tendon is part of a compound tendon the disease gradually creeps from tendon to tendon until all the sheaths are involved. As this affection is met with most frequently in the tendon-sheaths surrounding the carpus, and as these sheaths are not infrequently in direct communication with the wrist-joint by means of small synovial sacs, it extends to the joint by continuity of surface. When no such direct connection exists between the tendon-sheath and the subjacent joint, the joint may become secondarily involved after the granulations have perforated the capsule. Next to the region of the wrist-joint the tendo Achillis, the patellar, and other tendons about the knee-joint are most frequently affected. In tuberculosis of the sheaths of the tendons of the deep flexors of the fingers the swelling is often large, extending from the lower portion of the palm of the hand under- neath the annular ligament to the middle of the forearm. Underneath the annular ligament the swelling is constricted by this structure, which gives rise to considerable bulging in the palm of the hand and over the lower anterior aspect of the forearm. The fluctuating wave can be dis- tinctly felt above and below the annular ligament, showing that the two swellings are in direct communication. The tubercular product under- goes the same pathological regressive changes as in S3rnovial tuberculosis. If a sufficient number of tubercle bacilli is present in the granulation tissue the cells are destro3red by coagulation necrosis and caseation, the fungous masses breaking down into an amorphous, granular detritus. At this stage perforation of the tendon-sheath may take place in an out- ward direction, and a subcutaneous tubercular abscess develops. If such abscess open spontaneously, or is incised without regard to antiseptic precautions, infection with pus-microbes will lead to acute suppurative TUBERCULAR TENDO-VAGINITIS. 527 inflammation, which will often result disastrously from rapid extension of the phlegmonous inflammation and septic infection. The occurrence of rice-bodies in tendon-sheath and synovial tuberculosis can be traced to a specific action of the bacillus of tuberculosis on the tissues. Kdnig attributes to this bacillus properties which place it among the agents that produce fibrinous inflammation. The rice-bodies in the tendon- sheaths, the seat of a chronic inflammation, he considers as the product of a fibrinous inflammation caused by the action of the bacillus of tuber- culosis. Nicaise, Poulet, and Villard examined 4 cases of hygroma con- taining rice-bodies, and found in all of them the bacillus of tuberculosis. Symptoms and Diagnosis.—Tuberculosis of the tendon-sheaths is an exceedingly chronic affection. The disease is not painful, and patients often continue to follow their occupation after a number of tendons have become involved and the swelling has reached considerable dimensions. The swelling increases in length in the direction of the tendon first affected, and if the disease extend to neighboring sheaths it branches out in the direction of the tendons affected. In 9 out of 10 cases it attacks a flexor or extensor tendon in the region of the wrist-joint, and then extends upward and downward in the direction of the tendons. In tubercular hydrops of the tendon-sheaths the swelling often attains great size. In one such case I found the palm of the hand the seat of a swelling, the size of a large orange, that communicated with a smaller swelling above the annular ligament of the wrist-joint. In the fungous variety the swelling imparts to the palpating finger a semi-elastic resist- ance, and fluctuation is either entirely absent or not well marked. The disease often extends to the middle of the forearm, and in this locality attacks the muscular tissue in the same manner as the tendons farther below. Extension to a joint is attended by symptoms that point to synovial tuberculosis. The symptoms are so characteristic that a correct diagnosis can often be made on first sight. The only affections that must be excluded are the ordinary ganglion of tendon-sheaths and acute plastic tendo-vaginitis. A ganglion always remains as a circumscribed swelling without manifesting any tendencies to extend. The contents of a ganglion are a gelatinous mass, of the color and consistence of clarified honey. After evacuation of the sac no swelling remains, as the cyst-wall is not much thickened. A plastic tendo-vaginitis, resulting from injury or overexertion, is an acute affection not attended by much effusion or inflammatory exudation. The tendon-sheath is abnormally dry, giving rise to friction-sounds which can be plainly felt and often heard as the tendon moves within the inflamed and roughened sheath. Prognosis.—Spontaneous cure is the exception, progressive exten- sion the rule. The danger from regional extension arises from the 528 PRINCIPLES OF SURGERY. tendencies of the disease to invade adjacent joints, and to extend from tendon to tendon, and finally along these to the respective muscles. There is no reason why, occasionally at least, tendon-sheath tuberculosis should not be followed by pulmonary or general tuberculosis in conse- quence of secondary infection. Treatment.—The use of external applications, compression and aspiration, are of doubtful utility in the treatment of this affection. Sub- cutaneous evacuation, followed by iodoformization, promises more, especially in cases of tubercular hydrops with few or no rice-bodies. As the rice-bodies contain the essential cause of the disease, it will usually be found necessary to remove them in order to effect a permanent cure. Removal of these bodies, as well as extirpation of the granulation tissue, can only be accomplished by a radical operation. A radical operation has for its object the removal of all of the infected tissues, which means extirpation of the tendon-sheath and erasion of the granulations that have invaded the tendon. No operation should be undertaken unless the surgeon can count with almost positive certainty upon aseptic healing of the wound. Infection with pus-microbes under such circumstances would not only prevent a satisfactory functional result, but would place the patient's life in great peril. Fortunately, this form of surgical tuber- culosis attacks localities where the surgeon has it in his power to obtain, almost with absolute certainty, an aseptic healing of the wound. Extir- pation of a tubercular tendon-sheath is a tedious and difficult task. The operation must be made with the nicety of a dissection in the anatomical room. A large tenotomy knife and a small pair of curved scissors are the most useful cutting instruments in making the dissection. A number of small tenacula and toothed dissecting forceps are necessary to retract tendons and expose the parts fully to view. Esmarch's constrictor is an indispensable aid, as it renders the parts perfectly bloodless, which enables the operator to identify the parts concerned in the dissection. After the antiseptic precautions have been completed with the greatest care, the limb is rendered bloodless and the tendon-sheath is fully exposed by free external incision, which should reach on both sides a little beyond the visible limits of the disease. The tendon-sheath is now slit open, and the fluid contents are washed awa37 by an antiseptic irrigation. In operating upon the flexor tendons of the hand and fingers, it often becomes necessary to divide the annular ligament, which can be done without fear of impairing the functional result, as, after the opera- tion on the tendon has been completed, its continuity can be restored by a number of separate buried sutures. The large arteries and nerves are, of course, carefully avoided. In order to remove the tendon-sheath TUBERCULAR TENDO-VAGINITIS. 529 completely, it becomes necessary to liberate the tendon and to have it drawn out of the way by an assistant. The removal of the deep portion of the sheath requires special care, as it often is in close proximity to the underlying joint, which should not be opened unless the disease has invaded the capsule deeply. The extension of the disease to the mus- cular tissue can be readily ascertained from the naked-eye appearances of the muscle, which, if affected, presents a grayish appearance, and is firmer than in a normal condition. If the tendon is extensively infil- trated its size is often much diminished by the removal of the infected portion, which must be clone with a sharp tenotomy knife. If several tendons are affected, and access to the more remote ones is rendered im- possible without division of the more superficial tendons, these can be divided and again united after the dissection has been completed. I have repeatedby spent two hours in an operation for tendon tuberculosis in the wrist-joint region, and have always felt that the time was well spent, as a hasty operation is often attended by unnecessaiy injury to contiguous parts, and is frequently followed by local recurrence on account of incomplete removal of the infected tissue. Should it become necessaiy to resect a portion of a tendon on account of extensive disease of this structure, restoration of continuity must be effected by an auto- plastic operation. The tendon-end most suitable for this purpose is selected. The tendon is cut through one-half at a distance from its cut end which corresponds with the length of the defect, when it is split toward the cut end to within a few lines, and the piece is then laid over the defect and sutured at both ends. After the removal of the infected tissues the wound is irrigated once more with an antiseptic solution, dried, and iodoformized. The deep fascia is united separateby with buried sutures, and the skin is coaptated accurateby with interrupted stitches and the continued suture. A catgut capillary drain is inserted and a copious antiseptic dressing applied. The limb is placed upon a well- padded splint, and, if no indications for a change of dressing arise, the first dressing is allowed to remain from two to three weeks, when the wound will be found healed throughout. The functional result is almost always satisfactory if the wound heals by primaiy union. Massage and passive motion are instituted as soon as the wound is healed. If the operation is done early and with the necessary care, a local recurrence is not to be expected. For the purpose of illustrating the pathological conditions and the clinical tendencies of this disease, I will briefly describe one of the many cases of tendon-sheath tuberculosis that have come under my observation. This case is remarkable on account of the rapid extension of the disease. The patient was a man 60 years of age, laborer, and addicted to intemperate habits. I examined him. in consul- 34 530 PRINCIPLES OF SURGERY. tation with his family physician, about four months before the operation was performed. At that time I found an oblong swelling on the dorsum of the right hand, corresponding to the location of the extensor tendon of the index finger. The swelling was not painful, and but little tender on pressure. Fluctuation was well marked ; on deep pressure movable bodies could be distinctly felt, which were recognized as corpora ory- zoidea. An operation was advised, but was declined, as the patient was still able to follow his occupation. The swelling was first noticed six weeks before the examination, but steadily increased in size. Four months later he was admitted into the Milwaukee Hospital, as the pain and the size of the swelling now disabled him from performing manual labor. At this time the dorsum of the hand corresponding to the index and middle fingers and the radial aspect of the forearm as far as the middle presented a continuous swelling, with well-marked fluctuation. The swelling had lately become painful, and was tender on pressure. Under strict antiseptic precautions the swelling was incised in its entire length, and a large quantity of S37novia-like fluid and softened rice-bodies escaped. The sheaths of the extensor communis digitorum and exten- sors of the wrist were found lined with a thick layer of fungous granu- lations, and near the annular ligament numerous free and attached rice- bodies were found. The tendon-sheaths were carefully dissected out, and the whole wound, after thorough disinfection, was dusted with iodo- form, drained, and sutured. A copious dressing of iodoform gauze and sublimated moss was applied, and the forearm and hand fixed upon an anterior splint. Healing of the wound by primaiy intention. Almost complete restoration of function. No return after two years, and patient able to perform hard manual labor. Inoculations of the fluid upon potato remained sterile. Cultivation upon coagulated hydrocele-serum showed, after a few weeks, a scanty culture of the bacillus of tubercu- losis. Implantation of one of the rice-bodies into the subcutaneous connective tissue of a guinea-pig resulted in a typical tuberculosis, starting from the point of inoculation, spreading to adjacent lymphatic glands, and finally resulting, in six weeks, in death from diffuse miliary tuberculosis. FASCIA TUBERCULOSIS. The bacillus of tuberculosis has a special predilection for fascia, and primaiy localization in this tissue is a frequent occurrence. It is a well- known clinical fact that, as soon as a deep tubercular focus in a lymphatic gland, bones, or joints has reached the connective tissue outside of the organ primarily affected, the infection travels along the connective tissue, often resulting in extensive destruction of this tissue before the process reaches the surface. The extension of tubercular abscesses along FASCIA TUBERCULOSIS. 531 preformed connective-tissue spaces has been previously described. If the tubercular product, when it reaches the loose connective tissue, is composed of living embryonal tissue, the pathological lesions which are later produced in the connective tissue correspond with those of the primary lesion. The connective tissue is transformed into masses of granulation tissue, which remains in this state for along time before it is destroyed by coagulation necrosis, with subsequent cell disintegration. In primary tuberculosis of the fascia the disease often spreads with great rapidity, dipping down between the muscles along the intermuscular septa, and invading from here the muscles themselves. I have seen a number of cases during the last few years where the disease originated primarily in the deep fascia of the thigh, resulting in the most extensive regional dissemination in the course of two or tlwee years. In one case a veteran of the late war, 55 years of age, the disease commenced at a point between the greater trochanter and the crest of the ileum several years before he came under my observation. I found the thigh moder- ately swollen with several prominences from the crest of the ileum to the knee-joint, where fluctuation was quite distinct. I mistrusted a primary osteo-tuberculosis, but, on making free incisions at different points, I found no evidences of primary tuberculosis of any other tissue or organ. The deep fascia and intermuscular septa were found destroyed, and in their place masses of granulation tissue presenting foci of coagu- lation necrosis and caseation invading extensively the muscular tissue. Volkmann's spoon was freely used, but I soon found that this treatment was utterly inadequate to remove all of the infected tissue, as the deep muscles throughout were extensively infiltrated. Amputation was out of the question, as the gluteal region as far as the crest of the ileum w7as so extensively affected that it would have been impossible to obtain a covering for a hip-joint amputation. Iodoformization of the enormous spaces made by scraping out the fungous granulations had no effect in arresting further extension of the disease. The patient died, three months later, of general miliary tuberculosis. In a second somewhat parallel case the disease extended from near the knee-joint as far as the trochanter minor. This patient was only 25 years of age, and the disease had existed a 37ear and a half. Several incisions had been made, and a number of fistulous openings were found in communication with large cavities between the deep muscles of the thigh. The sinuses were laid open and scraped, and the most careful examination failed in disclosing a primary osteal or tendon-sheath tuber- culosis. The muscles were again found extensively infiltrated and of a grayish-white color, and almost of gristly hardness on being incised. The operation rather hastened than retarded the progress of the disease, 532 PRINCIPLES OF SURGERY. and I was forced, a few weeks later, to amputate the thigh just below the trochanters. The patient made a slow recoveiy, but at the present time. two years after the operation, he is in fair health, and there is nothing to point to a local recurrence. I have learned to regard fascia tuberculosis affecting the intermuscular septa of the thigh as an exceedingly grave form of local tuberculosis, and, if at all extensive, only amenable to successful treatment by amputation. TUBERCULOSIS OF MOUTH AND TONGUE. We have now every reason to believe that many cases of ulceration of the tongue, pharynx, and cavity of the mouth, which have been here- tofore diagnosticated and treated as carcinoma, were not carcinoma, but syphilis or tuberculosis. Professor von Esmarch, in a very able paper, has recently again called attention to the difficulties in the way in differ- entiating between these affections. Pathology.—There is no doubt that many reported cases of perma- nent recovery, after removal by operation of ulcerating swellings of the tongue, were not cases of carcinoma, but tuberculosis. Lupus of the pharynx and tongue are cases of local tuberculosis. Only a few weeks ago I had an opportunity to examine a case of primary tuberculosis of the pharynx occurring in a man 30 37ears of age. The disease had ex- isted for four months, and involved the posterior wall of the pharynx, and had extended to the left tonsil. Ragged, deep ulcers had formed, which were covered with flabby, yellowish-gra37 granulations. Numerous minute miliary nodules could be seen in the mucous membrane around the ulcers, and on scraping away the granulations they were also found present in the softened, inflamed tissues underneath the floor of the ulcers. A beginning hoarseness indicated that the disease was extend- ing by continuity of tissue to the laiynx. Laryngoscopy examination revealed numerous minute nodules, which studded the mucous membrane of the posterior surface of the epiglottis. The recent advances made in the microscopical, bacteriological, and experimental methods of exami- nation have succeeded in separating from syphilitic affections and malignant disease of the mouth and tongue many cases that belong to the long list of affections now classified under the head of surgical tuberculosis. The cavity of the mouth is often the seat of slight abra- sions and pathological conditions, which may become an infection-atrium for the entrance of micro-organisms that might be contained in the air we breathe, the food we eat, and the water we drink. Remembering the frequency with which superficial abrasions and ulcerations occur in this locality, it is not strange that primary tuberculosis should occasionally develop here. The tubercle bacillus produces the same tissue changes TUBERCULOSIS OF MOUTH AND TONGUE. 533 here as on the surface of the skin, the primary pathological product con- sisting of granulation tissue undergoing molecular retrograde tissue metamorphosis, followed by ulceration. Ulceration is an earlier occur- rence, and a more conspicuous clinical feature in tuberculosis of the mouth than in some other localities, as the new tissue is constantly macerated by the fluids with which it is moistened at all times. The tubercular ulcer is generally covered by the products of interstitial necrobiosis and superficial coagulation necrosis, which result in the formation of what appears as a false membrane. If this membrane, when present, is removed, the characteristic granulation surface is exposed. The ulcer is surrounded by a zone of inflammatory infiltra- tion, which, however, does not present the same feeling of hardness as carcinoma. The most characteristic feature of a tubercular ulcer of the mouth or tongue consists in the presence of minute tubercle-nodules in the margins and underneath the layer of granulations, and, if the infec- tion has extended to some distance, in the surrounding mucous mem- brane. Schliferowitsch has published an exhaustive resume of the literature on this subject to date, and has collected all the recorded cases in which the diagnosis of tubercular disease of the cavity of the mouth could be made with some degree of certainty. The cases number 88, and included those of primaiy and secondar37 tuberculosis. From a care- ful study of this affection he has come to the conclusion that it occurs seldom in the veiy young, and that it attacks most frequentby persons between 40 and 50 3rears of age. Symptoms and Diagnosis.—Tuberculosis of the mucous membrane of the cavity of the mouth appears as a flattened, submucous infiltration composed of granulation tissue, which, at an earl37 date, becomes the seat of a superficial ulceration in the centre that rapidl37 extends toward the margins of the swelling. Caseation is seldom observed. The cells are destined by coagulation necrosis, and as they become detached the defect increases in size. The appearance of the ulcer in this locality is characteristic. If on the tongue, it is found on the borders near the tip of the organ. It appears as an oblong ulcer, w7ith raised, ragged borders of firmer consistence, showing the color of fresh granulations. The ulcer often appears as if covered by a pseudo-membrane; if this cover- ing is removed, the surface left easily bleeds. The surface of the ulcer is uneven, as if covered with h37pertrophic papillae. The discharge of pus is slight, and, in many cases, miliary nodules may be found around the ulcer. Pain is not as severe as in carcinoma. L37mphatic glands may become secondarily infected, but this is not often the case. In the primary form of the disease, when a positive diagnosis is most difficult, the presence of tubercle bacilli will demonstrate the nature of the ulcer. 534 PRINCIPLES OF SURGERY. A gumma of the tongue, as a rule, develops into a larger swelling than a tubercular affection before ulceration takes place, and the resulting ulcer is more deeply excavated; at the same time, other evidences of syphilis can usually be detected. Miliary nodules in the immediate vicinity of the ulcer are absent in a syphilitic ulcer, and frequently present in tuberculosis. If any doubt remain as to the differential diag- nosis between these two affections, this should be set aside l)3r a course of antisyphilitic treatment before resorting to any serious operation. If the ulcer is syphilitic it will heal kindly under such treatment, while no improvement will be noticeable if it is tubercular. Epithelioma com- mences as a superficial infiltration and penetrates the tissues from with- out inward. Induration around and underneath the ulcer is more marked in an ulcerating epithelioma than in a tubercular ulcer. Glandu- lar infection takes place early, and is almost a constant occurrence in epithelioma, but is seldom observed in the course of a tubercular ulcer. A simple ulcer of the tongue caused by the mechanical irritation from a sharp projection of a carious or displaced tooth can be readily recog- nized by the location and character of the ulcer. Such an ulcer may become the seat of a tubercular ulcer or the starting-point of an epithelioma. Treatment.—The local treatment of a tubercular ulcer of the mouth or tongue is the same as when a similar ulcer is located upon the surface of the bod3r. If the lesion is circumscribed sufficiently that the wound, after complete excision, can be closed by suturing, this method of treat- ment should be adopted, as it is certainly the most radical, and results most speedily in complete recoveiy. If the extent of the disease render this treatment inapplicable, the diseased tissues should be removed as thoroughly as possible by a vigorous use of the sharp spoon, or b3r destroying it with the actual cautery, or both of these measures may be combined. The use of superficial caustics- has a tendency rather to aggravate the disease than to cure it. With a sharp spoon all of the soft tissues are scraped away, the healthy tissue being recognized by its greater firmness and resistance to the spoon. After bleeding has ceased, the surface is cauterized with the flat point of a Paquelin cautery, and, if the disease has dipped in farther at certain points, these are attacked by making ignipuncture with the needle-point. The cavity of the mouth during the after-treatment, must be kept as nearly as possible in an aseptic condition by dusting the surface daily with iodoform, and b3' the frequent use of a mild, antiseptic mouth-wash, such as a saturated solu- tion of acetate of aluminum or boric acid. If all the infected tissues have been destroyed, healing takes place rapidly by granulation, cicatrization, and epidermization after separation of the eschar. If any of the infected TUBERCULOSIS OF MUCOUS MEMBRANE OF INTESTINES. 535 tissues have remained, the process of healing is retarded or completely arrested; in the latter event, a repetition of the same local treatment will become necessary. TUBERCULOSIS OF THE MUCOUS MEMBRANE OF THE INTESTINES. Primary tuberculosis of the intestinal mucous membrane is a com- paratively frequent affection, but becomes a surgical lesion only in case it leads to intestinal obstruction or perforation. If, as is sometimes the case, the infection is limited to a single focus, a timeby operation not only relieves the symptoms which made surgical treatment a necessity, but it may result in a permanent cure. The tubercular lesions of the intestinal mucous membrane that occasionally indicate treatment b37 laparotomy are usually found in the lower portion of the ileum, the ileo-caecal region, caecum, or ascending colon. Tubercular inflammation of the large intestine ma37 cause so much swelling as to give rise to intestinal obstruction. When the inflammatory process is limited to a small portion of the bowel, operative removal of the affected segment is justifiable, and holds out a fair prospect of permanent relief. Schier reports a successful case of this kind. At the close of October, 1887, he was consulted b37 a man who had a painful swelling in the right lypochondrium; the swelling was as large as a man's fist, with a nodular surface. Considerable pain, tenderness, emaciation, and evidences of intestinal obstruction, which were gradually increasing in integrity. A tumor of the caecum was diagnosticated, and laparotomy was performed November 1st of the same 37ear. The abdomen wras opened by a lateral incision. The omentum near the swelling was much inflamed and covered with whitishyellow nodules, from the size of a pin to that of a pea. Twelve to sixteen enlarged glands, some as large as a walnut, situated along the vertebral column, were enucleated or removed with a sharp spoon. The caecum was so fragile that it ruptured during the manipulations and some faeces escaped. The bowel above and below the swelling, which involved the caecum, was emptied by expression, tied with rubber bands, and the affected portion excised. The part of the caecum containing the valve and the vermiform appendix was left. Circular suturing by a double row of sutures. The subsequent history of the case was favorable in every respect. Pain was severe for two days, and yielded to large doses of opium. Eighteen months after the operation the patient remained in good health. Examination of the part removed showed that the swelling was of a tubercular nature, the sub- mucosa and external layers of the bowel being mainly involved. Durante reported a somewhat similar case. The patient was a woman, aged 56, who, for four or five years, had suffered from obscure 536 PRINCIPLES OF SURGERY. pain in the right iliac fossa when at stool. The pain increased in intensity and became parox3rsmal, and the patient almost starved her- self with the object of avoiding the torture of defecation. On examina- tion a tumor was found in the right iliac fossa, extending downward toward the upper outlet of the pelvis. Carcinoma of the caecum or neighboring parts was suspected. The abdomen was opened. The swelling, as large as a lemon, was found adherent to the iliac fossa, the parietal peritoneum and coils of the small intestine being matted to it so firmly that the lower end of the latter, measuring 25 centimetres in length, together with the caecum and a portion of the ascending colon, were removed with it. The two ends of the divided intestine wrere brought together by three rows of sutures. The abdominal wound was closed, and the patient made a rapid and permanent recoverj\ The swelling, which had almost completely blocked up the lumen of the intestine, was found to be of a tubercular nature. If, in cases of intes- tinal tuberculosis indicating laparotomy, it should be found, after opening the abdomen, that the foci in the ileo-caecal region are too numerous to warrant a radical operation by enterectomy, the symptoms can be relieved and the inflamed parts excluded from the faecal circulation by establishing an anastomosis between the intestine above and below the affected segment by means of decalcified, perforated bone-plates. TUBERCULOSIS OF THE MAMMARY GLAND. A number of well-authenticated cases of primary tuberculosis of the mammary gland have recently been reported. So far as the infection is concerned, the breast must be considered as an appendage of the skin. The bacillus from without may effect entrance into the gland through the milk-ducts,in wdiieh case the inflammatory process commences in the parenchyma of the gland ; or it may enter through a fissure of the nipple, in which case the process is primarily interstitial. When direct infection from without can be excluded, the disease is the result of auto-infection, and on this account the prognosis is always more unfavorable. Regional dissemination takes place along the chain of axillary lymphatic glands. Orthmann examined the enlarged lymphatic glands in a case of primary tuberculosis of the mamma, and found numerous tubercle bacilli. The disease is differentiated from carcinoma by the absence of pain and hardness in the swelling, and from an ordinary suppurative mastitis by the absence of the prominent symptoms of acute inflammation. It might be mistaken for a lacteal cyst or an echinococcus-cyst, but all doubt as to the nature of the swelling can be set aside by an exploratory puncture. Treatment.—The more expectant plans of treatment recommended TUBERCULOSIS OF THE GENITO-URINARY ORGANS. 537 in the management of tubercular abscesses communicating with the primary foci in tissues and organs deeply situated should not be fol- lowed in the treatment of tubercular affections of the breast, as in these cases a radical operation is not attended by any danger to life, and usually results in a permanent cure. The plan to be pursued depends on the extent and location of the disease. A superficial limited tubercular focus of the mamma can be successful^7 treated by excising the infected tissues. If the process is more deeply located, it ma37 become necessa^ to remove a portion of the mammary gland with it. Partial excision of the gland should be done in such a manner as to include the tubercular focus in a wedge-shaped section of the gland, the base of the wedge being directed toward the periphery of the gland. After excision the cut surfaces of the gland are uuited with buried catgut sutures. If the disease has infiltrated the gland extensiveby, or if a number of sinuses have formed, it becomes necessary to extirpate the entire gland. Enlarged glands are removed in the same thorough manner as in operating for carcinoma of the breast. TUBERCULOSIS OF THE GENITO-URIXARY ORGANS. It is only within the last few years that a number of chronic inflam- matory processes of the genito-urinaiy organs in both sexes have been shown to be tubercular in their origin, clinical tendencies, and final ter- mination. The susceptibility of the mucous membrane of the genito- urinary tract to tubercular infection has been demonstrated experimental^7 by Cornet. In rubbing a pure culture of tubercle bacilli in superficial abrasions of the penis in dogs, he produced a tubercular lesion of that organ. In bitches, tuberculosis of the vagina and uterus could be pro- duced b37 injection of a pure culture into the vagina. The local lesions were followed by general tuberculosis. (a) Tuberculosis of Vulva, Vagina, and Uterus.—Direct tubercular infection of the genital tract in women has been observed, but the cases so far reported are few. Barbier believes that a woman can be infected b37 a tuberculous man during coitus, as bacilli have been demonstrated in the semen of tuberculous patients, as well as in the discharge attending tubercular epididymitis. The uterus maybe infected by extension from a tubercular lesion of the vulva without any intermediate trace of infection in the vagina. The author even admits the possibility that tubercular infection may be transmitted by the finger of the attendant, by infected instruments, or even through the medium of the air. Zweig- baum reports a case of primary tuberculosis of the portio vaginalis uteri, which, at the time of examination, appeared in the shape of an ulcer the size of a walnut, with thick, indurated margins and cheesy floor. 538 PRINCIPLES OF SURGERY. Numerous tubercle bacilli were found in the secretion taken from the surface of the ulcer. Evidences of tuberculosis were apparent at this time. After a few weeks the ulcer extended toward the left vaginal wall and left labia majora. A section of a fragment of tissue removed from these parts, on staining, showed numerous bacilli. This form of tuber- culosis is not frequent, as the author could find only 2 cases of vulvo- tuberculosis in literature, although genital tuberculosis is quite a frequent affection. Jonin believes that tubercular endometritis from local infec- tion is quite a common affection. Of 9 cases which were observed by him it was due to sexual contact with men suffering from genital tuber- culosis. In 2 others the husbands were tuberculous, but had no genital tuberculosis. He calls attention to the fact that Cornil and Chantemesse have produced this disease artificially in rabbits by injecting bacilli into the vagina. The cases of primary tuberculosis of the vulva, vagina, and uterus will undoubtedly become more numerous in the literature of the near future, when improved methods of examination will enable the surgeon to make a positive diagnosis between these affections and carci- noma and syphilitic lesions. The same points in differential diagnosis are to be remembered in this connection as have been enumerated in the consideration of tubercular affections of the mouth. Treatment.—Primary tuberculosis of the utero-vaginal canal and vulva should be treated b37 curetting, and, if the extent of the lesions make it necessaiy, by cauterization with the actual cautery. Before either of these procedures are put into practice, the parts must be ren- dered aseptic by antiseptic irrigation. Subsequent infection can be guarded against by the free use of iodoform, and tamponade of the vagina with iodoform gauze. Under ordinary circumstances, it is not necessary to remove the tampon oftener than once a w7eek, when the surface is again freely dusted with iodoform before a new tampon is inserted. (b) Tuberculosis of Fallopian Tubes.—In the absence of tubercular lesions of the vagina and uterus, it is doubtful if infection of the Fallopian tubes can take place by the entrance of the bacillus through the genital tract, and the relatively frequent occurrence of the disease in that part of the genital tract is only explainable by attributing it to auto-infection, in the same way as we have explained the occurrence, for instance, of primary tuberculosis of joints, bone, and peritoneum. We can safely assert that tubercular infection of the Fallopian tubes often, if not always, takes place upon the basis of pre-existing pathological conditions, taking it for granted that the healthy tubes do not present favorable conditions for the localization of the tubercle bacilli. A catarrhal con- dition of the mucous membrane lining the tubes, as in other organs, TUBERCULOSIS OF THE GENITO-URINARY ORGANS. 539 undoubtedly furnishes, in many instances, the locus minoris resistentiae for the localization of bacilli brought to the part through the circulating blood. An interesting case of primary tuberculosis of the Fallopian tubes has been recorded by Kotschau. The patient was 45 years old, having a good family history ; has suffered for a year with pains in the abdomen, profuse metrorrhagia, and various nervous disturbances. She was treated for retroflexion, and subsequently had an attack of pelveo- peritonitis. Vaginal examination disclosed a firm, smooth, movable swelling, as large as an apple, to the right of the uterus ; this was taken for a malignant ovarian growth, and laparotomy was done for its removal. On opening the abdominal cavity, a quantity of turbid, purulent fluid escaped. The swelling, of oblong shape, was found lying apparently in a bed of pus; on account of its intimate adhesions it could not be removed. The patient died from shock. The autopsy showed the uterus enlarged and retroverted. The right tube was tortuous and gen- erally thickened. Near its distal end it was dilated into a swelling the size of a hen's egg, in the centre of which was a cavity containing cheesy material. Other smaller caseous foci were found in the tubal wall in close proximity to the large swelling. The ovary on the same side was enlarged and transformed into a caseous mass. The left tube and ovary showed similar changes, though less extensive. The microscopic exami- nation of the pathological product confirmed the diagnosis of tubercu- losis. Although the disease appears to have been primary in the tubes, the affection occurs more frequently from the direct extension of a tuber- cular endometritis to the tubes. Lebedeff gives a full description of a case that came under his observation. The patient was the widow of a man who had died of pulmonary tuberculosis. An examination before the operation revealed a firm, nodulated, intra-abdominal tumor in the space of Douglas. An attempt was made to remove the tumor by laparotom3r, but had to be abandoned, as the disease had become too widel37 disseminated. Six weeks later the patient died with symptoms of general tuberculosis. At the post-mortem miliary tuberculosis was found in the peritoneum, lungs, colon, uterus, and Fallopian tubes. The most advanced stages of the disease were found in the uterus and Fallo- pian tubes, showing that the disease had commenced in these organs. Both of the Fallopian tubes were dilated and filled with pus, the epithe- lium in parts being absent. Stained sections from the uterus and tubes showed the presence of numerous bacilli. Symptoms and Diagnosis.—Tubercular salpingitis, occurring as a secondaiy lesion to a primary tuberculosis in the lower portion of the genital tract, can be suspected if, in connection with a cervical or 540 PRINCIPLES OF SURGERY. endometritic tuberculosis, examination reveal a swelling in the region of one or both Fallopian tubes. Primary tubercular disease of the Fallo- pian tubes gives rise to local conditions and S37mptoms that it would be impossible to differentiate from an ordinary pyosalpinx. The existence of a dilated, inflamed Fallopian tube can generally be made out with some degree of certainty by making the examination while the patient is under the influence of an anaesthetic. Werth has described an acute and chronic form of tubercular salpingitis. In the acute variety both the muscular and serous coats undergo caseous degeneration, numerous bacilli being found in the interior of the tube ; while in the chronic form the wall of the tube undergoes thickening and infiltration with new cells, and its contents contain only a few bacilli. The increase in size of the tube is due to the collection of pus in its interior as well as to the thick- ening of the wall. When suppuration takes place in the interior of the tube the tubercular product has become the seat of a secondary infection with pus-microbes ; hence, indications for operative treatment have become more urgent. If the tubercular inflammation extend from the abdominal extremity of the Fallopian tube to the peritoneum, symptoms of tubercular salpingitis are obscured later on by those of tubercular peritonitis. Treatment.—As a tubercular salpingitis calls for the same treatment as a pyosalpinx, it is, for all practical purposes, only necessary to narrow the diagnosis down to either one of those two affections before resorting to treatment by laparotomy. A median incision is preferable to a lateral, as frequently both tubes are affected simultaneously. Salpingectomy should be combined with oophorectomy, as the ovaries are frequently implicated in the tubercular process, and these organs would be of no further use after extirpation of the tubes. As tubercular tubes are usually found firmly adherent to the surrounding tissues, their removal is often attended with the greatest difficulties, and may become an impossible task. If the disease is limited to the tube-structures, and has not in- volved surrounding important organs, it would appear rational, under such circumstances, to lay the tube open, remove its contents, scrape out the infected tissues as far as possible, arrest bleeding by applying the actual cautery, and, after thorough iodoformization, pack with iodo- form gauze. This treatment would certainly appear more rational than to be content with an exploratory incision, and allow the patient to re- main a sufferer until relieved by death from tuberculosis. In one case that came under my treatment, where both tubes were imbedded in a mass of granulation tissue, I was unable to remove the entire mass, was compelled to pursue this course, and the patient recovered quickly and permanently, in spite of a faecal fistula that formed a few days after the operation. TUBERCULOSIS OF GLANS PENIS AND URETHRA. 541 TUBERCULOSIS OF GLANS PENIS AND URETHRA. Kraske has observed a case of tubercular ulceration of the urethra, extending from the membranous portion to the neck of the bladder, in a patient, 33 years of age, who was treated for chancre. The autopsy revealed advanced tuberculosis of the genito-urinary tract and pulmonary tuberculosis. In another case, a man 49 years old, a tubercular ulcera- tion existed on the dorsum of the glans the size of a cent piece. This sore was also mistaken for a primaiy lesion of syphilis. There were no signs of pulmonary tuberculosis. The glans was amputated, when it was observed that the tubercular infiltration extended deeply into the cavernous structure. The lesion could not be traced to genital contact, and under the *nicroscope showed the typical structure of tubercular tissue. In the examination of doubtful lesions of the glans penis, it is well to remember the possibility of tubercular infection in this locality, and, in case the tubercular nature of a lesion can be established on suffi- cient grounds, to resort to cauterization with the actual cauteiy, excision, or amputation, according to the location and extent of the disease. TUBERCULOSIS OF EPIDIDYMIS AND TESTICLE. In the male genital apparatus tuberculosis attacks most frequently the epidid37mis, for the reason that the vessels in this structure are more tortuous and smaller than in the remaining portion of the testicle or the vas deferens, both of which are important elements in determining locali- zation in that part from floating bacilli that reach it through the circu- lating blood. Saltzmann states that these anatomical conditions are im- portant factors in the arrest and localization of floating bacilli. That in cases of tuberculosis of the testicle we are only dealing with an external manifestation of an antecedent infection becomes apparent by the clini- cal observation that not infrequent^7 both testicles are infected, either simultaneous^7 or some time apart, showing that the infection came from the same source. Tuberculosis of the genital organs in the male fur- nishes one of the best examples of the typical clinical course of local tuberculosis. The disease extends by continuity of structure often to a great distance from its starting-point. Nothing is more familiar than the clinical course of a case of tuberculosis of the testicle. A small, hard nodule is first detected in the epididymis, and from this point the whole structure of the epididymis is infected, when the infection slowly, but surely, extends to the testicle; then along the vas deferens to the vesiculae seminalis, the prostate gland, and bladder, and from this viscus along the ureters to the pelvis of the kidney. As a rule, the disease remains limited to the genito-urinary organs, but in some instances metastatic infection takes place, either from the genito-urinary organs or 542 PRINCIPLES OF SURGERY. from the primary source of infection. A gentleman was recently under my care whose case illustrates a number of interesting points descriptive of the clinical behavior of genital tuberculosis. He was 35 years of age ; married for ten years ; the marriage had been childless. He claimed that he never had syphilis or gonorrhoea. Tuberculosis is hereditary in the family. Nine 37ears ago he noticed a small, hard swelling in the epidid37- mis of both testicles. Two years ago symptoms of cystitis appeared, which were not much improved by internal medication and antiseptic irrigation of the bladder. Six months ago his left knee became swollen and painful. Four months later he commenced to suffer severe pain in the region of the left kidney. Temperature varied from 100° to 103° F. A swelling soon formed in the left lumbar region, and four weeks later I evacuated a large quantity of pus through a lumbar incision. Through the incision the kidney could be seen and felt, and, b37 passing the index finger around it, it appeared to be extensively separated from the con- tiguous structures. The left knee presented all the appearances of ad- vanced synovial tuberculosis. No evidences of pulmonary tuberculosis. The disease in both testicles had made no progress for years, and the infiltration appears to be limited to the epididymis. The epididymis on both sides is moderately swollen and indurated. The vas deferens on each side is somewhat larger and firmer than normal. The disease had extended from the epididymis to the pelvis of the kidney on both sides, all of the intervening organs being involved in the tubercular process. The only apparent manifestation of general tuberculosis was presented by the left knee. An interesting feature in this case was the formation of a paranephritic abscess around a pyelo-nephritic kidney, which must be regarded as the result of a secondary infection with pus-microbes. Symptoms and Diagnosis.—Tubercular epididymitis alwa3rs appears as a chronic affection, in this respect differing from gonorrhoeal epididyr- mitis and the ordinary form of acute parenchymatous and suppurative orchitis. Pain and tenderness are either entirely absent or, at least, slight when present. Circumscribed hydrocele may develop as soon as the disease extends to the tunica vaginalis. The tubercular inflamma- tion is characterized by the same pathological conditions as in other organs, new nodules appearing in the neighborhood of the first one, which, by confluence, form masses of considerable size. Caseation is an early and almost constant condition. In many cases the process extends in the direction of the skin ; a tubercular abscess forms in the tunics of the scrotum; the skin presents a bluish-red color, and spontaneous perfo- ration gives rise to evacuation of the abscess. Frequently multiple abscesses form in this manner, and the fistulous openings lead down to caseous masses. In some cases, as the one reported, the disease in the TUBERCULOSIS OF THE VESICUL^ SEMINALIS. 543 epididymis becomes latent, but the infection extends at an early date along the vas deferens, which becomes swollen and indurated, and from which, if a cross-section is made, the characteristic cheesy material can be squeezed. From the vas deferens the disease extends to the vesiculae seminalis, prostate gland, bladder, and finally creeps along the ureters to the pelvis of the kidney, usually simultaneously on both sides. The only disease with which tubercular epididymitis might be confounded is tertiary syphilis, affecting the same part of the testicle. In cases of doubt the patient should be placed on antisyphilitic treatment for a few weeks, which, if the affection is tubercular, will produce no impression on the swelling ; on the other hand, if it is syphilitic, it will rapidly diminish in size. Treatment.—The only radical treatment in tuberculosis of the epi- didymis and testicle is castration. This operation is indicated if the disease is limited to one testicle, and no evidences of tuberculosis can be found in any other organ be37ond the reach of surgical treatment. I have removed both testicles in two cases, but in both patients tubercular cystitis developed one and two years, respective^7, after the operation, and in one of them the immediate cause of death was pulmonary tubercu- losis. My own cases and the experience of other surgeons would tend to dictate a conservative course of treatment if both testicles are affected. After the disease has extended to the organs at the base of the bladder or the bladder itself, castration is, of course, positively contra- indicated. The co-existence of pulmonaiy tuberculosis, or tuberculosis of any of the larger joints, would furnish a sufficient ground against the propriety of castration. Castration is a legitimate operation, and yields fair results if the patient is otherwise in good health and the disease is limited to one side, and has not extended along the cord beyond a point where all of the infected tissues can be removed. The tunica vaginalis should always be removed with the testicle, and, if the scrotum is adherent at any point, the adherent portions of the skin must be excised at the same time. In removing the testicle for tuberculosis, it is always necessary to carry the incision as far as the internal ring, in order to remove as much as possible of the cord. The vessels of the cord should be tied separately, as tying the cord en masse gives rise to unnecessary pain, and the ligature is liable to slip,—an occurrence that might be followed by troublesome haemorrhage. TUBERCULOSIS OF THE VESICULAE SEMINALIS. In 1829 Dahmar described a chronic inflammation of the seminal vesicles, the description of which corresponds closely to that of tubercu- losis. Since then this affection has been described by Albers, Jaye, 544 PRINCIPLES OF SURGERY. Naumann, Humphrey, and Kocher, and lateby it has been studied by Rayer, Cruveilhier, and Reclus as secondary to pulmonary tuberculosis. As a secondary affection this ailment is not only seen in connection with tuberculosis of the lungs, but is more common after primaiy tubercu- losis of the epididymis, either as a continuation of the cheesy degenera- tion in the vas deferens or spreading by contiguity of tissue from the sides of the prostate. Primaiy tuberculosis of these organs is ex- tremely rare, and still less often diagnosed, and up to quite recentby no surgical interference has been attempted. Ullmann now reports a case of primary tuberculosis of the right testicle, with secondary affection of the seminal vesicles on both sides, in a lad 17 37ears of age, where, after removal of the right testicle, he extirpated these organs through a semi-lunar incision in the perineum. The general health of the patient improved after the operation, but a small urinary fistula remained, which formed in consequence of injury to the base of the bladder during the operation. He is of the opinion that the seminal vesicles should be re- moved in primary tuberculosis of the testicle or epididymis, when no suspicious symptoms have appeared on the sound side, and when on the affected side the vesiculae seminalis are alread37 attacked ; also in cases of primary tuberculosis of the seminal vesicles. The impotence following the operation should be no contra-indication, for in all reported cases of tuberculosis of the seminal vesicles impotence alwa37s occurs in a short time ; in fact, it is regarded as a cardinal S37mptom of the disease. TUBERCULOSIS OF THE BLADDER. Tuberculosis occurs either as a primaiy or secondary affection. Several cases of well-marked primaiy tuberculosis of the bladder in the female have come under my observation, where the disease evidently commenced at the neck of the bladder, and, after spreading over the whole internal surface of the viscus, extended along the ureters to the pelves of the kidne3rs, and, finalty, in the course of a few 37ears, proved fatal from tubercular pyelo-nephritis. Prima^7 tubercular cystitis appears to be more frequent in females than in males, undoubtedly because, on ac- count of shortness of the urethra, direct infection is more liable to occur. Striimpell, after a careful study of 4 cases of primary tuberculosis of the bladder in men, came to the conclusion that infection takes place through the urethra. The tubercle bacilli, finding no favorable place for localization and growth in the urethra and bladder, finalty reach the prostate gland or the epididymis, the whole process resembling what occurs in inhalation tuberculosis, in which the disease manifests itself not in the mucous membrane of the bronchial tubes, but in the paren- chyma of the apices of the lungs. TUBERCULOSIS OF THE BLADDER. 545 Symptoms and Diagnosis.—Tuberculosis of the bladder is clinically characterized by symptoms of cystitis, the intensity of the symptoms varying according to the part of the bladder affected, the extent of the disease, and the presence or absence of complications. If the disease primarily involve the neck of the bladder, tenesmus and frequent desire to urinate are the most distressing symptoms. As long as no ulceration of the vesical mucous membrane has taken place, the urine may present a perfectly normal appearance, and, on examination, is found normal in other respects. Very frequently the symptoms become very much aggravated shortty after an examination of the bladder, made upon the supposition that the patient is suffering from stone in the bladder, as the introduction of a sound without the necessar37 antiseptic precautions is often followed by a secondary infection with pus-microbes, which gives rise to an acute suppurative cystitis. The general health of the patient now becomes rapidly undermined, and the extension of the local disease in the direction of the kidneys is hastened. The urine contains large quantities of pus and mucus, and becomes ammoniacal from the presence and action of putrefactive bacteria. The walls of the bladder become greatly thickened from inflammatory exudation and tubercular infiltra- tion ; the organ is unable to empty itself completely, and the decomposed residual urine becomes an additional source of irritation and progressive infection. Incontinence of urine is a frequent symptom in advanced vesical tuberculosis, and is usually an indication that the organ is ex- tensively diseased. In secondaiy tuberculosis of the bladder it is usually not difficult to locate the primary disease, and thus establish a positive diagnosis. The presence of tubercle bacilli in the urine in cases of primaiy tuberculosis of the organ furnishes a positive diagnostic crite- rion between ordinary C3rstitis and vesical tuberculosis. In the absence of ordinary causes of cystitis, such as gonorrhoea, stricture of the ure- thra, enlarged prostate, calculus, and tumors of the bladder, symptoms of cystitis point strongly toward a tubercular origin of the inflammation, and should induce the surgeon to make a most careful examination in reference to the etiology and nature of the cystitis. It is only by ex- cluding the presence of the different lesions of the bladder by a careful and thorough examination of that viscus and its neighboring organs, as well as a chemical, microscopical, and bacteriological examination of the urine, that a positive diagnosis of vesical tuberculosis can be made during the early stages of the disease. Tuberculous urine injected into the peritoneal cavity of a guinea-pig will produce tuberculosis in this animal, and in doubtful cases this diagnostic measure may prove of great value. Prognosis and Treatment.—In secondary tuberculosis of the bladder the regional infection has extended so far that even the most heroic 35 546 PRINCIPLES OF SURGERY. surgical measures will necessarily fail in eliminating the disease, and death from extension of the disease to the kidneys, or from secondary pulmonary or general tuberculosis, will follow as an inevitable result. In primaiy vesical tuberculosis, the disease, at the time a positive diagnosis can be made, has usually invaded so much of the walls of the bladder that a radical operation would necessitate an extensive resection of its walls, after which it would be found impossible to utilize the remaining portion of the organ as a reservoir for the urine. Resection of the wall of the bladder has been done in several instances in the treatment of malignant tumors at its base, but have usually terminated in the formation of a permanent urinary fistula. Dr. R. Harvey Reed, of Mansfield, Ohio, has recently made an in- teresting series of experiments on dogs, with a view to dispense with the bladder altogether in cases of extensive disease of this organ, neces- sitating partial or complete excision. He has shown that the ureters can be successful^7 implanted into the rectum, thus excluding permanently the urinary tract below this point from the urinary passages, and utiliz- ing the rectum as a reservoir for the urine. If the operation of im- plantation of the ureters into the rectum can be perfected to such an extent as to become a feasible and practical procedure in surgery, it may be possible, in the future, that vesical tuberculosis can be successfully dealt with by complete excision of the affected organ. The conservative treatment of vesical tuberculosis by injection of solutions of boric acid, benzoate of soda, the ordinary antiseptic solu- tions, and iodoform has little or no effect, either in affording palliation or in retarding the regional extension of the disease. Internal medicines, such as boric acid, benzoate of soda, uva ursi, buchu, and triticum repens, are of utility in relieving vesical tenesmus, before secondary infection with pus-microbes and putrefactive bacteria has occurred, by rendering the urine alkaline and more copious ; but during the later stages of the disease they are useless even as palliatives. If the tubercular process is limited to the urinary passages below the ureters, incision and drainage of the bladder secure rest to this organ and open up a direct route for the more effectual treatment of the tubercular lesions, and thus not only constitute the most efficient palliative measure, but also the most effective procedure in retarding the local extension of the disease by direct vigorous antitubercular treatment. I had an opportunity to observe the palliative effect of an opening in the bladder, in a case of primary vesical tuberculosis in a female aged 35 years, where the tuber- cular ulceration resulted in the formation of a vesico-vaoinal fistula. The tenesmus was promptly relieved, as soon as the bladder was placed in a condition of rest, by the escape of urine through the fistulous opening. TUBERCULOSIS OF THE BLADDER. 547 In the female the most direct route into the bladder, and affording the most efficient drainage and furnishing the most advantageous con- ditions for the local treatment of the tubercular lesions, is a vaginal cystotomy made near the neck of the bladder. The opening should be at least 1^ inches in length, extending from near the neck of the bladder in an upward direction. Tubular drainage should be dispensed with, as all foreign substances in the bladder not only act as irritants, but interfere with complete drainage. As the opening is made in the most dependent portion of the bladder, free drainage can be secured most efficiently by means which prevent contraction or closure of the vesico-vaginal open- ing. This can be done by suturing the mucous membrane of the bladder to the vaginal mucous membrane, thus establishing a permanent bimu- cous fistula between the bladder and the vagina. Through this opening accessible tubercular lesions can be treated by the use of the sharp spoon and the direct application of iodoform. The parts below this opening- should be protected against the irritating effect of urine by applications of vaselin or lanolin containing one of the milder antiseptic remedies. After the fistulous opening has been established the bladder can be irrigated with antiseptic solutions, or a mixture containing iodoform, through the urethra. In the male the same objects are attained most efficiently by making a suprapubic C37stotomy, as through a perineal incision the direct treat- ment of tubercular lesions is impossible. The fistulous communication should be made complete by suturing the margins of the visceral wound to skin-flaps taken from each side of the external incision,—a method first suggested by Morris, of New York. By lining the margins of the incision with mucous membrane and skin, the loose connective tissue in the pre-vesical space is protected against infection, and the fistulous opening is rendered permanently patent. At the time of operation visible tubercular ulcers are curetted and iodoformized. The bladder can be irrigated subsequently through the urethra or through the fistulous opening. In a case of advanced primary tuberculosis of the bladder where I pursued this method of treatment the operation afforded marked relief, but appeared to have no influence in retarding a fatal termination, as the disease had already extended to the kidneys. The patient lived for nearly two months in comparative comfort, the principal complaint made being the moisture caused by the constant escape of urine through the artificial urethra. A case is described by Battle in which recovery followed curetting through a suprapubic incision, after the failure of less formidable means. The patient was a girl aged 20 years. The operation was performed 548 PRINCIPLES OF SURGERY. July 29, 1889. The patient was discharged September 20th, and April 8, 1890, was in good health and working at her trade. In cases where the disease in the bladder is circumscribed, and the organ is opened early, the treatment might, occasionally at least, result in a permanent cure, if the infected tissues can be completely removed by curetting or destroyed b37 the actual cautery through the incision at the time of operation. In such favorable cases the opening should not be allowed to close until the surgeon can satisfy himself that the ulcers have completely healed, and that no new centres of infection are present. CHAPTER XXII. Actinomycosis Hominis. Actinomycosis is a form of chronic inflammation caused by the presence of actinomyces or ray-fungus. Until quite recently this disease was included among the malignant tumors, and we have reason to believe that, in man37 of the reported cases after operations for sarcoma, the disease for which the operations were done was not sarcoma, but actino- im'cosis. Before degeneration of the inflammatory product has taken place actinomycosis l-esembles a tumor more close^7 than any other inflammatoiy swelling. The swelling is composed largely of granulation tissue, which, on examination under the microscope, presents a histo- logical structure that, in the absence of other evidences, it would be difficult or impossible to differentiate from a round-celled sarcoma. The presence of the specific fungus in the granulation tissue settles the diagnosis. HISTORY OF THE DISEASE. The disease, as occurring in cattle, was first described by Bollinger, in 1877, as a condition in which sarcoma-like tumors were met with, associated with a peculiar growth which, from its structure, was named " Strahlen pilz" (ray-fungus), or actinomyces. James Israel was the first to recognize the disease in man, but it was not generally understood until the appearance of the classical work of Ponfick (" Die Aktino- mykose des Menschen," Berlin) in 1882. Numerous articles on this subject have since appeared in the current medical literature, so that Partsch, in 1888, mentioned in his monograph seventy-five references, with a supplemental list of thirty-three names furnished by Schuchardt. Since the publication of Israel's case numerous cases have been reported by different observers, representing Germany, England, Belgium, Switzer- land, Russia, Austria, France, and America ; so that Partsch in his paper estimates the whole number up to that time at not less than one hundred. While most of the articles in medical journals contain only a descrip- tion of isolated cases, it appears to have been the good fortune of some of the writers on this subject to meet with a number of cases in a com- paratively short time. Thus, Hochenegg reports 7 cases that came under his observation, and Moosbrugger has increased the list of published cases by 10 well-authenticated and carefully recorded cases. (549) 550 PRINCIPLES OF SURGERY. Rotter observed 13 cases in two years. Albert has seen not less than 38 cases of actinomycosis in man within the past few years ; of these 8 have come under his observation during the last two years. These cases have come mostly from Vienna and its vicinity. DESCRIPTION OF FUNGUS. The ray-fungus, or actinomyces, is not, strictly speaking, a microbe, as it is large enough to be seen with the naked eye; but its identity can only7 be ascertained from its characteristic structure, which requires the use of the microscope. Bollinger described as peculiar to this disease certain yellow bodies, visible to the naked eye, always found in the pus of actinomycotic abscesses and in the granulation tissue before suppu- ration had occurred. Microscopically, they were found to consist of threads similar to the ordinary nycelium, which terminated in bulbous ends. The threads radiate from the centre, and their clubbed extremities impart to the fungus the character- istic ra37-like appearance". Sometimes but one of these bulbs is connected with a thread; at other times there may be several. In some specimens one of the rays projects far beyond the others and terminates by several bulbous ends, as is shown in Fig. 99. In man the actinomyces occurs as a small, globular mass, commonly about the size of a millet-seed, usu- ally of a pale-yellow color,but at times white, brown, green, or speckled, the color being influenced by age and the consecutive pathological conditions by which it may be surrounded. In man the clubbed bodies are often absent, and the growth then consists of the radiating filaments alone. The rays, when immersed in water or in a weak solution of chloride of sodium, become enormously swollen and lose their shape ; while they effectually resist the action of acids, ether, and chloroform. Staining.—For staining the actinomyces, Weigert uses Wedl's orseille ; Marchand,eosin ; Dunker and Magnussen, cochineal-red ; Moos- briigger, haematoxylon-alum ; and Partsch, in section-staining, has had the with One of Fig. 99—Ray-Fungus the Rays More Projecting and Branching. (Ponfick.) DESCRIPTION OF FUNGUS. 551 best results with Gram's method. Recently, Babes has made beautiful dry preparations by using a 2-per-cent. solution of safranin in aniline-oil, followed by treatment with iodide of potassium. 0. Israel has found that a solution of orcein in acetic acid stains the rays a Bordeaux-red, while the filaments, if decolorization is not carried too far, present a blue tinge. Baranski uses picro-carmine for staining fresh preparations of actinomyces bo vis. A small amount of the contents of a yellow nodule, or pus from the part, is spread in a thin layer on a cover-glass and dried in the air. The cover is then passed three times through the flame of an alcohol-lamp, care being taken not to overheat the preparation. It is then floated in the picro-carmine solution, or a few drops of the staining fluid are placed on the cover. The whole process of staining is completed in two or three minutes. The cover is then carefully washed by agitating it in distilled water and alcohol, and examined in water and glycerin. The fungus takes a yellow color, while the remaining structure appears red. Cultivation Experiments.—It has been found extremely difficult to cultivate the actinom37ces outside of the bod37, probabty on account of the usual culture media not being well adapted for its growth. The first successful experiments were made in 1886 by Bostrom, of Giessen, upon plates of coagulated blood-serum and agar-agar, the fungus attaining its maturity in five or six days, when it presented the typical structure of actinomycosis as found in man. O. Israel cultivated the fungus success- fully upon coagulated blood-serum. Upon this medium the culture grows very slowly and the fungus often undergoes calcification. Israel made the observation that water, glycerin, blood-serum, and weak saline solutions seriously impair the vitality of the fungus, and he maintained that the effect of these agents on the actinomyces explains the failure of previous culture and inoculation experiments. If evaporation is pre- vented, a thin, velvety layer forms on the surface of the blood-serum in about eight weeks, in the vicinity of which, not before the expiration of fourteen days, cell-nodules appear more in a downward direction than on the sides of the inoculation streak. From the tenth to the fourteenth day numerous spores are produced and a thick wall of club-shaped mycelia in typical centrifugal arrangement. At a meeting of the Medical Society of Berlin, March 5, 1890, M. Wolff made a communication in which he described culture experiments with actinomyces which he made jointly with James Israel. He an- nounced that they had succeeded in cultivating the fungus in and upon coagulated albumen of egg and agar-agar. The material used was taken from a case of retromaxillary actinonycosis immediately after the abscess was incised. With the yellow granules stab and streak inocu- 552 PRINCIPLES OF SURGERY. lations were made, using agar-agar as a soil. It was found that the actinomyces is not a purely anaerobic fungus, as it grew upon the sur- face as well as in the depth of the culture soil. The agar culture appeared first as transparent little drops, which, by confluence, made an opaque, white mass. Under the microscope the culture was seen to be composed of short, thick rods, with an admixture of other elements. The egg cultures, on the other hand, were made up of short, thick rods besides a mass of threads, some of them twisted in the shape of a cork- screw, presenting an intricate net-work of threads. With these cultures successful inoculation experiments were made. Inoculation Experiments.—In 1883, James Israel succeeded in pro- ducing the disease artificially in a rabbit by introducing a fragment of actinomycotic tissue into the peritoneal cavity. Somewhat later, Poli- tick made successful inoculation experiments in calves by implantation of infected granulation tissue under the skin into the abdominal cavity or directly into veins. Rotter experimented on calves, pigs, dogs, guinea-pigs, and rabbits, and in only one instance, a rabbit, did he succeed in reproducing the disease. In this case a piece of granulation tissue the size of a bean was inserted into the peritoneal cavity, and the animal, having manifested no symptoms of disease, was killed six months after the inoculation. On opening the abdominal cavity, about twenty nodules, varying in size from the head of a pin to a hazel-nut, were found distributed over a considerable surface around the graft, each of them showing the typical histological structure of actinomycosis. The transplanted piece of tissue was found perfectly encapsulated in one of the nodules the size of a bean. As the fungus was found in all the nodules, it is only reasonable to conclude that the disease spread from the original focus by migration of some of the new fungi, which, at their respective points of localization, established independent centres of infection and tissue proliferation. While the actinomyces in the new nodules presented a perfect structure, and could be readily stained, the transplanted fungus in the graft had lost its structure, and could no longer be stained. The first successful inoculation experiments with pure cultures were made by Wolff and James Israel. Three rabbits were inoculated by injecting a pure culture into the peritoneal cavity. The post-mortem showed numerous nodules upon the parietal perito- neum, the omentum, and between the intestinal coils. The nodules varied in size from the head of a pin to that of a hazel-nut, and each of them was surrounded by a fibrous capsule. The interior of each nodule was composed of a yellow mass the consistence of tallow. Typical actinomyces were found imbedded in masses of round cells in a state of fatty degeneration. SOURCES OF INFECTION. 553 SOURCES OF INFECTION. As regards the history of the parasite outside the body, as yet only a few facts are known. It is found in pig-meat, and is peculiarly sus- ceptible to outside influences. Virchow found the fungus as a small, calcareous concretion in the muscle-fibres of the pig, and considered their flesh highly dangerous food unless well cooked. As the actino- m3rces found in man and beast resemble each other morphologically and in their effect on the tissues, as well as in their reaction to chemical sub- stances, it is evident that the etiology of the disease is similar in both. The fungus has never been found outside of the bod37. Israel is of the opinion that both man and animals are infected from the same source, such as vegetables or water. Jensen traced an epidemic in Seeland to the eating of rye grown on land recently reclaimed from the sea; and Johne discovered a fungus closely resembling actinomyces in grains of rye stuck in the tonsils of pigs. That the ears of barley or rye are sometimes the carriers of the fungus is well illustrated by the case reported by Soltmann. The patient was a boy who had swallowed an awn of barley. The foreign body lodged in the pharynx, where it gave rise to difficulty in deglutition ; afterward it perforated the pharyngeal wall,—an accident attended by haemorrhage,—and later an actinomycotic phlegmon developed; it spread rapidly, and finally opened below the scapula. Through this opening the foreign body was extracted. Piana examined the tongue of a cow suffering from a circumscribed actinomy- cosis of this organ, in which the disease could be traced to a similar origin,—perforation of the tissues and infection by a sharp beard of an ear of barle37. Actinomycosis has as yet only been found amongst herbivorous and omnivorous animals, including man, and the frequent location of the primary swelling in the mouth seems to indicate that the fungus gains entrance with food. PATHOLOGY AND MORBID ANATOMY. As to the manner in which the fungus exerts its pathogenic action much yet remains to be ascertained. The most striking effect is the transformation of mature connective tissue into embryonal or granula- tion tissue. The fungus possesses no pyogenic properties. It gives rise in the tissues to a low grade of chronic inflammation, and becomes imbedded in the specific product of tissue proliferation,—granulation tissue. The product of inflammation around each fungus consists of granu- lation tissue, which, under the microscope, might be easily mistaken for tubercle or sarcoma tissue. At first the cells are round ; at a later stage of the inflammation epithelioid and giant cells are formed immediately 554 PRINCIPLES OF SURGERY. around the fungus. As the disease is almost always attended by sup- puration at some time during its course, it has been customary to ascribe to the actinomyces pyogenic properties. Israel has always held that the actinomyces is a pus-producing fungus, in opposition to Ponfick and other pathologists, who claim that when suppuration takes place it is the result of a secondary infection with pus-microbes. As cases of actino- mycosis have been recorded in which the disease remained stationary in the granulation stage, for an indefinite period of time, without suppura- tion taking place, and pus-microbes have been cultivated from the pus of actinomycotic abscesses, it appears more than probable that suppura- tion occurred independently of the presence of the fungus, and was pro- duced by the specific action of pus-microbes on the granulation tissue. Firket asserts that the actinomyces does not appear to produce coagula- tion necrosis, but, from a study of the earliest-formed colonies, he finds that the first effect of the fungus is to induce cellular 113'per- plasia. It is as if the tissue ele- ments resented the intrusion of the parasite,which, however, mostby gains the upper hand ; so that the result is the formation of granula- tion tissue and, later, abscesses that characterize the disease. Suppura- tion takes place earliest when the disease occupies a location where secondary infection with pus-mi- crobes is most liable to occur. As a rule, it may be stated that, the earlier suppuration takes place, the more rapid is the spread of the disease and the graver the prognosis; while the absence of suppuration indicates comparative benignity, and points in the direction of a more chronic form of the affection. The localized chronic form of actinomycosis resembles, in its clini- cal features and its anatomical locations, more closely sarcoma than any other affection, and is most frequently mistaken for this form of malignant growth. In such cases it would be difficult, if not im- possible, in the absence of the specific fungus, to make a differential diagnosis between it and round-celled sarcoma, even by a most careful microscopical examination, as the histological structure of both is almost identical. Fig. 100.—Actinomyces. Section from Ac- tinomycotic Swelling. X300. (Fluegge.) CLINICAL VARIETIES. 555 CLINICAL VARIETIES. If infection take place by fully-developed actinomyces, it can only do so by the fungus gaining entrance into the tissues through some loss of continuity in the cutaneous or mucous surface; any other method of ingress is impossible on account of the large size of the fungus. In the cases in which no such primary infection-atrium could be found, it must be taken for granted that the local lesion had healed between the time infection took place and the first manifestations of the disease, or that infection was caused by7 the entrance of spores, which, from their smaller size, could possibby find their way into the tissues through intact mucous surfaces. In reference to the primary localization of the disease, Moosbriigger gives the following statistics : In 29 cases the lower jaw, mouth, and throat were affected; in 9, the upper jaw and cheek; in 1, the tongue; in 2, the region of the oesophagus; in 11, the intestines; in 14, the bronchial tract and the lungs; in 7 the point of entrance could not be ascertained. Infection may take place through aii3' abraded surface brought in contact with the specific cause, and for, clinical purposes the cases may be divided into the following three groups: 1. Cutaneous surface. 2. Alimentary canal. 3. Respiratory tract. I. Cutaneous Surface.—A number of well-authenticated cases of primary actinomycosis of the skin have been placed on record. Partsch describes a case of actinonrycosis developing in the scar left after extir- pation of the breast. The patient was a man aged 60 years. In June, 1884, his left breast was removed for an ulcerating carcinoma. As the wound did not heal by primary union, and the process of cicatrization was very slow, a number of small skin-grafts from a perfectly healthy young man were transplanted. The wound was practically healed in September. Two months later the cicatrix ulcerated and an abscess discharged itself. Actinomyces were found in the pus. The parts were excised, and the progress of the disease was apparently arrested. No explanation could be made as to how the infection occurred. Hochenegg reported a case of primary actinomycosis of the skin in the left submaxillary region. He attributed the disease to an invasion of the fungus through a small atheroma. In Kaposi's case, when the disease was first noticed, it appeared as a red spot, the size of a florin, on the left pectoral muscle, which gradu- ally increased to the size of a walnut and then gradually flattened down and disappeared. Meanwhile, fresh spots and lumps appeared, some as large as a pigeon's egg. Eleven years after the beginning of the disease, a swelling as large as an apple appeared over the spine of the sixth ver- tebra, which gradually extended forward and, a year later, formed a large 556 PRINCIPLES OF SURGERY. tumor behind the right axilla. A year later this swelling had diminished in size to that of a pigeon's egg, and then again increased in size. Ulcera- tion set in, exposing a fungous, bleeding surface. At this time the entire trunk, but not the limbs, was covered with nodules, spots, and stripes. The infiltration was located in the corium. This case is remarkable for the chronicity of the disease, the multiple points of regional infection, and the limitation of secondary infection with pus-microbes to a few isolated nodules. At the meeting of the German Society of Surgeons, in 1889, Leser reported 3 cases of primaiy actinomycosis of the skin that had come under his own observation in the course of a single year. In his remarks on this subject he placed special stress on the manner in which the disease extends. In the periphery of the primary lesion he found numerous minute nodules, later becoming the seat of destructive changes, resembling in this respect the clinical features of tuberculosis of the skin. The extension of the disease in the direction of the deep tissues takes place by the formation of passages corresponding to the size of a lead-pencil; these are filled with 3'ellowish-gray or reddish-gray granulations, which attack and destroy tissues, irrespective of their anatomical structure. The lymphatic glands were always found intact. 2. Alimentary Canal.—The frequency with which the disease affects the mouth and jaws of cattle is explained by the occurrence of numer- ous points of injury caused by masticating rough food, that furnishes the necessary infection-atrium through which the fungus invades the tissues. Teeth.—In man infection takes place frequently through carious teeth, and through abrasions in the gums and mucous membrane of the mouth. Israel found the fungus in the cavities of carious teeth, and Partsch detected in the same locality almost pure cultures without any manifestation of disease except chronic peri-odontitis. The fungus occurs here often side by side with leptothrix. Tongue.—Hochenegg saw a case of actinomycosis of the tongue caused by an infected carious tooth. The swelling was the size of a cherry, located near the apex of the organ. The affection had existed for two months. The growth was excised, and on examination was found to consist of granulation tissue, with a central yellow mass the size of a millet-seed. Besides this case only 3 cases of actinomycosis of the tongue are on record,—1 primary, 1 secondary to disease of the jaw, and 1 metastatic. Jaws.—That carious teeth furnish a frequent infection-atrium in maxillary actinomycosis is well known, and in many instances the disease in its early stages has been mistaken for an ordinary dental CLINICAL VARIETIES. 557 affection, and patients have often sought relief at the hands of a dentist. The lower jaw is most frequently affected, the growth being connected with the bone or situated close to it, or it has already extended to the submental or submaxillary region. The disease often pursues a chronic course, closely simulating periosteal sarcoma, until it reaches the loose tissues of the neck, when rapid extension takes place, in a downward direction, along the subcutaneous connective tissue and the inter- muscular septa. Israel refers to a case in which the actinomycotic swelling in the submaxillary region extended, in five months (August to December), to the level of the thyroid cartilage. When the disease is primarily located in the upper jaw, which, however, occurs only in excep- tional cases, it tends to invade rapidly the adjacent soft parts, and even to implicate the base of the skull and the brain. The prognosis is always more serious when the disease affects the upper than the lower jaw, as the tendency here to invade the deep structure is much greater. Two cases of actinomycosis in man have come under my observation, and as both of them originated in the mouth, and repre- sent, from a prognostic point of view, two distinct classes, I will describe them briefly. The first patient was a man 30 years of age, German by birth, and a soda-water manufacturer by occupation. His business required him to make frequent trips into the county by team. He had no recollection of having come in contact with cattle suffering from " swelled head" or "lumpy jaw." During the winter of 1886 he suffered from what he supposed was an ordinary cold ; the right side of the lower jaw was swollen and painful. As one of the molar teeth showed evidences of decay and had become loose, it was extracted. The pain and swelling, however, did not improve, and the attending physician extracted all of the molar teeth of the lower jaw on that side. At this time a fungous mass commenced to appear over the surface of the edentulous bone. The cheek on the affected side was also greatly swollen. The patient was admitted into the Milwaukee Hospital about six months after the first symptoms had appeared. At this time the lower jaw, in the mouth, presented a fungous mass extending from the angle of the bone to the first bicuspid; the swelling extended as far as the tonsil. The cheek was enormously swollen from the angle of the mouth to the lower margin of the parotid gland. The skin over the swollen part presented a pale, glossy appearance, and the superficial veins were considerably dilated. Around the margin of the swelling no distinct border-line could be felt, the infiltrated parts fading gradually into the healthy sur- rounding tissues. Free suppuration from the surface of the fungous granulations, and a number of small abscesses had discharged themselves 558 PRINCIPLES OF SURGERY. into the cavity of the mouth. As some doubt existed as to the char- acter of the inflammation, careful and repeated examinations were made of the pus removed from the small abscess-cavities, and on several occa- sions fragments of actinomyces were found. The discovery of the specific cause of the inflammation cleared up the diagnosis and furnished an urgent indication for operative treatment. An incision was made along the lower border of the jaw from just below the articulation to near the symphysis, and, after arresting all haemorrhage, it was carried into the cavity of the mouth. The alveolar processes of the jaw were affected, and were removed with chisel and cutting-forceps. Wherever the periosteum showed signs of infiltration it was carefully scraped away, and finalby the whole bone surface was thoroughly cauterized. The infiltrated soft tissues were dissected out with knife and scissors; the disease was found to have extended as far as the tonsil. The bottom of the wound was iodoformized and packed with iodoform gauze, while the external wound was sutured. The entire external wound healed by primary union, and the cavity in the mouth closed slowly by granula- tion. The patient's general health continued to improve rapidly, until six weeks after the operation, when the neck below the scar became swollen, followed in a short time by the formation of abscesses reaching from the angle of the jaw to the clavicle, and posteriorly as far as the spine of the scapula. Numerous openings were made and efficient drainage established, but suppuration continued unabated, and the patient became extremely emaciated. The suppurative inflammation extended, and four months after the first operation the patient died ; the symptoms during the last days of life pointed to a hypostatic pneumo- nia. Actinomyces were continuously found in the pus during the entire course of the disease. I believe that the recurrence of the disease was due to imperfect removal of infected tissues in the posterior and lower portion of the pharynx. The second case came under my care during the summer of 1887. The patient was a young man, employed on a farm. About five months before he was admitted into the Milwaukee Hospital he had a number of teeth extracted from the right upper jaw, under the belief that the teeth, some of which were decayed, were the cause of the pain and swelling in that region. The physician in attendance diagnosed sarcoma of the upper jaw, and sent the case to me for operation. On my first examina- tion, I found a swelling involving the right side of the face, extending from the zygomatic arch to near the lower border of the lower jar, in- volving the deep tissues, and connected with the alveolar processes of the posterior portion of the upper jaw. The swelling was firm and with- out well-defined margins. No evidences of suppuration. The history CLINICAL VARIETIES. 559 of the case, and particularly the location, extent, and physical properties of the swelling, led me to the opinion that it was the result of actinony- cotic infection. All infected tissue was thoroughly excised through a large external incision, the jaw-bone scraped and cauterized. The entire thickness of the cheek, with the exception of the skin and superficial fascia, appeared to be transformed into granulation tissue. In the granu- lations numerous minute yellowish-gray bodies were found, which, under the microscope, showed the typical structure of the ray-fungus. The mycelia were not so bulbous as we find them pictured in the books, but the distal extremity appeared to be surrounded by dust-like bodies, pre- senting the appearance of a small brush. These minute granules I re- garded as spores. In the first case, in which suppuration had taken place, I never succeeded in finding the actinomyces perfect and com- plete; in the second case the granulation tissue had not been destroyed by suppuration, and the fungus was found in a perfect condition and in a state of fructification. These cases present a striking contrast, both in regard to the local condition and the ultimate termination. In the first case secondary infection with pus-microbes had already taken place, and the phlegmonous inflammation that followed this occurrence prepared the tissues again for the diffusion of the actinomycotic process; while in the second case the inflammator37 process had not passed beyond the granulating stage, and the boundary-line between healthy and diseased tissue was also more distinct^7 marked,—a most important factor in the operative treatment. The first patient died from recurrence of the disease in the vicinity of the operation wound and its extension to the neck and chest; while in the second case the wound healed, and the patient has remained in perfect health since. 3. Intestinal Canal.—In primary intestinal actinomycosis the disease is caused by ingress of the fungus with food or water, and its implanta- tion upon the mucous surface. At the point of implantation the fungus multiplies, and by its growth invades the submucous tissue, which becomes the seat of active tissue proliferation. Arrest and implantation of the actinomyces are determined by antecedent pathological changes. Chiari has given an excellent account of the pathological condition found in a case of intestinal actinomycosis that came under his observation. The patient was a man 36 years of age, who during life presented, as the most prominent clinical feature, progressive marasmus. At the necropsy chronic tuberculosis in the apices of the lungs and a few tubercular ulcerations in the lower portion of the ileum were found. The large intestine presented a very remarkable appearance, the mucous mem- brane of which, except the caecum and ascending colon, was covered with whitish deposits, forming round and oblong patches, some of them I 560 PRINCIPLES OF SURGERY. cubic centimetre in diameter and 5 millimetres in thickness. In some of these patches could be seen minute 37ellowish-brown and yellowish-green granules. The patches were firmly adherent, and when removed left a loss of substance in the mucous membrane. The mucous membrane throughout was in a state of catarrhal inflammation. On microscopical examination the granules proved to be actinomyces. The mycelium had penetrated into the tubular glands and showed calcified, club-shaped conidia. The calcification of the club-shaped extremities had undoubt- edly prevented deeper penetration of the fungus. Hochenegg presented a case of actinonrycosis to the Medical Society in Vienna in a man 43 years of age, who had sustained an injury of the abdomen nine months previously, and had since that time noticed a painful swelling at the seat of injury. In the region of the umbilicus a fistulous opening formed, which continued to discharge a thin secretion, in which actinomyces were constantly found. The patient was veiy much emaciated and many of the teeth carious. There was no swelling about the jaws or neck. Ex- amination of the organs of the chest and the sputum revealed no addi- tional diagnostic information. The author expressed the opinion that the inflammatory swelling caused by the contusion furnished the necessary conditions for the localization of actinon^-ces from the intestinal canal. Zemann reports 5 cases of actinonycosis of the abdomen. In 4 of them the disease commenced with sharp, lancinating pains in the abdomen, and during their course presented the clinical picture of chronic peritonitis. Swellings could be found in one or more places in the anterior abdominal wall, and the abscesses were either incised or opened spontaneously, and in 3 cases they communicated with the in- testinal canal. The first case was a woman, 30 3rears of age, who had a fistulous opening in the anterior abdominal Avail which communicated with a swelling in the left parametrium. The patient stated that this swelling appeared soon after her last childbed. A constant discharge of yellowish-red pus was maintained, in which, under the microscope, nu- merous actinom37ces could be seen. The patient died of exhaustion, and at the post-mortem chronic para- and peri- metritis were found, with ex- tensive pus-cavities that communicated with the rectum and bladder. The second case occurred in a person 18 years of age, who, during life, had suffered from a large abscess in the abdominal cavity, under the right lobe of the liver, which communicated with the intestinal canal, and had led to numerous fistulous openings in the anterior abdominal wall. At the necropsy a loop of the ileum was found perforated and in communication with the abscess-cavity. The pus contained numerous actinomyces. In the third case the diagnosis was made post-mortem by CLINICAL VARIETIES. 561 the discovery of actinomyces in the pus. The disease was located in the lower portion of the ileum and caecum, where it had caused suppura- tion and numerous adhesions. A most remarkable and interesting history is connected with the fourth case. A robust, well-nourished woman, 40 years of age,'was attacked quite suddenly with pain in the stomach, high temperature, diarrhoea, and vomiting, followed by cerebral symptoms and death. At the necropsy the right Fallopian tube was found transformed into a large abscess, both extremities of the tube closed, and walls of sac lined with granulations containing actinomyces. The fifth patient was 50 years of age, and had suffered for a long time from lancinating pain in the abdomen; a fistulous opening formed in the umbilical region and discharged a thin, yellowish-green pus. The post- mortem showed actinomycosis of the peritoneum, small intestine, left ovaiy, and liver ; large abscess among the intestinal coils; perforation of small intestine and bladder. In the upper part of the small intestine small pigmented cicatrices were found. In all of the above cases the microscopical examination revealed the presence of actinomyces in the granulation tissue as well as in the pus of the abscess-cavities. In a case of intestinal actinomycosis reported by Langhans, the disease started evidently from the appendix vermiformis, 4 centimetres in length, the end of which appeared as if transverse^7 cut in an abscess- cavity the size of a walnut. The abscess was on the right side of the bladder, and safdeep in the pelvis that during life it could not be located. The abscess pursued a chronic course, and the walls were well defined ; no signs of chronic or acute peritonitis. Furthermore, the mucous membrane of the appendix was studded with cicatrices, and presented a slate color. The principal seat of the actinomycotic process was in the liver. In a second case reported D37 the same author the clinical course of the disease resembled perityphlic abscess. The necrops37 showed perforation of the caecum and ascending colon. No cicatrices in the mucous membrane or surrounding tissues. In all probability, the perforations occurred from without inward. Lnening and Hamm have recently reported, with interesting details, a case of primaiy actinomycosis of the colon with metastatic deposits in the liver. The patient was a man 28 years of age, who, in 1880, suffered from an acute abdominal affection, which at the time was diagnosed as typhlitis. Four years later a second attack occurred, attended by symptoms of intestinal obstruction. Patient was very ill for eight days, when the symptoms of obstruction subsided, and he made a slow recoveiy. During the year 1887 he had a third attack, attended by high fever and absolute constipation for eight to ten days. During the month of December of the same year he had another but less 36 562 PRINCIPLES OF SURGERY. severe attack, and at this time a hard swelling made its appearance in the right side of the abdomen. From this time until he was admitted into the hospital, April 5, 1888, he was confined to bed. The patient was at this time greatly emaciated, with a temperature of from 38.4° C. to 39.8° C. Swelling the size of a fist in the right side of the abdomen, half-way between umbilicus and anterior superior spine of the ileum. Externally this swelling presented redness and oedema. Fluctuation indistinct. Deep palpation showed that the swelling extended to right hypochondrium ; abdomen not tympanitic. Swelling painful and tender, pain extending to spermatic cord and testicle on same side. A few days later abscess was incised, and nearly a quart of brownish pus, having a faecal odor, escaped. Digital exploration revealed an irregular cavity, whose walls at some points were plainly lined with intestinal coils. Disinfection and drainage. As the symptoms did not improve materially, the abscess-cavity was again scraped out and disinfected four weeks later. After the second operation it was noticed that the pus contained yellow granules, which, under the microscope, were shown to be actino- uyces. The abscess was incised a third time, but the patient kept losing ground, and died October 9th. The autopsy revealed primary actino- m37cosis of the ascending colon, with multiple fistulous perforations. A metastatic actinom37cotic abscess of the liver had perforated into the hepatic vein, resulting in multiple metastases in the lungs. The cases of intestinal actinomycosis reported above warrant the opinion that the mucous membrane of the intestinal canal is frequently the seat of primary localization of the actinom37ces, thus corroborating the state- ments of Johne in reference to this disease in animals. BRONCHIAL TUBES AND LUNGS. If an actinomyces should be inhaled with the inspired air, and should become implanted upon the bronchial mucous membrane, and find favorable conditions for its growth, the granule will become sur^ rounded by new cells derived from the pre-existing epithelial cells, and thus become the centre of a minute granuloma. By multiplication of the actinomyces new nodules are produced, around each of which the pre-existing tissue is transformed into embryonal tissue, which in time is destroyed, resulting in suppuration and loss of tissue. Israel reported a case of actinomycotic abscess of the lung caused by the entrance of an infected tooth into the air- passages. In this instance the fungus was conveyed into the bronchial tube with the carious tooth, and the infected foreign body became the centre of the specific inflammation. Cases of primary actinomycosis of the lungs, however, have been BRONCHIAL TUBES AND LUNGS. 563 observed where no such direct carrier of the contagium could be found, and in which infection must have occurred by the direct inhalation of the fungus or its spores with the inspired air. Szenasy found, in the case of the wife of a butcher, who had suffered for nine years from severe pain in the right side of the chest, latterly attended by a severe cough, in the right mammary region, a fluctuating swelling, the size of a hen's egg, covered with normal skin. On the outer side of this swelling, in the intercostal space between the third and fourth ribs, another swell- ing existed, double in size and elongated in shape, and with indistinct margins. This latter swelling has been noticed for nine years, and was tender to the touch. Auscultation over the fourth and fifth intercostal spaces on the healthy side revealed bronchial breathing and diffuse bronchial rales. Temperature, 38.4° C. (101.1° F.). The urine contained a trace of albumen. By aspiration 150 cubic centimetres of thick, yellow Fig. 101.—Actinomyces from Lung of Cow. Fungus in the Centre of Inflammatory Product. X 350. (Marchand.) A, normal epithelial cells of bronchus attached to connective tissue; B, large epithelioid cells; C, leucocytes. pus were removed, and contained colonies of actinomyces. Actinomyces were also found in the sputum. The patient had carious teeth, but no signs of actinomycosis could be detected in the mouth. Canali relates the clinical histoiy of a girl, 15 years of age, who had suffered for eight years from a cough, attended by a scanty, fetid expectoration. Inspection and percussion yielded only negative results. Auscultatory symptoms pointed to a diffuse catarrh. Under the micro- scope the sputum was seen to contain pus-corpuscles, epithelial cells, and numerous actinomyces. No primary source of infection could be found in the mouth, pharynx, or nose. Moosbriigger interprets the mechanism of the ingress of actinomyces by assuming that the fungus enters the bronchial tubes during inspira- tion, and becomes at first deposited upon the mucous membrane, where its presence and growth cause a destruction of the epithelial cells, when it reaches the submucous and peri-bronchial tissues, in which a nodule 564 PRINCIPLES OF SURGERY. of granulation tissue is produced that by pressure induces degenerative changes and gradual destruction of the bronchial wall for further infec- tion. He believes that the peri-bronchial lymphatic vessels and glands take an active part in the local diffusion of the process, as they furnish an avenue for the dissemination of the fungus or its spores. He claims the existence of an actinomycotic lymphangitis, but confesses that he has never seen the fungus inside of lymphatic vessels. As soon as the fungus reaches the pulmonary tissues, it gives rise to parenclymatous inflammation, whose first product is alwa37s granulation tissue, which, at a later stage, and under the influence of a secondary infection with pus- microbes, undergoes transformation into pus-corpuscles and the formation of abscesses. ACTINOMYCOSIS OF BRAIN. Quite recently, Bollinger placed on record the first case of primary actinomycosis of the brain. The patient was 26 3rears of age. The intra vitam diagnosis was tumor of the brain ; the most prominent symp- toms were severe headache, paralysis of left abducens, congestion of optic papilla, and momentary unconsciousness. The swelling in the brain, found on autopsy, presented the characteristic features of a cysto- myxoma in the third ventricle; all of the ventricles were found consid- erably dilated. The swelling contained numerous colonies of actinomyces in all possible stages of development. The tendency to suppuration of the tissues, usually found in all cases of actinomycosis in man, was entirely absent in this case. This case, if any, appears to be one of cryptogenetic infection, as the fungus or spores must have entered somewhere through the cutaneous or mucous surface without producing the disease at the primaiy portio invasionis, and, localizing in the brain by embolism, resulted in primaiy actinomycosis in this organ. Keller (Brit. Med. Journal, March 29, 1890) reported, this year, a case of metastatic actinomycosis of the brain in which a correct diagnosis was made during life. The patient was a middle-aged woman, who suffered from pleurisy, and six months thereafter abscess developed over the cartilages of the sixth and eleventh ribs, in the pus of which actino- myces were found. Two years later increasing paresis of left arm developed, followed by convulsions, confined at first to the arm, then becoming general, and at times identical with cortical epilepsy. Diag- nosis of actinomycosis affecting the motor area was made; operation was suggested and declined. The paresis extended to left lower extremity and left side of face; later, convulsions, headache, vomiting, and loss of consciousness, soon deepening into coma. Burger then obtained consent to operate. The patient was moribund, and required no anaesthetic. He exposed the right ascending parietal convolution, incised the dura mater SYMPTOMS AND DIAGNOSIS. 565 and the discolored brain-surface, and removed 2 ounces of thin, greenish pus, in which were found actinomyces in great abundance. When the pus was evacuated, she recovered from the deep coma,and, while still on the operating-table, called for water. On the following day consciousness returned, and on the eighth the facial paralysis disappeared. In two months the wound had healed and the paralytic lesions improved, but there remained some paresis of left arm, with contraction of the fingers. In less than one year there was a recurrence of the symptoms, and Burger re-opened the brain-abscess, followed by the escape of a considerable quantity of pus. No material improvement followed, and the patient died a few days thereafter. At the post-mortem, the middle third of the right frontal and parietal convolutions was occupied by a large mass of newly-formed tissue, protruding over the surface and reaching into the substance of the brain for one inch. Underneath it, deeply buried in the white sub- stance, an unopened, encapsulated abscess, the size of a nutmeg, was discovered. SYMPTOMS AND DIAGNOSIS. Actinomycosis is an inflammatory disease that clinically is noted for its chronicity. The specific product, composed of granulated tissue, is abundant, and the swelling, often of considerable size, resembles more a tumor than an inflammatory swelling. The extension of the morbid process takes place by effusion of the actinomyces in loco, in preference along the loose connective-tissue spaces, each fungus constituting a nucleus for a nodule of granulation tissue. By confluence of many such nodules the inflammatory swelling often attains a very large size, and when suppuration occurs in the interior the further history is that of chronic abscess. Regional dissemination of the infective process never takes place through the lymphatic glands. When the lymphatic struc- tures become implicated, it is an indication that secondary infection has taken place. In exceptional cases the disease pursues quite a rapid course, and may then be mistaken for an acute phlegmonous inflamma- tion, osteomyelitis, or, when diffused over a large surface of the body, for syphilis. A good illustration of the former class is furnished by the case reported by Kapper. A soldier, 22 years of age, became suddenly ill with febrile symptoms and a rapidly-increasing swelling of the lower jaw. An early incision was made and liberated a large quantity of pus, which, on microscopical examination, was found to contain actinomyces. It is interesting to note that in this case the various teeth from where the infection had evidently taken place contained threads of leptothrix and actinomyces. At a meeting of the Berlin Medical Society, about two years ago, 566 PRINCIPLES OF SURGERY. 0. Israel gave an accurate description of the post-mortem appearances of a case of diffuse actinomycosis. The patient, a woman 44 years of age, had been treated for syphilis in one of the surgical clinics. The heart contained a number of minute abscesses containing the fungus in large numbers. A large abscess between the diaphragm, stomach, and spleen contained thick pus of a greenish color,—an unusual occurrence in cases of actinomycosis,—but no actinomyces. The spleen was the seat of large and numerous minute abscesses, and the liver and kidneys also contained small abscesses, and in all of them actinomyces were found. Israel claims that this case affords a good illustration of his view that the actinomyces, as regards its effect on the tissues, occupies a position half-way between the bacillus of tuberculosis, which produces only granu- lation tissue, and the pus-microbes, which produce pus. It was im- possible in this case, as in so many others in which multiple deposits have been found, to locate with accuracy the primary seat of infection. The teeth were perfect and the whole digestive tract showed no evidence of disease. Metastasis in actinomycosis takes place in the same manner as in pyaemia and malignant tumors. At the primary seat of infection the fungus or its spores gain entrance through a defective vein-wall into the general circulation, and, at the point of arrest in a distant capillar vessel, establish an independent centre of infection, with all the attri- butes of the primary infection. General infection is of rare occurrence in actinomycosis, as this disease is noted for its tendency to extend locally, where it often results in external regional dissemination and destruction of tissue. Actinomycosis resembles, in its clinical behavior, very closely the malignant tumors, in that it will invade every tissue with which it comes in contact, irrespective of its anatomical structure. Primary localization is very apt to occur in the connective tissue, and in preference it extends along this structure; but periosteum,bone, muscles, tendons, cartilage,—in fact, all of the tissues of the body,—succumb to the fungus as quickly as they become infected. In actinomycosis of the jaws and the vertebrae we often find exten- sive destruction of bone, with large abscesses communicating with the primaiy lesion. Before suppuration takes place the actinomycotic swell- ing is quite firm on pressure, and, if the disease extend rapidly, it is surrounded by a diffuse oedema. Pain and tenderness are usually never severe, and often almost wanting. Redness appears as soon as the in- fection has extended to the skin. Suppuration usually develops in con- sequence of direct infection with pus-microbes through some minute surface defect in the swelling. As soon as suppuration sets in, the swell- ing not only increases rapidly in size, but regional diffusion is hastened by the breaking down of the granulation tissue that before held the PROGNOSIS. 567 fungi fixed in their respective localities. The same tendency to migra- tion of an actinomycotic abscess is observed as in tubercular abscess. The characteristic feature of actinomycotic pus is the presence of minute, macroscopical, yellowish granules ; the actinomyces, on careful inspection, can almost always be discovered. If these granules are placed under the microscope their characteristic structure will at once become apparent. In cases of actinomycosis of any of the internal organs, attended by suppuration and discharge of pus through some one of the outlets of the body, the diagnosis will usually depend almost exclusively upon the detection of the fungus in the discharges. Microscopical examina- tion of the sputum and faecal discharges, in cases of suspected actinonry7- cosis of the lungs or the intestines, is the only positive means of making a differential diagnosis between these affections and pulmonary and in- testinal tuberculosis. Actinomycosis of the skin, mouth, tongue, and jaws might be mistaken for sarcoma, carcinoma, tuberculosis, and syph- ilis. As, with the exception of carcinoma, all of these affections present under the microscope a histological structure that it would be often dif- ficult to identify microscopically, the differential diagnosis by means of the microscope must rest on the detection of the ray-fungus imbedded in the granulation tissue. Sarcoma does not suppurate or break down as earl37 as the actinomycotic or tubercular swelling. Carcinoma primarily starts in the epiblast or hypoblast, and, even during the earliest period of the growth, there is no difficulty in demonstrating an intimate relation- ship between the skin or mucous membrane and the tumor encroaching upon the mesoblast. In actinomycosis, tissue proliferation takes place around each fungus in the mesoblast, and the skin or mucous membrane is infected and destroyed from within outward. In tuberculosis, regional infection almost always occurs through the medium of the lymphatic vessels and glands, while these structures are seldom or never invaded in actinomycosis. In the absence of microscopical proof of the nature of the lesion, it may become necessary to resort to a therapeutic test in differentiating between syphilis and actinomycosis. Large doses of po- tassic iodide, administered four times a day, will have a decided effect in reducing the size of a gumma in the course of two or three weeks, while no such result will be obtained if the lesion is of an actinomycotic nature. PROGNOSIS. Actinomycosis is a more dangerous affection than tuberculosis. While a spontaneous cure not infrequently takes place in the latter, we have no proof that actinomycosis ever terminates in such a satisfactory manner without the surgeon's aid. Actinomycosis of the internal organs proves fatal almost without exception on account of the inaccessibility 568 PRINCIPLES OF SURGERY. of the disease to radical surgical treatment. In such cases numerous fistulous openings form, discharging profuse quantities of pus, and the patient dies in from one to two or three years from exhaustion or amy- loid degeneration of the internal organs. If the disease is located in external parts, local extension often takes place very slowly until sup- puration sets in, when the actinomycotic abscess migrates from place to place, attacking all the tissues that come in its way, and life is finally destroyed by pyaemia, sepsis, or exhaustion. The prognosis is always favorable when the disease is recognized early, and when it is located in parts accessible to a radical operation. As metastasis is of rare occur- rence in actinomycosis, complete removal of the primaiy focus is followed by a permanent cure. TREATMENT. General treatment in actinomycosis is of no avail, and all local measures, short of complete removal of the infected tissues, result in more harm than good, as they often give rise to secondary infection with pus-microbes, which always aggravates the local conditions and hastens a fatal termination. In cases where a radical operation is out of question on account of the extent of the disease or the importance of organs involved in the process, parenchymatous injections of a 2-per- cent, solution of boric acid, a l-to-1000 solution of corrosive sublimate, or a l-to-1500 solution of nitrate of silver might be tried ; but, on the whole, such injections have little influence in arresting the local exten- sion of the disease. The surgical treatment of actinomycosis, before suppuration has occurred, consists in the excision of the infected tissues in all cases where such a procedure is practicable. The incision should be carried some distance, at least ^ to 1 inch, from the visible granula- tions, with a view of-removing not only the inflammatory tissue, but also the minute invisible foci in its immediate vicinity. If, after the excision, suspicious tissue is found in the wound, this should be removed by a careful dissection with forceps, knife, and scissors, or destroyed by using the actual cautery. Acids and other chemical caustics should not be relied upon in destroying the infected tissues. An actinomycotic abscess should be treated on the same principles as a tubercular abscess. The abscess-cavity is freely exposed by laying open the fistulous openings, and the granulation tissue is removed with a sharp spoon. Undermined skin is cut away with scissors. If the disease has extended to bone, this is also thoroughly scraped, and it is a good plan, after the cavity has been thoroughly irrigated and dried, to cauterize the whole surface with the actual cautery. Such wounds should not be sutured, but packed with iodoform gauze in order to keep the infected area readily accessible to inspection, so as to enable the surgeon at each dressing to recognize a TREATMENT. 569 local recurrence. Should this occur, the same means are to be repeated in eliminating the infected tissues. As soon as the wound is covered with healthy granulations it may be closed by secondaiy suturing, or, if this cannot be done on account of too great loss of skin-tissue, the defect is covered with large skin-grafts according to Thiersch's method. Repeated scraping operations will often succeed in finally eradicating the disease, provided the infected parts are accessible to vigorous curetting and the application of the actual cautery. CHAPTER XXIII. Anthrax. Synonyms : Contagious carbuncle ; charbon ; Milzbrand ; malignant pustule ; wool-sorters' disease. The mycology of anthrax is better under- stood than that of any other microbic disease. The bacillus of anthrax is the largest of the known pathogenic microbes, and ever since it was discovered it has been a favorite subject of investigation in every labora- tory and by every bacteriologist. HISTORY. As a disease among animals, anthrax has been known since the earliest records of history. The contagiousness of this disease has been recognized since the beginning of the eighteenth century. During the first part of the present century it was described as a blood disease. Heusinger, in his classical work, " Die Milzbrand Krankheiten der Thiere und des Menschen " (Erlangen, 1850), declared anthrax to be a malarial neurosis. In the year 1855 Pollender published his discoveries, which inaugurated a new era in the study of anthrax. As early as 1849 he discovered, in the blood of cattle suffering from anthrax, a mass of innu- merable, fine, rod-like bodies, which appeared to be of a vegetable nature and resembled vibriones. Branell found the same rods in the blood of men, horses, and sheep which had died of anthrax. He also detected the same bodies during life in the blood of the diseased animals. Dela- fond regarded this parasite as a variety of leptothrix. In 1863 appeared the work of Davaine, wherein he pronounced these rods to be bacteria, and later he called them bacteridia. He believed them to be the essential cause of anthrax, as the disease could not be found in blood that did not contain them. Through the labors of Pasteur, Koch, Naegeli, Bollinger, and others, the bacterium found so constantly in the blood and tissues of anthracic animals finally found a permanent place as the bacillus anthracis among the schizomycetes. The first reliable and positive accounts of the disease in man we owe to Fournier, Montfils, Thomassin, and Chabert, who published their de- scription of the disease between the years 1769 and 1780. Fournier first distinguished the spontaneous and the communicated carbuncle of man. The primary existence of anthrax in man was asserted by Bayle in 1800 and by Dav3T la Chevrie in 1807. (571) 572 PRINCIPLES OF SURGERY. DESCRIPTION OF THE BACILLUS OF ANTHRAX. Non-motile rods, 5 to 10 micro-millimetres long and 1 to 1.25 micro- millimetres broad, and threads made up of rods and cocci. The rods, as a rule, are straight; only when they grow to a con- siderable length and meet with resistance they become slightly curved. The rods and threads are round, and, with their threads truncated at right angles, appear as though they had been cut off obliquely. The interior, as long as fission does not proceed, is perfectly homogeneous, and absorbs aniline dyes very readily and uniformly. The development of spores in long, undivided threads, as we find them in fluid culture media, takes place at regular intervals, where we find them as bright, oval spots that become more and more apparent, marking the direction of the rods. Upon solid culture media the development of spores is preceded Fig. 102.—Anthrax Bacilli. Spore Formation and Spore Germination. (Koch.) A. From the spleen of a mouse after twenty-four hours' cultivation in aqueous humor. Spores arranged in rods like a string of pearls. X650- B- Germination of spores. X650- C The same greatly magnified. X1650. by transverse segmentation of the rods. The cell-membrane of each section finally becomes the membrane of the spore, each pole of the spore presenting a small mass of protoplasm that can be stained. (a) Staining.—Cover-glass preparations of fluid specimens can be stained with a watery solution of any of the aniline dyes. They can be rapidly stained with a drop of fuchsin or gentian-violet, but more satis- factorily by floating the cover-glass for twenty-four hours. The prepara- tions are dried and mounted in Canada balsam. The spores are not stained by the ordinary methods. Tissue-sections containing bacilli are best stained by Gram's method, and after-stained with eosin or picro- carminate of ammonium. By double staining the rods are seen to consist of a lr^aline sheath with protoplasmic contents. (b) Cultivation.—The bacillus of anthrax grows luxuriantly in dif- ANTHRAX BACILLI IN THE LIVING BODY AND THE SOIL. 573 ferent fluid and solid nutrient media. Bouillon and aqueous humor of the e37e furnish an excellent soil, but for inoculation purposes the cultures are now general^7 grown upon solid nutrient media. Gelatin.—If a nutrient medium containing from 5 to 8 per cent, of gelatin is inoculated, a whitish line develops in the track of the needle- puncture, and from it fine filaments spread out on the sides. In a more solid nutrient gelatin the growth appears only as a thick, white thread. The culture liquefies the gelatin, and the growth subsides as a white, flocculent mass. Plate Cultures.—Cultures upon a sloping sur- face of solid nutrient agar-agar or gelatin form a viscous, snow-white plaque. Without access of air the culture does not grow, the bacilli being aerobic. Potato.—Inoculation of sterilized potato yields a veiy characteristic growth. The deep chamber containing the potato is placed in the incubator, and in about thirty-six or forty-eight hours a cream37, ver3r faintly yellowish la37er forms over the inoculated surface, with, usualby, a peculiar trans- lucent edge. On removing the cover of the damp chamber, a strong, penetrating odor of sour milk is emitted. MULTIPLICATION OF ANTHRAX BACILLI IN THE LIVING BODY AND THE SOIL. In the body of living animals the bacilli multiply exclusively by segmentation, and never produce spores. Spores are produced only in dead nutrient media, and under certain conditions only, among which a proper temperature is the most im- portant factor. The limits of the temperature vary between 12 to 18° C. and 43° C.; at a temperature of less than 12° C. growth of the rods and spore production no longer take place. Pasteur's assertion that bacilli and spores in the cadavers of buried animals are active when brought to the surface by earth-worms is im- probable. The disease, according to Koch, is spread among animals by germinating spores which attach themselves to plants and grass in swamps and along river-banks, and which, when taken in with the food, become the cause of intestinal anthrax. Schrakamp and Friedrich are of the opinion that bacilli can multiply in the superficial layer of the soil, while Kitt maintains Fig. 103.—Stab Cul- ture op Anthrax Bacilli in Gelatin, Grown at Room-Tem- perature (16° to 18° C). Four Days Old. Natu- ral Size. (Baumgarten.) 574 PRINCIPLES OF SURGERY. that fructification of the bacilli takes place in the manure deposited in pastures. INOCULATION EXPERIMENTS. In order to cause death of animals by inoculation with the bacillus of anthrax, a pure culture or anthracic blood must be injected into the subcutaneous tissue or into the circulation, or the virus ma3r be trans- mitted by inhalation or by feeding. Goats, hedgehogs, mice, sparrows, cows, horses, guinea-pigs, and sheep can be readily infected. Rats are less susceptible. Pigs, dogs, cats, white rats, and Algerian sheep are immune. Frogs and fish have been rendered susceptible to anthracic infection by raising the temperature of the water in which they Fig. 104.—Anthrax Colony upon Gelatin. X80. (Fluegge.) A, after twenty-four hours: B, after forty-eight hours. lived. Koch produced the disease artificially in rabbits and mice by injecting a drop of anthracic blood, with the result of producing death usually within twenty-four hours. After death sections taken from different organs, stained in methyl-violet with carbonate of potash, were examined under the microscope, and the bacillus was found in great abundance in all of them. When magnified fifty diameters such prepara- tions present, at the first glance, an appearance as if a blue coloring- material had been injected into the vessels. Each intestinal villus is permeated by an exceedingly delicate blue net-work; in the mucous membrane of the stomach all the capillaries surrounding the gastric glands are stained blue; in the ciliary processes each projection is injected, and a spiral vessel stained of a dark-blue color leads from INOCULATION EXPERIMENTS. 575 thence to the iris and breaks up into a fine, blue net-work, with loops directed toward the edge of the iris. The liver and lungs and the glandular structures, such as the pancreas and salivary glands, are com- pletely permeated by the same blue, vascular net-work. Indeed, there is no organ which is not more or less injected with the blue mass. It is, however, very striking that this injection is only present in the capillary vessels. All the larger vessels, even the arteries and veins of an intes- tinal villus, are either not at all stained or have but a light-blue streak in their interior, and that only here and there. When magnified 250 times one can see that the blue capillary net-work is composed of numerous delicate rods, and when a power of 700 diameters is used it is found that Fig. 105.—Intestinal Villus of Anthracic Rabbit. The Bacilli in Capillary Vessels Alone Stained. X250. (Koch.)* the apparent injection is nothing more or less than the bacillus anthracis, stained dark-blue, and present in incredible numbers in the whole capillar}7 s}7stem. In the other vessels, especially in the larger ones, often only a single bacillus may be met with at long intervals, or they may be quite absent. The distribution of the bacillus in the capillaries is not, however, quite uniform. There are fewer in the brain, in the skin, in the capil- laries of the muscle, and in the tongue than elsewhere; on the other hand, in the liver, lungs, kidneys, spleen, intestines, and stomach they are always present in enormous numbers. In the capillaries themselves 'Copied from "Traumatic Infective Diseases," by permission of the New Sydenham Society, I-iondon. 576 PRINCIPLES OF SURGERY. the bacilli accumulate in largest numbers at the point most distant from the nearest afferent arter37 and the efferent vein,—that is, at points where the blood-current is slowest. Where the bacilli are present in greatest abundance it not unfrequently happens that the capillaries become torn, and blood with the contained bacilli is extravasated. This occurs most frequently in the glomeruli. Many of these burst, and the bacilli pass into the uriniferous tubules. In mice the spleen is more especially the seat of the bacilli; then come the lungs, and, last of all, the kidneys. Frisch inoculated the cornea in animals and produced a keratitis, caused by the bacilli, which multiplied with great rapidity, local dissemination taking place through the corneal spaces. INFECTION IN MAN. An intact skin furnishes ample protection against infection with bacilli or spores, but the slightest abrasion may become the necessary infection-atrium for either method of infection. Infection may occur through a healthy mucous membrane, either with bacilli or spores. As the anthrax bacillus is a non-motile parasite, penetration of the epithelial lining can only occur D37 local growth of the bacillus. Spores are such minute structures that they can reach the circulation through a healtly mucous membrane in the same manner and b}7 means of the same agencies as we have found necessary for the transportation of other minute foreign parasites from a mucous surface into the circulation. In man infection frequently takes place through a small wound or abrasion in persons handling the infected products of anthracic animals, such as wool, hair, and hides. In other instances, insects, such as mosquitoes and flies, that have fed on the blood of living anthracic animals or the dead tissues of animals that died of the disease, may become disease carriers. The sting of such an infected insect may communicate the disease with the same degree of certainty as an intentional inoculation with a drop of anthracic blood or a minute quantity of a pure culture. INTENSIFICATION OF VIRUS. While it is known that some chemical substances exert an attenuating influence on the virulence of the anthrax bacillus, it has also been found that an attenuated virus will again become more virulent by adding certain substances. It must, therefore, be taken for granted that the chemical composition in which the bacillus is suspended influences, in one wa37 or the other, its virulence. It has been found, for instance, that the addition of a minute quantity of lactic acid to a fluid containing the bacillus in an attenuated form greatly intensifies its virulence within a very short time. Thus, Arloing, Cornevin, and Thomas found that the ATTENUATION OF VIRUS AND PROPHYLACTIC INOCULATIONS. 577 pathogenic power of a fluid containing these bacilli, to which gJ0 part of lactic acid had been added, and the mixture allowed to stand for twenty-four hours, was increased twofold; if, then, a little water, con- taining a very easily fermentescible sugar, is added to the mixture, and another twenty-four hours allowed to elapse, the virulence attains its maximum, and frogs inoculated with this virus die in from twelve to fifteen hours ; whereas, when inoculated with ordinary virus, the}7 live from forty to fifty hours. Kitt has repeated and confirmed these experi- ments. ATTENUATION OF VIRUS AND PROPHYLACTIC INOCULATIONS. By cultivating the bacillus of anthrax in neutralized bouillon at 42° to 43° C. (107.6° to 109.4° F.), for about twenty days, the infecting power is weakened, and animals inoculated with it are protected against the disease. A still greater degree of immunity is obtained by inoculat- ing a second time with material that has been less weakened. Animals thus treated are then protected against the most virulent form of anthrax, but onh7 for a time. A temperature of 55° C. (131° F.), or treatment with 1- to 5-per-cent. solution of carbolic acid, deprives the bacilli of their virulence. The virulence of the bacillus is also altered by passing it through different species of animals. Woolbridge secured immunity against anthrax in animals by cultivating the bacillus in an alkaline solution at a temperature of 37° C. (98.6° F.) for two days. At this time the fluid was filtered, and a small quantity of the filtrate injected into the subcutaneous tissue of rabbits ; these rabbits remained well, and subsequently resisted injection of most virulent anthracic blood. Hankin, under the guidance of Koch, at the Hygienic Institute of Berlin, isolated an albuminose from anthrax cultures, which, when in- jected into rabbits and mice in small quantities, rendered these animals immune against the most virulent cultures. The albuminose was pre- pared from the cultures by precipitation with absolute alcohol; the precipitate was well washed in this liquid to free it from ptomaines,— since it is known that all such substances are soluble in alcohol. After the addition of alcohol it was filtered off and dried, then re-dissolved, and filtered through Chamberland's filter. Four rabbits were inoculated with virulent anthrax spores, and 3 of them received an injection of albuminose into the ear-vein at the same time; the latter recovered, while the remaining animal not thus protected died, in about forty-eight hours, of anthrax. In another experiment, 10 mice were each injected with the millionth part of their bod37-weight of anthrax albuminose and with active vaccine at the same time. Of these 3 died after 108 to 116 hours ; the others recovered. Three others had only the two-millionth part of 37 578 PRINCIPLES OF SURGERY. their body-weight of anthrax albuminose and active culture. Two ol them survived. Four control mice were inoculated, and all died of anthrax. He has come to the conclusion that when a large dose of albuminose is injected into an animal the entrance of anthrax bacilli into the system is aided, and when a small dose is administered immu- nity is acquired against its poisonous properties, protecting the animal against subsequent inoculations with active cultures. Prophylactic inoculations of sheep with mitigated virus is carried on upon an exten- sive scale in France by Pasteur and his pupils, and recent statistics bearing upon their value in protecting the animals against anthrax have shown them effective in preventing the spread of the disease in infected districts. CLINICAL VARIETIES OF ANTHRAX. Primary bronchial and pulmonary anthrax, caused by the inhalation of dust containing bacilli or spores, and primary anthrax of the intes- tines, caused by eating anthracic meat or by drinking water infected with spores, are diseases that are occasionally met with in man; but, as these affections belong to the physician and not to the surgeon, the student should consult any of the modern text-books on the practice of medicine to become familiar with their symptomatology. Buchner has studied experimentally the entrance of the anthrax bacillus through the intact mucous membrane of the bronchial tubes. The bacillus and spores were administered by inhalations, in the shape of dry powder, and suspended in steam. On examining the bronchial mucous membrane at different stages under the microscope, it was seen that the spores were transformed in a very short time into bacilli, and that the latter, by their growth, pushed themselves between the cells and into the capillary vessels. It was observed that the greater the pulmo- nary irritation, the more the passage of the microbes was retarded. The entrance of the bacilli from the surface of the mucous membrane into the capillary vessels was seen to depend on an active process. Secondary anthracic bronchitis, pneumonia, and enteritis are met with in almost all cases of localized anthrax followed by secondary general infection. Primary intestinal anthrax in man was studied by Wahl, Recklinghausen, Buhl, Wagner, Bollinger, Leube, and Frankel, and all of these authors succeeded in demonstrating the presence of the essential microbic cause in the inflamed mucous membrane. When the microbe enters the body through the mucous membrane of the gastro- intestinal canal with the food or drink, it gives rise to a primary anthrax of the intestinal canal, that again may become general by metastatic dis- semination through the systemic circulation. Localization upon the mucous surface first takes place upon the most prominent part of the CLINICAL VARIETIES OF ANTHRAX. 579 valvulae conniventes on the mesenteric side of the bowel, and from here the infection spreads over the entire surface. Vierhoff has collected 41 cases of anthrax intestinalis, the total number found reported up to 1885. The author himself observed 2 cases of secondary intestinal anthrax in the hospital at Riga. Cases of secondary intestinal anthrax—that is, localization of the bacillus of anthrax in the mucous membrane of the intestinal canal after external infection—were known to the older authors while observations of primaiy localization in the digestive tract date only from the middle of the last centur}7. As soon as general infection has taken place, the diffusion throughout the capillary system is the same as has been described under the head of Inoculation Experiments. The forms of anthrax that concern the surgeon most are those which result from infection of the external surface by the introduction of the bacilli or spores through a small wound, abrasion, or the sting of an infected insect. The favorite location for the development and growth of the anthrax bacillus in man and beast is in the connective tissue; it is, therefore, immaterial in what manner the microbe reaches this tissue, as localization here marks the beginning of the disease. The clinical forms vary according to the location of the disease, its extent, and the intensity of the infection. Most all authors follow Bollinger's classifica- tion, according to which all cases are brought under one of the follow- ing varieties : 1. Anthrax acutissimus, or apoplectiformis. 2. Acutis. 3. Subacutis. The primary location of the disease is in accordance with the manner in which infection has taken place. W. Koch states that in animals and man the bacillus can enter the organism through one of the following routes : (a) through the skin ; (b) gastro-intestinal canal; (c) respiratory passages. Anthrax of the External Surface.—Infection of the sub-epidermal connective tissue can only occur through a defect in the epidermis; hence, every anthrax of the external surface corresponds in its location with an infection-atrium, through which the essential microbic cause has entered the connective tissue. The bacillus of anthrax, when brought in contact with living tissue susceptible to its pathogenic action, causes an acute inflammation characterized by grave alterations of the capillary wall and rapid exudation. The microbe first multiplies at the primary point of invasion, and, if it does not meet with sufficient tissue resist- ance, it enters the blood-vessels and causes general infection, which always proves fatal. Infection occurs most frequently in exposed parts of the body; thus, of 63 cases of anthrax in man, collected by Slessarewskji, the disease showed itself 6 times on the face, 21 times on the neck, and 36 times in other places. Trousseau relates that in Paris 20 persons 580 PRINCIPLES OF SURGERY. were attacked with anthrax in ten 37ears, and in all of them the source of infection could be traced to horse-hair imported from South America. The pathologico-anatomical conditions vary according to the primary seat of invasion, the structure of the organ, and seat of the disease. The first tissue changes are observed at the point of inoculation. From a prognostic and pathological point of view, external anthrax can be divided into two distinct varieties : 1. Anthrax pustule. 2. Anthrax oedema. I. Anthrax Pustule.—This is the so-called malignant pustule. It is usually met with in parts not covered by clothing, as the fingers, hands, and face. This form of the disease is determined by the anatomical structure of the part affected, which must be dense and vascular. The pustule begins as a small, red point that resembles the bite of a flea, in the middle of which a small vesicle appears, which, at first, contains a transparent serum, and, later, becomes sanguineous. The patient com- plains of an itching, burning sensation. The skin around the centre of the pustule is at first slightly raised by the inflammatory infiltration underneath it. Within twenty-four or forty-eight hours the size of the infiltrated area is as large as a nickel, and the inflamed part presents all the evidences of a very acute circumscribed inflammation. The swelling is now painful, tender on pressure, and exceedingly firm to the touch. The centre, previously occupied by a vesicle, is of a brownish-red or blackish-gra37 color, and presents indications of approaching gangrene. The epidermis exfoliates, exposing a necrosed area the size of a pea to a silver half-dollar. The dead tissue remains firmly connected with the surrounding indurated parts, until it becomes gradually detached in the course of the suppurative inflammation, which ensues sooner or later. After separation of the slough, spontaneous healing may take place, alwa37s leaving a depressed scar. In this form of anthrax general infec- tion seldom occurs, as the infection remains local, the earby and abun- dant inflammatory exudation forming an impermeable wall around the infected zone, beyond which the bacilli cannot escape. General infection, however, in such cases occasionally takes place where a vein becomes implicated in the process, and general infection is not prevented by the formation of a plastic thrombus on the proximal side of the intra-venous culture. The acuteness of the inflammation, and probabby, also, the direct necrotic effect of the ptomaines of the bacilli, invariably result in necrosis of the central portion of the pustule, which is the most characteristic pathological and clinical feature of this form of anthrax. 2. Anthrax CEdema.—This form of anthrax follows infection, if the tissues around the infection-atrium are freely supplied with loose con- nective tissue and the blood-suppby to the part is scanty,—conditions PATHOLOGY AND MORBID ANATOMY. 581 which are present about the eyelids, neck, and forearm. Anthrax in these localities appears as a flat infiltration without well-defined borders, and with little or no discoloration of the skin. From the infiltrated tissues a rapidly-spreading oedema extends in all directions. This form of anthrax is attended by greater danger of general infection than an- thrax pustule, as the bacilli are less effectually walled in by the inflam- matory product. Vesication, exfoliation of cuticle, and gangrene may also take place, and in milder cases a spontaneous cure is possible. As long as the infection remains local general symptoms are absent, but as soon as general infection has occurred the symptoms point to progressive septicaemia. • PATHOLOGY AND MORBID ANATOMY. If the tissues of a primary anthrax of the external surface are examined under the microscope, all the appearances of an acute non- suppurative inflammation are shown. The specific effect of the bacillus on the tissues results in serious alteration of the capillary vessels, which gives rise to an abundant inflammatory exudation. In malignant pus- tule, or anthrax pustule, the para-vascular and connective-tissue spaces become completely blocked with leucocytes in a remarkably short time, and necrosis of the central portion of the inflammatory product is a constant result of the acute ischaemia and the speedy coagulation necrosis thus produced. Anthracic inflammation never terminates in suppura- tion unless secondary infection with pus-microbes takes place. The local oedema in the oedematous variety, at the point of infection, is caused by vascular disturbances due to the presence of the bacilli within the blood- vessels and the interstitial inflammatory exudation caused by their pres- ence. In fatal cases the necropsy reveals the same changes in different organs as Koch has described in his experiments on rabbits. The capil- lary vessels in every part of the body will be found completely or par- tially blocked with bacilli, but the number of microbes is always greatest in the most vascular organs, as the spleen, liver, and kidneys. The bacilli, as in mice-septicaemia, will be found in the capillary ves- sels arranged in the direction of the blood-current, and most numerous where the flow of blood is most impeded, as at points of intersection. General infection always takes place through blood-vessels. The inter- nal organs are found enlarged and exceedingly vascular from engorge- ment caused by the capillary obstruction. Minute extravasations are found in different organs where the bacilli are most numerous, resulting in complete destruction of the capillary wall and rhexis. The secondary intestinal affection most frequently assumes the form of inflammatory haemorrhagic infiltration, more seldom that of haemorrhagic catarrh; ulcerations the size of a split pea to 2 inches in diameter are frequently 582 PRINCIPLES OF SURGERY. present, the remaining portion of the mucous membrane showing well- marked evidences of acute inflammation, great vascularity, and infiltra- tion. Mesenteric glands are swollen and contain numerous bacilli. The bronchial and intestinal mucous membranes show all the appearances of recent inflammatory changes, great vascularity, slight thickening, and here and there minute extravasations. In some cases the meninges of the brain show well-marked lesions that account for the cerebral symptoms during life. Pathologists have often failed in locating the immediate Fig. 106.—Anthrax. Section from Liver. X 700. (Fluegge.) cause of death in fatal cases of anthrax, and various theories have been advanced at different times to determine this point. In the most virulent form, the anthrax acutissimus, Bollinger be- lieves that the rapid growth of the bacillus in the blood brings about a sudden diminution of oxygen and a surplus of carbonic acid, and that death takes place by a slow process of asphyxia. Against this theory it can be maintained that, in the blood of animals that have died of the acutest form of the disease, comparative!}7 few bacilli are found ; and, further, that in the experiments made by Nencki, on the blood of rabbits that had died of this form of anthrax, it was found as capable of oxy- genation as the blood of healthy animals. The theory that death results PATHOLOGY AND MORBID ANATOMY. 583 from purely mechanical causes, due to the presence of bacilli in great abundance in the blood-vessels, is likewise not tenable, because no such fatal degree of obstruction in the capillary circulation has been found at the post-mortem examinations. As a third hypothesis, Bollinger advanced that the bacillus may generate a chemical poison that may cause death by intoxication. In reference to the last-mentioned cause, Hoffa calls attention to the following three possibilities:— 1. The bacilli of anthrax are in themselves poisonous, and the in- crease in their number increases the quantity of the poison in the same ratio. Against this supposition the results of the experiments made by Hoffa himself furnish the most conclusive proof. Of a pure culture of anthrax bacilli he injected a large quantity directly into the jugular veins of rabbits. The animals thus infected showed no symptoms of acute intoxication, but died in the same manner as animals infected in the usual way. 2. The bacilli of anthrax produce a poison capable of causing fer- mentation in the blood ; this poison is soluble in the blood. The fact that filtered blood of animals that had died of anthrax did not produce toxic symptoms when injected into healthy animals speaks against this argument. 3. The bacillus of anthrax separates toxic substances from complex combinations in the organism. This last explanation appears, from analogy of the views that are now entertained of bacteria and ptomaines, to be the most plausible, and he made an effort to produce such sub- stances outside of the animal body upon artificial culture media. For this purpose he cultivated the bacillus with the greatest precautions upon sterilized meat kept for several weeks in an incubator at 37° C. (98.6° F.). The chemical product thus obtained he attenuated according to the methods advised by Stass-Otto, Brieger, and after the more recent method of Fischer. By the methods of Stass-Otto and Fischer he succeeded in pro- ducing a substance that possessed an alkaline reaction, and produced toxic effects in animals. A strictby-pure article and an accurate chemical description of it could not be obtained, on account of the smallness of the quantity produced. The substance produced by Stass-Otto's method was used in experimenting on frogs, mice, guinea-pigs, and rabbits ; both of them produced symptoms of intoxication. After a short period of intoxication, with increased action of the heart and accelerated respira- tion, the animals became somnolent; respirations deep, slow, and irregu- lar, assisted by the action of all accessory muscles of respiration ; pupils dilated, temperature normal, diarrhoea, faeces bloody ; speedy death. At the necropsy the heart was found contracted, the blood was of a dark 584 PRINCIPLES OF SURGERY. color, and ecchymosis of the pericardium and peritoneum existed. There were no micro-organisms in the blood. The pathological conditions described here are an accurate duplication of the post-mortem descrip- tion in fatal cases of anthrax. The same author succeeded subsequently in isolating, by a complicated process, a toxic substance from the bodies of anthracic rabbits with the formula C3H6N2, which he called anthracin, besides a small quantity of metli37lguanidin. To the former substance he attributes the toxic symptoms in cases of anthrax. Injected subcu- taneously in rabbits, it produced first restlessness, rapid pulse, and accelerated respiration, followed by somnolence, deeper and slower respi- ration, diarrhoea, asphyictic symptoms, convulsions, and death. This substance is closely allied to kreatin, and contains 23 per cent, of nitrogen. These experiments leave but little doubt that the fatal termi- nation in cases of anthrax is caused by the action of toxic ptomaines formed in the body in consequence of the action of the bacilli upon certain as yet unknown combinations in the organism. DIFFERENTIAL DIAGNOSIS. Anthrax must be distinguished from other forms of acute circum- scribed inflammation, notably from furuncle and carbuncle. A furuncle is conical from the beginning, and the summit is transformed into a small slough. A carbuncle is nothing more nor less than a multiple furuncle, and is produced by the same microbic cause. Anthrax develops from a single centre, and the infiltration proceeds from this point in all directions. Necrosis is preceded by vesication, and the black, necrosed tissue is fully exposed after exfoliation of the epidermis. The oedema- tous form of anthrax might be mistaken for erysipelas or acute phlegmo- nous inflammation. Anthrax oedema is usually not attended by much discoloration of the skin, and there is no such distinct and abrupt line of limitation as in erysipelas. Phlegmonous inflammation, when advanced to the extent where it may resemble anthrax oedema, has gone on to the stage of suppuration. The differential diagnosis between malignant oedema and anthrax can only be made by searching for the primary cause by the use of the microscope. A positive differential diagnosis between suppurative lesions and anthrax can be made in the course of one or two days by inoculation experiments. If a rabbit or mouse is infected with a drop of anthracic blood or serum taken from the centre of the inflam- matory product, death from anthrax will follow within two days; while the same amount of fluid taken from a suppurative depot will produce no effect, or, at most, only a circumscribed abscess. As the anthrax bacillus can be readily stained and identified under the microscope, a positive differential diagnosis between these affections can always be made by the use of the microscope. PROGNOSIS. 585 PROGNOSIS. The location of the disease, the character of the tissues primarily affected, and the general condition of the patient greatly influence the prognosis in cases of anthrax. The prognosis is most favorable in young, healthy individuals suffering from anthracic pustule, as in such instances the general strength of the patient and the active tissue proliferation at the seat of infection are well calculated to prevent general infection ; while, in persons debilitated from any cause affected with the oedematous variety, general infection is very liable to follow. An anthrax oedema of the hand or arm is a less serious condition than a similar affection of the face or neck. Asa general rule, it may be stated that, the firmer and more circumscribed the local lesion, the more favorable the prognosis, and, vice versa, the more extensive the area of infection and the more diffuse the oedema, the greater the danger to life from general infection. The occurrence of general infection may be recognized without difficulty by the general symptoms which indicate the existence of progressive septic infection. The bacillus of anthrax multiplies with great rapidity after its entrance into the circulation, and the anthracin, which produces the septic S3-mptoms, is elaborated in amounts proportionate to the number of bacilli in the bod37. Fever, cough, rapid respiration, feeble and rapid pulse, diarrhoea, and delirium are some of the symptoms indicating that the disease has become general. All hope of recovery must be abandoned as soon as general infection has occurred ; death from pro- gressive infection and intoxication will be certain to take place, in spite of the most heroic local and general treatment. TREATMENT. The surgical treatment of anthrax must be directed toward the elimination or neutralization of the primary microbic cause. As within the living body the reproduction of the primary cause takes place ex- clusively by segmentation of the bacilli, any germicidal agents that inhibit or destroy the pathogenic property of the bacilli will be found useful in the local treatment of anthrax. It has been found experiment- ally that a 5-per-cent. solution of carbolic acid will arrest the growth of anthrax cultures, and clinical experience has demonstrated that the same solution, when brought in contact with the infected tissues by parenchymatous injections, has a decided influence in arresting further extension of the infection. Lande reports 2 cases of malignant anthrax saved by parenchyma- tous injections of carbolic acid. In the first case, a man aged 27, the upper lip was the seat of the disease ; in the second, a woman aged 65, the anthrax occupied the region below the scapula. Both patients were 586 PRINCIPLES OF SURGERY. very ill, low delirium and other symptoms of toxaemia being present. The injections were made into the subcutaneous tissue around the pustule. The strongest solution used consisted of 15 grammes of neutral glycerin and an equal part of distilled water, in which 3 grammes of pure carbolic acid were dissolved. The injections were made at five points around the pustule, and represented a total dose of 50 centi- grammes of the acid. The injections caused considerable pain, but rapid improvement followed. The solution used—10 per cent.—was stronger than any previously employed for the same purpose by Boeckel, Raimbert, and others. A 5-per-cent. solution in ordinary cases is strong enough, but in grave cases the 10-per-cent. solution must be used until improvement takes place, which should occur within forty-eight hours. The object of the parenchymatous injections should be to saturate, as far as possible, all of the infected tissues with the antiseptic for the purpose of destroying the bacilli, and, at the same time, to permeate the surrounding healthy tissue for some distance, with a view of destroying the soil for the growth of the microbes in advance of the invasion. The surface over the entire infected area should be rendered thoroughly aseptic, in order to prevent secondary infection with pus-microbes through the needle-punctures. The punctures should be made a few lines from the border of infiltration, but always toward the centre of the infected district. The injection is made gradually as the needle is with- drawn, so as to saturate the tissues for some distance along the entire length of the track of the needle. At one sitting from four to twelve injections are made, according to the size of the anthrax and the urgency of the symptoms. A compress wrung out of a l-to-1000 solution of corrosive sublimate should be kept constantly applied. Application of an ice-bag over the antiseptic compress will assist the germicidal agents in retarding or arresting further multiplication of the bacilli in the tissues. The injections should be repeated every six hours until the disease is under control, or until it is deemed unsafe, from the quantity injected, to administer more carbolic acid for fear of causing intoxica- tion. Excision has been objected to on the ground that the wound might become a new source of infection, and thus leave the patient in a more precarious condition, so far as general infection is concerned, than before the operation; but such is not the case if the area of infection is limited and the incisions can be made through healthy tissue. The following case affords a good illustration of the value of excision of anthrax in well-selected cases. Kaloff, of St. Petersburg, in making experiments with anthrax on animals, accidentally infected himself, either by a needle-puncture or by handling the organs of anthracic animals. The local infection appeared TREATMENT. 587 on the outer side of the thumb of the left hand as a small vesicle, that soon disappeared, but gave place to circumscribed infiltration on the second day. This inflammation rapidly extended, and was surrounded with haemorrhagic vesicles. The indurated tissues were promptly removed by excision; nevertheless, on the next day, swelling of axillary glands on same side, fever, great prostration, also diarrhoea, set in. The skin in the axillary region and side of chest was much swollen, and at different points bright-red, at others bluish-red. One of the axillary glands, the size of a hen's egg, and glands along the margins of the pectoralis major muscle were removed, and field of operation thoroughly disinfected with a 5-per-cent. solution of carbolic acid ; the same solu- tion was also thrown into the surrounding tissues with a hypodermic syringe. Cessation of fever and rapid healing of wound, followed by recoveiy. The diagnosis was confirmed by successful cultivations made with fragments of the excised tissue in bouillon and gelatin. Excision should always be resorted to in cases of anthrax pustule, as it fulfills the etiological indications more promptly and thoroughby than an}7 other treatment. The incisions should be made outside of the indurated tissues, and, for the purpose of preventing traumatic dissemination of the disease, the surface, after thorough irrigation, should be brushed over with a 10-per-cent. solution of carbolic acid before the wound is sutured. This procedure will destroy any bacilli that may have become deposited upon the surface of the wound. In the case just cited it is possible that lymphatic infection—an unusual occurrence in anthrax—developed in consequence of the entrance of bacilli into the open lymphatic vessels on the surface of the wound. Excision under strict antiseptic precautions is also justifiable in anthrax oedema, even if all of the infected tissues cannot be removed, as sterili- zation of the remaining portion of the infected tissues can be secured subsequently more efficiently by parenchymatous injections than if the primary focus of infection is allowed to remain as a hot-bed for pro- gressive infection. In such cases it would be good practice to sear the whole surface of the wound with the actual cautery, for the purpose of preventing general and regional dissemination by the entrance of bacilli into the open lumina of veins and lymphatics, and also to increase the resisting capacity of the tissues to infection by exciting an active tissue proliferation. The actual cautery would prove successful in recent cases, in cutting short an attack, if resorted to before any considerable infiltra- tion has occurred. It is said that shepherds, in districts where anthrax is endemic, destroy the vesicle with a red-hot needle as soon as it is detected, and it is seldom that the infection does not yield to this treat- ment. At this early stage the whole area of infection is limited, and 588 PRINCIPLES OF SURGERY. could be most effectually destroyed with the sharp point of a Paquelin cautery. The general symptoms in severe cases of local anthrax, and after general infection has occurred, resemble the clinical aspects of septicaemia produced by other causes, and patients suffering from general primary or secondary anthrax require the same stimulating, tonic, and supporting treatment that has been laid down in the treatment of septicaemia. CHAPTER XXIV. Glanders. Synonyms : Farcy ; equinia ; malleus humid us ; Morve ; Rotzkrank- heit. A contagious disease characterized by multiple foci of inflamma- tion and suppuration, and caused b37 infection with a specific microbe,— the bacillus mallei. The disease originates in the horse and occurs in men by contagion. Although glanders in man is a rare affection, it pre- sents, from a bacteriological study, so many points of interest that it merits more than a passing notice. It is one of the infectious diseases whose microbic cause is now thoroughly understood. BACTERIOLOGICAL HISTORY OF THE DISEASE. That glanders in man occurred as an infection from the horse species of animals has been known for a long time. Its contagiousness among horses was asserted by Sollegsel in the seventeenth century. Rindfleisch believed that he saw vibriones in the granular contents of glanderous abscesses. Klebs detected, in cultures of pus taken from animals suffering from this disease, small rods and granules, but further cultivations and inoculations in rabbits failed. The presence of minute organisms in cases of glanders was pointed out by Christatt and Kiener in 1868, and their observations were corroborated by Bouchard, Capitan, and Charrin, who found the organisms not only in parts exposed to the air, such as nasal ulcerations and pulmonary abscesses, but also in parts not so exposed, such as the spleen, liver, and lymphatic glands. Chaveau demonstrated by his experiments that the virus of glanders was fixed to small, solid particles, as he found the sediment, which formed after di- lating pus with water, active. This discovery marked an advance in the knowledge of the physical nature of the virus. Loffler and Schutz are the discoverers of the bacillus of glanders in horses. In 1882 they made a preliminary report of their researches (Deutsche Med. Wochenschrift, 1882, No. 52). In 1886 Loffler published his elaborate monograph on this subject (" Die ^Etiologie der Rotzkrankheit," Arbeiten aus dem Kaiserlichen Gesundheitsamte zu Berlin, Bd. i, pp. 141-199). About the same time, O. Israel made cultures upon blood-serum from nodules of three glanderous horses, with which he produced the disease artificially in rabbits The bacilli contained in these cultures correspond with the (589) 590 PRINCIPLES OF SURGERY. description of those isolated by Schiitz and Loffler. Soon after Loffler's first paper appeared, Bouchard, Capitan, and Charrin published almost simultaneously the results of their researches and observations ; but it appears from Loffler's second paper that none of them had been able to produce a pure culture. Kitt and Weichselbaum were the first who, by their own investigations, were able to corroborate the correctness of Loffler's discovery: the former by his observations and experiments on animals, the latter by a case of glanders in the human subject that came under his own observation. DESCRIPTION OF BACILLUS MALLEI. According to Loffler, the bacillus of glanders appears as a small rod, which is somewhat shorter and broader than the tubercle bacillus; its length varies but little, and corresponds to about two-thirds of the di- ameter of a red blood-corpuscle; the thickness varies between one-fifth and one-eighth of its length. These bacilli are either straight or slightly curved and rounded at their ends. Usually, they are found in pairs in a parallel direction, held together by a delicate, unstained pellicle. Examined in a drop of fluid, they show active molecular movements. Spontaneous movements could Pig 107.—bacilli no* De observed by Loffler. The colorless and some- a.F younqE potato times even somewhat dilated portions of the stained ^Baumgarten )X 95°' DaciUus are not spores, but, as Loffler affirms, indica- tions of commencing death. Loffler found that bacilli kept in a dry state for three months could occasionally be made to grow, but in most instances, after a few weeks, they could no longer be cultivated, which fact speaks against the existence of spores. On the other hand, in favor of the presence of endo-spores must be regarded the results obtained by Rosenthal, in Baumgarten's laboratory, with Neisser's method of staining spores, who showed that at least some of the bacilli contain spores, while in others the points which refuse staining material are undoubtedly, as Loffler claims, evidences of vacuolar degeneration. (a) Staining.—The method of staining the bacilli of glanders is characteristic; when the bacilli are treated by basic and aniline dyes no effect is produced. Method of Schiitz.—The sections are placed for twenty-four hours in the following mixture: Potash solution (1 in 10,000), concentrated alcohol, methylene-blue solution,—equal parts. Wash the sections in a watch-glass with water acidulated with 4 drops of acetic acid. Transfer for five minutes to 50-per-cent. alcohol, clarify in clove-oil, and mount in Canada balsam. TENACITY OF BACILLUS MALLEI. 591 Loffler's Method.—Sections are immersed for a few minutes in a solution of potash (1 in 10,000), then for a few minutes in an alkaline solution of methyl-blue ; after which they are decolorized with a solution of tropaeolin in acetic acid, or, what is still better, in a fluid composed of 10 centimetres of distilled water, 2 drops of sulphuric acid, and 1 drop of a 5-per-cent. solution of oxalic acid. (b) Cultivation.—When cultivated on solid sterilized blood-serum at a temperature of 38° C. (100.4° F.), the growth appears in the form of minute transparent drops on the surface, which consist exclusively of the characteristic bacilli. Cultures upon boiled potato, according to Loffler, Kitt, and Weichselbaum, form in three days a uniform amber-yellow layer, that about the sixth to the eighth day assumes a reddish hue, resem- bling the color of oxide of copper, which is not easily mistaken for any other culture upon the same soil. Upon this nutrient medium the bacilli were cultivated through twelve generations, and the cultures retained their activity for a year ; whether the bacillus was capable of cultivation after this time is not mentioned. The temperature at which cultures could be made to grow varied from 30° to 40° C. (86° to 104° F.). The bacillus also grows in neutralized bouillon, with and without the addition of pep- tone. The culture first renders the fluid turbid, and, later, settles on the bottom of the vessel as a white, shining mass. Weichselbaum succeeded in growing the bacillus upon ordinary nutrient agar and gelatin. Ras- kina rendered these nutrient media more fertile for the growth of this microbe by the addition of chicken-natron albuminate. Kranzfeld suc- ceeded best with Nocard and Roux's mixture,—meat-peptone, glycerin, agar-agar. TENACITY OF BACILLUS MALLEI. Loffler ascertained that this bacillus shows the same degree of re- sistance to heat and germicidal substances as other bacilli without spores. The bacillus-is destroyed by exposure for ten minutes to a temperature of 55° C. (131° F.). It is also destroyed by a 3- to 5-per-cent. solution of carbolic acid in five minutes, and in two minutes in a l-to-5000 solu- tion of corrosive sublimate. INOCULATION EXPERIMENTS. Kitt enumerates the following animals as being susceptible of inocu- lation with the virus of glanders : Tiger, lion, cat, sheep, goats, guinea- pigs, horse, ass, rabbits, and white rat. Pigs, dogs, the common rat, ducks, and chickens possess great immunity; the inoculations at best produce only a slight local reaction. Loffler made his first experiments on guinea-pigs and the field-mouse. In the guinea-pigs he observed, three to five days after subcutaneous injection of a pure culture, an ulcer 592 PRINCIPLES OF SURGERY. at the point of inoculation, and at the end of the first week swelling of the nearest lymphatic glands, attended by suppuration. At this stage of the disease the process often came to a stand-still and the animals recovered. In many animals the disease progressed quite rapidly to a fatal termination. Abscesses were frequently found in the testicle and the epididymis in the male, and in the breast and external genital organs of the female. The face, nasal cavity, and ankle-joint were also fre- quently the seat of ulcerative processes. In case the disease proved Fig. 108.—Glanderous Nodule from the Liver of a Field-Mouse. Bismarck-Brown Staining. Bacilli Stained after Loffler's Method. Bacilli Magnified and Drawn Twice this Size. X250. (Baumgarten.) K, karyokinetic figures in epithelioid cells. fatal, death usually occurred three or four weeks after inoculation. At the post-mortem, aside of the affections enumerated, nodules were found in the spleen, lungs, and frequently in the liver. The histological struc- ture of a recent nodule bears a great resemblance to tubercle. The bacilli are always found more numerous in the nodules if the disease is produced artificially by inoculation. The inflammatory product is first composed almost exclusively of epithelioid cells, between which leuco- cytes from the periphery insinuate themselves. Giant cells are never INOCULATION EXPERIMENTS. 593 found in glanderous nodules ; the epithelioid cells are derivatives of con- nective tissue and endothelial cells; while the leucocytes escape from the inflamed capillary vessels. Baumgarten constantly observed karyokinetic figures in the epithelioid cells. The leucocytes that enter the nodule soon show evidences of frag- mentation, and are converted into pus-corpuscles. The bacilli are dis- tributed among the cellular elements singly, in pairs, and in groups. Some of them may be seen also within the cellular elements, especially the epithelioid cells. Field-mice proved a great deal more susceptible to the virus of glanders than guinea-pigs, as they usually died three or four days after inoculation. The necropsy in these animals showed, at the point of inoculation, an infiltration from which swollen lymphatic vessels led to the nearest lymphatic glands. In the spleen and liver, which were always found greatly enlarged, numerous small nodules could be seen, while the remaining internal organs presented a normal appearance. Glanders in guinea-pigs and field-mice presents a series of pathological changes that cannot be mistaken for any other affection. The bacilli of glanders in the different organs can be detected most readily in recent specimens. In the blood bacilli were detected only in very acute cases,—a circum- stance that explains why so man37 inoculations with the blood of glan- derous horses proved unsuccessful. The bacilli of glanders are evidently strictly tissue- and not blood- parasites. Lundgren took a nodule from the lungs of a horse that had died of glanders, and implanted fragments of it under the skin of rabbits. The animals died about the nineteenth day after inoculation, and the necropsy revealed induration and small abscesses at the point of infection, and small, yellow nodules in the spleen, liver, lungs, testicles, and mucous membrane of the nose. Implantation of spleen-tissue into other rabbits fixed the period of incubation in this animal at from eleven to twelve days. Kranzfeld has recently published the results he obtained by inocula- tions with the virus of glanders in an animal hitherto not subjected to experimentation of this kind. He procured a pure culture from a nodule of a man who had died of glanders after a brief illness. Inoculations were made in a small rodent which is very numerous in the southern part of Russia, the Spermophilus guttatus. The course of the disease in this animal was almost the same as in the field-mice that were used by Loffler. Of 28 animals infected with different cultures, 16 died on the fourth day, 9 on the fifth, 2 on the seventh, and 1 on the tenth. The post-mortem appearances were always characteristic: a greenish-gray infiltration at the point of inoculation and a number of nodules in the 38 594 PRINCIPLES OF SURGERY. spleen; in one animal also very small, white nodules in the liver. Culti- vations from these nodules yielded a pure growth of the bacillus of glanders. If animals are infected by direct injection of a pure culture into a vein, no serious symptoms are produced ; but, if soon thereafter one or more muscles are injured subcutaneously, the microbes escape through the lacerated vessels, localize at the seat of injury, and produce a grave form of the disease. It has been determined by experiment that the farther from the trunk the inoculations are made, the less intense is the local reaction. When an animal is inoculated at a distance from the trunk, and shows no general symptoms, a subcutaneous injury of any portion of the trunk will furnish the necessary conditions for the development of a local form of infection. It had been generally believed that the intact skin furnished an adequate protection against infection with the bacillus of glanders until shown very recently by the experiments of Babes and Nocard that infec- tion can take place through the healthy skin. Nocard rubbed a pure culture of the bacillus into the skin in two guinea-pigs, and found on the fifteenth day some of the hair-follicles the seat of glanderous inflamma- tion. Histological examination showed numerous bacilli in the follicles, the epithelial layer much thickened, and the surrounding connective tissue in a state of proliferation. The infection had extended from the follicles through the connective tissues into the lymphatic vessels underneath, as was evident from the presence of bacilli in the lymphatic glands, vessels, and connective-tissue spaces in the immediate vicinity of the primaiy lesion of the skin. GLANDERS IN THE HORSE. Glanders and farcy in the horse are different manifestations of the same disease, and, as each of them is divided into an acute and chronic form, we find described four varieties of the disease in this animal,— acute and chronic glanders, acute and chronic farcy. Acute Glanders.—This form of glanders is attended by a high tem- perature (106° to 109° F.) and other symptoms of acute sepsis, and proves uniformly fatal in a few days. The breathing is accelerated, the pulse feeble and rapid, and there is complete loss of appetite. The nasal mucous membrane, at first of a dark, coppery color, with dark-red ecchy- motic patches, becomes purple ; these ecchymoses are rapidly converted into ulcers, from which issues a copious sero-sanguinolent discharge. Lymphatic infection is a characteristic feature of acute glanders. The submaxillary and cervical glands enlarge and suppurate, discharging unhealthy-looking, ichorous pus. Abscesses also form in the lymphatics of the face. GLANDERS IN THE HORSE. 595 Chronic Glanders.—This is the form most commonly seen in the horse. The disease begins in the mucous membrane of the nose. Small, whitish nodules, composed of small, round cells, are formed in the mucous membrane. These nodules soften and ulcerate. Similar nodules may be found in the larynx, trachea, and bronchi. The ulcerations may remain superficial, or they may extend to the deep tissues, even attacking cartilage and bone. The internal organs, especially the lungs, may become the seat of metastatic foci. The left nostril appears to be affected more frequently than the right. The lymphatic glands under- neath the lower jaw enlarge very rapidly, often reaching considerable dimensions during a single night. The glandular swellings may continue for several days, afterward slowly disappear, and then re-appear as rapidly as before. The discharge from the nostrils presents a starchy or glue-like appearance, adheres to the mucous membrane, where it dries and accumulates, causing narrowing of the nasal opening. Acute Farcy.—Acute farcy, together with chronic farcy, is simply another manifestation of glanders, and is initiated in a very similar manner to acute glanders. There are the same lesions of the lymphatics and nodules, and abscesses are found in the skin. A general swelling of the cutaneous tissues takes place, varying in size for a time, but suddenly a number of distinct swellings or nodules will appear, termed " farcy buds." These specific nodules, so characteristic of farcy in either its acute or chronic form, involve the skin, subcutaneous connective tissue, or they may extend to the deeper tissues. They vary in size from a pea to a hazel-nut. These nodules suppurate, and, after evacuation of their contents, leave ragged ulcers that discharge a foul, grayish-white, creamy liquid tinged with blood. When several ulcers are in close proximity they may become confluent and form an extensive ulcerating surface. With the appearance of the nodules the lymphatics become inflamed, swollen, and indurated. Not infrequently acute farcy terminates in the development of acute glanders, with all the pathological conditions that have been described as characteristic of that disease, thus showing their etiological identity. Chronic Farcy.—In this form of glanders the lymphatic glands are principally involved. The disease is not attended by much febrile dis- turbance, and all of the other general symptoms are less marked than in the other varieties of glanders. The lymphatic glands become enlarged, and nodules are formed in the skin, lungs, and other viscera. Central softening and suppuration of the nodules is a regular occurrence. Long, fistulous tracts often result from extensive undermining of the skin. In all of these different forms of glanders in the horse the cause remains the same and the pathological conditions are identical; only the clinical 596 PRINCIPLES OF SURGERY. aspects vary from the location, intensity, and extent of the primary infection. GLANDERS IN MAN. In man the disease occurs in an acute and chronic form, but does not exactly resembe any of the varieties of the disease in the horse or the disease artificially produced in animals by inoculation. The discharge from the nostrils of a diseased horse, brought in contact with an abraded surface or a mucous membrane, will communicate the disease. Notwith- standing the positive results that followed the cutaneous inoculations in guinea-pigs with a pure culture of the bacilli of glanders by Nocard, it is, for all practical purposes, safe to make the assertion that the virus of glanders can only find entrance into the organism through a wounded surface. Whether infection may not take place through the alimentary canal has, so far, not been definitely ascertained. It is certain that the disease cannot be contracted by eating boiled or fried flesh of animals. Infection through the respiratory organs is possible, as cases have been reported in which the lungs were the primary and only seat of the dis- ease. The fact that man can be infected with a pure culture of the bacilli of glanders as successfully as the animals that have been successfully experimented on received a sad illustration last winter in Vienna. Dr. Hoffman, a young and promising physician, who was making some experimental investigations on animals with pure cultures, accident- ally inoculated himself with the needle used for making the inoculations, and died from acute glanders in a few days. Observations of veterinary surgeons and experimental researches have shown, conclusively, that the disease can be transmitted from the mother to the foetus 'in utero by passage of the bacilli through the placenta from the maternal into the foetal circulation. When man is the subject of glanders, bacilli are found more constantly in the blood than in glanderous animals. In the case described by Weichselbaum, numerous bacilli could be seen in the blood. In this case a thrombus was found in one of the large meningeal veins, containing numerous bacilli, and which, undoubtedly, was one of the sources of the bacilli in the circulation. In man the nasal mucous mem- brane is not so frequently affected as in animals, although Bollinger has shown that in horses the nasal cavity is not always affected, and that it may present a normal condition, even when the larynx and lungs are seriously affected. Muscular abscesses, that may assimilate rheumatism, are a frequent occurrence, especially in the chronic form of the disease. SYMPTOMS AND DIAGNOSIS. The symptomatology of glanders is variable, as it is greatly modi- fied by the intensity of the infection, the primary location of the disease, SYMPTOMS AND DIAGNOSIS. 597 and the number and distribution of the metastatic foci. The disease may begin at a single point, and may then be mistaken for a carbuncle or a gangrenous erysipelas. Grsefe reports a case which began as an acute exophthalmos, and the nature of the disease was not ascertained until after death. In this case there were nodules in the choroid of the eye. Acute glanders runs a rapid and malignant course. Infection usually takes place through a small wound-puncture or abrasion about the face or hands. At the point of inoculation a somewhat elongated, soft, inflammatory swelling or nodule forms in a few days. Central softening and suppuration soon transform the inflammatory product into an undermined ulcer, with irregular, ragged margins, surrounded by a wall of infiltration. In mild cases the disease may remain local, and the ulcer heals under proper treatment in a few weeks. In other cases regional infection takes place, and the lymphatic glands become swollen and suppurate, leaving the same kind of ulcers as at the primary seat of infection. In the fatal cases general infection takes place either through the veins or the lymphatic vessels, and the symptoms then resemble septi- caemia or pyaemia, or a combination of these two diseases,—septico- pyaemia. If infection take place directly through the veins, a thrombo- phlebitis develops in connection with one of the nodules and the bacilli in the thrombus, which multiply in this nutrient medium and gain entrance into the general circulation singly or through the medium of infected emboli. Under such circumstances, nodules are found in the lungs, kidneys, and other internal organs, as suppurating metastatic deposits in muscles, bone, joints, and testicle. In such cases the general symp- toms may simulate to perfection typhoid fever, pyaemia, suppurative osteomyelitis, and acute general miliary tuberculosis. In acute cases, where general infection occurs early and rapidly, death results in from one to three or four weeks, while in chronic cases the final fatal termi- nation is often postponed for months. In illustration of the clinical history of this disease I will quote briefly a few cases. A Russian medical journal of recent date states that a young soldier who had been a wagoner before his admission into the army, was received into the military hospital suffering from two foul ulcers on the hard palate, which had perforated the nasal fossa and destroyed the inferior turbinated bones. Three weeks later a swelling appeared over the eyebrow; a fortnight afterward he complained of pain on the inner side of the left knee, around the internal tuberosity of the tibia. A purulent discharge occurred from the left ear, and, at the same time, an abscess developed on the back of the right hand which appeared as a deep-purple tubercle, with a hard circumference, and sunken toward the 598 PRINCIPLES OF SURGERY. centre ; a purulent discharge oozed from the surface. At first, for a short time after admission, the temperature varied, rising in the evening to 103° to 104° F.; later on it fell to normal. The disease was mistaken for syphilis, and iodide of potassium was given without the least benefit. About ten weeks after admission he was in better health, and left the hospital, receiving his discharge from the army. Within a few weeks he returned, with extension of ulceration of the hard palate; the uvula was destroyed. The characteristic nodules, the " farcy buds," appeared in the face; the metastatic abscess on the back of the hand remained. The patient ultimately died of exhaustion. Before death some of the nodules were extirpated ; they were found to contain micro-organisms resembling to perfection the bacillus of Loffler and Schiitz. Kuttner reports a number of cases in which the skin was the seat of numerous points of suppuration in the form of pustules, or more diffuse abscesses followed by ulcera- tion. The disease has been mistaken more frequently for syphilis than any other affection. This mistake in diagnosis is very liable to be made in the chronic form, in which the nodules grow very slowly, are hard, and may occur in groups or like a string of beads. The nodules usually soften, and form chronic ulcers, that closely resemble the ulcers resulting from the breaking down of gummata. If the disease primarily attack the nasal cavity, the mucous membrane presents hard nodules, and a copious discharge from the nose is present. In acute glanders affecting the nose and face, extensive destruction of tissue by the rapid breaking down of the nodules is one of the prominent clinical features of the disease. Complete destruction of the nose, with formation of large ulcers of the face, may happen in the course of a week. Chronic glanders may also be easily mistaken for tuberculosis of the skin, mucous membranes, and lymphatic glands. Acute glanders may simulate furuncle, carbuncle, and other acute suppurative lesions, as well as lymphangitis and erysipelas. In making a differential diagnosis be- tween these different affections and glanders, it is important, if possible, to trace the infection to its proper source. If the clinical history point to the possibility of infection by contact with a glanderous horse, it Fig. 109.—Acute Glanders, involv- ing Nose and Face, showing Extent of Local Lesions Eight Days after the Commencement of the First Symp- toms. (Birch-Hirschfeld.) PATHOLOGY AND MORBID ANATOMY. 599 should be remembered that the period of incubation in man varies from two days to three weeks. A positive diagnosis must necessarily rest on the detection of the specific microbe in the granulation tissue or in the discharges, and the results obtained by inoculation experiments. As soon as general infection has taken place, the symptoms resemble pyaemia or septicaemia; so that a differential diagnosis between metastatic glanders and general infectiou with pus-microbes cannot be made without the aid of the microscope and inoculation experiments. PATHOLOGY AND MORBID ANATOMY. The bacillus of glanders resembles, in its immediate action on the tissues, both the bacillus of tuberculosis and the pus-microbes. The histological change first observed in the infected tissues is a transforma- tion of mature into embr37onal tissue, the microscopical picture, with the exception of the absence of giant cells, resembling tubercle ; but this stage is of short duration, as the pyogenic effect of the bacillus of glanders soon produces purulent softening b37 the speedy conversion of the embry- onal cells and leucoc37tes into pus-corpuscles. The formation of abscesses is a constant occurrence, wherever localization has taken place, either by direct infection, secondaiy infection from regional diffusion through the lymphatic vessels and connective-tissue spaces, or by general infection by embolic diffusion through the general circulation. As soon as the disease has become general, the clinical picture and pathological conditions are the same as in pyaemia caused by a suppu- rative lesion. The differentiation between the two forms of metastasis can be made only by demonstrating the primary cause, by use of the microscope, or by the results obtained from inoculation experiments. The pus found in glanders is grayish red in color, and quite tenacious in recent lesions, but after opening the abscesses it assumes the character of ordinary pus, as the abscess-cavities then become the seat of secondary infection with pus-microbes. Swelling and abscesses of the testicles have been frequently observed in cases where the disease has become general, the affection in these organs being one of the clinical manifestations that embolic dissemination has occurred. Primary glanders of the lungs from inhalation of the microbes into the air-passages gives rise to symp- toms and pathological conditions that cannot be distinguished from pul- monary tuberculosis, unless the essential cause can be demonstrated in the sputa under the microscope, or glanders can be artificially produced by the injection of sputum into the subcutaneous tissue or the peritoneal cavity of guinea-pigs. The pulmonary nodules soften and suppurate, and cavities form in the same manner as in pulmonary tuberculosis. 600 PRINCIPLES OF SURGERY. PROGNOSIS. The prognosis in glanders should always be guarded, as a limited local lesion may be followed by a fatal form of general infection. The prognosis is comparatively favorable if the infection remain limited to a circumscribed area accessible to direct surgical treatment. It must be more guarded if regional infection through the lymphatic vessels has occurred, and it is absolutely fatal in cases of primary glanders of im- portant internal organs, and when general infection has followed in the course of a local lesion with or without regional dissemination. In the local form of the disease the ulcerations usually prove inveterate to treatment, and final recovery is often retarded for months by extensive undermining of the skin. Acute glanders with general infection, as a rule, proves fatal within one to three weeks, and death occurs in conse- quence of septic infection. TREATMENT. The prophylactic treatment consists in preventing infection from glanderous horses and substances which have become contaminated with the specific virus from diseased animals, and requires early recognition of the disease and killing of the affected animals, as well as thorough disinfection of the premises occupied by the diseased beast. The ca- davers should be cremated or deeply buried. Abrasions or granulating surfaces that have been exposed to infection should be cauterized. In cases of primary pulmonary or intestinal glanders, and after general infection from a local form of the disease has occurred, the treatment must be necessarily symptomatic, as such cases are beyond the reach of local or general treatment. The embarrassed respiration and feeble and rapid pulse indicate the use of alcoholic stimulants. A primary nodule should be removed by excision, taking all necessary pre- cautions to prevent infection of the wound in case the skin has been destroyed by ulceration. Limited regional infection should be treated in the same manner if ulceration has not taken place, and the conditions are such that all of the infected tissues can be removed with safety. After multiple abscesses have formed a radical operation is no longer indicated, the extent of the affection precluding the possibility of removing all of the infected tissues. In such cases the abscesses should be freely incised, fistulous tracts laid open, undermined skin cut away, and, as far as possible, the infected tissues removed with a sharp spoon ; then the entire surface should be disinfected with a 12-per-cent. solution of chloride of zinc. No attempt should be made, under such circumstances, to obtain healing of the superficial wounds until it be- comes apparent that the specific microbic cause has been eliminated or TREATMENT. 601 destroyed, and several repetitions of the curetting and disinfection may become necessary until this object is realized. The scraped surfaces should be kept covered with a moist antiseptic compress gauze, wrung out of l-to-2000 solution of corrosive sublimate or a 2-per-cent. solution of carbolic acid. If the prolonged use of these antiseptics is objection- able, on account of danger from absorption of toxic doses of drugs, strong iodine-water can be used in the same way. The internal use of iodine, creasote, and arsenic have been recommended as specifics in the treat- ment of glanders, but clinical experience has not supported this claim, and the surgeon must rely upon local measures in his efforts to pro- tect the patient against the dangers arising from regional and general infection ; while he must aim, at the same time, to maintain the resisting power of the tissues to the microbic invasion by a supporting tonic and stimulating treatment- INDEX. Abnobmal and defective callus, 53 Abscess, 212 acute, 214 diagnosis, 215 treatment, 217 chronic, 219 diagnosis, 219 treatment, 220 of brain, 271 cerebral localization, 273-277 prognosis, 272 symptoms and diagnosis, 272 treatment, 273 of internal organs, 259 of lung, diagnosis, 287 exploration, 288 operation, 288 tubercular, 450 pathological anatomy, 450, 451 prognosis, 453 symptoms and diagnosis, 452 treatment, 453-457 Absolute asepsis, 23 Accurate suturing, 25 Achromatine, 8 Actinomycosis hoininis, 549 clinical varieties, 555-562 description of fungus, 550-552 history, 549 of brain, 564 of bronchial tubes and lungs, 562 pathology and morbid anatomy, 553, 554 prognosis, 567 sources of infection, 553 symptoms and diagnosis, 565, 566 treatment, 568 Action of bacteria on tissues of body, 134 Acute suppuration, 209 tetanus, 397 Amputation in tuberculosis of joints, 524 Anthrax, 571 attenuation of virus, 577 clinical varieties, 578 description of bacillus, 572 differential diagnosis, 584 history, 571 in living body and in soil, 573 infection in man, 576 inoculation experiments, 574, 575 intensification of virus, 576 multiplication, 573 oedema, 580 of external surface, 579 pathology and morbid anatomy, 581 prognosis, 585 prophylactic inoculations, 577 pustule, 580 treatment, 585-588 Antiphlogistic treatment of inflamma- tion, 120 Arterial blood-supply, defective, 165 Arteries, ligation of, 165 Arthrectomy in tuberculosis of joints, 518, 519 Arthritis, suppurative, 259 Ascites, 482 Aspiration in tuberculosis of joints, 517 Attenuation of pathogenic bacteria, 136 Atypical resection, 520-522 Bacilli of putrefaction, 315-322 Bacillus of anthrax, description of, 572 multiplication of, 573 mallei, 589 description of, 590 tenacity of, 591 pyocyaneus, 204 pyogenes fcetidus, 204 saprogenes, 315 316 (603) 604 INDEX. Bacillus tetani, 384 ptomaines of, 390, 391 tuberculosis, 423 cultivation, 426 description, 423 manner of infection and dissemi- nation, 469, 470 staining, 424, 425 Bacteria, 127 action of, on tissues of body, 134 attenuation, 136 classification, 127 cultivation, 131-133 elimination, 149, 150 fission, 129 growth, 134 inoculation experiments, 135 localization, 141-146 multiplication, 129 outside of the body, 138 presence of, in healthy body, 139 140 putrefactive, 163 secondary or mixed infection, 146- 149 specific, 160-162 spores, 130 therapeutic inoculation, 137 transmission of, from parents to foetus, 151-155 Bacteridia, 571 Bacteriological causes of suppuration, 191 researches, 232, 233, 259, 260, 280, 281, 291-298, 303-311, 334-337, 383-391, 461, 462, 491, 492 Bladder, tuberculosis of, 544 prognosis and treatment, 545 symptoms and diagnosis, 545 Blood-corpuscles, red, 71 white, 70 Blood-plates, 72 Blood-vessels, 42 Bone, 49 tuberculosis of, 489 artificial, 490 clinical and bacteriological re- searches, 491, 492 means of differential diagnosis, 500, 501 Bone, tuberculosis of, pathology and morbid anatomy, 493-496 prognosis, 502 symptoms and diagnosis, 497-500 treatment, 503-507 Brain-abscess, 271-280 Brain, actinomycosis of, 564 exploration of, 278-280 Bronchial tubes and lungs, actinomy- cosis of, 562 Callus, 53 Capillary vessels, 68, 69 Cancer aquaticus, 180 Carbuncle, 229 diagnosis, 230 treatment, 230 Cartilage, 34, 107 Catarrhal inflammation, 101 Caustics producing necrosis, 167 Cauterization of wounds, 413 Cavum Retzii, 215 Cell division, 13 Central nervous system, 57 Chemical pyogenic substances, 194 Chromatin, 8 Chronic circumscribed suppurative os- teomyelitis, 256 pathological anatomy, 257 symptoms, 257 treatment, 257, 258 inflammation, 111-114 suppuration, 210 tetanus, 398 Cicatrization, 19 Classification of bacteria, 127 Clinical forms of septicaemia, 312-331 surgical tuberculosis, 447 Coagulation necrosis, 175, 176 Cold producing necrosis, 167 Color in gangrene, 171 Condition of tissues in necrosis, 171 Connective tissue, 41 Cornea, 31, 103-107 Corpuscle, third, 72 Croupous inflammation, 102, 103 Cultivation of bacteria, 131, 133 Decubitus, 164, 180 Defective arterial blood-supply, 165 INDEX. 605 Diabetic gangrene, 179 Diapedesis, 87 Direct causes of suppuration, 194-205 transmission of bacteria, 151 Disturbance of function, 91 Division of cells, 13 Dry gangrene, 178 Elimination of gangrenous part, 173 pathogenic bacteria, 149, 150 Embolism, 343-348 Emigration of leucocytes, 83-87 Emphysema, 171 Empyema, 280 after-treatment, 285 multiple resection, 286 thoracoplastic operation, 286 bacteriological studies, 280, 281 diagnosis, 282 prognosis, 282 treatment, 283 drainage, 285 evacuation of pus and removal of membranes, 284 incisions, 283 irrigation, 285 resection of rib, 284 Encapsulation of necrosed tissue, 173 Endocranial suppuration, 263-271 Epidermization, 22 Epididymis and testicle, tuberculosis of, 541 symptoms and diagnosis, 542 treatment, 543 Epiphyseolysis, 239 Epithelia, 36 Epithelioid cells, 439 Ergot the cause of gangrene, 167 Ergotine, 184 Erysipelas, 359 bullosum, 373 clinical forms, 373-376 cultivation, 361 description of streptococcus erysipe- latosus, 361 erythematosum, 373 facialis, 376 gangrenosum, 374 history of microbic origin, 359, 360 inoculation experiments, 362 | Erysipelas, inoculation experiments, for therapeutic purposes, 362 manner of infection, 364-366 metastaticum, 375 migrans, 375 prognosis, 377 relation of, to puerperal fever, 367 to phlegmonous inflammation and suppuration, 368, 369 symptoms and diagnosis, 370-372 traumatic, 376 treatment, 377-379 Erysipeloid, 380, 381 Essential condition for growth of bac- teria, 134 Excision of wounds, 413 Experiments, inoculation, .of bacteria, 135 Exploration of brain, 278-280 of lung, 288 External parts, gangrene of, 168 Exudation, inflammatory, 83 Fallopian tubes, tuberculosis of, 538 symptoms and diagnosis, 539 treatment, 540 Farcy, acute, 595 chronic, 595 Fascia tuberculosis, 530 Fermentation fever, 313 symptoms and diagnosis, 314 Fibrous tubercle, 443 Fission of bacteria, 129 Five phases of chromatin substance, 9 Fixed tissue-cells, 73 Foot, perforating ulcer of, 183 Fragmentation of nucleus, 12 Function, disturbance of, 91 Furuncle, 227 Gangbene, caused by ergot, 167 color in, 171 diabetic, 179 dry, 178 hospital, 181, 182 line of demarcation, 173 moist, 178 of external parts, 168 prognosis, 184 progressive, 177, 178 606 INDEX. Gangrene, senile, 179 swelling, 171 treatment, 185-189 Genito-urinary organs, tuberculosis of, 537 Giant cells, 437-439 Glanders, 589 acute, 594 bacteriological history of, 589 chronic, 595 in the horse, 594 in man, 596 inoculation experiments, 591-594 pathology and morbid anatomy, 599 prognosis, 600 symptoms and diagnosis, 596-598 treatment, 600, 601 Glands, 56 Glans penis and urethra, tuberculosis of, 541 Granulating surfaces, skin-grafting in, 38 Granulation tissue, 13 vascularization of, 16 Granulomata, 112 Growth of bacteria, 134 H^EMOBBHAGIC INFLAMMATION, 95 Haemostasis, 24 Head tetanus, 398 Healing of wounds, 2 Heat producing necrosis, 166 Histogenesis of suppuration, 191 of tubercle, 435, 436 Histological structure of tubercle, 437- 442 Histology of tubercle, 433, 434 Histozym, 313 Hospital gangrene, 181, 182 Hyaline tubercle, 444 Hydrophobia, 403 a microbic disease, 405, 406 causes, 407 in the dog, 404 pathology and morbid anatomy, 411, 412 prognosis, 410 symptoms and diagnosis, 407-409 treatment, 413 Hydrophobia, treatment, cauterization of wound, 413 excision of wound, 413 palliative, 416, 417 prophylactic, 413, 414 Ictebus, haematogenous, 349 Immediate or direct union of wounds, 3 Incubation period of tetanus, 392 Indirect causes of suppuration, 193 Infection-atrium of bacillus tetani, 393, 394 Inflammation, 67, 158, 159 chronic, 111, 114 haemorrhagic, 95 histological elements in, 68 interstitial, 95 modification of, 93 of mucous membranes, 101, 102 of non-vascular tissue, 103 of serous membranes, 96-100 parenchymatous, 93 prognosis, 116 suppurative, 96 symptoms, 74-91 symptoms and diagnosis, 114-116 treatment, 117 anodynes, 125 antiphlogistic, 120 antipyretics, 123 antiseptic fomentations, 122 application of cold, 122 counter-irritation, 126 diet, 124 elevation of part, 121 ignipuncture, 126 massage, 125 parenchymatous injections, 118, 119 physiological rest, 121 stimulants, 124 tonics and alteratives, 125 Inflammatory exudation, 83 transudation, 90 Inoculation experiments of bacteria, 135 of tuberculosis, 426-428 Inoculation-tuberculosis in man, 429- 433 Inoculations, prophylactic, 414-416 Internal ear, tuberculosis of, 457 INDI Internal ear, necrosis, 168 organs, abscess of, 259 Iris, tuberculosis of, 458 Joints, tuberculosis of, 507 etiology, 507 pathology and morbid anatomy, 508 prognosis, 514 symptoms and diagnosis, 511-514 treatment, 515 amputation, 524 arthrectomy, 518, 519 aspiration, 517 atypical resection, 520-522 rest, 516 subcutaneous evacuation, 517 typical resection, 523 varieties of, 509-511 Kabyokinesis, 8 Karyolysis, 168 Karyomitosis, 8 Karyorhexis, 168, 17ri Labge cavities, suppuration in, 259 Leptomeningitis, suppurative, 267,268 Leucocyte, 70, 437 emigration of, 83-87 Ligation of arteries in their continuity, 165 Liquefaction of necrosed tissue, 173 Localization of bacteria, 141-146 Loss of function in osteomyelitis, 239 Lung-abscess, 287-289 Lupus, tubercular nature of, 459-462 Lymphatic glands, tuberculosis of, 469 pathological histology and morbid anatomy, 471 prognosis, 475 symptoms and diagnosis, 472-474 treatment, 476-480 Lyssa nervosa falsa, 410 Macbocytes, 438 Malignant oedema, 309-311 Mammary gland, tuberculosis of, 536 Metastatic suppuration, 349-351 Microbe enchapelet, 334 Microbic cause of tetanus, 392 origin of erysipelas, 359, 360 sx. 607 Microbic origin of suppuration, 191,192 of tuberculosis, 419-422 Micrococcus pyogenes tenuis, 202 Modification of inflammation, 93 Moist gangrene, 178 Mouth and tongue, tuberculosis of, 532 pathology, 532 symptoms and diagnosis, 533 treatment, 534 Mucous membrane, inflammation of 101, 102 of intestines, tuberculosis of, 535 suppurative inflammation of, 212 transplantation of, 41 Mummification, 172 Muscles, 46 non-striated muscular fibre, 46 striated muscular fibre, 46 suture of, 49 Myeloplaques, 438 Necbobiosis, 177 Necrosed tissue, liquefaction of, 173 Necrosis, 157 coagulation, 175, 176 etiology, 158-167 general symptoms, 174 internal, 168 pathological and clinical varieties, 175-189 prognosis, 184 symptoms, 168-174 treatment, 185-189 Nerve suture, 62 primary, 63 secondary, 63 Nerves, peripheral, 58 Nervous system, central, 57 Noma, 180 Non-vascular tissue, 31 cartilage, 34 cornea, 31 inflammation of, 103 Nucleus, fragmentation of, 12 Obstbucted venous circulation, 166 Odor of necrosed tissue, 172 CEdema, malignant, 309-311 Opening of the skull, 278 Operation, thoracoplastic, 286 608 INDEX. Origin of suppuration, 191, 192 Osseous tuberculosis, cause of, 489 Osteomyelitis, suppurative, 231 early operations, 248 intermediate operations, 249, 250 late operations, 251-256 Pachymeningitis, suppurative, 263 Pain a symptom of necrosis, 169 of osteomyelitis, 237 Parenchymatous inflammation, 93 Paronychia, 226 Pathogenic bacteria, 127 attenuation, 136 classification, 127 cultivation, 131-133 elimination, 149, 150 inoculation, 137 localization, 141-146 multiplication, 129 presence of, in healthy body, 139, 140 secondary or mixed infection, 146- 149 transmission of, from parents to fcetus, 151-155 Perforating ulcer of foot, 183 of stomach and duodenum, 183 Pericarditis, suppurative, 289 Pericardium, incision and drainage, 290 puncture and aspiration, 290 Peripheral nerves, 58 Peritoneum, tuberculosis of, 480 bacteriological remarks, 480 clinical studies, 481 pathology and morbid anatomy,482 symptoms and diagnosis, 483 treatment, 484-487 Peritonitis, adhesive, 483 fibrino-plastic, 483 plastic and suppurative, 295 suppurative, 291-302 Phagocytosis, 108-111 Phlegmonous inflammation, relation of erysipelas to, 368 with suppuration, 220 Physiological rest, 26 Plasma rhexis, 177 Progressive gangrene, 177 with emphysema, 178 Prophylactic inoculations, 414—416 Proteus mirabilis, 317 vulgaris, 316 Zenkeri, 317 Ptomaines, 134, 198-200, 317-322 of bacillus tetani, 390, 391 of pus-microbes as a cause of sup- puration, 198-200 Puerperal fever, relation of erysipelas to, 367 Pulse, after ligation of artery, 170 Purulent infiltration, progressive, 223 Pus, 205 corpuscles, 206-208 microbes, 195-198 description and specific action of, 200-205 ptomaines of, 198-200 serum, 206 Putrefactive bacteria, 163 Pyaemia, 333 bacteriological and experimental researches, 334-837 etiology, 338-347 in rabbits, 335 pathological anatomy, 352, 353 prognosis, 352 symptoms and diagnosis, 348-351 treatment, 354-356 Pyogenic microbes as a cause of sepsis, 311 substances, chemical, 194 Redness a symptom of osteomyelitis, 238 Regeneration, 1 of different tissues, 31 Reticulum, tubercle, 440 Rib, resection of, 284 Ribs, multiple resection of, 286 Sapb^mia, 315 prognosis, 323 symptoms and diagnosis, 322 treatment, 323, 324 Senile gangrene, 179 Sepsis, pyogenic microbes as a cause of, 311 Septicaemia, 303 bacteriological researches, 308-311 INDEX. 609 Septicaemia, clinical forms of, 312-331 in mice, 304, 305 in rabbits, 306-309 progressive, 325 causes, 325, 326 pathology and morbid anatomy, 330 prognosis, 329 symptoms and diagnosis, 327, 328 treatment, 330, 331 Septicopyaemia, 356-358 kryptogenetic, 357 spontaneous, 357 Serous membranes, inflammation of, 96-100 Skin-grafting, 38, 39 Skin, tuberculosis of, 459 pathology and morbid anatomy, 462 prognosis, 466 symptoms and diagnosis, 463-465 treatment, 466-468 Skull, opening of, 278 Specific bacteria, 160-162 Spores of bacteria, 130 Staphylococcus cereus albus, 202 cereus flavus, 202 flavescens, 202 pyogenes albus, 201 pyogenes aureus, 201 pyogenes citreus, 201 Stomach and duodenum, perforating ulcer of, 183 Streptococcus erysipelatosus, 361 pyogenes, 203 Subacute suppuration, 210 Suppuration, 191 acute, 207 bacterial causes and histogenesis of, 191 chronic, 210 clinical forms, 209 direct causes, 194-205 endocranial, 263-271 history of microbic origin, 191, 192 in large cavities, 259 in wounds, 211 indirect causes, 193 pus, 205-208 relation of erysipelas to, 368, 369 subacute, 210 39 uppurative arthritis, 259 bacteriological researches,259,260 symptoms and diagnosis, 261 treatment, 261-263 inflammation, 96, 101 of mucous membrane, 213-230 leptomeningitis, 267, 268 symptoms and diagnosis, 269 treatment, 270 osteomyelitis, 231 bacteriological and experimental investigations, 232, 233 causes, 234, 235 chronic circumscribed, 256-258 diagnosis, 239, 240 history, 231 pathological anatomy, 242, 243 prognosis, 241 symptoms, 236-238 treatment, 244-255 pachymeningitis, 263 symptoms and diagnosis, 264 treatment, 265-267 pericarditis, 289 peritonitis, 291 bacteriological and experimental researches, 291-298 causes, 295-297 clinical and bacteriological stud- ies, 294 symptoms and diagnosis, 298, 299 treatment, 300-302 tendo-vaginitis, 224 Surgical tuberculosis, 419-446 clinical forms, 447-468 Suture of muscles, 49 of nerves, 62-66 Suturing, 25 of granulating wounds, 29 Symptoms of inflammation, 74-91, 114- 116 Synovitis, 238 Swelling a symptom of osteomyelitis, 237 in moist gangrene, 170 Tempebatube in gangrene, 170 Tenderness a symptom of osteomyelitis, 237 in diagnosis of necrosis, 169 610 INDEX. Tetanus, 383 acute, 397 bacteriological studies, 383-391 clinical forms, 397, 398 cultivation, 384 etiology, 392-394 hydrophobicus, 398 infection-atrium, 393, 394 inoculation experiments, 385-390 neonatorum, 398 pathology and morbid anatomy, 399 period of incubation, 392 prognosis, 398 specific microbic cause, 392 symptoms and diagnosis, 395-397 treatment, 399-401 Therapeutic inoculation of bacteria, 137 Third corpuscle, 72 Thoracoplastic operation, 286 Thrombosis, 340-342 Tissue-cells, 73 Tissue, condition of, 171 connective, 41 non-vascular, 31 vascular, 35 Tissues, action of bacteria on, 134 Transmission of bacteria, 151-155 Transplantation of mucous membrane, 41 of skin, 38 Transudation, inflammatory, 90 Trauma, 163 Traumatic erysipelas, 376 Treatment of acute abscess, 217, 218 anthrax, 585-588 brain-abscess, 273 carbuncle, 230 chronic abscess, 220 empyema, 283-287 erysipelas, 377-379 furuncle, 228 gangrene, 185-189 glanders, 600, 601 hydrophobia, 413-417 inflammation, 117-126 necrosis, 185-189 paronychia, 226 phlegmonous inflammation, 221, £ purulent inflammation, 223 Treatment of pyaemia, 354^356 sapraemia, 323, 324 septicaemia, 330, 331 suppurating wounds, 28 suppurative arthritis, 261-263 leptomeningitis, 270 osteomyelitis, 244-255 pachymeningitis, 265-267 peritonitis, 300-302 tendo-vaginitis, 225 tetanus, 399-401 tubercular abscess, 453-457 tendo-vaginitis, 528-5:30 tuberculosis of actinomycosis hom- inis, 568 bladder, 545-548 bone, 503-507 epididymis and testicle, 54:j Fallopian tubes, 540 joints, 515-524 lymphatic glands, 470-480 mammary gland, 536 mouth and tongue, 531 peritoneum, 48-4-487 skin, 406-468 vulva, vagina, and uterus, 537 wounds, 23 skin-grafting in, 39 Trismus, 398 Tubercle, fibrous, 443 hyaline, 444 nodule, arrangement of cells in, 440, 441 growth of, 442 reticulated, 443 Tubercular abscess, 450 ascites, 482 tendo-vaginitis, 525 pathology, 525 prognosis, 527 symptoms and diagnosis, 527 treatment, 528-530 Tuberculosis, surgical, 419 calcification, 446 caseation, 444, 445 description of bacillus, 423 growth of tubercle-nodules, 442 hereditary and acquired disposi- tion, 448, 449 histogenesis of tubercle, 435, 436 INDEX. 611 Tuberculosis, surgical, histological structure of tubercle, 437-441 histology of tubercle, 433, 434 history of microbic origin, 419-422 inoculation experiments, 426-428 tuberculosis in man, 429-432 pathological varieties, 443 Tuberculosis of bladder, 544 bones, 489-507 epididymis and testicle, 541 Fallopian tubes, 538 fascia, 530 genito-urinary organs, 537 glans penis and urethra, 541 internal ear, 457 joints, 507-524 lymphatic glands, 469-480 mammary gland, 536 mouth and tongue, 532 mucous membrane of intestines, 535 peritoneum, 480-487 the iris, 458 the skin, 459-468 vesiculae seminalis, 543 vulva, vagina, and uterus, 537 treatment, 538 Ulceb of foot, 183 of stomach and duodenum, 183 I Union of wounds by primary inteii; tion, 6 by secondary intention, 2T Vacuolar degeneration, 177 Varieties of necrosis, 175-189 of tuberculosis of joints, 509-511 Vascular tissue, 35 surface epithelia, 36 Vascularization of granulation tissue, Hi Venous circulation, obstructed, 166 Vesiculae seminalis, tuberculosis of, 543 Vessels, capillary, 68, 69 Vulva, vagina, and uterus, tuberculosis of, 537 Wounds, cauterization of, 413 excision of, 413 healing of, 2 immediate or direct union, 3 of blood-vessels, 42 skin-grafting in, 39 suppuration in, 211 suturing of granulating, 29 treatment of, 23 absolute asepsis in, 23, 28 of suppurating, 28 union by primary intention, 6 by secondary intention, 27 snn^nn^^iiiiiiiiPiisiii^^ Revised Edition, 1892. Catalogue OF THE Medical Publications OF THE F. A. DAVIS CO. Publishers, Philadelphia, Pa. MAIN OFFICE—1231 Filbert Street, Philadelphia. 117 W. Forty-Second Street, New York. 20 Lakeside Building, 214-220 S. Clark Street, Chicago. 40 Berners St., Oxford. St., London, W., Eng. ORDER FROM NEAREST OFFICE. FOR SALE BY ALL BOOKSELLERS. 'h> i SPECIAL NOTICE. Prices of books, as given in our catalogues and circulars, include =J1 full prepa37ment of postage, freight, or express charges. Customers in Canada and Mexico must pa}r the cost of duty, in addition, at point of destination. IdjT N. B.—Remittances should be made by Express Money-Order, [n= Post-Offlce Money-Order, Registered Letter, or Draft on New York r^J City, Philadelphia, Boston, or Chicago. We do not hold ourselves responsible for books sent by mail; to insure safe arrival of books sent to distant parts, the package should =H be registered. Charges for registering (at purchaser's expense), ten cents for every four pounds, or less. I km m I JJjT 1 INDEX TO CATALOGUE. BOOKS IN PKESS AND IN PREPARATION, PAGES 31 AND 32. PAGE Annual of the Universal Medical Sciences..............27, 28, 29 Anatomy. Practical Anatomy—Boenning...... 4 Structure of the Central Nervous Sys- tem—Edinger............. 8 Charts of the Nervo-Vascular System— Price and Eagleton......'. . . . 17 Synopsis of Human Anatomy—Young . . 25 Bacteriology. Bacteriological Diagnosis—Eisenberg . . 8 Clinical Charts. Improved Clinical Charts—Bashore .... 3 Domestic Hygiene, etc. The Daughter: Her Health, Education, and Wedlock—Capp.......... 5 Consumption : How to Prevent it, etc.— Davis.................. 7 Plain Talks on Avoided Subjects- Guernsey ................ 9 Heredity, Health, and Personal Beauty— Shoemaker.............'. . 21 Electricity. Practical Electricity in Medicine and Surgery—Liebig and Rohe...... 12 Electricity' in the Diseases of Women— Massc'y................. 13 Fever. Fever: its Pathology and Treatment— Hare.................. 10 Hay Fever—Sajous............ 20 Gynecology. Lessons in Gynecology—Goodell..... 9 Practical Gynecology—Montgomery ... 32 Heart, Lungs, Kidneys, etc. Diseases of the Heart, Lungs, and Kidneys—Davis............ 32 Diseases of the Heart and Circulation in Children—Keating and Edwards ... 12 Diabetes: its Cause, Symptoms, and Treatment—Purdy........... IT Hygiene. Climatology of Southern California— Remondino............... 18 Text-Book of Hygiene—Rohe....... 19 Materia Medica and Thera- peutics. Hand-Book of Materia Medica, Pharmacy, and Therapeutics—Bowen..... 4 Ointments and Oleates—Shoemaker ... 21 Materia Medica and Therapeutics—Shoe- maker ................. 22 International Pocket Medical Formulary— Witherstine.............. 26 Miscellaneous. PAGE Book on the Physician Himself—Cathell . "> Oxygen—Demafquay and W alii an .... 7 Record-Book of Medical Examinations for Life-insurance—Keating....... 11 The Medical Bulletin, Monthly...... 2 Physician's Interpreter.......... 13 Circumcision—Remondino........ 18 Medical Symbolism—Sozinskey...... 23 International Pocket Medical Formulajv— Witherstine.............' . 2G The Chinese: Medical, Political, and Social—Coltman........... 6 ABC of the Swedisti System of Educa- tional Gymnastics—Nissen...... 15 Lectures on Auto-Intoxication—Bouchard .'J2 Nervous System, Spine, etc. Spinal Concussion—Clevenger...... 6 Structure of the Central Nervous System —Edinger................ 8 Epilepsy: its Pathology and Treatment— Hare.................. 10 Lectures on Nervous Diseases—Ranney . 30 Obstetrics. Childbed : its Management; Diseases and Their Treatment—Manton ...... 32 Eclampsia—Micliener and ethers..... 13 Obstetric Synopsis—Stewart....... 24 Physiogn omy. Practical and Scientific Physiognomy— Stanton ................ 30 Physiology. Physiology of Domestic Animals—Smith . 23 Surgery and Surgical Operations. Practice of Snrgerv—Packard...... 32 Tuberculosis o!'theBones and Joints—Senn 32 Circumcision—Remondino........ 18 Principles of Surgery—Senn....... 20 Swedish Movement and Massage. Swedish Movement and Massage Treat- ment—Nissen............. ],r> Throat and Nose. Journal of Laryngology and Rhinology . 11 Hay Fever—Sajous............ 20 Diphtheria, Croup, etc.—Sanne...... 2"i Lectures on the Diseases of the Nose and Throat. Sajous............ 31 Venereal Diseases. Syphilis To-day and in Antiquity—Buret 4 & 32 Neuroses of the Genito-Urinary System in the Male—Ultzmann.......24 Veterinary. Age of Domestic Animals—Hnidekoper . 11 Physiology of Domestic Animals—Smith . 23 Visiting-Lists and Account- Books. Medical Bulletin Visiting-List or Pliysi- sicians' Call-Record........". . 14 Physicians' All-Requisite Account-Book . 10 MEDICAL BULLETIN. A Monthly Journal of Medicine and Surgery. Edited by John V. Shoemaker, A.M., M.D. Bright, original, and readable. Articles by the best practical writers procurable. Everv article as brief as is consistent with the preser- vation of its scientific value. Therapeutic Notes by the leaders of the medical profession throughout the world. These and many other unique features help to keep The Medical Bulletin in its present position as the leading low-price Medical Monthly of the world. Subscribe now. TERMS: $1.00 a year in advance in Vnited States, Canada, and Mexico. Foreign Subscription Terms: England, 5s.; France, 6 fr.; Germany, 6 marks; Japan, 1 yen; Australia, 5s.; Holland, 3 florins. (2) Medical Publications of The F. A. Davis Co., Philadelphia. Bashore's Improved Clinical Chart. For the Separate Plotting of Temperature, Pulse, and Respiration. Designed for the Convenient. Accurate, and Permanent Daily Recording of Cases in Hospital and Private Practice. By HARVEY B. BASHORE, UI.B. .gyy-J 1111 arm COPYEIGHTED, 1888, BT F. A. DAVIS. 50 Charts, in Tablet Form. Size 8 x 12 inches. Price, post-paid, in the United States and Canada, 50 Cents, net; in Great Britain, 3s. 6d.; in Prance, 6 fr. 60. The above diagram is a little more than one-fifth (1-5) the actual size of the chart and shows the method of plotting, the upper curve being the Temperature, the middle the Pulse, and the lower the Respiration. By this methba a full record of each can easily be kept with but one color ink. It is so arranged that all practitioners will find it an invaluable aid in the treatment of their patients. On the back of each chart will be found ample space conveniently arranged for recording "Clinical History and Svmptoms" and "Treatment." Bv its use the physician will secure such a complete record of his cases as will enable him to review them at any time. Thus he will always have at hand a source of individual improvement and benefit in the practice of his profession, the value of which can hardly be overestimated. (3) Medical Publication* of The F. A. Davis Co., Philadelphia. BOENWING A Text-Book on Practical Anatomy, Including a Section on Surgical Anatomy. By Henry C. Boenning, M.D., Lecturer on Anatomy and Surgery in the Philadelphia School of Anatomy ; Demonstrator of Anatomy in the Medico- Chirurgical College, etc., etc. Fully illustrated throughout with about 200 Wood-Engravings. In one handsome Octavo volume, printed in extra-large, clear type, making it specially desirable for use in the dissecting-room. Nearly 500 pages. Substantially bound in Extra Cloth. Also in Oil-Cloth, for use in the dissecting-room without soiling. Price, post-paid, in the United States, $2.50, net; Canada (duty paid), $2.75, net; Great Britain, 14s.; France, 16 fr. 20. This work is fully illustrated throughout with clear and instructive engravings. It is not as large as the usual text-books on anatomy, nor yet so small as many of the ready remem- brances, but it oecupies the middle ground, and will find an acceptable place with many students.—Columbus Med. Journal. There is not an unnecessary word in this book of nearly five hundred pages. As a typo- graphical specimen it is elegant. Systematic, comprehensive, and intensely practical, we heartily commend it to all medical students and practitioners.—Denver Med. Times. BO WEN Hand-Book of Materia Medica, Pharmacy, and Therapeutics. By Cuthbert Bowen, M.D., B.A., Editor of " Notes on Practice." The second volume in the Physicians' and Students' Ready Reference Series. One 12mo volume of 370 psjges. Handsomely bound in Dark-Blue Cloth. Price, post-paid, in the United States and Canada, $1.40, net; in Great Britain, 8s. 6d.; in France, 9 fr. 25. This excellent manual comprises in its II cated in its title as could well be crowded S66 pages about as much sound and rain- into the compass.—St. Louis Medical and able information on the subjects indi- || SurgieaUournal. BUBET SYPHILIS ,n Ancient and Prehistoric Times. With a Chapter on the Rational Treatment of Syphilis in the Nineteenth Century. By Dr. F. Buret, Paris, France. Translated from the French, with the author's permission, with notes, by A. H. Ohmann-Dumesnil, Professor of Dermatology and Syphilology in the St. Louis College of Physicians and Surgeoms. No. 12 in the Physicians' and Students' Ready-Reference Series. 230 pages. 12mo. Extra Dark-Blue Cloth. Price, post-paid, in the United States and Canada, $1.25, net; in Great Britain, 6s. 6d.; in France, 7 fr. 75. This volume, which is one of a series of three (the other two, treating of Syphilis in the Middle Ages and in modern times, now in active preparation), gives the most com- plete history of Syphilis from prehistoric times up to the Christian Era. The subject throughout is treated in a clear, concise manner, and readers will find many things which are historically new. In order to give some idea of the contents of this first volume, the following are cited as among the subjects treated :— In What does Syphilis Consist? Origin of the Word Syphilis. The Age of Syphilis. Syphilis in Prehistoric Times. Tchoang.—Syphilis Among the Chinese 5000 Years Ago. Kasa— Syphilis in Japan in the Ninth Century B.C. Syphilis Among the Ancient Egyptians, 1400 B.C. Syphilis Amontr the Ancient Assyrians and Babylonians. Syphilis Among the Hebrews in Biblical Times. Upadansa.— Syphilis Among the Hindoos, 1000 B.C. Sukon.— Syphilis Among the Greeks. Ficus— Syphilis at Rome under the Caesars. Conclusion : Rational Treatment of Syphilis in the Nineteenth Century. (4) Medical Publications of The F. A. Davis Co., Philadelphia. CAPP The Daughter. Her Healt^edioc^tiOM' and Homely Suggestions to Mothers and Daughters. By Willtam M. Capp, M.D., Philadelphia. This is just such a book as a family physician would advise his lady patients to obtain and read. It answers marry questions which eveiy busy practitioner of medicine has put to him in the sick-room at a time when it is neither expedient nor wise to impart the information sought. It is complete in one beautifully printed (large, clear type) 12mo volume of 150 pages. Attractively bound in Extra Cloth. Price, post-paid, in the United States and Canada, $1.00, net; In Grea, Britain, 5s. 6d.; France, 6 fr. 20. In the 144 pages allotted to him he has com- pressed an amount of homely wisdom on the physical, mental, and moral "development of the female ch Id from birth to maturity which is to be found elsewhere in only the great book of experience. It is, of course, a book for mothers, but is one so void of offense in expression or ideas that it can safely be recom- mended for all whose minds are sufficiently developed to appreciate its teachings.—Phila- delphia Public Ledger. Many delicate subjects are treated with skill and in a manner which cannot strike any one as improper or bold. The absolute ignor- ance in which most young girls are allowed to exist, even until adult life, is often productive of much misery, both mental and physical. Quite a number of books written by physi- cians for popular use have been prepared in such a way that the professional man can read between the lines strong bids for popular favor, etc. These objectionable features will not be found in Dr. Capp's brochure, and for this reason it is worthy the confidence of physicians.—Medical News. CATHELL Book on the Physician Himself And Things that Concern his Reputation and Success. By D. W. Cathell, M.D., Baltimore, Md. Being the Ninth Edition (enlarged and thoroughly revised) of the " Physician Himself, and what he should add to his Scientific Acquirements in order to Secure Success." In one handsome Octavo Volume of 298 pages, bound in Extra Cloth. Thousands of physicians have won success in their chosen profession through the aid of this invaluable work. This remarkable book has passed through eight (8) editions in less than five years. It has just undergone a thorough revison by the author, who has added much new matter covering many points and elucidating many excellent ideas not included in former editions. Price, post-paid, in the United States and Canada, $2.00, net; in Great Britain, Us. 6d.; France, 12 fr. 40. I am most favorably impressed with the wisdom and force of the points made in "The Physician Himself," and believe the work in the hands of a young graduate will greatly en- hance his chances for professional success.— From Prof. D. Hayes Agnew, Phila., Pa. We strongly advise every actual and intend- ing practitioner of medicine or surgery to have " The Physician Himself," and the more it in- fluences his future conduct the better he will be.— From the Canada Medical and Surgical Journal, Montreal. In the present edition the entire work has been revised and some new matter introduced. The publisher's part is well done; paper is cood and the print large; altogether it is a very readable and enjoyable hook.-Montreal Medical Journal We have read it carefully and regret much that we had not done so earlier and followed its precepts. The book is furl of good advice. Get it at once.—Pacific Record of Medicine and Surgery. We cannot imagine a more profitable Invest- ment for the junior practitioner than the pur. chase and careful study of "The Physiciat Himself."—Occidental Medical Times. To the physician who has discovered tba' there is something else besides dry book-learn ing needed to make him a desirable visitor ax the bedside, we commend this volume, that he may assimilate some of the ready crystallized worldly wisdom which otherwise he may be many years acquiring by natural processes.— North Carolina Medical Journal. (5; Medical Publications of The F. A. Davis Co., Philadelphia. CLEVENGEB Spinal Concussion. Surgically Considered as a Cause of Spimal Injury, and Xeiro- logically restricted to a certain symptom group, for which is Suggested the Designation Erichsen's Disease, as One Form of the Traumatic Neuroses. By S. V. Clevenger, M.D., Consulting Physician Reese and Alexian Hospitals; Late Pathologist Count}7 Insane Asylum, Chicago, etc. Special features consist in a description of modern methods of diag- nosis by Electricity, a discussion of the controversy concerning hysteria, and the author's original pathological view that the lesion is one involv- ing the spinal sympathetic nervous system. Every Physician and Lawyer should own this work. In one handsome Royal Octavo Volume of nearly 400 pages, with thirty Wood-Engravings. Price, post-paid, in United States and Canada, $2.50, net; in Great Britain, 14s.; in France, 15 fr. This work really does, if we may be per- mitted to use a trite and hackneyed expres- sion, "All a long-felt want." The subject is treated in all its bearings; electro-diagnosis receives a large share of attention, and the chapter devoted to illustrative cases will be found to possess especial importance.—Med- ical Weekly Review. Erysipelas is rare and enteric fever infrequent. Cholera appears in epidemics and is then frightfully fatal. Leprosy, of course, is com- mon, and the author states that it cannot be contagious, as is supposed by many, or it would assume a terrible prevalence iii China, where lepers are permitted to go about free. We will not further mention the subjects discussed in this excellent book. The style of the author is very interesting and taking, and much information is given in an entertaining manner. The political situation is very intelli- gently handled in its various bearings. The photo-engravings are handsome and well-ex- ecuted, the hook in general being gotten up in a very artistic manner. We can heartily com- mend this work not only to physicians, but to intelligent lay readers-.—fife. Louis Medical Review. COLT2 the CHINESE: T Mec By Robert Coltman, Jr., M.D., terian Hospital and Dispensary at 1 sician of the American Southern Bap* Beautifully printed in large, clear Engravings on Extra Plate Paper, frc and objects characteristic of China. In one Royal Octavo volume of I Extra Cloth, with Chinese Side Stam] Price, post-paid, in United States a Britain, 10s.; in F The Chinaman is a source of absolute curi- osity to the American, and anything in regard to liis relationship to the medical profession will prove more than usuallv attractive to the average doctor. Such is the case with the work before us. It is difficult to put it aside after one has begun to read it.—Memphis Med. Monthly. Dr. Coltman has written a very readable book, illustrated with reproductions of photo- graphs taken by himself.—Boston Med. and Surg. Journal. Attached to a number of hospitals and dis- pensaries, he has had ample opportunity to observe the medical aspect of the Chinese. The most prevalent diseases are such as affect the alimentary tract and eye troubles. Renal troubles are also frequent! Skin diseases are abundant and syphilis is far from infrequent. (6) COLTMAF the CHINESE: Their Present and Future; Medical, Political, and Social. By Robert Coltman, Jr., M.D., Surgeon in Charge of the Presby- terian Hospital and Dispensary at Teng Chow Pu ; Consulting Ph}7- sician of the American Southern Baptist Mission Society, etc. Beautifully printed in large, clear type, illustrated with Fifteen Fine Engravings on Extra Plate Paper, from photographs of persons, places, and objects characteristic of China. In one Royal Octavo volume of 212 Pages. Handsomely bound in Extra Cloth, with Chinese Side Stamp in gold. Price, post-paid, in United States and Canada, $1.75, net; in Great Britain, 10s.; in France, 12 fr. 20. Medical Publications of The F. A. Davis Co., Philadelphia. DAVIS CONSUMPTION: How t0 PB£1^ ?"d H°w " Its Nature, Causes, Prevention, and the Mode of Life, Climate, Exercise, Food, and Clothing Necessary for its Cure. By N. S. Davis, Jr., A.M., M.D., Professor of Principles and Practice of Medicine, Chicago Medical College; Physician to Mercy Hospital, Chicago; Member of the American Medical Association, etc. This plain, practical treatise thoroughly discusses the prevention of Con- sumption, Hygiene for Consumptives, gives timely suggestions concerning the different climates and the important part they play in the treatment of this disease, etc., etc.,—all presented in such a succinct and intelligible style as to make the perusal of the book a pleasant pastime. In one neat 12mo volume of 148 pages. Handsomely bound in Extra Cloth, with Back and Side Stamps in Gold. Price, post-paid, in United States and Canada, 75 Cents, net; in Great Britain, 4s.; in France, 4 fr. The questions of heredity, predisposition, prevention, and hygienic treatment of eon- sumption are simply and sensibly dealt with. The chapters on how to live with "tuberculosis are excellent.—Indiana Medical Journal. The author is very thorough in his dis- cussion of the subject, and the practical hints which he tnves are of real worth and value. His directions are given in such a manner as to make life enjoyable to a consumptive patient and not a burden, as is too frequently the case.— Weekly Medical Review. There is much good ordinary common sense in this book of only 150 pages. The part of the brochure devoted to Climatology is espe- cially commendable.—Denver Medical Times. BEMABQUAY f\ f\ A Practical Investigation of the Clinical UI! UXVQSn. and Therapeutic Value of the Gases " ° in Medical and Surgical Practice, "With Especial Reference to the Yalue and Availability of Oxygen Nitrogen, Hydrogen, and Nitrogen Monoxide. By J. N. Demarquay, Surgeon to the Municipal Hospital, Paris, and of the Council of State ; Member of the Imperial Society of Surgery, etc. Translated, with notes, additions, and omissions, by Samuel, S. \Vallian, A.M., M.D.; Ex- President of the Medical Association of Northern New York ; Member of the New York County Medical Society, etc. In one handsome Octavo Volume of 316 pages, printed on fine paper, in the best style of the printer's art, and illustrated with 21 Wood-Cuts. Price, post-paid, in United States and Canada, Cloth, $2.00, net; Half- Russia, $3.00, net. In Great Britain, Cloth, lis. 6d.; Half-Russia, 17s. 6d. In France, Cloth, 12 fr. 40; Half-Russia, 18 fr. GO. For some years past there has been a growing demand for something more satisfactory and more practical in the way of literature on the subject of aero- therapeutics. On all sides professional men of standing and ability are turning their attention to the use of the gaseous elements, as remedies in disease, as well as sustainers in health. In prosecuting their inquiries, the first hindrance has been the want of any reliable or satisfactory literature on the subject. This work, translated from the French of Professor Demarquay, contains also a very full account of recent English, German, and American experiences, prepared by Dr. Samuel S. Wallian, of New York, whose experience in this field has been more extensive than that of any other American writer on the subject. This is a handsome volume of 300 pages, in large print, on good paper, and nicely illus- trated. Although nominally pleading for the use of oxvgen inhalations, the author shows in a philosophical manner how much greater eood physicians might do if they more fullv appreciated the value of fresh-air exercise and water, especially in diseases of the lungs, kid- nevs and skin. We commend its perusal to our readers.—TJie Canada Medical Record. The book should be widely read, for to many it will bring the addition of a new weapon to their therapeutic armament.— Northwestern Lancet. Altogether the book is a valuable one, which will be found of service to the busv practitioner who wishes to keep abreast of the improvements in therapeutics.—Medical News. (7) Medical Publications of The F. A. Davis Co., Philadel]>hia. EISENBEBG Bacteriological Diagnosis. Tabular Aids for Use in Practical Work. By James Eisenberg, Ph.D., M.D., Vienna. Translated and augmented, with the permission of the author, from the second German Edition, by Norval H. Pierce, M.D., Surgeon to the Out-Door Department of Michael Reese Hospital ; Assistant to Surgical Clinic, College of Physicians and Surgeons, Chicago, 111. Nearly 200 pages. In one Royal Octavo volume, handsomely bound in Cloth and in Oil-Cloth (for laboratory use). Frice, post-paid, in the United States and Canada, $1.50, net; in Great Britain, 8s. 6d.; in France, 9 fr. 35. This book is a novelty in Bacteriological Science. It is a work of great importance to the teacher as well as to the student. It will be of inestimable value to the private worker, and is designed throughout as a practical guide in laboratory work. It is arranged in a. tabular form, in which are given the specific characteristics of the various well established bacteria, so that the worker may, at a glance, inform himself as to the identity of a given organism. There is also an appendix, in which is given, in a concise and practical form, the technique employed by the best laboratories in the cultivation and staining of bacteria ; the composition and preparation of the various solid, semi-solid, and fluid media, together with their employment ; a complete list of stains and re- agents, with formula? for same ; the methods of microscopic examination of bacteria, etc., etc., etc. EBINGEB Twelve Lectures on the Structure of the Central Nervous System. For Physicians and Students. By Dr. Ludwig Edinger, Frankfort-on-the-Main. Second Revised Edi- tion. With 133 Illustrations. Translated by Willis Hall Vitttjm, M.D., St. Paul, Minn. Edited by C. Eugene Riggs, A.M , M.D., Professor of Mental and Nervous Diseases, University of Minnesota ; Member of the American Neuro- logical Association. The illustrations are exactly the same as those used in the latest German edition (with the German names translated into English), and are very satisfac- tory to the Physician and Student using the book. The work is complete in one Royal Octavo Volume of about 250 pages, bound in Extra Cloth. Price, post-paid, in the United States and Canada, $1.75, net; in Great Britain, 10s.; in France, 12 fr. 20. One of the most instructive and valuable works on the minute anatomy of the human brain extant. It is written in the form of lectures, profusely illustrated, and in clear language.—The Pacific Record of Medicine and Surgery. Since the first works on anatomy, up to the present day. no work has appeared on the sub- ject of the general and minute anatomy of the central nervous system so complete and ex- haustive as this work of Dr. Ludwig Edinger. Being himself an original worker, and having the benefits of such masters as Stilling, Wei- geit, Geilach, Meynert, and others, he has succeeded in transforming the mazy wilder- ness of nerve-fibres and cells into a district of well-marked pathways and centres, and by so doing has made a pleasure out of an anatom- ical bugbear.—The Southern Medical Record. Every point is clearly dwelt upon in the text, and where description alone might leave a subject obscure clever drawings and diagrams are introduced to render misconception of the author's meaning impossible. The book is eminently practical. It unravels the intricate entanglement of different tracts and paths in a way that no other book has done so explic- itly or so concisely.—Northwestern Lancet. (8) Medical Publications of The F. A. Dams Go., Philadelphia. GOOBELL Lessons in Gynecology. By William Goodell, A.M., M.D., etc., Professor of Clinical Gyne- cology in the University of Pennsylvania. This exceedingly valuable work, from one of the most eminent specialists and teachers in gynecology in the United States, is now offered to the profession in a much more complete condition than either of the previous editions. It embraces all the more important diseases and the principal operations in the field of gynecology, and brings to bear upon them all the extensive practical experience and wide reading of the author. It is an indispensable guide to every practitioner who has to do with the diseases peculiar to women. Third Edition/ With 112 illustrations. Thoroughly revised and greatly enlarged. One volume, large octavo, 578 pages. Price, in United States and Canada, Cloth, $5.00; Full Sheep, $6.00. Discount, 20 per cent., making it, net, Cloth, $4.00; Sheep, $180. Postage, 27 cents estra. Great Britain, Cloth, 22s. 6i; Sheep, 28s., post-paid. France, 30 fr. 80. It is too good a book to have been allowed to remain out of print, and it has unquestionably been missed. The author has revised the work with special care, adding to each lesson such fresh matter as the progress in the art ren- dered necessary, and he has enlarged it by the insertion of six new lessons. This edition will, without question, be as eagerly sought for as were its predecessors.—American Journal of Obstetrics. His literary style is peculiarly charming. There is a directness and simplicity about it which is easier to admire than to copy. His chain of plain words and almost blunt expres- sions, his familiar comparison and homely illustrations, make his writings, like his lec- tures, unusually entertaining. The substance of his teachings we regard as equally excel- lent.— Philadelphia Medical and Surgical Reporter. Extended mention of the contents of the book is unnecessary; suffice it to say that every important disease found in the female sex is taken up and discussed in a common- sense kind of a way. We wish every physician in America could read and carry out the sug- gestions of the chapter on "the sexual rela- tions as causes of uterine disorders—conjugal onanism and kindred sins." The department treating of nervous counterfeits of uterine diseases is a most valuable one.—Kansas City Medical Index. GUEBWSEY Plain Talks on Avoided Subjects. By Henry N. Guernsey, M.D., formerly Professor of Materia Medica and Institutes in the Hahnemann Medical College of Philadelphia; author of Guernsey's " Obstetrics," including the Disorders Peculiar to Women and Young Children ; Lectures on Materia Medica, etc. The following Table of Contents shows the scope of the book: Contents.—Chapter I. Introductory. II. The Infant. III. Child- hood. IY. Adolescence of the Mnle. Y. Adolescence of the Female. VI. Marriage: The Husband. VII. The Wife. VIII. Husband and Wife. IX. To the Unfortunate. X. Origin of the Sex. In one neat 16mo volume, bound in Extra Cloth. Price, post-paid, in the United States and Canada, $1.00; Great Britain, 6s.; France, 6 fr. 20. (9) Medical Publications of TJie F. A. Davis Co., Philadelphia. BZABE Epilepsy: Its Pathology and Treatment. Being an Essay to which was Awarded a Prize of Four Thousand Francs by the Academie Royale de Medecine de Belgique, December 31, 1889. By Hobart Amort Hare, M.D. (Univ. of Penna.), B.Sc, Professor ol Materia Medica and Therapeutics in the Jefferson Medical College, Phila. ; Physician to St. Agnes' Hospital and to the Children's Dispensary of the Chil- dren's Hospital ; Laureate of the Royal Academy of Medicine in Belgium, of the Medical Society of London, etc. ; Member of the Association of American Physicians. No. 7 in the Physicians' and Students' Ready-Reference Series. 12mo. 228 Rages. Neatly bound in Dark-blue Cloth. Price, post-paid, in United States and Canada, $1.25, net; in Great Britain, 6s. 6d.; in France, 7 fr. 75. It is representative of the most advanced views of the profession, and the subject is pruned of the vast amount of superstition and nonsense that generally obtains in connection with epilepsy.—Medical Age. Every physician who would get at the gist of all that is worth knowing on epilepsy, and who would avoid useless research among the mass of literary nonsense which pervades all medical libraries, should get this work."—The Sanitarian. It contains all that is known of the pathology of this strange disorder, a clear discussion of the diagnosis from allied neuroses, and the very latest therapeutic measures for relief. It is remarkable for its clearness, brevity, and beauty of style. It is, so far as the reviewer knows, altogether the best essay ever written upon this important subject.—Kansas City Medical Index. The task of preparing the work must have been most laborious, but we think that Dr. Hare will he repaid for his efforts by a wide appreciation of the work by the profession; for the book will be instructive to those who have not kept abreast with the recent litera- ture upon this subject. Indeed, the work is a sort of Dictionary of epilepsy—a reference guide-book upon the subject.—Alienist and Neurologist. BZABE Fever: Its Pathology and Treatment. Being the Boylston Prize Essay op Harvard University for 1890. Containing Directions and the Latest Information Con- cerning the Use of the So-Called Anti- pyretics in Fever and Pain. By Hobart Amory Hare, M.D. (Univ. of Penna.), B.Sc, Professor of Materia Medica and Therapeutics in the Jefferson Medical College, Phila.; Physician to St. Agnes' Hospital and to the Children's Dispensary ©f the Chil- dren's Hospital; Laureate of the Royal Academy of Medicine in Belgium, of the Medical Society of London, etc.; Member of the Association of American Physicians. No. 10 in the Physicians' and Students' Ready-Reference Series. 12mo. Neatly bound in Dark-blue Cloth. Illustrated with more than 25 new plates of tracings of various fever cases, showing beautifully and accurately the action of the Antipyretics. The work also contains 35 carefully prepared statistical tables of 249 cases showing the untoward effects of the antipyretics. Price, post-paid, in the United States and Canada, $1.25, net; in Great Britain, 6s. 6d.; in France, 7 fr. 75. As is usual with this author, the subject is thoroughly handled, and much experimental and clinical evidence, both from the author's experience and that of others, is adduced in support of the view taken.—New York Medical Abstract. The author has done an able piece of work in showing the facts as far as they are known concerning the action of antipyrin, anti- febrin, phenacetin, thallin, and salicylic acid. The reader will certainly find the work oae of the most interesting of its excellent group, the Physicians' and Students' Ready-Refer- ence Series.—The Dosimetric Medical Review. Such books as the present one are of service to the student, the scientific therapeutist, and the general practitioner alike, for much can be found of real value in Dr. Hare's book, with the additional advantage that it is up to the latest researches upon the sjubject.—Univer- sity Medical Magazine. (10) Medical Publications of The F. A. Davis Co., Philadelphia. BZUIBEKOPEB Age of the Domestic Animals. Being a Complete Treatise on the Dentition of the Horse, Ox, Sheep, Hog, and Dog, and on the Various Other Means of Determining the Age of these Animals. a .. By ^USH Shippen Hoidekoper, M.D., Veterinarian (Alfort, France) ; Professor of aamtary .Medicine and \ eterinary Jurisprudence, American Veterinary College, New York ; Late Dean of the Veterinary Department, University of Pennsylvania. Complete in one handsome Royal Octavo volume of 225 pages, bound in Extra Cloth. Illustrated with 200 engravings. Price, post-paid, in the United States and Canada, $1.75, net; in Great Britain, 10s.; in France, 12 fr. 20. This work presents a careful study of all that has been written on the subject from the earliest Italiau writers. The author has drawn much valuable material from the ablest English, French, and German writers, and has given his own deductions and opinions, whether they agree or disagree with such investigators as Bracy Clark, Simonds (in Eng- lish), Girard, Chauveau, Leyh, Le Coque, Goubaux, and Barrier (in German and French). narian, this book will be of interest to the dentist, physiologist,, anatomist, and physician. Its wealth of illustration and careful prepara- tion are alike commendable.—Chicago Med. Recorder. The literary execution of the book is very satisfactory, the text is profusely illustrated, and the student will find abundant means in the cuts for familiarizing himself with the various aspects presented by the incisive arches during the different stages of life. Illustrations do not always illustrate ; these do.—Amer. Vet. Review. Although written primarily for the veteri- It is profusely illustrated with 200 engrav- ings, and the text forms a study well worth the price of the book to every dental practitioner. —Ohio Journal of Dental Sciences. Journal of Laryngology, Rhinology, and Otology. An Analytical Record of Current Literature Relating to the Throat, Nose, and Ear. Issued on the First of Each Month. Edited by Dr. Ncwiris Wolfenden, of London, and Dr. John Macinttre, of Glas- gow, with the active aid and co-operation of Drs. Dundas Grant, Barclay J. Baron, and Hunter Mackenzie. Besides those specialists in Europe and America who have so ably assisted in the collaboration of the Journal, a number of new correspondents have under- taken to assist the editors in keeping the Journal up to date, and furnishing it with matters of interest. Amongst these are : Drs. Sajous, of Philadelphia; Middlemass Sunt, of Liverpool; Mellow, of Rio Janeiro ; Sedziak, of Warsaw • Draispul, of St. Petersburg, etc. Drs. Michael, Joal, Holger Mygind, Prof. Massei, and Dr. Valerius Idelsou will still collab- orate the literature of their respective countries. Price, 13s. or $3.00 per annum (inclusive of Postage). For single copies, however, a charge of Is. 3d. (30 Cents) will be made. Sample Copy, 25 Cents. KEATING Record-Book of Medical Examinations For Life-Insurance. Designed by John M. Keating, M.D. This record-book is small, neat, and complete, and embraces all the principal points that are required by the different companies. It is made in two sizes, viz. : No. 1, covering one hundred (100) examinations, and No. 2, covering two hundred (200) examinations. The size of the book is 7 x '6% inches, and can be conveniently carried in the pocket. U. S. and Canada. Great Britain. France. No. 1. For 100 Ezaminations, in Cloth, - - $ .50, Net 3s. 6d. 3 fr. 60 No. 2. For 200 Ezaminations, in Full Leather, with Side Flap, .... 1.00, " 6s. 6 fr. 20 '-- (ii) Medical Publications of The F. A. Davis Co., Philadelphia. HEATING and EBWABBS Diseases of the Heart and Circulation. In Infancy and Adolescence. With an Appendix entitled " Clinical Studies on the Pulse in Childhood." By John M. Keating, M.D., Obstetrician to the Philadelphia Hospital, and Lecturer on Diseases of Women and Children; Surgeon to the Maternity Hospital; Physician to St. Joseph's Hospital; Fellow of the College of Physicians of Philadelphia, etc.; and William A. Edwards, M.D., Instructor in Clinical Medicine and Physician to the Medical Dispensary in the University of Pennsylvania; Physician to St. Joseph's Hospital; Fellow of the College of Physicians; formerly Assistant Pathologist to the Philadelphia Hospital, etc. Illustrated by Photographs and Wood-Engravings. About 225 pages. Oc- tavo. Bound in Cloth. Price, post-paid, in the United States and Canada, $1.50, net; in Great Britain, 8s. 6d.; in France, 9 fr. 35. Drs. Keating and Edwards have produced a work that will give material aid to every doctor in his practice among children. The style of the book is graphic and pleasing, the diagnostic points are explicit and exact, and the therapeutical resources include the novel- ties of medicine as well as the old and tried agents.—Pittsburgh Med. Review. Any physician, especially if he be a beginner in electro-therapeutics, will be well repaid by a careful study of this work by Liebig and Rohe. For a work on a special subject the price is low, and no one can give % good ex- cuse for remaining in ignorance of so impor- tant a subject as electricity in medicine.— Toledo Medical and Surgical Reporter. The entire work is thoroughly scientific and practical, and is really what the authors have aimed to produce, "a trustworthy guide to the application of electricity in the practice of medicine and Surgery."—New York Medical Times. It is not a mere compilation, but a systematic treatise, and bears evidence of considerable labor and observation on the part of the authors. Two fine photographs of dissections exhibit mitral stenosis and mitral regurgita- tion ; there are also a number of wood-cuts. —Cleveland Medical Gazette. In its perusal, with each succeeding page, we have been more and more impressed with the fact that here, at last, we have a treatise on electricity in medicine and surgery which amply fulfills its purpose, and which is sure of general adoption by reason of its thorough excellence and superiority to other works in- tended to cover the same field.—Pharmaceu- tical Era. After carefully looking over this work, we incline to the beiief that the intelligent physi- cian who is familiar with the general subject will be greatly interested and profited.— American Lancet. LIEBIG and BOBZE Practical Electricity in Medicine $ Surgery. By G. A. Liebig, Jr., Ph D., Assistant in Electricity, Johns Hopkins University ; Lecturer on Medical Electricity, College of Physicians and Surgeons, Baltimore ; Member of the American Institute of Electrical Engineers, etc. ; and George H. Rohe, M.D., Professor of Obstetrics and Hygiene, College of Physi- cians and Surgeons, Baltimore ; Visiting Physician to Bay View and City Hos- pitals ; Director of the Maryland Matemite ; Associate Editor "Annual of the Universal Medical Sciences," etc. Profusely Illustrated by Wood-Engravings and Original Diagrams, and published in one handsome Royal Octavo volume of 383 pages, bound in Extra Cloth. The constantly increasing demand for this work attests its thorough relia- bility and its popularity with the profession, and points to the fact that it is already the standard work on this very important subject. The part on Physical Electricity, written by Dr. Liebig, one of the recognized authorities on the science in the United States, treats fully such topics of interest as Storage Bat- teries, Dynamos, the Electric Light, and the Principles and Practice of Electrical Measurement in their Relations to Medical Practice. Professor Rohe, who writes on Electro-Therapeutics, discusses at length the recent developments of Electricity in the treatment of stricture, enlarged prostate, uterine fibroids, pelvic cellulitis, and other diseases of the male and female genito-urinary organs. The applica- tions of Electricity ki dermatology, as well as in the diseases of the nervous system, are also fully considered. Price, post-paid, in the United States and Canada, $2.00, net; in Great Britain, lis. 6d.; France, 12 fr. 40. (12) Medical Publications of The F. A. Davis Co., Philadelphia. 3JASSEY Electricity in the Diseases of Women. With Special Reference to the Application of Strong Currents. By G. Betton Massey, M.D., Physician to the Gynaecological Department of the Howard Hospital ; late Electro-therapeutist to the'Philadelphia Orthopaedic Hospital and Infirmary for Nervous Diseases, etc. Second Edition. Revised and Enlarged. With New and Original Wood-Engravinsrs. Handsomely bound in Dark-Blue Cloth. 240 pages. 12mo. No. 5 in the Physicians' and Students' Ready-Reference Series. This work is presented to the profession as the most complete treatise yet issued on the electrical treatment of the diseases of women, and is destined to fill the increasing demand for clear and practical instruction in the handling and use of strong currents after the recent methods first advocated by Apostoli. The whole subject is treated from the present stand-point of electric science with new and original illustrations, the thorough studies of the author and his wide clinical experience rendering him an authority upon electricity itself and its therapeutic applications. The author has enhanced the practical value of the work by including the exact details of treatment and results in a number of cases taken from his private and hospital practice. Price, post-paid, in the United States and Canada, $1.50, net; in Great ' Britain, 8s. 6i; in France, 9 fr. 35. A new edition of this practical manual at- tests the utility of its existence and the recog- nition of its merits. The directions are simple, easy to follow and to put into practice; the ground is well covered, and nothing is assumed, the entire book being the record of expe- rience.—Journal of Nervous and Mental diseases. It is only a few months since we noticed the first edition of this little book ; and it is only necessary to add now that we consider it the best treatise on this subject we have seen, and that the improvements introduced into this edition make it more valuable still.—Boston Medical and Surgical Journ. The style is clear, but condensed. Useless details are omitted, the reports of cases being pruned of all irrelevant material. The book is an exceedingly valuable one, and represents an amount of study and experience which is only appreciated after a careful reading.— Medical Record. Physicians' Interpreter. In Four Languages (English, French, German, and Italian). Specially Arranged for Diagnosis by M. von Y. The object of this little work is to meet a need often keenly felt by the busy, physician, namely, the need of some quick and reliable method of com- municating intelligibly with patients of those nationalites and languages unfa- miliar to the practitioner. The plan of the book is a systematic arrangement of questions upon the various branches of Practical Medicine, and each question is so worded that the only answer required of the patient is merely Yes or No. The questions are all numbered, and a complete Index renders them always available for quick reference. The book is written by one who is well versed in English, French, German, and Italian, being an excellent teacher in all those languages, and who has also had considerable hospital experience. Bound in Full Russia Leather, for carrying in the pocket. Size, 5 x 2f inches. 206 pages. Price, post-paid, in the United States and Canada, $1.00, net; in Great Britain, 6s.; in France, 6 fr. 20. Many other books of the same sort, with more extensive vocabularies, have been pub- lished, but, from their size, and from their being usually devoted to equivalents in Eng- lish and one other language only, they have not had the advantage which is pre-eminent in this—convenience. It is handsomely printed, and bound in flexible red leather in the form of a diary. It would scarcely make itself felt in one's hip-pocket, and would insure its bearer against any ordinary conversational difficulty in dealing with foneign-speaking people, who are constantly coming into our city hospitals.—New York Medical Journal. This little volume is one of. the most inge- nious aids to the physician Nvhich we have seen. We heartily commend the hook to any one who, being without a knowledge of the foreign languages, is obliged to treat those who do not know our own language.—St. Louis Courier of Medicine. (13) Medical Publications of The F. A. Davis Co., Philadelphia. The Medical Bulletin Visiting-List or Physicians' Call Record. arranged upon an original and convenient monthly and weekly Plan for the Daily Recording of Professional Visits. Frequent Rewriting of Names Unnecessary. THIS Visiting-List is arranged so that the names of patients need be written but once a month instead of four times a month, as in the old-style lists. By means of a new feature, a simple device consisting of stub or half leaves in the form of inserts, the first week's visits are recorded in the usual way, and the second week's visits are begun by simply turning over the half-leaf without the necessity of rewriting the patients' names. This very easily under- stood process is repeated until the month is ended and the record has been kept complete in every detail of visit, charge, credit, etc., and the labor and time of entering and transferring names at least three times in the month has been saved. There are no intricate rulings ; not the least amount of time can be lost in comprehending the plan, for it is acquired at a glance. THE THREE DIFFERENT STYLES MADE. The No. 1 Style of this List provides space for the daily record of seventy different names each month for a year ; for physicians who prefer a List that will accommodate a larger practice we have made a No. 2 Style, which provides space for the daily record of 105 different names each month for a year, and for physicians who may prefer a Pocket Record-Book of less thickness than either of these styles we have made a No. 3 Style, in which "The Blanks for the Record- ing of Visits in " have been made into removable sections. These sections are very thin, and are made up so as to answer in full the demand of the largest practice, each section providing ample space for the daily record of 210 dif- ferent names for two months ; or 105 different names daily each month for four months; or seventy different names daily each month for six months. Six sets of these sections go with each copy of No. 3 Style. SPECIAL FEATURES NOT FOUND IN ANY OTHER LIST. In this No. 3 Style the printed matter, and such matter as the blank forms for Addresses of Patients, Obstetric Record, Vaccination Record, Cash Account, Birth and Death Records, etc., are fastened permanently in the back of the book, thus reducing its thickness. The addition of one of these removable sections does not increase the thickness more than an eighth of an inch. This brings the book into such a small compass that no one can object to it on account of its thickness, as its bulk is very much less than that of any visiting- list ever published. Every physician will at once understand that as soon as a section is full it can be taken out, filed away, and another inserted without the least inconvenience or trouble. Extra or additional sections will be furnished at any time for 15 cents each or $1.75 per dozen. This Visiting-List contains calen- dars, valuable miscellaneous data, important tables, and other useful printed matter usually placed in Physicians' Visiting-Lists. Physicians of many years' standing and with large practices pronounce it the Best List they have ever seen. It is handsomely bound in fine, strong leather, with flap, including a pocket for loose memoranda, etc., and is furnished with a Dixon lead-pencil of excellent quality and finish. It is compact and con- venient for carrying in the pocket. Size, 4 x 6| inches. IIST THREE STyL.ES. net pricbs. No. 1. Regular size, to accommodate 70 patients daily each month for one year, . . . $1.25 No. 2. Large size, to accommodate 105 patients daily each month for one year, .... SI.50 No. 3. In which the " Blanks for Recording Visits in" are in removable sections, . . . 81.75 Special Edition for Great Britain, without printed matter, ........4 s. 6d. N. B.—The Recording of Visits in this List may be Commenced at any time during the Year. (14) Medical Publications of The F. A. Davis Co., Philadelphia. 3IICBZENEB ■ I l r-t I f r- ■ • «>»*» NOTES AND CASKS Hand-Book of Eclampsia: °* ™»™«. C 7 CONVULSIONS. By E. Michener, M.D. ; J. H. Stubbs, M.D. ; R. B. Ewing, M.D. ; B. Thompson, M.D. ; S. Stebbins, M.D. 16mo. Cloth. Price, 60 cents, net; in Great Britain, 4s. 6d.; Trance, 4 fr. 20. NISSEN A MANUAL OF INSTRUCTION FOR GIVING Swedish Movement $ Massage Treatment By Prop. Hartvig Nissen, late Director of the Swedish Health Institute, Washington, D. C. ; late Instructor in Physical Culture and Gymnastics at the Johns Hopkins University, Baltimore, Md. ; Instructor of Swedish and German Gymnastics at Harvard University's Summer School, 1891, etc., etc. This excellent little volume treats this very important subject in a practical manner. Full instructions are given regarding the mode of applying the Swedish Movement and Massage Treatment i various diseases and conditions of the human system with the greatest degree >f effectiveness. This book is indispens- able to every physician who wishes to k ow how to usg these valuable handmaids of medicine. Illustrated with 29 Original Wood-Engravings. In one 12mo volume of 128 Pages. Neatly bound in Cloth. Price, post-paid, in the United States and Canada, $1.00, net; in Great Britain, 6s.; in France, 6 fr. 20. This manual is valuable to the practitioner, as it contains a terse description of a subject but too little understood in this country. . . The book is got up very creditably.—N. Y. Med. Journal. The present volume is a modest account of the application of the Swedish Movement and Massage Treatment, in which the technique of the various procedures are clearly stated as well as illustrated in a very excellent manner. —North American Practitioner. This attractive little book presents the sub- ject in a very practical shape, and makes it possible frff every physician to understand at least how it is applied, if it does not give him dexterity i n the art of its application.—Chicago Med. Ttmes. By the Same Author A B C of the Swedish System of Educational Gymnastics. A Practical Hand-Book for School-Teachers and the Home. By Hartvig Nissen. The author has avoided the use of difficult scientific terms, and made it as popular and plain as possible. The fullest instructions and commands are given for each exercise, and Seventy-seven Excellent Engravings illustrate them and add greatly to the practical value of the book. It is complete in one neat, small 12mo volume of about 125 Pages, and may be conveniently carried in the pocket. Bound in Extra Flexible Cloth. Price, post-paid, in United States and Canada, 75 Cents, net; in Great Britain, 4s.; in France, 4 fr. This is one of the books which it is a delight to notice, on account of its sterling worth and practical utility.—Educational Monthly, At- lanta, Ga. We wish this little book were placed in the hands of every teacher, and the practice of its exercises enforced upon every child of the schools of every State as well as in Boston.— American Lancet. (15) Tlie most intelligent and complete gymnastic primer ever published. It is perfectly simple, and any child will be able to comprehend it. Its illustrations of the different movements of the body explain themselves.—The Pacific Record of Med. and Surgery. This small volume is useful for physicians, students, and all who may be interested in public health.— Med. Bulletin. Medical Publications of The F. A. Davis Co., Philadelj)hia. Physician's All-Requisite Time- and Labor- Saving Account-Book. Being a Ledger and Account-Book for Physicians' Use, Meeting all the Requirements of the Law and Courts. Designed by William A. Seibert, M.D , of Easton, Pa. Probably no class of people lose more money through carelessly kept accounts and overlooked or neglected bills than physicians. Often detained at the bedside of the sick until late at night, or deprived of even a modicum of rest, it is with great difficulty that he spares the time or puts himself in condition to give the same care to his own financial interests that a merchant, a lawyer, or even a farmer devotes. It is then plainly apparent that a system of bookkeeping and accounts that, without sacrificing accuracy, but, on the other hand, ensuring it, at the same time relieves the keeping of a physician's book of half their complexity and two-thirds the labor, is a convenience which will be eagerly welcomed by thousands of overworked physicians. Such a system has at last been devised, and we take pleasure in offering it to the profession in the form ot The Physician's All-Requisite Time- and Labor- Saving Account-Book. There is no exaggeration in stating that this Account-Book and Ledger reduces the labor of keeping your accounts more than one-half, and at the same time secures the greatest degree of accuracy. We may mention a few of the superior advantages of The Physician's All-Requisite Time- and Labor- Saving Account-Book, as follows :— First—Will meet all the requirements of the law and courts. Second—Self-explanatory ; no cipher code. Third—Its completeness without sacri- ficing anything. Fourth—No posting ; one entry only. Fifth—Universal; can be commenced at any time of the year, and can be continued indefinitely until every account is filled. Sixth—Absolutely no waste of space. Seventh—One person must needs be sick every day of the year to fill his account, or might be ten years about it and require no more than the space for one account in this ledger. Eighth—Double the number and many times more than the number of ac- To all physicians desiring a quick, accurate, and comprehensive method of keeping their accounts, we can safely say that no book as suitable as this one has ever been devised. A descriptive circular showing the plan of the book will be sent on application. counts in any similar book ; the 300-page book contains space for 900 accounts, and the 600-page book contains space for 1800 ac- counts. Ninth—There are no smaller spaces. Tenth—Compact without sacrificing completeness ; every account com- plete on same page—a decided ad- vantage and recommendation. Eleventh—Uniform size of leaves. Twelfth—The statement of the most complicated account is at once be- fore you at any time of month or year—in other words, the account itself as it stands is its simplest statement. Thirteenth—No transferring of accounts, balances, etc. NET PRICES, SHIPPING EXPENSES PREPAID. No. 1. 300 Pages, for 900 Accounts per Year, Size 10x12, Bound in K'-Russia, Raised in u. s Back Bands, Cloth Sides, . . . $5.00 No. 2. 600 Pages, for 1800 Accounts per Year, Size 10x12, Bound in &-Russia, Raised Back-Bands, Cloth Sides, . . . 8.00 8.80 (16) Canada (dutv paid). $5.50 Great Britain. 28s. 42s. France. 30 fr. 30. 49 fr. 40 Medical Publications of Tlxe F. A. Davis Co., Philadelphia. PBICE and EAGLETON Three Charts of the Nervo-Uascular System. Part I.—The Nerves. Part II.—The Arteries. Part III.—The Veins. A New Edition, Revised and Perfected. Arranged by W. Henry Price, M.D., and S. Potts Eagleton, M.D. Endorsed by leading anatomists. Clearly and beautifully printed upon extra durable paper. PART I. The Nerves—Gives in a clear form not only the Cranial and Spinal Nerves, show- ing the formation of the different Plexuses and their branches, but also the complete distribution of the Sympathetic Nerves. PART II. The Arteries—Gives a unique grouping of the Arterial system, showing the divisions and subdivisions of all th6 vessels, beginning from the heart and tracing "their continuous distribution to the periphery, and showing at a glance the terminal branches of each artery. PART III. The Veins—Shows how the blood from the periphery of the body is gradually collected by the larger veins, and these coalescing forming still larger vessels, until they finally trace themselves into the Right Auricle of the heart. It is therefore readily seen that "The Nervo-Vascular System of Charts " offers the following superior advantages :— 1. It is the only arrangement which combines the Three Systems, and yet each is perfect and distinct in itself. 2. It is the only instance of the Cranial, Spinal, and Sympathetic Nervous Systems being represented on one chart. 3. From its neat size and clear type, and being printed only upon one side, it may be tacked up in any convenient place, and is always ready for freshening up the memory and reviewing for examination. Price, post-paid, in United States and Canada, 50 cents, net, complete; in Great Britain, 3s. 6d.; in France, 3 fr. 60. For the student of anatomy there can pos- sibly be no more concise way of acquiring a knowledge of the nerves, veins, anil arteries of the human system. It presents at a glance their trunks and branches in the great divis- ions of the body. It will save a world of tedi- ous reading, and will impress itself on the mind as no ordinary vade mecum, even, could. Its price is nominal and its value inestimable. No student should be without it.—Pacific Record of Medicine and Surgery. These are three admirably arranged charts for the use of students, to assist in memor- izing their anatomical sudies.—Buffalo Med. and Surg. Jour. PUBBY Diabetes: Its Cause,Symptoms a£d Treatment By Chas. W. Purdy, M.D. (Queen's University), Honorary Fellow of the Royal College of Physicians and Surgeons of Kingston ; Member of the College of Physicians and Sunreons of Ontario ; Author of "Bright's Disease and Allied Affections of the Kidneys ;" Member of the Association of American Physicians ; Member of the American Medical Association ; Member of the Chicago Academy of Sciences, etc. Contents.—Section I. Historical, Geographical, and Climatological Con- siderations of Diabetes Mellitus. II. Physiological and Pathological Considera- tions of Diabetes Mellitus III. Etiology of Diabetes Mellitus. IV. Morbid Anatomy of Diabetes Mellitus. V. Symptomatology of Diabetes Mellitus. \ I. Treatment of Diabetes Mellitus. VII. Clinical Illustrations of Diabetes Mellitus. VIII. Diabetes Insipidus ; Bibliography. l2mo. Dark Blue Extra Cloth. Nearly 200 pages. With Clinical Illus- trations. No. 8 in the Physicians' and Students' Ready-Reference Series. Price, post-paid, in the United States and Canada, 91.25, net; in Great Britain, 6s. 6i; in France, 7 fr. 75. This will prove a most entertaining as well as most interesting treatise upon a disease which frequently falls to the lot of every practitioner. The work has been written with a special view of bringing out the features of the disease as it occurs in the United States. The author has very judiciously arranged the little volume, and it will offer many pleasant attractions to the practitioner.—Nashville Journal of Medicine and Surgery. While many monographs have been pub- lished which have dealt with the subject of diabetes, we know of none which so thoroughly considers its relations to the geographical conditions which exist in the United States, nor which is more complete in its summary of the symptomatology and treatment of this affection. A number of tables, showing the percentage of sugar in a very large number of alcoholic beverages, adds very considerably to the value of the work.—Medical News. U7) Medioal Publications of The F. A. Davis Co., Philadelphia. BEMONBINO History of Circumcision. From the Earliest Times to the Present. Moral and Physical Reasons for its Performance ; with a History of Eunuchism, Hermaphrodism, etc, and of the Different Opera- tions Practiced upon the Prepuce. By P. C. Remondino, M.D. (Jefferson), Member of the American Med- ical Association ; of the American Public Health Association ; Vice- President of California State Medical Society and of Southern California Medical Society, etc. In one neat 12mo volume of 346 pages. Handsomely bound in Extra Dark-Blue Cloth, and illustrated with two fine wood-engravings, showing the two principal modes of Circumcision in ancient times. No. 11 in the Physicians'1 and Students'1 Ready-Reference Series. Price, post-paid, in United States and Canada, $1.25, net; in Great Britain, 6s. 6d.; in France, 7 fr. 75. A Popular Edition (unabridged), bound in Paper Covers, is also issued. Price, 50 Cents, net; in Great Britain, 3s.; in France, 3 fr. 60. Every physician should read this book; he will there find, in a condensed and S}7stematized form, what there is known concerning Circumcision. The book deals with simple facts, and it is not a disserta- tion on theories. It deals, in plain, pointed language, with the relation that the prepuce bears to physical degeneracy and disease, bases all its utterances on what has occurred and on what is known. The author has here gathered from every source the material for his subject, and the deductions are unmistakable. This is a very full and readable book. To the reader who wishes to know all about the antiquity of the operation, with the views pro and con of the right of this appendage to exist, its advantages, dangers, etc., this is the book.—The Southern Clinic. The operative chapter will be particu- larly useful and interesting to physicians, as it contains a careful and impartial review of all the operative procedures, from the most simple to the most elaborate, paying particular attention to the subject of after-dressings It is a very interesting and instructive work, and should be read very liberally by the profes- sion.— The Med. Brief. The author's views in regard to circum- cision, its necessity, and its results, are well founded, and its performance as a prophylactic measure is well established.—Columbus Med. Journal. By the Same Author The Mediterranean Shores of America. Southern California: Its Climatic, Physical, and Meteorological Conditions. By P. C. Remondino, M.D. (Jefferson), etc. Complete in one handsomely printed Octavo volume of nearly 175 pages, with 45 appropriate illustrations and 2 finely executed maps of the region, showing altitudes, ocean currents, etc. Bound in Extra Cloth. Price, post-paid, in United States and Canada, $1.25, net; in Great Britain, 6s. 6d.; in France, 7 fr. 75. Cheaper Edition (unabridged), bound in Paper, post-paid, in United States and Canada, 75 Cents, net; in Great Britain, is.; in France, 5 fr. Italy, of the Old World, does not excel nor even approach this region in point of salubrity of climate and all-around healthfulness of environ- ment. This book fully describes and discusses this wonderfully charming county. The medical profession, who have long desired a trustworthy treatise of true scientific value on this celebrated region, will find in this volume a satisfactory response to this long-felt and oft-expressed wish. (18) & Medical Publications of The F. A. Dams Co., Plniaaeip/ua. BOBZE Text-Book of Hygiene. A Comprehensive Treatise on the Principles and Practice of Preventive Medicine from an American Stand-point. By George H. Rohe, M.D., Professor of Obstetrics and Hygiene in the College of Physicians and Surgeons, Baltimore; Member of the American Public Health Association, etc. Every Sanitarian should have Rohe's " Text-Book of Hygiene " as a work of reference. Second Edition, thoroughly revised and largely rewritten, with many illustrations and valuable tables. In one handsome Royal Octavo volume of over 400 pages, bound in Extra Cloth. Price, post-paid, in United States, $2.50, net; Canada (duty paid), $2.75, net; Great Britain, Hs.; France, 16 fr. 20. One prominent feature is that there are no superfluous words; every sentence is direct to the point sought. It is, therefore, easy reading, and conveys very much information in little space.—The Pacific Record of Medi- cine and Surgery. It is unquestionably a work that should be in the hands of every physician in the country, and medical students wdl find it a most excel- lent and valuable text-book.—The Southern Practitioner. The first edition was rapidly exhausted, and the book justly became an authority to physi- cians and sanitary officers, and a text-book very generally adopted in the colleges through- out America. The second edition is a great improvement over the first, all of the matter being thoroughly revised, much of it being rewritten, and many additions being made. The size of the book is increased one hundred pages. The book has the original recommenda- tion of being a handsomely-bound, clearly- printed octavo volume, profusely illustrated with reliable references for every branch of the subject matter.—Medical Record The wonder is how Professor Rohe has made the book so readable and entertaining with so much matter necessarily condensed. Alto- gether, the manual is a good exponent of hygiene and sanitary science from the present American stand-point, and will repay with pleasure and profit any time that may be given to its perusal.—University Medical Magazine. By the Same Author A Practical Manual of Diseases of the Skin. By George H. Rohe, M.D., Professor of Materia Medica, Thera- peutics, and Hygiene, and formerly Professor of Dermatology in the College of Physicians and Surgeons, Baltimore, etc., assisted by J. Williams Lord, A.B., M.D., Lecturer on Dermatology and Bandaging in the College of Physicians and Surgeons; Assistant Physician to the Skin Department in the Dispensary of Johns Hopkins Hospital. In one neat 12mo volume of over 300 pages, bound in Extra Dark-Blue Cloth. No. 13 in the Physicians'1 and Students' Ready-Reference Series. Price, post-paid, in the United States and Canada, $1.25, net; in Great Britain, 6s. 6d.; in France, 7 fr. 75. The practical character of this work makes it specially desirable for the use of students and general practitioners. The nearly one hundred (100) reliable and carefully prepared For- mulae at the end of the volume add not a little to its practical value. All the various forms of skin diseases, from Acne to Zoster (alpha- betically speaking), are succinctly yet amply treated of, and the arrange- ment of the book, with its excellent index and unusually full table of contents, goes to make up a truly satisfactory volume for ready reference in daity practice. (19) Medical Publications of The F. A. Davis Co., Philadelphia. SENN Principles of Surgery. By N. Sexn, M.D., Ph.D., Professor of Practice of Surgery and Clinical Surgery in Rush Medical College, Chicago, 111.; Professor of Surgery in the Chicago Polyclinic; At- tendiDg Surgeon to the Milwaukee Hospital; Consulting Surgeon to the Milwaukee County Hospital and to the Milwaukee County Insane Asylum. This work, by one of America's greatest surgeons, is thoroughly complete ; its clearness and brevity of statement are among its conspicuous merits. The author's long, able, and conscientious researches in every direction in this important field are a guarantee, of unusual trustworthiness, that every branch of the subject is treated authoritatively, and in such a manner as to bring the greatest gain in knowledge to the practitioner and student. In one handsome Royal Octavo volume, with 109 fine Wood-Engravings and 624 United States. Canada (duty paid). Great Britain. France $150, Net $5.00, Net 24s. 6d. 27 fr. 20 5.50 " 6.10 " 30s. 33 fr. 10 Price in Cloth, " Sheep or ^-Russia, Stephen Smith, M.D., Professor of Clin- ical Surgery Medical Department University of the City of New York, writes:—"I have examined the work with great satisfaction, and regard it as a most valuable addition to American surgical literature. There has long been great need of a work on the principles of surgery which would fully illustrate the pres- ent advanced state of knowledge of the various subjects embraced in this volume. The work seems to me to meet this want admirably." Lewis A. Sayre, M.D., Professor Ortho- paedic Surgerv Bellevue Hospital Medical College, New York, writes :—" My Dear Doctor Senn : Your very valuable work on surgery, sent to me some time since, I have studied with great satisfaction and improvement. 1 congratulate you most heartily on having pro- duced the most classical and practical work on surgery yet published." Frank J. Ltjtz, M.D., St. Louis, Mo., says : —" It seeins incredible that those who pretend to teach have done without such a guide before, and I do not understand how our stu- dents succeeded in mastering the principles of modern surgery by attempting to read our obsolete text-books. American surgery should feel proud of the production, and the present generation of surgeons owe you a debt of gratitude." Wm. Osler, M.D., The Johns Hopkins Hos- pital, Baltimore, says:—"You certainly have covered the ground* thoroughly and well, and with a thoroughness I do not know of in any similar work. I should think it would prove a great boon to the students and also to very many teachers." The work is systematic and compact, without a fact omitted or a sentence too much, and it not only makes instructive but fascinating reading. A conspicuous merit of Senn's work is his method, his persistent and tireless search through original investigations for additions to knowledge, and the practical character of his discoveries.—The Review of Insanity and Nervous Diseases. Every chapter is a mine of information con- taining all the recent advances on the subjects presented in such a systematic, instructive, and entertaining style that the reader will not willingly lay it aside, but will read and re-read with pleasure and profit.—Kansas Medical Journal. After perusing this work on several different occasions, we have come to the conclusion that it is a remarkable work, by a man of unusual ability. The author seems to have had a very large personal experience, which is freely made use of in the text, besides which he is familiar with almost all that has been written in Eng- lish and German on the above topics.—Tlie Canada Medical Record. The work is exceedingly practical, as the chapters on the treatment of the various con- ditions considered are based on sound deduc- tions, are complete, and easily carried out by any painstaking surgeon. All in all, the book is a most excellent one, and deserves a place in every well-selected library.—Medical Record. It will prove exceedingly valuable in the diffusion of more thorough knowledge of the subject-matter among English-speaking sur- geons. As in the case of all his work, he has done this in a truly admirable manner. The book throughout is worthy of the highest praise. It should be adopted as a text-book in all of our schools.— University Medical Magazine. The principles of surgery, as expounded by Dr. Senn, are such as to place the student in the independent position of evolving from them methods of treatment; the master of the principles readily becomes equally a master of practice. And this, of course, is really the whole purpose of the volume.—Weekly Med- ical Review. HAY FEVER SAJOUS And Its Successful Treatment by Superficial Organic Alteration of the Nasal mucous Membrane. By Charles E. Sajotts, M.D., formerly Lecturer on Rhinology and Laryngology in Jefferson Medical College ; Cnief Editor of the Annual of the Universal Medical Sciences, etc. With 13 Engravings on Wood. 103 pages. 12mo. Bound in Cloth, Beveled Edges. Price, post-paid, in the United States and Canada, $1.00, net; in Great Britain, 6s.; in France, 6 fr. 20. (20) Medical Publications of The F. A. Dan* Co., Philadelphia. SBZOEMAKEB Heredity, Health, and Personal Beauty. Including the Selection of the Best Cosmetics for the Skin, Hair, Nails, and all Parts Relating to the Body. m*r.ni,?y J£?N V- S«OEMA™'. 4 M- MD- Professor of Materia Medica, Phar- macology, Therapeutics, and Clinical Medicine, and Clinical Professor of Diseases ?LlnS. m ^e^dico-Chirurgical College of Philadelphia; Physician to the -uedico-Clnrurgical Hospital, etc., etc. ti.A t.Tlle he.alt?»,of the.,skin »nd «air, and how to promote them, are discussed; the treatment of the nails; the subjects of ventilation, food, clothing, warmth bathmg; the circulation ol the blood, digestion, ventilation; in fact, all that in tlJ hT COt?duce* to th% ^ell-being of the body and refinement is duly enlarged upon. 1 o these stores of popular information is added a list of the best medicated soaps and toilet soaps, and a whole chapter of the work is devoted to household remedies. I he work is largely suggestive, and gives wise and timely advice as to when a physician should be consulted. This is just the book to place on the waiting-room table of every physician, and a work that will prove usefal in the hands of your patients. Complete in one handsome Roval Octavo volume of 425 pages beautifully and clearly printed, and bound in Extra Cloth, Beveled Edges, with side and back gilt stamps and in Half-Morocco Gilt Top. Price, in United States, post-paid, Cloth, $2.50; Half-Morocco, $3.50, net. Canada (duty paid), Cloth, $2.75; Half-Morocco, $3.90, net. Great Britain, Cloth, 14s.; Half-Morocco, 19s. 6i France, Cloth, 15 fr.; Half-Morocco, 22 fr. The book reads not like the f nlfillment of a task, but like the researches and observations of one thoroughly in love with his subject, fully appreciating its importance, and writing for the pleasure he experiences in it. The work is very comprehensive and complete in its scope.—Medical World. The book before us is a most remarkable production and a most entertaining one. The book is equally well adapted for the laitv or the profession." It tells us how to be healthv, happy, and as beautiful as possible. We can't review this book : it is aifferent from anything we have ever read. It runs like a novel, and will be perused until finished with pleasure and profit. Buy it, read it. and be surprised, pleased, and improved.—The Southern Clinic, This book is written primarily for the laity, but will prove of interest to the physician as well. Though the author goes to some extent into technicalities, he confines himself to the use of good, plain English, and in that respect sets a notable example to many other writers on similar subjects. Furthermore, the book is written from a thoroughly American stand- point.—Medical Record. This is an exceedingly interesting book. both scientific and practical in character, in- tended for both professional and lay readers. The book is well written and presented in ad- mirable form by the publisher.—Canadian Practitioner. SHOEMAKEB Ointments and Oleates : E9pec*?"S in Diseases of the Skin. By John V. Shoemaker, A.M., M.D., Professor of Materia Medica, Phar- macology, Therapeutics, and Clinical Medicine, and Clinical Professor of Diseases of the Skin in the Medico-Chirurgical College of Philadelphia, etc., etc. The author concisely concludes his preface as follows : "The reader may thus obtain a conspectus of the whole subject of inunction as it exists to-day in the civilized world. In all cases the mode of preparation is given, and the thera- peutical application described seriatim, in so far as may be done without needless repetition." Second Edition, revised and enlarged. 298 pages. 12mo. Neatly bound in Dark-Blue Cloth. No. 6 in the Physicians' and Students' Ready-Reference Series. Price, post-paid, in the United States and Canada, $1.50, net; in Great Britain, 8s. 6i; in Prance, 9 fr. 35. It is invaluable as a ready reference when ointments or oleates are to be used, and is serviceable to both druggist and physician.— Canada Medical Record. To the physician who feels uncertain as to the best form in which to prescribe medicines by way of the skin the book will prove valu- able, owing to the many prescriptions and formulae which dot its pages, while the copious index at the back materially aids in making the book a useful one.—Medical News. (21) Medical Publications of The F. A. Davis Co., Philadelphia. SBZOEMAKEB Materia Medica and Therapeutics. With Especial Reference to the Clinical Application of Drugs. Being the Second and Last Volume of a Treatise on Materia Medica, Pharmacology, and Therapeutics, and an Independent Volume upon Drugs. By John V. Shoemaker, A.M., M.D., Professor of Materia Medica, Pharmacology, Therapeutics, and Clinical Medicine, and Clinical Professor of Diseases of the Skin in the Medico-Chirurgical College of Philadelphia; Physician to the Medico-Chirurgical Hospital, etc., etc. This, the second volume of Shoemaker's "Materia Medica, Pharmacology, and Therapeutics," is wholly taken up with the consideration of drugs, each remedy being studied from three points of view, viz.: the Preparations, or Materia Medica; the Physiology and Toxicology, or Pharmacology; and, lastly, its Therapy. It is thoroughly abreast of the progress of Therapeutic Science, and is really an indispensable book to every student and practitioner of medicine. Royal Octavo, about 675 pages. Thoroughly and carefully indexed. Price, in United States, post-paid, Cloth, $3.50; Sheep, $4.50, net. Canada (duty paid), Cloth, $4.00; Sheep, $5.00, net. Great Brit- ain, Cloth, 20s.; Sheep, 26s. Prance, Cloth, 22 fr. 40; Sheep, 28 fr. 60- The first volume of this work is devoted to Pharmacy, General Pharma- cology, and Therapeutics, and remedial agents not properly classed with drugs. Royal Octavo, 353 pages. Price of Volume I, post-paid, in United States, Cloth, $2.50, net; Sheep, $3.25, net. Canada, duty paid, Cloth, $2.75, net; Sheep, $3.60, net. Great Britain, Cloth, 14s.; Sheep, 18s. Prance, Cloth, 16 fr. ?,0; Sheep, 20 fr. 20. The volumes are sold separately. SHOEMAKER'S TREATISE ON MATERIA MEDICA, PHARMACOLOGY, AND THERA- PEUTICS STANDS ALONE. (1) Among Materia Medica text-books, in that it includes every officinal drug and every preparation contained in the United States Pharmacopoeia. (2) In that it is the only work on therapeutics giving the strength, composition, and dosage of every officinal preparation. (3) In giving the latest investigations with regard to the physiological action of drugs and the most recent applications in therapeutics. (4) In combining with officinal drugs the most reliable reports of the actions and uses of all the noteworthy new remedies, such as acetanilid, antipyrin, bromoform, exalgin, pyok- tanin, pyridin, somnal, spermine (Brown-Sequard), tuberculin (Koch'slymph), sulphonal, thiol, urethan, etc., etc. (5) As a complete encyclopaedia of modern therapeutics in condensed form, arranged alpha- betically for convenience of reference for either physician, dentist, or pharmacist, when immediate information is wanted concerning the action, composition, dose, or antidotes for any officinal preparation or new remedy. (6) In giving the physical characters and chemical formulae of the new remedies, especially the recently-introduced antipyretics and analgesics. (7) In the fact that it gives special attention to the consideration of the diagnosis and treat- ment of poisoning by the more active drugs, both officinal and non-officinal. (8) And unrivaled in the number and variety of the prescriptions and practical formulae, representing the latest achievements of clinical medicine. (9) In that, while summarizing foreign therapeutical literature, it fully recognizes the work done in this department by American physicians. It is an epitome of the present state of American medical practice, which is universally acknowledged to be the best practice. (10) Because it is the most complete, convenient, and compendious work of reference, heing, in fact, a companion to the United States Pharmacopoeia, a drug-encyclopaedia, and a therapeutic hand-book all in one volume. The value of the book lies in the fact that it contains all that is authentic and trust- worthy about the host of new remedies which have deluged us in the last five years. The pages are remarkably free from useless infor- mation. The author has done well in following the alphabetical order.—N. Y. Med. Record. In perusing the pages devoted to the special consideration of drugs, their pharmacology, physiological action, toxic action, and therapy, one is constantly surprised at the amount of material compressed in so limited a space. The book will prove a valuable addition to the physician 's library.—Occidental Med. Times. It is a meritorious work, with many unique features. It is richly illustrated by well-tried prescriptions showing the practical applica- tion of the various drugs discussed. In short, this work makes a pretty complete encyclo- paedia of the science of therapeutics, conve- niently arranged for handy reference.—Med. World. (22) Medical Publications of The F. A. Davis Co., Philadelphia. SMITBZ Physiology of the Domestic Animals. A Text-Book for Veterinary and Medical Students and Practitioners. By Robert Meade Smith, A.M., M.D , Professor of Comparative Physi- ology in University of Pennsylvania; Fellow of the College of Physicians and Academy of the Natural Sciences, Philadelphia; of American Physiological Society; of the American Society of Naturalists, etc. This new and important work, the most thoroughly complete in the English language on this subject, treats of the physiology of the domestic animals in a most comprehensive manner, especial prominencebeing given to the subject of toods and fodders, and the character of the diet for the herbivora under different conditions, with a full consideration of their digestive peculiarities. Without being overburdened with details, it forms a complete text-book of physiology adapted to the use of students and practitioners of both veterinary and human medicine. This work has already been adopted as the Text-Book on Physiology in the Veterinary Colleges of the United States, Great Britain, and Canada. In one Handsome Royal Octavo Volume of over 95*0 pages, profusely illustrated with more than 400 Fine Wood-Engravings and many Colored Plates. United States. Canada (duty paid) Great Britain. France. Price, Cloth, - - $5.00, Net $5.50, Net 28s. 30 fr. 30 " Sheep, - - 6.00 " 6.60 " 32s. 36 fr. 20 A. Li.vttard, M.D., H.F.R.C.. VS., Pro- fessor of Anatomy. Operative Surgery, and Sanitary Medicine in the American Veterinary College" New York, writes:—"I have exam- ined the work of Dr. R. M. Smith on the 'Physiology of the Domestic Animals,' and con- sider it one of the best additions to veterinary literature that we have had for some time." E. M. Reading, A.M.. M.D.. Professor of Physiology in the Chicago Veterinary College, writes :—"I have carefully examined the •Smith's Physiology,' published by you, and like it. It is comprehensive, exhaustive, and complete, and is especially adapted to those who desire to obtain a full knowledge of the principles of physiology, and are not satisfied with a mere smattering of the cardinal points.'' Dr. Smith's presentment of his subject is as brief as the status of the science permits, and to thi» much-desired conciseness he has added an equally welcome clearness of statement. The illustrations in the work are exceedingly good, and must prove a valuable aid to the full understanding of the text.—Journal of Comparative Medicine and Surgery. Veterinary practitioners and graduates will read it with pleasure. Veterinary students will readily acquire needed knowledge from its pages, and veterinary schools, which would be well equipped for the work they aim to perform, cannot ignore it as their text-book in physiology.—American Veterinary Review. Altogether, Professor Smith's -'Physiology of the Domestic Animals" is a happy produc- tion, and will be hailed with delight in both the human medical and veterinary medical worlds. It should find its place, besides, in all agricultural libraries.—Paul Paquin, M.D., VS., in the Weekly Medical Review. The author has judiciously made the nutri- tive functions the strong point of the work, and has devoted special attention to the sub- ject of foods and digestion. In looking through other seetions of the work, it appears tousthatajust proportion of space is asMgned to each, in view of their relative importance to the practitioner.—London Lancet. SOZINSKEY Medical Symbolism. Historical Studies in tlie Arts of Healing: and Hygiene. Bv Thomas S. Sozinskey, M.D., Ph.D., Author of "The Culture of Beautv." "The Care and Culture of Children," etc. 'l2mo. Nearly 200 pages. Neatly bound in Dark-Blue Cloth. ately illustrated with upward of thirty (30) new Wood-Engravings. Physicians' and Students' Ready-Reference Series. Appropri- No. 9 in the Price, post-paid, in United States and Canada, $1.00, net; Great Britain, 6s.; Prance, 6 fr. 20. He who has not time to more fully study the more extended records of the past, will highly prize this little book. Its interesting discourse upon the past is full of suggestive thought.— American Lancet. Like an oasis in a dry and dusty desert of medical literature, through which we wearily stagger, is this work devoted to medical sym- bolism and mythology. As the author aptly quotes: " "What some light braines may esteem as foolish toyes, deeper judgments can and will value as sound and serious matter."'—Can- adian Practitioner. In the volume before us we have an admira- ble and successful attempt to set forth in order those medical symbols which have come down to us, and to explain on historical grounds their significance. An astonishing amount of information is contained within the covers of the book, and every page of the work bears token of the painstaking genius and erudite mind of the now unhappily deceased author. —London Lancet. '23) Medical Publications of The F. A. Davis Co., Philadelphia. STEWABT Obstetric Synopsis. By John S. Stewart, M.D., formerly Demonstrator of Obstetrics and Chief Assistant in the Gynaecological Clinic of the Medico-Chirurgical College of Philadelphia: with an introductory note by William S. Sti:wart, A.M., M.D., Professor of Obstetrics and Gynaecology in the Medico-Chirurgical College of Philadelphia. By students this work will be found particularly useful. It is based upon the teachings of such well-known authors as Playfair, Parvin, Lusk, Galabin, and Cazeaux and Tarnier, and contains much new and important matter of great value to both student and practitioner. With 42 Illustrations. 202 pages. 12mo. Handsomely bound in Dark- Blue Cloth. No. 1 in the Physicians' and Students' Ready-Reference Series. Price, post-paid, in the United States and Canada, $1.00, net; in Great Britain, 6s.; Prance, 6 fr. 20. DbLaskie Miller, M.D., Professor of Obstetrics, Rush Medical College, Chicago, 111., says:—"I have examined the 'Obstetric Synopsis,' by John S. Stewart, M.D., and it gives me pleasure to characterize the work as systematic, concise, perspicuous, and authen- tic. Among manuals it is one of the best." It is well written, excellently illustrated, and fully up to date in every respect. Here we find all the essentials of Obstetrics in a nutshell, Anatomy, Embryology, Physiology, Pregnancy, Labor, Puerperal State, and Ob- stetric Operations all being carefully and ac- This book is to be highly recommended, owing to its clearness and brevity. Altogether, we do not know of any book of the same size which contains so much useful information in such a short space.—Medical News. Its scope is large, not being confined to the one condition,—neurasthenia,—but embracing all of the neuroses, motor and sensory of the genito-urinary organs in the male. No one who has read after Dr. Ultzmann need be re- rurately described.—Buffalo Medical and Surgical Journal. It is clear and concise. The chapter on the development of the ovum is especially satis- factory. The judicious use of bold-faced type for headings and italics for important statements gives the book a pleasing typo- graphical appearance.—Medical Record. This volume is done with a masterly hand. The scheme is an excellent one. The whole is freely and most admirably illustrated with well-drawn, new engravings, and the book is of a very convenient size.—St. Louis Medical and Surgical Journal. minded of his delightful manner of presenting his thoughts, whic.li ever sparkle with original- ity and appositeness.— Weekly Med. Review. It engenders sound pathological teaching, and will aid in no small degree in throwing light on the management of many of the dif- ficult and more refractory cases of the classes to which these essays especially refer.—The Medical Age. ULTZMANN The Neuroses of the Genito-Urinary System in the Male. With Sterility and Impotence. By Dr. R. Ultzmann, Professor of Genito-Urinary Diseases in the Uni- versity of Vienna. Translated, with the author's permission, by Gardner W. Allen, M.D., Surgeon in the Genito-Urinary Department, Boston Dispensary. Full and complete, yet terse and concise, it handles the subject with such a vigor of touch, such a clearness of detail and description, and such a directness to the result, that no medical man who once takes it up will be content to lay it down until its perusal is complete,—nor will one reading be enough. Professor Ultzmann has approached the subject from a somewhat differc.t point of view from most surgeons, and this gives a peculiar value to the work. It is believed, moreover, that there is no convenient hand-book in English treat- ing in a broad manner the Genito-Urinary Neuroses. Synopsis op Contents.—First Part—I. Chemical Changes in the Urine in Cases of Neuroses. II. Neuroses of the Urinary and of the Sexual Organs, classified as : (1) Sensory Neuroses; (2) Motor Neuroses ; (3) Secretory Neuroses. Second Part—Sterility and Impotence. The treatment in all cases is described clearly and minutely. Illustrated. 12mo. Handsomely bound in Dark-Blue Cloth. No. 4 in the Physicians' and Students' Ready-Reference Series. Price, post-paid, in the United States and Canada, $1.00, net; in Great Eritain, 6s.; in Prance, 6 fr. 20. (24) Medical Publications of The F. A. Davis Co., Philadelphia. SANNE Diphtheria, Croup: Tracheotomy and Intubation. From the French of A. Sanne. Translated and enlarged by Henry Z. Gill, M.D., LL.D., Late Professor of Surgery In Cleveland, Ohio. Saiine's work is quoted, directly or indirectly, by every writer since its publication, as the highest authority, statistically, theoretically, and practically. The translator, having given special study to the subject for many years, has added over fifty pages, including the Surgical Anatomy, Intubation, and the recent progress in other branches, making it, beyond question, the most complete work extant on the subject of Diphtheria in the English language. Facing the title-page is found a very fine Colored Lithograph Plate of the parts con- cerned in Tracheotomy. Next follows an illustration of a cast of the entire Trachea and Bronchi to the third or fourth division, in one piece, taken from a photograph of a case in which the cast was expelled during life from a patieut sixteen years old. This is the most complete cast of any one recorded. Over fifty other illustrations of the surgical anatomy of instruments, etc., add to the practical value of the work. A full Index accompanies the enlarged volume, also a List of Authors, making altogether a very handsome illustrated octavo volume of over 680 pages. United States. Canada (duty paid). Great Britain. France. Price, post-paid, Cloth, $4.00, Net $4.40, Net 22s. 6d. 24 fr. 60 Leather, 5.00 " 5.50 " 28s. 30 fr. 30 YOUNG Synopsis of Human Anatomy. Being a Complete Compend of Anatomy, Including the Anatomy of the Viscera, and Numerous Tables. By James E. Young, M.D., Instructor in Orthopaedic Surgery and Assistant Demon- strator of Surgery, University of Pennsylvania; Attending Orthopaedic Surgeon, Out- Patient Depaitment, University Hospital, etc. While the author has prepared this work especially for students, sufficient descriptive matter has been added to render it extremely valuable to the busy practitioner, particularly the sections on the Viscera, Special Senses, and Surgical Anatomy. The work includes a complete account of Osteology, Articulations and Ligaments, Muscles, Fascias, Vascular and Nervous Systems, Alimentary, Vocal, and Respiratory and Genito-Urinary Apparatus, the Organs of Special Sense, and Surgical Anatomy. In addition to a most carefully and accurately prepared text, wherever possible, the value of the work has been enhanced by tables to facilitate aud minimize the labor of stu- dents in acquiring a thorough knowledge of this important subject. The section on the teeth has also been especially prepared to meet the requirements of students of dentistry. Illustrated with 76 Wood-Engravings. 390 pages. 12mo. Bound in Extra Dark- Blue Cloth. No. 3 in the fhysicians' and Students' Beady-Reference Series. Price, post-paid, in the United States and Canada, $1.40, net; in Great Britain, 8s. 6d; in Prance, 9 fr. 25. Every unnecessary word has been excluded, out of regard to the very limited time at the medical student's disposal. It is also good as a reference-book, as it presents the facts about which he wishes to refresh his memory in the briefest manner consistent with clearness.— New York Medical Journal. As a companion to the dissecting-table, and a convenient reference for the practitioner, it has a definite field of usefulness.—Pittsburgh Medical Review. The book is much more satisfactory than the "remembrances" in vogue, and yet is not too cumbersome to he carried around and read at odd moments—a property which the student will readily appreciate. — Weekly Medical Review. Medical Publications of The F. A. Davis Co., Philadelphia. WITBZEBSTINE The International Pocket Medical Formulary Arranged Therapeutically. By C. Sumner Witherstine, M.S., M.D., Associate Editor of the "Annual of the Universal Medical Sciences;" Visiting Physician of the Home for the Aged, Germantown, Philadelphia ; Late House-Surgeon Charity Hospital, New York. More than 1800 formulae from several hundred well-known authorities. With an Appendix containing a Posological Table, the newer remedies included ; Important Incompatibles ; Tables on Dentition and the Pulse ; Table of Drops in a Fluidrachm and Doses of Laudanum graduated for age ; Formulae and Doses of Hypodermatic Medication, including the newer remedies ; Uses of the Hypo- dermatic Syringe ; Formulae and Doses for Inhalations, Nasal Douches, Gargles, and Eye-washes ; Formulae for Suppositories ; Use of the Thermometer in Dis- ease ; Poisons, Antidotes, and Treatment; Directions for Post-Mortem and Medico-Legal Examinations ; Treatment of Asphyxia, Sun-stroke, etc. ; Anti- emetic Remedies and Disinfectants ; Obstetrical Table ; Directions for Ligations of Arteries ; Urinary Analysis ; Table of Eruptive Fevers ; Motor Points for Electrical Treatment, etc. This work, the best and most complete of its kind, contains about 27o printed pages, besides extra blank leaves—the book being interleaved throughout —elegantly printed, with red lines, edges, and borders; with illustrations. Bound in leather, with side flap. It is a handy book of reference, replete with the choicest formulas (over 1800 in number) of more than six huudred of the most prominent classical writers and modern practitioners. The remedies given are not only those whose efficiency lias stood the test of time, but also the newest and latest discoveries in pharmacy and medical science, as prescribed and used by the best-known American and foreign modern authorities. It contains the latest, largest (G6 formulae), and most complete collection of hypodermatic formulae (including the latest new remedies) ever published, with closes and directions for their use in over fifty different diseases and diseased conditions. Its appendix is brimful of information, invaluable in office work, emergency cases, and the daily routine of practice. It is a reliable friend to consult when, in a perplexing or obstinate case, the usual line of treatment is of no avail. (A hint or a help from the best authorities, as to choice of remedies, correct dosage, and the eligible, elegant, and most palat- able mode of exhibition of the same.) It is compact, elegantly printed and bound, well illustrated, and of conve- nient size and shape for the pocket. The alphabetical arrangement of the diseases and a thumb-letter index render reference rapid and easy. Blank leaves, judiciously distributed throughout the book, afford a place to record and index favorite formulae. As a student, the physician needs it for study, collateral reading, and for recording the favorite prescriptions of his professors, in lecture and clinic; as a recent graduate, he needs it as a reference hand-book for daily use in prescribing (gargles, nasal douches, inhalations, eye-washes, suppositories, incompatibles, poisons, etc.); as an old practitioner, he needs it to refresh his memory on old remedies and combinations, and for information concerning newer remedies and more modern approved plans of treatment/ No live, progressive medical man can afford to be without it. Price, post-paid, in United States and Canada $2.00, net; Great Britain, lis. 6d.; France, 12 fr. 40. It is sometimes important that such prescrip- | enough of incompatibilities before commenc- tions as have been well established in their ing practice to avoid writing incompatible and usefulness be preserved for reference, and dangerous prescriptions. The constant use of this little volume serves such a purpose better such a book by such prescribers would save than any other we have seen.—Columbus Med- l the pharmacist much anxiety.—Tlie Drug- ical Journal. ! gist^ Circular. To the young physiciun just starting out in ' In judicious selection, in accurate nomen- piaetice this little book will prove an accept- | clature, in arrangement, and in stvle, it leaves able companion.—Omaha Clinic. \ nothing to be desired. The editor and the As long .is "combinations" are sought, such publisher are to be congratulated on the pro- a book will be of value, especially to those dnction of the very best book of its class.— who cannot spare the time required to learn | Pittsburgh Medical Review. (26) Medical Publications of The F. A. Davis Co., Philadelphia. Annual of the Universal Medical Sciences. A Yearly Report op the Progress of the General Sanitary Sciences Throughout the World. Edited by Charles E. Sajous, M.D., formerly Lecturer on Laryngology and Rhinology in Jefferson Medical College, Philadelphia, etc., and Seventy Associate Editors, assisted by over Two Hundred Corresponding Editors and Collaborators. In Five Royal Octavo Volumes of about 500 pages each, bound in Cloth and Half-Russia, Magnificently Illustrated with Chromo-Lithographs, Engravings, Maps, Charts, and Dia-grams. Being intended to enable any physi- cian to possess, at a moderate cost, a complete Contemporary History of Universal Medicine, edited by many of America's ablest teachers, and superior in every detail of print, paper, binding, etc., a befitting continuation of such great works as "Pepper's System of Medicine," "Ashhurst's International Encyclopaedia of Surgery," "Buck's Reference Hand-Book of the Medical Sciences." SOLD ONLY BY SUBSCRIPTION, OR SENT DIRECT ON RECEIPT OF PRICE, SHIPPING EXPENSES PREPAID. Subscription Price per Year (including the " SATELLITE " for one year): In United States, Cloth, 5 vols., Royal Octavo, $15.00; Half-Russia, 5 vols., Royal Octavo, $20.00. Canada (duty paid), Cloth, $16 50; Half-Russia, $22.00. Great Britain, Cloth, £4 7s.; Half-Russia, £5 15s. France, Cloth, 93 fr. 95; Half-Russia, 124 fr. 35. The Satellite of the " Annual of the Universal Medical Sciences." A Monthly Review of the most important articles upon the practical branches of Medicine appearing in the medical press at large, edited by the Chief Editor of the Annual and an able staff. Published in connection with the Annual, and for its Subscribers Only. Editorial Staff of the Annual of the Universal Medical Sciences. CONTRIBUTORS TO SERIES 1888, 1889, 1890, 1891. Editor-in-Chief, CHARLES E. SAJOUS, M.D., Philadelphia. SENIOR ASSOCIATE EDITORS. A**o. * ,: PIS ^r .:■'■', \^^M0^:' - I'M J/.