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RELATIVE INCIDENCE OF

CASES OF PUERPERAL FEVER

IN LONDON PARISHES 1891-5.

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and a younger race of men came upon the scene it was not unnaturally hoped that an improvement would take place, and that a mortality which had been conclusively shown to be preventable would show some signs of diminution. How is it that this hope has not been realised? Either the profession is not convinced of the possibility of stamping out puerperal fever by the methods that have been proposed or it has failed to carry out those methods with the thoroughness that can alone ensure success. As a responsible teacher of midwifery I have often asked myself the question how far the teaching is at fault. Do we teachers sufficiently impress upon the minds of our students the infinite importance of this subject? Are we ourselves careful to show by our own example the importance of the precautions that we lay down in the lecture theatre ? Are we careful never to convey, by thoughtless word or careless act, the impression that the rigid adoption of antiseptic measures is excellent in theory, but does not, after all, matter so very much in practice? If we are not, is it to be wondered at that when our students go out into the world and are released from the discipline of the school and hospital they should forget how much depends on attention to minute detail, and should discharge their consciences in this matter of antiseptics by pouring a few drops of carbolic acid or a drachm of tincture of iodine into the water in which they wash their hands, or even by simply bidding the nurse administer a similarly prepared solution as a douche? I am not painting an imaginary picture. The methods at present employed by many who if questioned would be quite ready to proclaim their belief in antiseptics, and who glibly assure one they have used "every antiseptic precaution," are often so crude and imperfect as to be a Îudicrous travesty of genuine antiseptic midwifery.

midwives shall possess at least such an elementary knowledge of the subject as shall enable them to know how to prevent septic infection. The remedy for the second evil is thoroughness.

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It is now nearly nine years since I published, in the form of an introductory address at St. Thomas's Hospital, a plea for the more general adoption of antiseptics in midwifery practice. In that address I brought together as concisely as possible the evidence that had been gradually accumulated in proof of the preventability of puerperal fever, and I showed in a series of tables the magnificent results that had followed the introduction of antiseptic measures into the leading maternity hospitals of Europe and the United States. I have reason to know that the arguments I then brought forward were not without effect upon the practice of individual members of the profession. I ought perhaps to apologise for returning to-night to a subject that may seem to many to have been long ago thrashed out. The temptation was indeed great to choose some newer topic for an occasion like the present. But the more I reflected on the matter the more it was borne in upon me that it was my duty once more to raise my voice on behalf of the mothers of this country. The Obstetrical Society of London has always been foremost in the effort to reduce the present terrible mortality from childbirth. It seemed to me that I could not more suitably signalise my succession to this chair than by calling attention to the sad and disappointing fact that has formed the text of this address. If anything I have said shall have the effect of stirring the minds of my professional brethren on this subject and of diminishing to ever so slight an extent the present terrible death-rate from a disease which is now generally acknowledged, nay, proved, to be almost wholly preventable, I shall feel that I have achieved something worthy of the occasion and have done something towards justifying your choice of a president.

The Erasmus Wilson Lectures

ON

The questions I have just been asking I ask of myself as well as others. It is clear that something is wrong. We shall be most likely to find out what that something is by a process of self-examination, both on the part of teacher and taught, however disagreeable that process may be. A great deal has been written on the superiority of asepsis as compared with antisepsis, and it has become the fashion in some quarters to speak of antiseptics as though they had had their day and to maintain that a condition of asepsis can be attained by cleanliness alone. It is well, however, to bear in mind that the triumphs of our lying-in hospitals have all THE PATHOLOGY OF THE LYMPHADENOID been won by the scrupulous use of antiseptics, and that sterilisation, which is the essential element in aseptic surgery, is impossible in midwifery practice. When we have thoroughly washed our hands, as we all now recognise the necessity of doing before making an examination in the lying-in room, it costs very little trouble to adopt the additional safeguard of immersing them for a few moments in an efficient antiseptic solution. And as a matter of experience those who are most diligent in the use of antiseptics SURGEON TO OUT-PATIENTS AND THROAT DEPARTMENT, WESTMINSTER are also the most diligent in carrying out all the details of elementary cleanliness. I firmly believe that if the simple antiseptic precautions with which everyone is familiar were conscientiously adopted puerperal fever would be as rare in private practice as it is now in the best lying-in hospitals.

The only way," as I have elsewhere observed, "to avoid (the present) terrible mortality, and to avoid also the terrible amount of puerperal disease, which, because it is not fatal, is apt to remain unrecorded, is for every practitioner in midwifery to recognise his personal responsibility in the matter."

In an excellent little book of advice to mothers the writer, herself a woman, after doing me the honour to quote the foregoing passage, makes the following significant comment : "Now I maintain," she says, "that women themselves bave a personal responsibility in this matter also. They should not be content passively to allow their lives to lie in the hands of others who may or may not choose to use antiseptics. Women who are expecting their confinements should satisfy themselves beforehand that the doctor and the nurse engaged to attend will conscientiously use these safeguards." This is plain speaking, but who will be disposed to find fault with it? It will be gathered from what I have said this evening that, in my opinion, the high death-rate from puerperal fever in this country is attributable mainly to the large number of confinements attended by ignorant and untrained midwives and to laxity and half-heartedness in the use of antiseptic precautions in private practice. The remedy for the first of these evils is to insist that women who call themselves

4 Stacpoole, F.: Advice to Women on the Care of the Health Before, During, and After Confinement. London: Cassell and Co., 1892, p. 81.

Delivered at

By W.

STRUCTURES.1

the Royal College of Surgeons of England on
March 1st, 3rd, and 5th, 1897,

G. SPENCER, M.S., M.B. LOND.,
F.R.C.S. ENG.,

HOSPITAL, AND LECTURER ON PHYSIOLOGY AT WESTMINSTER
HOSPITAL MEDICAL SCHOOL.

LECTURE I.

Delivered on March 1st.

GENTLEMEN,-The organs composed of lymphadenoid tissue are the bone marrow, the spleen, the thymus, and the glands and follicles in the mucous membrane of the alimentary and respiratory canals, but new formations may also appear in connective tissue where normally there is little sign of it. Lymphadenoid tissue is a specialised kind

of white fibrous tissue in the meshwork of which free cells collect. These cells produce blood corpuscles and also retain the fundamental digestive powers of unicellular organisms. In consequence of the situations in which lymphadenoid tissue is developed waste products of tissue change are prevented from entering the circulation until they have been rendered harmless, and thus its function of protecting the body from waste products-metabolites-of normal origin is capable of extension and is thus able to offer some resistance to the spread of disease, either by counteracting the poisonous substance resulting from diseased tissues or by actually destroying the germs of disease themselves. The pathological conditions to which lymphadenoid tissue is itself subject arise in the course of the performance of the protective functions. Being excited to over action lymphadenoid

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tissue becomes the starting point of new growth, or it is replaced by scar tissue as a consequence of inflammation, so that the production of the red and white blood corpuscles is disturbed and the rest of the body thereby affected.

THE ORIGIN OF LYMPHADENOID TISSUE. Lymphadenoid tissue is produced-(1) as lymphatic glands around the plexus of lymphatic trunks where they join in the axilla, groin, &c.; (2) around epithelial masses and glands, as the tonsils, thymus, salivary glands, and intestinal follicles; or (3) in the wall and sheath of the small bloodvessels in the spleen and bone marrow, favoured by the slow rate of the circulation. Fibrous connective tissue is changed into retiform tissue by a splitting up of its individual fibres, and into the meshwork so formed white cells emigrate from the capillary blood vessels, and there, by multiplying, establish germinating centres. Fine capillaries permeate these germinating masses, but not so the lymphatics. The latter begin in a sinus outside the follicle, into which the young cells pass as they are pushed out from the centre by still newer formations.

Lymphadenoid tissue, like connective tissue generally, is prone to vary. An increase of the blood flow accelerates the multiplication of cells and so causes an overgrowth; a diminution in the blood-supply promotes a fatty metamorphosis, from which a renewal of lymphadenoid tissue may at any time take place-red marrow replaces the yellow, lumps of apparent fat develop again into glands, or minute glands consisting of only a single follicle can as the result of irritation become compound glands.

side by side, and according to Kostanecki3 they have an origin in common. In late embryonic life this formation in the liver diminishes and ceases before birth. Erythroblasts are also seen during the latter part of embryonic life in the hilum and follicles of lymphatic glands, in the spleen, and in the thymus.

3. After birth the formation of red corpuscles becomes gradually confined to the red marrow in the higher mammals and man, although in lower vertebrates lymphadenoid tissue, especially the spleen, retains this function throughout life. The red marrow of birds forms a good material for demonstrating the various structures (Muir and Drummond).* In the capillary lumen are seen fully developed red corpuscles, in the wall are young red cells or erythroblasts which, although they project into the lumen, are fixed and show signs of mitosis; in the tissue around the capillary are the white cells rapidly dividing and passing towards the capillary channel.

On the whole it would appear most probable that the red corpuscles originate after birth from the small white cells of the marrow, and that the erythroblasts represent an intermediary stage. The alternative view is that the erythroblasts seen in the red marrow of the adult are a special class of cells directly derived from those found in the embryo.

Anæmia and regeneration of the red corpuscles.-There is an entire absence of clinical and experimental evidence as to the production of red corpuscles in excess. At any rate there is nothing comparable to leucocytosis and leucocythemia in the case of the red corpuscle. A diminution in the rate of production of the red corpuscles seems to be the cause of the anæmia which occurs in women leading an indoor life, in those who have an insufficient supply of albuminous food, as well as in old age. And clinical experience definitely shows that the recovery up to the normal rate of production is a slow process. Anæmia can be produced experimentally in one of two ways, either by removing a considerable amount of blood or by the introduction into the circulation of some material which will increase the rate at which the red corpuscles are destroyed.

THE FUNCTIONS OF LYMPHADENOID TISSUE. A.-The Formation and Destruction of Red Corpuscles. The red corpuscle, although varying in type among vertebrates, is uniform in each species after embryonic life and during health. Its sole function is to carry oxygen, and in no other way can this action be carried out; the imperfect red corpuscles which gain access to the blood in disease appear incapable of properly doing this work. Further points of difference between it and the white corpuscle are that the red are never produced in excess, neither do they take part in new formations of any kind, nor have they any digestive powers, nor do they produce a pro-and becomes more red, the spleen swells up and erythroblasts

tective secretion.

The regeneration of the blood after loss is seen when a considerable amount of blood has been taken from an animal

by repeated venesections; the marrow then exhibits an

increased mitosis both of colourless and coloured cells

5

7

1. Red blood corpuscles are first formed from colourless showing mitosis are found within it, and similar immature cells outside the bloodvessels. They are first seen in the nucleated red corpuscles are seen free in the blood stream According to Grünberg area vasculosa of the chick-i.e., outside the embryo itself, (Freiberg also Autokonenko"). arising from cells of the mesoblast, previously colourless, erythroblasts are also to be seen in lymph glands, the which develop hæmoglobin in their protoplasm. There is intestinal follicles and tonsils, more especially when the therefore no a priori objection to the development at later spleen had been removed before the venesections were made. periods also of young red cells or erythroblasts from colourThe lymph glands most affected were those of the mesentery, less cells since the erythroblasts have in the beginning an axilla, groin, and neck, which appeared to the naked eye origin in common with the young white corpuscles or enlarged and reddened. The lymphatics leading from the leucoblasts (Neumann). On the other hand it is held that enlarged glands were filled with true red corpuscles, nucleated the erythroblasts of the embryo form a distinct order of ones, and white cells. The germinating follicles of the lymph cells which remain throughout life the only source of the red glands were exceedingly rich in leucoblasts undergoing corpuscle (Bizzɔzero). The cells which form the blood mitosis. He speaks of the erythroblasts and red corpuscles islands begin to show hæmoglobin before the blood vessel has as being in the lymphatic gland sinus, but only of leucoblasts developed around them, so that the first formation of red cells within the stroma of the gland itself-under the foregoing may be called extra-vascular. Later there is a very similar condition no erythroblasts and red corpuscles were seen in appearance in all the blood-forming organs, but it has not the thymus (Braunschweig ). Venesection appears thereyet been settled whether the groups of erythroblasts under-fore to excite the leucoblasts to more rapid production, and going division are placed in the lumen of the capillary or there is a return to the embryonic state as regards the prowithin a diverticulum of the capillary, whether they form duction of the red corpuscles. The alternative explanation the capillary wall itself at the point, or whether they are in of the appearances seen after great loss of blood is that the the tissue outside separated from the blood stream by a layer and that some are detached and carried to the spleen and production of erythroblasts in the marrow is stimulated lymph glands, where they continue to divide until the loss is restored, when the formation of red cells is again confined to the red marrow (Zenoni; also Disse 1o).

of endothelium.

2

2. Red corpuscles after being formed in connective tissues are produced in later embryonic life in special organs. Erythroblasts are met with widely in the connective tissue and especially in the case of the mammalian embryo, in the walls of the umbilical vesicle, intestines, and bladder, as well as in the subcutaneous tissue (Saxer). As the lymphadenoid tissues develop erythroblasts gradually disappear from the blood and only re-appear under abnormal circumstances. They also gradually disappear from the walls of the intestines and umbilical vesicle and their production becomes concentrated in the liver. The liver of the mammalian embryo takes a very important part in blood formation; it is relatively a very large organ, in the capillaries of which erythroblasts and leucoblasts are seen undergoing mitosis

2 Saxer: Centralblatt für Allgemeine Patholo und Pathologische Anatomie, 1896, vol. vii., p. 421.

Destruction of red cells in connexion with the spleen and also in the liver is attended by an increased production of leucocytes, and it is the increased production of these cells which appears to be the cause of the hæmolysis. According

3 Vide Kostanecki: Anatomische Hefte, 1892, Band i.

4 Muir and Drummond: Journal of Anatomy and Physiology, 1894, vol. xxviii., p. 125.

5 Freiberg: Inaugural Dissertation, Dorpat, 1892. Centralblatt für Pathologie, &c., 1893, Band iv., S. 460.

6 Autokonenko: Archives des Sciences Biologiques, 1893, vol. ii.,

p. 516.

7 Grünberg: Dissertation, Dorpat, 1891; quoted by Disse, vide infra. 8 Braunschweig: Ibid.

9 Zenoni: Virchow's Archiv, 1895, Band cxxxix., p. 185.

10 Disse: Ergebnisse der Anatomie und Entwickelungsgeschichte von Merkel und Bonnet, 1895, Baud v., s. 30.

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to Hunter an increased destruction of red cells takes place during digestion in the spleen at a time when there is an increased production of leucocytes by that organ and by the gastro-intestinal wall. Hæmolysis in a greater degree can be brought about by aeting either directly upon the blood or indirectly through the spleen and gastro-intestinal lymphadenoid tissue by injecting such a drug as toluylendiamin. The spleen enlarges several fold owing to engorgement with venous blood, iron containing pigments collect in the spleen and liver, and there is an increased secretion of bile, some of which may be absorbed and produce jaundice. Red corpuscles in various stages of degeneration are to be seen in the spleen. When, however, the spleen is first of all removed much larger doses of the drug are required to produce the hæmolysis which then takes place through the lymphadenoid tissue of the intestinal wall. The toluylendiamin at the same time markedly increases the number of white cells in the blood, and the explanation of its action is that it first excites leucocytosis, especially in the spleen, but also in the intestinal wall, and that it is the leucocytosis which is the cause of the hemolysis. When drugs are injected which destroy the blood directly the removal of the spleen causes no alteration in the result (Hunter). The anemia, therefore, which is seen in the diseases of the lymphadenoid structures appears to originate in an excessive production of white cells, which hurry on and push out into the circulation whilst immature the red corpuscles in such a state that they cannot act fully as normal oxygen carriers and are liable to be destroyed.

ways. They may be destroyed in the blood stream, an increased production of leucocytes being excited in all the lymphadenoid organs by the destruction of cells, or the organism may lodge in the spleen, as in anthrax and relapsing fever, and be there included by the splenic cells. If the animal, however, presents no great resistance, the microorganisms quickly develop, whilst but few leucocytes gather round them. Even if they are checked for a time at the lymphatic glands, the organism succeeds in growing through and gains the circulation, which before death contains numbers free in the plasma, not included either in the white blood corpuscles or in the spleen cells.

The destruction of diseased germs may be due either to the cell ingesting them whilst still alive or by the secretions or products of the cell killing the organisms, and after they are dead the white cells swallow and digest them. It is generally agreed that white cells swallow and digest dead bacilli in the same way that unicellular organisms take in their food, a vesicle containing a peptic secretion is developed, the food material is dissolved, and the débris evacuated. But there has been much opposition to Metchnikoff's view that bacilli are ingested alive.

Wooldridge was the first to show that the secretions and cell products of lymphadenoid tissue can hinder or prevent the development of micro-organisms. In some experiments which I had the opportunity of watching he demonstrated that rabbits could be made immune to the inoculation of anthrax bacilli by injecting material derived from the thymus gland. Hankin and others have since then developed the large subject connected with the defensive proteids or alexins which are formed in connexion with the white cells. One method of experiment to show the power of the fluids in a resisting animal is to wrap the bacteria up so that no cells can come in contact with them, and in this way the most resisting anthrax spores may be destroyed. According to Kanthack and Hardy 12 the granules seen in some leucocytes, such as those which stain with eosin, represent the

B. The White Blood Corpuscles. Leucocytes are all alike throughout the vertebrata, although in many species they can be divided into several kinds. They seem to be distinct from the fixed cells of the tissues, but this point is by no means definitely settled. White blood corpuscles, small marrow cells, the wandering cells, the lymphocytes as well as the free cells in the mouth, intestines, and bronchi, all originate from the cells in the meshes of lymphadenoid tissue. They are practically protozoa which Leucocytosis.-The production of leucocytes in excess of can be kept alive outside the body and so be studied under the normal can be brought about by the injection of the the microscope. In the course of lymphadenoid disease the products of animal and of vegetable cells. Of animal leucocytes, except for a temporary occasional diminution to products there are especially those derived from nuclei a slight degree, are increased, sometimes, indeed, ten or such as nucleo-albumin, nuclein, nucleic acid, uric acid, also twenty times, due to the abnormal excitation of lymph-other nitrogenous products such as urea, peptone, albumose,

adenoid tissue.

1. In whatever situation these cells are found they exert a protective function due either to their secretion or to their ingesting and digesting powers. In the course of normal digestion an excess of leucocytes appears in the blood, and at the same time there is a marked enlargement of the spleen from which the cells are derived. This normal leucocytosis seems to have as its object the removal of some harmful products of digestion. In a less regular way some leucocytosis may occur during pregnancy and in the newborn infant.

2. Leucocytes play an active part in the removal of embryonic structures. Metchnikoff has described the removal by this means of the tadpole's tail, and Kowalewski that of the organs of the larva to make way for those of the imago. The epithelial structure of which the thymus is at first composed disappears before the invasion of the lymph

adenoid tissue.

3 Free leucocytes in the mouth derived from the tonsils, in the intestine from the solitary and agminated follicles, and also similar cells in the bronchi, all have a deterrent action upon the growth of micro-organisms in these cavities. 4. As to inflammatory reaction, upon the inoculation of disease germs into an animal capable of offering a resistance to their attack, a local inflammatory reaction takes place, consisting of an increased circulation, but more especially of a rapid collection of leucocytes, and by multiplying rapidly these cells and their secretion may prevent the spread of the disease. If the organisms succeed in developing, the lymphadenoid tissues placed on the line of the lymphatics running from the site of inoculation may present a second line of defence against the invasion of the body. There is an increased circulation through the gland and rapid mitosis, so that more cells are produced, the gland appearing swollen and redder than usual. In it bacilli such as those of tubercle may lodge and be there digested. If, however, the bacilli gain the circulation they may be destroyed in one of two

11 Hunter: Physiology and Pathology of Blood Destruction, THE LANCET, Nov. 26th, Dec. 3rd, 10th, and 17th, 1892, pp. 1259, 1318, 1371. The Pathology of Jaundice, Journal of Pathology and Bacteriology, 1895, p. 259.

secretion of the cell.

spermin, and bacterial products, pyocyanin, tuberculin; among vegetable materials are curara, papayotin, abrin, pilocarpin, terebinthin, and cinnamic acid. These either excite lymphadenoid tissue directly or do so indirectly by destroying cells. Many diseases cause a considerable leucocytosis probably in the same way; it is met with in cancerous cachexia, in the stage before death, after hæmorrhage, in inflammation of serous membranes, and in pneumonia. This leucocytosis when it occurs in the general diseases of lymphadenoid tissue is termed leucocythæmia or leukemia. A slight degree of leucocytosis may exert a favourable influence. Löwy and Richter 18 found that rabbits required much larger doses of such virulent materials as culture of diphtheria, chicken cholera, pig typhoid organisms, or pneumococci, in order to affect them after a certain degree of leucocytosis had previously been produced whether by the injection of spermin, pilocarpin, &C., or by the production of hyperpyrexia by puncture of the corpus striatum. Pawlowsky found rabbits in which a local leucocytosis was produced at the site of the inoculation of an anthrax culture by the injection of papayotin or abrin recovered, whereas the control animals similarly inoculated, but in which no leucocytosis was afterward produced, died. An excessive leucocytosis or leucocythæmia is unfavourable, not only by destroying red cells and disturbing the production as already pointed out, but by promoting an excessive destruction of white ones also. This continued cell destruction keeps up the excessive production by the lymphadenoid tissue and liberates from the nuclei of the cells proteids which set up intra-vascular coagulation, and hence the thromboses, ulcerations, and hæmorrhages which accompany leucocythæmia. It is the mature white corpuscles probably which have the chief protective power; the young white cells hurried into the blood in leucocythæmia

14

12 Kanthack and Hardy: Philosophical Transactions, 1894, vol. clxxxv., p. 279. 13 Löwy und Richter: Centralblatt für Wissenschaftliche Medicin, 1895, S. 445. 14 Pawlowsky: Atti dell' XI. Congresso Medico, Roma, 1894, vol. ii., Patologia generale, 165.

before they have developed cannot exercise the power, and they also tend quickly to break down.

where the spleen appears also to play, in part at least, a protecting rôle. But, on the other hand, there are conditions in which it remains unaffected.

The pathological changes in the spleen arise either in coninflammatory changes consequent upon the collection of morbid products in it. A diseased spleen affects the body generally either by producing leucocythemia and anæmia or by acting as an abdominal tumour.

We have thus traced back the anemia and leucocytosis or leucocythæmia seen in connexion with the diseases of lymphadenoid tissue to the same cause-an excess of cell-nexion with disturbances of its circulation or are due to products which excite the divisions of the leucoblasts, in consequence of which unripe red cells are hurried into the circulation from the bone-marrow, and, being inefficient as oxygen carriers, are soon included and destroyed in the spleen; at the same time the immature white cells which get into the circulation cannot fulfil their protective functions and may soon liberate substances which cause intravascular coagulation.

THE SPLEIN.

The spleen is an important blood-forming organ in amphibia and fish, and also in the mammalian embryo, but no proliferating red cells are to be seen in the healthy adult spleen of man. The centre of the Malpighian bodies is the site of the active germination of white cells, which pass to the periphery of the follicle and so get into the lymphatics, leaving the spleen; thence they pass through glands about the tail of the pancreas through the coeliac glands into the thoracic duct. The cells lining the spaces of the spleen pulp, through which the blood slowly flows, englobe and destroy red corpuscles and other foreign and harmful material. This function is especially active during digestion when the organ swells. The inherent rhythmical contractility residing in the unstriped muscle of the capsule and trabecule of the spleen favours the return of venous blood from the pulp spaces, especially after these have become distended during digestion. This rhythmical contractility has been not only the subject of experiment in animals, but has been observed during operations upon man. The spleen has been seen to contract under the eye when the return of venous blood had been hindered previously by its displacement. The spleen when prolapsed into a wound, so that the efferent veins are compressed, quickly becomes enormously swollen.

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Circulatory disturbance.-Venous obstruction concurrent with obstruction to the portal circulation causes first an engorgement of the pulp, then a general increase of connective tissue which does not especially pick out the follicles. Embolism affects the spleen according to the vessel, whether a main vessel is affected or several small ones. In pyæmia the necrosis goes on to suppuration around the bacteria which have lodged there. Infarcts from thrombosis are a special feature of the spleen. They are met with in typhoid fever, malaria, and leucocythemia owing to the coagulation produced by the breaking down of leucocytes. A wedgeshaped mass is formed abutting on the surface, which can thus be distinguished from other changes.

The

Inflammatory changes the result of infection.-The spleen is rarely affected by tubercle until the disease has become generalised. The bacilli have to pass through lymphatics and lymphatic glands into the blood stream before they can reach the spleen. The tubercles generally form in the sheath of the blood vessels and in the Malpighian bodies. Malpighian bodies appear as pale, firm masses which may easily be confounded with the changes due to lymphadenoma. Syphilis, especially when inherited, affects the spleen either directly in the form of gummata or by a general overgrowth of connective tissue or indirectly by starting amyloid disease. Amyloid disease may commence in a previously healthy spleen from some cause other than disease of lymphadenoid tissue, and by commencing in the follicles form the so-called sago spleen," or it may be widely diffused around the vessels of the pulp, and give rise to a hyalin appearance on section which has been compared to bacon rind. Amyloid discase may also affect a spleen previously altered by malaria, tubercle, syphilis, &c.

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The effect of removal of the spleen.-Complete splenectomy produces a temporary anæmia and enlargement of lymph glands, but neither condition is well marked. They occur both after experimental splenectomy in animals and also in the human subject when à spleen has been removed which had up to a short time before been healthy-e.g., when the spleen has been removed for injury or on account of a twisted pedicle (Ballance), 15 No change follows upon the removal of a diseased spleen, either in the blood or in the lymph glands, for the functions of the spleen have already been assumed by the lymph glands, &c., before the operation. Some experimenters on animals have found them little affected by it. The existence of a spleniculus which hyper-may be so far successful that the patient ceases to suffer trophies when the spleen is removed may explain this absence of symptoms, or, owing to a small portion of the spleen being left on the proximal side of the ligature, the spleen may re-form (Laudenbach).10 After partial resection, however, healing takes place simply by scar tissue without any hypertrophy.

The protective functions of the spleen. The cells of the spleen pulp can stop and remove from the circulation abnormal blood corpuscles, pigment, and some forms of organisms. Large cells are seen enclosing red or white corpuscles, bacteria, &c. (cellules d'arrêt: Cæsaris Demel). L7 According to Metchnikoff and Soudakewitch 1" the spirilla of relapsing fever multiply rapidly in the blood, but on reaching the spleen they are taken up and destroyed. If the cells become exhausted spirilla escape, and becoming again free in the blood rapidly increase again. Werigo 20 noted that anthrax bacilli injected into the ear vein of a rabbit reach the spleen and liver and are there included by cells. But soon free bacteria are found in the spaces of the spleen pulp, and then they multiply rapidly and cause the spleen to swell. During the last stages of the disease the bacteria escape into the general blood stream. There are other parasitic diseases-such as typhoid fever, diphtheria, and malaria

15 Pitts and Ballance: Transactions of the Clinical Society, 1896, vol. xxix., p. 102. Also discussion by Ballance, Bland Sutton, &c., THE LANCET, Feb. 22nd, 1896. 16 Laudenbach: Virchow's Archiv, 1895, Band exli., s. 201. 17 Casaris Demel: Archives Italiennes de Biologie, 1896, tome xxvi., D. 83.

18 Metchnikoff: Virchow's Archiv, 1887, Band cix., S. 176. 19 Soudakewitch: Annales de l'Institut Pasteur, 1891, tome v., p. 545. 20 Werigo: Ibid., 1894, tome viii., p. 1.

The spleen in malaria.-In malaria the spleen is primarily affected by an increased vascularity, in connexion with which there is an inclusion by the cells of the pulp of the corpuscles which are degenerating owing to the parasites, and there is left behind much pigment. This increased vascularity may cause only a temporary swelling of the spleen, and the organ afterwards subsides. The more permanent enlargement is due to an increased connective tissue formation whether specially of the follicles or diffusely of the pulp. Infarcts also occur. The stopping function of the spleen from malaria. Presumably in such a case the spleen has taken a prominent part in removing the parasites from the circulation. The spleen may not, however, subside after the cessation of the malaria, but remains an abdominal tumour, obstructing by its large size the abdominal circulation, and being in danger of causing at any time intra-peritoneal hæmorrhage either by the rupture of the tumour itself from some slight injury or often adhesions which have formed between the capsule and neighbouring structures. Such patients remain thin and anæmic, and an improvement in health may follow on splenectomy, always provided that the malaria has subsided and there is no leucocythæmia present. improvement may be due simply to. the removal of an abdominal tumour forming a mass of diseased tissue.

THE BONE MARROW.

The

Red and yellow marrow.-From the time when ossification commences in the previously non-vascular foetal cartilage by an invasion of bloodvessels from the perichondrium there appear erythroblasts developing into red corpuscles, and at a later period leucoblasts, which form the small colourless cells. Wherever ossification is going on there is an active formation of red corpuscles; and not only in cartilage and membrane, but also in exceptional cases of ossification, such as those which occur late in life in the laryngeal and rib cartilages, Neumann found erythroblasts. The formation of the red corpuscles in the red marrow is a feature common to all vertebrates, and is only absent in those fish whose cartilage persists throughout life as solid rods. In adult mammals it is the sole manufactory for the red corpuscles. The red marrow, however, gradually disappears from the bones of the extremities, being last of all found in the cancellous tissue of the upper

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