A system of practical medicine. By American authors. Vol. 3 (part 7 of 8)

Introduction

The blood is a fluid tissue composed of cells floating in an albuminous plasma, and it differs from other tissues not less in the arrangement of its elements than in the activity of the changes which go on in it. It is the mart into which is poured from the alimentary canal the commodities needed in nutrition, and the elements of the body select from it the various materials which they require, giving in exchange those chemical combinations which result from the metabolism of the tissues. In spite of ceaseless changes, a uniformity of composition is one of the most striking features of the blood in health. This is maintained, as regards the constituents of the plasma, by the activity of the organs which regulate income and expenditure--the alimentary canal and liver on the one hand, and the kidneys, lungs, and skin on the other; while histological uniformity is maintained by the adenoid or cytogenous tissue throughout the body, the function of which is to replace the wornout blood-corpuscles.

The corpuscles form rather less than one-half by weight of the blood. The plasma contains about 90 per cent. of water, which holds in solution proteids in the form of serum, albumen, and the fibrin-forming factors; sugar in traces; creatin, hypoxanthin, and urea; various fatty bodies in small amount; salts, chiefly sodium; and gases. The corpuscles (red) consist of hæmoglobin (90 per cent.), proteid bodies, and traces of lecithin and cholesterin.

So far as we know at present of the function of these two portions of the blood, the plasma ministers to the general nutrition of the tissues, while the corpuscles (red) are chiefly concerned with respiratory processes, acting as the carriers of oxygen and carbonic oxide.

We shall first give a brief account of the histological characters of the blood, and of the relation of the groups of adenoid or cytogenous tissue to the corpuscles.

Two forms of corpuscles are usually described, but we can recognize four varieties of blood-corpuscles in the body: (1) red, (2) white, (3) nucleated red, and (4) the hæmatoblasts (Hayem), or blood-plates of Bizzozero.

(1) Red Corpuscles.--In each cubic millimeter of plasma there are about 5,000,000 red cells. The percentage may vary within health limits from 90 to 110. The corpuscles are circular, non-nucleated, biconcave disks, homogeneous, to ordinary inspection structureless, and consist of a colorless stroma which is possibly reticulated, and a red coloring matter, the hæmoglobin. In {883} health they are tolerably uniform in size, about 7.9 µ[1] in diameter, or in English measurement 1/3200 of an inch (Gulliver). Even in normal blood there may be slight variations in size between 6.5 µ and 8.5 µ, the average, according to Hayem, being 7.5 µ.

[Footnote 1: µ is used to signify a micro-millimeter or 1/1000 part of a millimeter.]

(2) Colorless or white corpuscles, nucleated masses of protoplasm, with an average diameter of 10 µ, or about 1/2500 of an inch. The majority have a finely granular protoplasm, but in a few the granules are coarse and do not completely fill the clear protoplasm. The ultimate structure is reticular (Heitzman). Erhlich[2] has shown by their varying reaction to eosin that there are chemical differences among the colorless cells quite unrecognizable by other means. In healthy blood they display active amoeboid changes at ordinary temperatures. Their protoplasm does not, as is commonly stated, rapidly disintegrate, but if kept at a medium temperature retains its vitality, as shown by movements, for hours. The number per cubic millimeter is from 8 to 15 millions, and the ratio to the red is variously computed as 1 to 300 or 1 to 500.

[Footnote 2: Frerichs find Leyden's Archiv, Bd. i.]

(3) Nucleated red corpuscles, which occur in the blood of the foetus and the infant, gradually diminishing until at the third or fourth year they disappear. In the adult they do not occur in the blood in health, but are normal constituents of the red marrow of the short bones. They measure from 1/1500 to 1/2000 of an inch, and are of somewhat variable intensity of color, often quite as deep as the ordinary red forms. There may be two or even three nuclei, not colored, grouped together, often eccentric, and in some instances protruding from the cell.

(4) The hæmatoblasts of Hayem, the blood-plates of Bizzozero, the elementary or intermediate corpuscles, are small discoid colorless corpuscles about 3 µ in diameter, and are normal constituents of healthy blood. When the blood is withdrawn, they aggregate together into irregular clumps or masses, which have long been known as Schultze's granule-masses. It can be readily demonstrated in new-born rats or kittens, in which these masses abound, that the corpuscles composing them are isolated in the vessels, and only run together when the blood is drawn. The statement is commonly made that the granule-masses of Schultze result from the disintegration of the white corpuscle (of the red, Erhlich), but half an hour's study of the question in a new-born rat will convince any competent histologist that we have here to do with a separate blood-element.[3] It appears to have important relations with the production of fibrin.

[Footnote 3: Consult Proceedings Royal Society, 1874; Centralblatt f. d. Med. Wissenschaften; Medical News, 1882, 2; Bizzozero, Virchow's Archiv, Bd. xi.; Hayem, Recherches sur l'Anatomie normal et pathologique du Sang, Paris, 1878.]

Of the origin and life-history of the red corpuscles during post-embryonic life we have still much to learn. They are stated to develop--

(1) From colorless corpuscles, the lymph-cells or leucocytes. In the lymph-glands, the Malpighian bodies of the spleen, in the thymus, or the adenoid tissue of the tonsil, of the lymph-elements in the intestines and other regions, colorless cells are constantly being manufactured, and the general belief has been since Hewson's time that the red corpuscles develop in some way or other from these leucocytes. How or where has not yet been settled. It does not apparently go on in the blood, or we should surely catch, in the many observations and with the excellent powers now in use, a glimpse of the birth of one of them. Some observers (Johnstone[4]) maintain that they develop from the granular protoplasm of the adenoid reticulum by a process of budding. This may be so, but we should expect to find the lymph in the efferent {884} vessels and of the thoracic duct much more rich in red cells than is usually the case, and in specimens of healthy glands we should find young-looking elements such as he describes.

[Footnote 4: Seguin's Archiv, vol. vi.]

(2) From the nucleated red corpuscles. In the embryo this undoubtedly takes place, and as the weeks of development proceed, the ordinary red forms gradually predominate. In the child the red nucleated cells disappear early, and are then found only in the red marrow. So far as my observations go,[5] they apparently originate from colorless marrow-cells, which gradually become more homogeneous, and hæmoglobin develops in the protoplasm. The nucleus degenerates and disappears, when the cell has the appearance of an ordinary red disk. Rindfleisch thinks that the nucleus of the nucleated red is extruded in the development. It is possible that from these nucleated red corpuscles cells may originate in another way--viz. by budding. This I have seen and sketched in the marrow-cells,[6] and Malassez has studied the same process.[7] The gemmæ are small, and sprout from the protoplasm, not the nuclei, and when they break off they resemble the microcytes which occur so abundantly in certain anæmic states. Bizzozero[8] holds that these nucleated red corpuscles are independent elements which do not develop from the colorless marrow-cells. They multiply by fission, and develop into the ordinary red forms with the disappearance of the nuclei. Several recent investigations support this view.[9]

[Footnote 5: Centralblatt f. d. Med. Wissensch., 1878.]

[Footnote 6: Trans. Am. Ass. Ad. Science, 1882.]

[Footnote 7: Archives de Physiologie, 1882.]

[Footnote 8: Centralblatt f. d. Med. Wissenschaften, Bd. xix.]

[Footnote 9: Fortschritte der Medicin, 1885, No. 1.]

(3) Hayem believes that the red corpuscles develop from the small hæmatoblasts, but, so far as I know, his observations have never been confirmed. He states that in normal blood they occur in the proportion of about 1 to 20 red. In all states of blood reparation they increase greatly. He describes a hæmatoblastic crisis as occurring after hemorrhage, fevers, etc., when the number of these elements rapidly augments, and is succeeded by the addition of many small pale-red corpuscles, which he looks upon as intermediate between the hæmatoblasts and the ordinary red forms.

The colorless corpuscles are regarded as the direct offspring of the cells of the follicular cords in the lymph-glands and adenoid tissue, but whether by process of division of existing leucocytes or by sprouting from the endothelial places, or from the protoplasm in the fibres of the reticulum, remains to be settled.

The nucleated red corpuscles are in the healthy adult confined to red marrow, in which they probably develop from colorless cells, and may be regarded, as Neumann originally suggested, as transitional or intermediate forms between white and red cells. In anæmic states they may occur in the spleen and in the lymph-glands.

Of the origin of the hæmatoblasts or blood-plates we know absolutely nothing. They occur most abundantly under two most opposite conditions--in the young growing animal just entering upon life, and in the diseased, cachectic, wornout animal just preparing to abandon it.

Our knowledge of the relation of the cytogenetic organs to blood-formation may be thus briefly stated: The spleen certainly takes part in the development of colorless corpuscles, but its participation in red blood-formation is more doubtful. The nucleated red or embryonal forms do not occur, at least in any numbers, in health, though some observers have noted that after a repeated bleeding the organ was swollen and contained many such cells, as if it was the seat of an active development. Though the opinion prevails widely that the spleen is one of the important organs in the formation of red corpuscles, the evidence for this belief is of an exceedingly scanty nature.

The lymphatic glands and the adenoid tissue in other regions are the seats {885} of constant production of colorless corpuscles, but of their relation to the red corpuscles there is the same lack of information as in the spleen. I do not know of any corroboration of the observation of Johnstone above mentioned, and in any case the number of red cells in the efferent vessels of a lymph-gland is so small--and indeed in the thoracic duct itself--that we cannot believe they are produced as red corpuscles in large numbers within the lymphatic system.

The red bone-marrow, as pointed out by Neumann[10] and Bizzozero,[11] appears to be the seat of blood-formation, and in the adult body is the only region in which the embryonic or nucleated red cells are found. It is a tissue similar in many respects to the spleen, and, though confined to the short and flat bones, the total amount in the body is very considerable. In the young it also fills the long bones. The evidence of the development of red corpuscles in the marrow rests upon the constant presence of nucleated cells infiltrated with hæmoglobin, and of their fission. Forms undergoing the process of karyokinesis can be seen without difficulty. In excessive hemorrhage, natural or induced, it appears to undergo an active proliferation, and in the long bones a red marrow may replace the fatty tissue.

[Footnote 10: Centralblatt f. d. Med. Wissenschaften, 1868.]

[Footnote 11: Ibid., 1868.]

The liver is doubtless the seat of blood-destruction, for the bile-pigments and leucocytes with red corpuscles in their interior have been found in its tissue. Nicolaides[12] has shown that in the blood of the hepatic vein there may be a reduction of from one million to one million and a half of red corpuscles per c.m. In the embryo Neumann[13] has shown that it may be the seat of the production of corpuscles, but there is no satisfactory evidence that in the adult this ever takes place.

[Footnote 12: Archives de Physiologie, 1882.]

[Footnote 13: Archiv der Heilkunde, xv.]

The remarkable rapidity with which, after a profuse bleeding, the normal proportion of red corpuscles is reached shows with what activity the development may proceed, and how favorable the conditions must be for their production. After the loss of a large quantity of blood the manufacture of new corpuscles may proceed at the rate of 30,000, 40,000, or even 50,000 a day.

What becomes of the red corpuscles? Here, again, is a question not satisfactorily settled. We do not know the average length of life of corpuscles. They are supposed to be short-lived--three weeks, according to Quincke. The need for their dissolution is assumed to provide pigment for the various secretions and tissues, and we occasionally see a few cells in the blood with a pallor which may be regarded as an indication of senility.

Positive evidence, however, of their destruction is afforded by the occurrence of the so-called corpuscles containing red corpuscles, which occur normally in red marrow and in the spleen, and under some circumstances in the lymphatic glands and liver. The red cells undergo gradual transformation into a yellow granular, and finally black, pigment. In normal spleen and marrow the numbers found are very variable; in fevers and cachectic states they may be in extraordinary numbers. Quincke and his pupil Peters[14] have studied with great care this process of transformation of the red corpuscles and accumulation of the pigment in the cells of the marrow, spleen, liver, and lymph-glands, to which the term siderosis is applied. These pigment-granules are in the form of an iron albuminate, and are used in the development of new corpuscles. Thus, after repeated bleedings in animals, they may disappear completely in the restoration of the blood, while in animals into whose vessels blood has been transfused or injected subcutaneously the iron-containing cells in the various organs are very numerous, and even the cortical cells of the kidney contain numerous granules.

[Footnote 14: Deutsches Archiv f. klin. Med., Bds. xxv., xxvii., xxxii., xxxiii.]

The amount of hæmoglobin in 100 grammes of healthy blood is {886} 13.45 grm. (Preyer). Malassez estimated the quantity in a cubic millimeter of blood at between 0.125 and 0.134 milligramme, and, taking the corpuscular richness at from 4,000,000 to 4,600,000, he has estimated approximately the amount of hæmoglobin in each corpuscle.

PLETHORA.

General and persistent polyæmia or plethora has scarcely a place in recent pathology. Formerly it was thought that either from over-production or lowered expenditure the total amount of blood accumulated and filled the blood-vessels to an abnormal extent. The amount of blood undergoes, within limits, constant daily alterations, and after a full meal the vessels are in a state of plethora compared with their condition at the end of a ten hours' fast. If a plethysmograph could be devised to record graphically the variations in the total quantity of blood, each ingestion of food or drink into the vessels would be followed by a rise, and each interval by a gradual decline. So long as the organs of secretion and excretion are active the quantitative and qualitative condition of the blood is maintained at a tolerably uniform standard in each individual. At different periods of life the relation of blood-weight to body-weight varies. In the new-born the blood amounts to one-eighteenth part by weight of the body, while in the adult the average is from one-twelfth to one-fourteenth; so that in the infant there is a condition of comparative plethora. There are no reliable observations on the proportion of blood- to body-weight at respective ages, but there appears to be a reduction in old age. In women it is stated that just before each menstrual period there is a state of polyæmia.[15]

[Footnote 15: Mary Putnam Jacobi, The Question of Rest for Women, New York.]

Worm-Müller[16] and Cohnheim[17] have made some very interesting experiments on this question of plethora. By transfusion in dogs a state of artificial plethora is readily established, and the animals stand the injection of as much as 10 or 12 per cent. of the body-weight of blood, above which quantity a fatal result ensues. After an injection of 20 or 30 per cent. of the total amount of blood, the superfluous plasma and corpuscles are got rid of in a few days, while with a larger injection of 60 to 80 per cent. it takes two or three weeks before the normal state is again reached. The albuminous and nitrogenous materials are largely got rid of by the urine, which increases rapidly in quantity and also in the amount of urea. The excess of corpuscles gradually disappears, and the hæmoglobin becomes deposited, as Quincke has shown, in the form of small granules in the cells of the liver, spleen, and bone-marrow.

[Footnote 16: Transfusion and Plethora, Christiania, 1875.]

[Footnote 17: Allgemeine Pathologie, 2te Auflage.]

In a similar way, it is reasonable to think that the body is quite capable of disposing of surplus albuminous materials in over-fed, lazy individuals with active digestion, whose red faces, full vessels, and bounding pulses give the impression of a distended circulatory system, and whom we term plethoric. Their appearance is the result rather of blood-distribution than of actual increase in the total volume, and there is no evidence that under any circumstances a rich and abundant diet without much exercise can permanently increase the amount of blood. It was formerly held that the healing of an old sore or the cessation of an accustomed discharge or loss of blood, by diminishing expenditure while the blood-making power was maintained, could induce plethora if no local disorder was excited "before the vessels {887} in general reached a state of plethoric tension." Of such a condition, and of the plethora apocoptica that was thought to occur after the amputation of a limb, we do not hear much now, and the prevalent opinion of pathologists is expressed by Cohnheim, when he says "that, except as a transitory state, polyæmia does not occur under any circumstances." What, then, is the meaning of the full-blooded, rubicund condition which we see in some men, not necessarily large feeders, but often with vigorous active constitutions and perfect types of health? The appearance of plethora is caused chiefly by the distension of the superficial vessels; the circulation of the skin is remarkably active, particularly in the face, and it is probable that we have here to deal with local peculiarities of the vessels or of their innervation, and not with any general augmentation of the total blood-mass. It may be, however, that in such persons there is a plethora of certain of the constituents of the blood--viz. the red corpuscles--and there may be a state of polycythæmia rubra, as it has been called, in which the percentage of red cells is increased. In several such cases I have found, as has been previously noted, the number of red corpuscles considerably over the average. A relative increase in the number of red corpuscles also occurs in those sudden and excessive losses of fluid, as in cholera, in which the blood may become thick and sticky from the great reduction in the plasma, particularly of the water and salts--anhydræmia--or in cases in which the income of fluid is greatly restricted. Henry (F. P.) has recorded a case[18] of stenosis of the cardia, in which, with great emaciation, the corpuscles per c.m. were 5,525,000.

[Footnote 18: Archives of Medicine, New York, vol. vii.]

The condition known as hydræmic plethora develops whenever there is a great reduction in the number of corpuscles, as after a hemorrhage, or when the blood has been impoverished by long-standing suppuration, albuminuria, or in the growth of large tumors. So also when the secretion of urine is diminished, as in some cases of Bright's disease, and at the same time charged with albumen, the blood may become very watery; but in these states there is not an absolute increase in the entire blood, but only a relative excess of the water. Occasionally, this great excess can be noticed in the blood-drop as it comes from the finger-tip; the corpuscles do not fill the entire drop, and consequently leave irregular areas unoccupied by the red disks.

ANÆMIA.

A reduction in the amount of the blood or of its corpuscles occurs under a great variety of circumstances. Broadly speaking, we can recognize two great clinical and pathological groups of cases: I. Those induced by causes acting upon the blood itself; and, II. Those induced by disturbance in the functions of the blood-making organs.

I. Of causes acting directly upon the blood, we shall consider--

1st. Hemorrhage, traumatic or spontaneous. A high grade of anæmia may be quickly produced by loss of a large quantity of blood, and the reduction is in all the constituents; there is a true oligæmia. If the amount lost be excessive, death results from the diminution in the total volume of blood and general lowering of the arterial pressure. If the hemorrhage is sudden and profuse, as from a large vessel, the loss of four or five pounds of blood, or even less, may be sufficient to induce fatal syncope. In hemorrhage into the pleura or peritoneum from rupture of aneurisms, etc., it is rare to meet with more than three or four pounds of clot and serum; seven and a half {888} pounds is the largest amount I know of shed into one of the cavities (pleura) by rupture of an aneurism. When the bleeding extends over several days, the amount lost may be very much greater. In cases of hæmophilia extraordinary accounts are given of the amount collected in the course of a few days. In a case of hæmoptysis a patient lost over ten pounds by measurement in one week, and then recovered from the immediate effects. After the most severe hemorrhages the reduction in the number of red corpuscles is not nearly so great as in forms of idiopathic anæmia. Thus in the case just mentioned at the termination of the week of bleeding there were 1,390,000 red corpuscles to the cubic millimeter. In any single bleeding a fatal result follows the loss of one-third or one-half of the total blood-volume. The process of regeneration of the blood goes on with astonishing rapidity, and in some bleeders a week or ten days will suffice to re-establish the normal amount. The restitution begins even during a hemorrhage by the absorption of lymph from the tissues under the lowered pressure in the vessels. The dryness and stickiness of the serous membranes after death from a profuse hemorrhage is usually very marked. The water and saline constituents of the blood are readily restored by absorption from the gastro-intestinal tract. The albuminous elements are also quickly renewed, but it may take weeks or months before the number of corpuscles reaches the normal standard. Indeed, this condition of oligocythæmia, as it is called, may persist, grow worse, and ultimately prove fatal. The microscopical characters of the blood after severe hemorrhage are not much changed, except as regards the white corpuscles, which are relatively increased, and the fibrin network, which is much less marked than in health. The white corpuscles may be very slightly reduced in number per cubic millimeter--a fact to be accounted for either by a relatively diminished loss during the bleeding, owing to their adhesiveness and wall-loving properties, or to a quick restitution from the lymph which is poured into the blood-stream. It has been observed both in dogs and men by Lyon[19] that after a severe hemorrhage the number of red per cubic millimeter diminished for several days after the bleeding had been checked. How and where does the regeneration of red corpuscles take place after a severe hemorrhage? One would think that under these circumstances, if any, we should be able to get information which might be of service in determining the problem of blood-development; but, in spite of the numerous experiments on the subject, we are still far from a knowledge of full details. The observations of Neumann,[20] Litten and Orth,[21] Bizzozero,[22] Lepine,[23] and others appear to prove conclusively that the bone-marrow plays an important part in the formation of the new red disks, becoming lymphoid, losing its fat, and the nucleated red cells increase enormously. The same process has been observed in many cases in man. In a case of profuse metrorrhagia with profound anæmia Neumann[24] found the marrow in all the bones of a rich raspberry red, full of the nucleated forms, which were also very abundant in the blood, and more in the vena azygos than in the aorta. The evidence in favor of the active participation of the spleen is not so conclusive. Neumann[25] concludes that the spleen takes no share in the process, and holds that the nucleated red cells found in it are probably derived from the bone-marrow. Bizzozero, on the other hand, has found the spleen swollen and showing signs of lively blood-formation. He states that after removal of the spleen the restitution of the red corpuscles takes place much more slowly. Pouchet, on the contrary, says the regeneration goes on just as rapidly without the spleen. {889} Of the action of the lymph-glands there is even less evidence. They have been found swollen, but in traumatic anæmia I do not know of any observations on their swelling and conversion into a red spleen-like tissue, such as have been found in some cases of idiopathic anæmia.

[Footnote 19: Of Norwich, Conn.: Virchow's Archiv, lxxxiv.]

[Footnote 20: Archiv der Heilkunde, Bd. x.; Frerichs and Leyden's Archiv, Bd. iii.]

[Footnote 21: Berliner klin. Wochenschrift, 1877, li.]

[Footnote 22: Centralblatt f. d. Med. Wissenschaften, 1879, xvi.]

[Footnote 23: Revue Mensuelle de Méd. et de Chirurg., 1877.]

[Footnote 24: Loc. cit.]

[Footnote 25: Loc. cit.]

The microcytes which occur in numbers in blood in some cases of traumatic anæmia have been regarded as young developmental forms, but there is a great diversity of opinion as to their real nature, and their connection with productive blood-processes is somewhat doubtful.

Cohnheim suggests[26] that after a profuse hemorrhage the rapid consumption of red corpuscles may be reduced, in which case we need not suppose such an active development; but the fact noted by Lyon[27] and others of the increased reduction after a bleeding is against the view. In any case, if Quincke is right in assuming that the average life of a red corpuscle is only three or four weeks, what is the restitution of a couple of millions of corpuscles per cubic millimeter in comparison with the monthly renovation of the entire mass?

[Footnote 26: Loc. cit.]

[Footnote 27: Loc. cit.]

In the regeneration of the blood the development of the hæmoglobin does not keep pace with that of the corpuscles, so that they may, even when normal in amount, have a lowered hæmoglobin percentage, indicated under the microscope by a paleness in the cells.

2d. There is a large group of cases in which the anæmia is induced by a long-continued drain on the albuminous material of the blood--pus in a chronic suppuration, albumen in Bright's disease, prolonged lactation, etc. Rapidly-growing tumors act in the same way.

3d. The anæmia of inanition, brought about by defective food-supply or by conditions of the digestive organs which interfere with the proper reception and preparation of nourishment, as cancer of the gullet, chronic dyspepsia, etc. The reduction in the blood-mass may be extreme, but the plasma suffers proportionately more than the corpuscles, which even in the extreme wasting of cancer of the oesophagus may not be reduced more than one-half or three-fourths.

4th. Toxic anæmia, induced by the action of certain poisons in the blood, such as lead, mercury, and arsenic among inorganic substances, and the virus of syphilis and malaria among organic poisons. They act by increasing the rate of consumption of the red corpuscles, and the reduction may be considerable. The gradual impoverishment of the blood in pyrexia may be in part due to the toxic action of the fever-producing agent on the blood itself; but in this there is probably also disturbance of function in the blood-making organs.

The last three groups comprise what are known as secondary anæmias, and the condition of the blood is characterized by an increase in the water and diminution in the albuminous elements; the fibrin is often increased, and the network which separates, as seen under the microscope, is unusually dense; the white corpuscles are not much increased; there is rarely microcytosis or poikilocytosis; the reduction in the number of red corpuscles is not so great; hemorrhages do not often occur; when fever is present it is due to the disease or some complication, and is not the pyrexia of anæmia; and, lastly, they are more or less amenable to the action of iron and other remedies.

II. A consideration of the anæmias induced by disturbance in the blood-making organs themselves presents difficulties proportionate to our ignorance of the details of hæmatogenesis. We may regard, as above stated, the spleen, the general lymphatic tissue, and the marrow as the sites of production of corpuscles which are passed into the circulation fully formed. Certain of these organs--the spleen and marrow particularly--are also concerned with blood-destruction as well as blood-elaboration; but there is evidence to show[28] that {890} they, to use an ordinary simile, consume their own smoke, using the waste products for the purpose of further manufacture. Looking now upon the hæmatogenetic tissues as a single organ scattered through the body, let us consider what general disturbances of function it may suffer comparable to those met with in other structures. We can evidently suppose the physiological activity to be diminished or increased, and we should expect to find corresponding to these changes equivalent alterations in the character of the blood. Unfortunately, our knowledge of the normal processes as they go on in these tissues is so scanty that it amounts to a discussion upon the disturbances of a function itself imperfectly understood.

[Footnote 28: Quincke, quoted above.]

With diminished functional activity in an organ we commonly meet with reduction in volume, the one depending on the other: now, the only instance in the blood-making organs in which a decrease in size and diminished functional activity go together is in the senile atrophy in which the spleen becomes small, the marrow more fatty, and the lymph-glands sclerotic, and in consequence the blood also is reduced in amount; but this is only a part of the general failure of nutrition in old age. Pathologically, there is no such well-recognized condition of uniform atrophy of spleen, lymph-gland, and bone-marrow, with a corresponding general reduction in the elements of the blood. Certain cases of idiopathic anæmia come close to it, in which these parts are wasted, but there are other differences which make the two conditions scarcely comparable. In fact, as we shall see, diminished activity in blood-making is usually associated with an increase in what we call hæmatogenetic tissues. Of increased functional activity in these parts we know very little, apart from the changes met with in cases of traumatic anæmia, in which the hyperplasia of the spleen and bone-marrow may be regarded as intimately connected with the rapid development of red corpuscles.

One fact is evident: that a progressive increase in the cytogenic tissues, local or general, is associated with disturbance in the process of blood-formation, and sooner or later induces anæmia. Thus, progressive enlargement of the spleen or of the lymph-glands or marked hyperplasia of the marrow, either singly or combined, is invariably accompanied with alteration in the characters of the blood. Even in those rare instances in which the lymphoid elements of the tonsils and fauces or of the gastro-intestinal canal are chiefly involved the same change may take place.

The nature of the process in the organs is of a hyperplastic character. In the spleen the pulp at first increases and the Malpighian bodies enlarge, but ultimately there is such a development of the fibrous reticulum that the consistence is greatly augmented and the organ becomes indurated. Histologically, there is very little distinction to be made between forms of chronic enlargement of this organ. In the lymph-glands there is increase in the cells; the tissue becomes more succulent, and is in a state of hyperplasia which may terminate in a great development of the fibrous elements, with induration. So also with the bone-marrow: in the short and flat bones, where in the adult a reddish or slightly fatty tissue exists, the fat disappears entirely, and the long bones, normally filled with yellow marrow, become occupied with a red-gray or greenish-gray cytogenous tissue not unlike spleen-pulp, and in many instances more consistent than the red marrow of early life.

A reduction in the number of red corpuscles is the chief and most constant change in the blood; anæmia seems to be the invariable result, whether the spleen, marrow, or lymph-glands are affected singly or together, and is the central feature in the entire group of cases. This diminution in the red cells may or may not be accompanied by an increase in the white corpuscles, which in some cases may be so striking as to be regarded as the special blood-change, and is, as a rule, permanent, though it may be a variable or even a transitory state.

{891} The general and histological differences between forms of hypertrophy of these blood-making organs are exceedingly slight, and in their clinical features they present a large number of symptoms in common; indeed, we may say that all the important symptoms are present, whether the spleen is affected alone or with the lymph-glands and bone-marrow, or whether these parts are independently involved, and whether there is simple reduction in the red or with it an increase in the white corpuscles. Such common features are--the progressive anæmia with its group of circulatory symptoms; the irregular febrile reaction, essential fever of anæmia; the absence of marked emaciation; the tendency to effusions of serum; the progressive debility; the occurrence of hemorrhages; gastric and intestinal disturbances; and resistance to treatment.

The affections characterized pathologically and clinically by so many similar features are known and recognized as distinct diseases under the names leukæmia, Hodgkin's disease or pseudo-leukæmia, splenic anæmia, and idiopathic anæmia (some cases); and we shall now consider these a little more closely.

First, of the hyperplasias of the cytogenic tissues associated with simple anæmia. The various groups, spleen, lymph-glands, and marrow, may be involved singly or together; usually one is first affected, and the others, if at all, subsequently. Progressive enlargement of the spleen induces sooner or later anæmia, the anæmia splenica of Griesinger. These cases are by no means rare: certain of them represent the final stage of a malarial intoxication, but there are others in which the enlargement seems causeless. There may also be hyperplasia of the bone-marrow, less often of the lymph-glands. The anæmia may be profound, and the clinical picture is that mentioned above. Two cases of it under my care died of hæmatemesis. The diagnosis of this affection from splenic leukæmia rests solely on the microscopical examination of the blood. It is also classed as the splenic form of Hodgkin's disease or pseudo-leukæmia.

Primary enlargement of the lymph-glands with anæmia constitutes Hodgkin's disease or pseudo-leukæmia, in which there may be general hyperplasia of the lymphatic elements throughout the body, with nodular growths of adenoid tissue in other organs. The spleen and marrow are not often affected. Here, too, the diagnosis from lymphatic leukæmia rests with the microscope.

Is there a form of anæmia dependent upon hyperplasia of the bone-marrow--an anæmia medullaris? In 1875, Pepper and Tyson[29] found affection of the marrow in idiopathic anæmia, and Pepper suggested that this might be the starting-point of the disease, which could thus be regarded as a medullary form of pseudo-leukæmia. Cohnheim in 1876[30] described the same condition, and I had an opportunity of examining several cases.[31] Granting that the marrow is a tissue which shares in the blood-making functions, it seemed reasonable to suppose that a general hyperplasia of its elements might disturb the processes of hæmatosis and produce anæmia, just as in hyperplasia of the spleen and lymph-glands. Two facts soon came to light which seem opposed to this explanation of the pathology of idiopathic anæmia. A hyperplasia of the marrow was found in cases of chronic disease with wasting, and cases of idiopathic anæmia were described in which the marrow was normal. The numerous observations of the past five or six years have not brought us nearer to a solution of the problem. The observations of Neumann,[32] and those of Litten and Orth,[33] on the changes in the marrow in chronic diseases have been abundantly confirmed, and a red lymphoid marrow may be met with in various cachectic states. This, too, I have frequently seen, {892} yet it is in my experience rare to find such marked, rich hyperplasia of the marrow, such an entire absence of fat, as in some cases of idiopathic anæmia. In 9 autopsies in typical cases at Montreal, not parturition cases, the marrow of the long bones was lymphoid and red in 6; in 1 it was not examined; in 1, which I did not see, the marrow was stated to be normal; and in 1, an old woman over sixty years of age, the marrow of the short bones was rich in lymphoid cells and nucleated red corpuscles, and the long bones contained a grayish gelatinoid--atrophic--marrow. It does not appear possible with our present knowledge to arrive at a satisfactory conclusion on this question. Some regard the marrow-change as the consequence, others as the cause, of the anæmia. Both Cohnheim[34] and Pye-Smith[35] regard those cases of idiopathic anæmia in which the marrow-changes are pronounced as cases of anæmia medullaris.

[Footnote 29: American Journal Med. Sciences, 1875, ii.]

[Footnote 30: Virchow's Archiv, Bd. lxviii.]

[Footnote 31: Centralblatt f. d. Med. Wissenschaften, 1877, Nos. 15 and 28; 1878, No. 26.]

[Footnote 32: Berl. klin. Wochenschrift, 1877, xlvii.]

[Footnote 33: Ibid., 1877, li.]

[Footnote 34: Loc. cit., Bd. i. S. 467.]

[Footnote 35: Loc cit.]

Next of the parallel series of hyperplasias of the blood-forming organs with anæmia, plus an increase of the colorless corpuscles--leukæmia. Here, too, we have the three forms--splenic, lymphatic, and medullary.

The splenic leukæmia is the most common, and in its general features is identical with splenic anæmia, the excess of white corpuscles being the only distinguishing feature. It is almost invariably associated with changes in the marrow.

The lymphatic leukæmia may arise in connection with hyperplasia of the lymph-glands or of the adenoid elements in the alimentary tract--tonsils and Peyer's glands. It is much less common than lymphatic anæmia or Hodgkin's disease, and there are not many uncomplicated cases on record. Apparently, a very limited bunch of glands--cervical--may induce the change in the blood.[36] Medullary changes are almost invariably associated with a great increase of colorless corpuscles in the blood, and a myelogenous form of leukæmia is now, owing chiefly to the investigations of Neumann, well established. Indeed, he would regard the change in this tissue as the primary and important, and those in the lymph-glands and spleen as secondary.

[Footnote 36: Gowers, Reynolds's System of Medicine, art. "Leucocythæmia."]

The hyperplasia, either lymphadenoid in character or pyoid, may result in the expansion and softening of the bones, with the production of irregular tumor-like masses.

We have, then, the following group of anæmias induced by a primary disturbance of function in the blood-making organs:

PRIMARY OR | Leucocytic | Splenic, | CYTOGENIC | | Lymphatic, | Leukæmia. ANÆMIA. | | Medullary, | | | Non-leucocytic | Splenic, Anæmia splenica. | Lymphatic, Hodgkin's disease. | Medullary, Idiopathic anæmia (certain cases).

There remain for consideration the relation of the tissue-change to the anæmia and the nature of the leucocytosis; but until the chief facts in the development of the corpuscles are thoroughly known we cannot expect a satisfactory solution of these problems.

The anæmia may be explained on the view of diminished production (anæmatosis) or increased consumption of the red corpuscles (hæmophthisis). We know nothing of the intimate processes connected with lessened production, but as anæmia so constantly accompanies the hyperplasia, we assume they are intimately connected with each other, and the diminution in the number of corpuscles in some way the result of disturbed functional activity in the blood-making organs. An increased consumption of corpuscles in anæmia is {893} indicated by the presence in large numbers of cells containing red blood-corpuscles in the spleen and marrow, and occasionally in the lymph-glands; by the increased amount of iron which has been found in the liver; and in some cases by the deep color of the muscles and an intensification of the color of the urine. Either a failing production with normal rate of consumption, or a normal output with heightened destruction, would produce anæmia. Possibly, in some instances, both factors may prevail. Quincke's interesting observations[37] may enable us to determine the cases in which one or other has been dominant. Where there is great destruction we shall expect to find the granules of iron albuminate in the spleen, bone marrow, and liver-cells, possibly in the cells of the cortex of the kidneys, and the iron reaction should be present.

[Footnote 37: Loc. cit.]

The relation of the hyperplasia of the cytogenic tissues to the increase in the colorless corpuscles is even more obscure. A prime difficulty is the circumstance that apparently identical tissue-changes may be associated with either a leucocytic or non-leucocytic anæmia. The splenic hyperplasia of leukæmia and of anæmia splenica are histologically identical. The excess of white corpuscles may be due either to over-production or to failure in their transformation into red. That they develop in the hyperplastic spleen, marrow, and lymph-glands is not to be doubted, and it seems reasonable to attribute the excess to the hyperplasia. Their variable size, as spleen or lymph-glands are chiefly affected, was early observed by Virchow, and when the marrow is involved there may be many large leucocytes similar to the larger marrow-cells. Virchow's original explanation, that the excess of colorless cells was due to a failure in their transformation into red corpuscles, rests upon the presumption that such a transformation is the normal process--a view not fully established. If this is the case, we should expect to find some relation between the increase of the white and the decrease in the red, but this is not always constant; as a general rule, with a diminution of the white there is an increase in the red, but the red and the white cells may increase or diminish in numbers simultaneously, or, again, the leucocytes may be greatly reduced while the red corpuscles remain about stationary. Griesinger,[38] Biesiadecki,[39] and others regard the increase in leucocytes as a primary blood-change. Several recent French writers support this view, as Renant,[40] who believes that the unequal size of the leucocytes indicates their division in the blood, and Variot.[41] One of the most interesting features in connection with an increase in the colorless cells is that it may be only transitory, and a case which clinically and pathologically may present the features of idiopathic anæmia to-day may to-morrow present the characters of leukæmia; a case of splenic anæmia may become one of splenic leukæmia, or vice versâ. Thus, in Litten's oft-quoted case--about which there can be no doubt[42]--of acute anæmia of three weeks' duration, an enormous increase of colorless corpuscles took place, and finally a ratio of one white to four red was reached. Quite as interesting is the case of Fleischer and Penzoldt,[43] in which for eight months the patient presented the ordinary symptoms of anæmia lymphatica or Hodgkin's disease, and then, before death, the blood became intensely leukæmic, the ratio 1:9. Still more so as the case of Goodhart's,[44] in which, with an enlarged spleen and lymphoid growths in liver and kidneys, there were variations in the number of corpuscles every few days--at one time great excess of white, at another no increase whatever. Again, a case may early come under observation as one of leukæmia, with a ratio of 1:20 or 1:30, and in the course of a few months, with persistence or even aggravation of {894} the general symptoms, the normal ratio of white to red may be reached. This was the history in one of the Montreal cases.[45]

[Footnote 38: Virch. Archiv, Bd. v.]

[Footnote 39: Wien. Med. Jahrbuch., 1876.]

[Footnote 40: Archives de Physiologie, 1881.]

[Footnote 41: Thèse de Paris, 1882.]

[Footnote 42: Berl. klin. Wochenschrift, 1877.]

[Footnote 43: Deutsches Archiv f. klin. Medicin, Bd. xxvi.]

[Footnote 44: Clin. Society's Transactions, London, 1877.]

[Footnote 45: Howard, Montreal General Hospital Reports, vol. i. p. 39.]

It seems questionable whether such a variable feature as increase in the colorless corpuscles should be permitted to separate diseases which have all essential characters in common. We shall probably, however, continue for a long time to speak of these conditions as separate and distinct, but it is evident that as time goes on, and our knowledge of the diseases and of blood-development increases, the identity of many of them will be acknowledged, and we shall find that here, as so often the case in natural history, the multiplication of species has been the result of imperfect information, and that as points of resemblance in essential characters and development are studied minor differences disappear.

With reference to the general tissue-changes in anæmia there are two points of interest: The metabolism of the proteids is increased, as shown by the increased excretion of urea, and owing to defective exudation the decomposition of the fats is lessened; hence the retention of fat, or even increase, in anæmic persons. The influence of repeated small bleedings in hastening the fattening of cattle has been known since the time of Aristotle, and horse-dealers still affirm that there is nothing like bloodletting to put an animal into good condition.

CHLOROSIS

is a special form of anæmia distinguished by certain etiological and anatomical peculiarities. In the first place, it is a disease of the female sex; cases in the male are of extreme rarity. In the majority of instances it is associated with disturbed menstrual function or with the evolution of the reproductive organs at the period of puberty. Occasionally it occurs in pregnant women and in children. It is a common disease among the ill-fed, overworked young girls in large towns who are confined all day in close, badly-lighted rooms or who have to do much stair-climbing. Girls of the better classes are by no means exempt; indeed, some writers speak of it as specially prone to affect the higher ranks of life. Lack of proper exercise, good food, and fresh air, the mental stimulation of unhealthy literature, and masturbation, are important factors. Emotional and nervous symptoms may be prominent--so much so that the disease is regarded by some as a neurosis.

The anatomical peculiarities relate to the blood and circulatory system. There is anæmia, but the impoverishment is less in the number than in the corpuscular richness in hæmoglobin. This fact, first pointed out by Duncan,[46] has been abundantly confirmed. Thus, for example, in one case, with a globular richness of 85 per cent., the hæmoglobin was only 52 per cent., and in another, with 92 per cent. of red, the hæmoglobin percentage was as low as 64. The numerous investigations of the past few years[47] have, among other points, fully established this as perhaps one of the most striking features in chlorosis. The color-value of the individual corpuscle is very much reduced. Of 22 observations of Hayem, the average number of red corpuscles was {895} 3,740,000, and the hæmoglobin reduced to about 50 per cent. In Laache's 13 cases the average percentage of corpuscles was 72, and of hæmoglobin 45. This author has pointed out that in certain cases with all the clinical symptoms of chlorosis well marked there may be very slight reduction in the corpuscles or hæmoglobin; and such he terms pseudo-chlorosis. The red corpuscles in chlorosis vary much in size. Very large forms--giant red cells--are common, and microcytes are sometimes to be seen; but there is not the extreme irregularity in size and outline of the blood in idiopathic anæmia. The presence of a large number of young, imperfectly-formed corpuscles, especially as regards the hæmoglobin, is the distinguishing feature of chlorotic blood. Hayem and Willcocks both regard the average corpuscular diameter to be lower than normal, though many large forms occur. The color of the red corpuscles is noticeably pale, and the marked deficiency in hæmoglobin can be observed in individual corpuscles as well as in the blood-mixture prepared for counting. Quinquaud found the serum normal in quality, but the solids were slightly reduced in amount. Hunt[48] has shown that there are peculiar inter-menstrual oscillations in the blood in chlorotics. There is usually a fall in numbers just before the flow, but the individual value remains good; subsequently the number rises, but the color-value is not maintained (Willcocks). Virchow[49] pointed out that in many cases of chlorosis there was a defective development of the circulatory system, either congenital or resulting in failure of the normal rate of growth; the parts remained infantile. The heart and arteries were small, the walls of the latter thin, and the calibre of the aorta narrowed. In some instances there was found a compensatory hypertrophy of the heart. Defective development of the uterus and ovaries has also been noted, but these changes on the part of the circulatory and generative organs are not constant features in chlorosis.

[Footnote 46: Sitzungsbericht d. Kais. Akad. d. Wissenschaften zu Wien, 1867.]

[Footnote 47: Leichtenstern, Hæmoglobingehalt des Blutes, Leipzig, 1878; Hayem, Recherches sur l'Anatomie, etc. du Sang, 1878; Malassez, Archives de Physiologie, 1877; Moriez, La Chlorose, Paris, 1880; Laache, Die Anämie, Christiania, 1883; Willcocks, Practitioner, 1883.]

[Footnote 48: Lancet, ii., 1880.]

[Footnote 49: Ueber die Chlorose, etc., Berlin, 1872.]

The SYMPTOMS of chlorosis are those of anæmia of moderate grade. As in idiopathic anæmia, the subcutaneous fat is in full, or even extra, amount. The complexion is most peculiar, neither the blanched aspect of hemorrhage nor the muddy pallor of grave anæmia; but there is a curious yellow-green tinge in marked cases which has given the name to the disease ([Greek: chlôros]), and also its popular designation, the green sickness. Breathlessness, palpitation, and tendency to fainting are due to the anæmia. Digestive troubles are also common, and the appetite is often depraved. There are venous and cardiac murmurs. The menstrual functions are almost always deranged, and there may be hysterical and nervous manifestations. Relapses are not uncommon. The intimate pathology of the disease is unknown. In its insidious onset, sometimes causeless, and in certain features of the blood-state, it resembles pernicious anæmia, but it differs from it in many essential particulars. The association with menstrual disorders, the hypoplasia of the circulatory and generative organs in some cases, the favorable course and response to suitable treatment, as well as the sex and period of life, are features peculiar to chlorosis. Then, again, the anæmia is not so intense, and the relation of the hæmoglobin is just the reverse; in chlorosis the individual corpuscles are deficient in hæmoglobin, while in idiopathic anæmia the reverse appears to be the case.

Some regard the blood circulatory and uterine condition as the expression of a congenital defect leading to the formation of a diathesis--and in certain cases this may be so--but some of the most marked cases I have seen have been in girls of healthy families, who after a healthy childhood developed chlorosis at puberty, from which, under suitable treatment, they recovered to become robust and vigorous women. The almost specific action of iron suggests failure of the digestion or assimilation of the minute traces of this substance which are contained in our ordinary foods, and from which {896} the iron of the corpuscles must be derived. Zander[50] holds that it is largely due to a defect in the hydrochloric acid of the gastric juice, by which the iron-holding compounds are dissolved, and claims that in chlorosis the administration of this remedy after eating fulfils every indication and enables the iron in the foods to be converted into an absorbable compound.

[Footnote 50: Virchow's Archiv, lxxxiv.]

The condition of the blood-making organs themselves throw no light on the PATHOLOGY of the disease.

The TREATMENT of chlorosis requires special mention. Iron may be regarded as a specific when given in sufficient doses. I have found Blaud's formula, as given in Niemeyer's textbook (ferri sulph. potass. carb. et tart. aa ounce ss; tragacanth q. s. Make ninety-six pills. Two or three pills to be taken three times a day), the most satisfactory method of administering the drug. Under their use I have repeatedly seen the number of the red corpuscles per cubic millimeter double in a fortnight; and it is one of the most interesting therapeutic phenomena to watch with the hæmacytometer the progressive development and increase of red corpuscles under the influence of fifteen or twenty grains of iron daily. Other forms may be used--reduced iron, dialyzed, the lactate, the tinct. of the perchloride--and it does not really make much difference which form is employed so long as enough is administered. Dilute hydrochloric acids or the vegetable acids may be given, and special attention should be devoted to dietetic and hygienic regulations.

MELANÆMIA

is a condition characterized by an accumulation of granular pigment in the blood and various organs, particularly the spleen, liver, marrow, and brain. It is almost invariably associated with prolonged malarial infection, and the pigment results from the transformation of the hæmoglobin of the corpuscles, many of which undergo destruction as a direct consequence of the influence of marsh miasm. Very exceptionally, however, the dark particles are extraneous, and result from the passage of carbon-granules into the circulation in cases of intense anthracosis. Soyka[51] met with a case of this kind in which the coal particles were distributed throughout the spleen, liver, and kidneys. In blood the pigment occurs either free in the form of fine granules or in cloud-like collections of various sizes and shapes, often surrounded by a hyaline margin, or it occurs enclosed in cells. The free pigment, not often met with, is either molecular or in the form of irregular particles which may equal a red corpuscle in size. Aggregations of the granules are not uncommon, forming various-sized masses which may be imbedded in a hyaline substance. More commonly the pigment is contained in cells, ordinary leucocytes or large flattened--endothelial--cells derived from the spleen or liver. The color varies from yellowish-brown to a deep black. Except during periods of intense malarial infection and in the most severe and chronic cases melanæmia is rarely observed. In most ordinary cases of intermittent one may seek in vain for the pigment-granules, and I have examined many chronic cases with well-marked ague-cake with negative results. In other instances the pigment is found during or after a paroxysm; and this is the period when an examination of the blood should be made. The greatest care and cleanliness should be exercised in obtaining the blood-drop; and it should be remembered that in some of the glass slips used for microscopic purposes {897} irregular brownish flakes may occur which I have known to be mistaken for pigment.

[Footnote 51: Quoted by Hindenlang, Virchow's Archiv, lxxix.]

The melanæmia is but the expression of extensive destruction of corpuscles and accumulation of pigment in the spleen, liver, and bone-marrow; and these organs in cases of fatal intermittent or remittent fevers may present important changes. In the spleen, which is usually enlarged and indurated, the pigment is chiefly in the vicinity of the arteries and veins, the tissues about which may be absolutely black, and in both stroma and pulp innumerable cells are found filled with blood-corpuscles and blood-pigment in all stages of transformation to melanin. The color of the organ may be of a deep reddish-brown, or in very chronic states gray or even a dark olive. In the liver the dark granules are chiefly at the periphery of the lobules, fixed within the connective-tissue elements and leucocytes, not in the liver-cells themselves. It may be abundant about the portal branches, staining the connective tissue of Glisson's sheath, and it is also met with in the vicinity of the hepatic veins. When much affected the liver may have a deep bronze tint. As Arnstein has shown,[52] the bone-marrow may present similar changes and have a grayish-brown color. There may be deep pigmentation of peritoneum and omentum. The deposition of the granules in and about the vessels of the cortex cerebri may give a slate-gray color to the brain, or even a graphite tint in very severe cases. The capillaries have been found occluded with cells filled with the pigment-granules. The kidneys--particularly the Malpighian tufts--the mucous surfaces, and the skin may also be the seat of pigmentary deposition. These coarse changes in the organs in chronic malaria were known to the older writers, and in Bright's Medical Observations a beautiful representation is given of the condition of the brain. To American physicians, with their extensive experience of malarial fevers, these changes were well known, and Stewardson of the Pennsylvania Hospital gave an admirable description of them in 1841;[53] and from the same institution in 1868 came another important contribution to the subject by Meigs, Pepper, and Rhoads.[54] Meckel[55] and Virchow[56] gave the first satisfactory explanation of the discoloration, showing that it was due to pigment, which might also be free in the blood. Frerichs in his well-known work on the liver gave an exhaustive account of the coarse and microscopical appearances.

[Footnote 52: Virchow's Archiv, lxi.]

[Footnote 53: Am. Journal Medical Sciences.]

[Footnote 54: "On the Morphological Changes of the Blood in Malarial Fever," Penn. Hospital Reports, 1868.]

[Footnote 55: Deutsche Klinik, 1850.]

[Footnote 56: Virchow's Archiv, Bd. i.]

There is still some difference of opinion as to the mode of origin of the pigment. Most writers hold that it results from the destruction of the red corpuscles in the spleen and liver, and from these situations the pigment gets into the blood; but more recently Arnstein[57] and Kelsch[58] have urged the view that the melanæmia is the primary process, the destruction of corpuscles going on in the blood itself, and the particles and coloring material taken up by the leucocytes are transformed into melanin, and then the cells collect in the spleen, liver, and bone-marrow, producing the condition of melanosis. It is probable that the older view is the true one, and we may regard the process as an exaggeration or intensification, under the stimulus of the malarial poison, of the normal process of blood-destruction which goes on in the spleen and bone-marrow, and under some circumstances in the liver and lymph-glands. We can often trace in the cells of these organs the stages of transformation from red corpuscles to melanin-granules, just as can be done in the tissues in the neighborhood of an extravasation, where also the process is chiefly intracellular (Langhans). On the other hand, in those very states in which the red corpuscles are destroyed in the blood and the hæmoglobin set free, we do {898} not find melanæmia. It happens occasionally in fevers that we meet with colorless cells in the blood containing red blood-corpuscles, which in time would be transformed into pigment, but, so far as we know, such a condition has not been observed in the blood in malaria. The connection between the fever paroxysm and the appearance of the pigment in the blood depends, most likely, on changes in the volume of the organs under the influence of the fever, whereby cells containing the pigment are dislodged and get into the circulation. This explains, too, their rapid appearance in some cases with the onset of a paroxysm. No doubt, as Virchow originally taught and as well shown in Gussenbauer's[59] observations, the pigment may result from the diffusion of the coloring matter and gradual precipitation of it in the granular form within the protoplasm of colorless cells; but of the occurrence of such a process in the circulating blood in malaria we have no satisfactory evidence, and we incline to the belief that the melanosis of the organs is the primary condition, while the melanæmia is secondary and inconstant.

[Footnote 57: Loc. cit., and ibid., lxxi.]

[Footnote 58: Archiv de Physiologie, 1875.]

[Footnote 59: Virchow's Archiv, lxiii.]

Occasionally, in cases of extensive melano-sarcoma, pigment-granules may be found in the blood in large numbers, and even appear in the urine and be deposited in the organs and skin. In a few instances also free pigment has been observed in the blood in Addison's disease.

PROGRESSIVE PERNICIOUS ANÆMIA.

DEFINITION.--Extreme and progressive anæmia developing without evident or apparently adequate cause.

SYNONYMS.--Idiopathic anæmia (Addison); Essential anæmia (Lebert); Anæmatosis (Pepper).

HISTORY.--During the first two or three decades of this century cases of severe and fatal anæmia were noted by Andral and others, but the credit of having given the first accurate series of cases belongs to Walter Channing of Harvard, who in the New England Quarterly Journal of Medicine for 1842 published a paper entitled "Notes on Anhæmia, particularly in connection with the Puerperal State and with Functional Disease of the Uterus, with Cases."[60] Any one who reads this communication will be convinced that Channing's description, particularly of the seven cases occurring in the puerperal state, is that of the disease to which Gusserow and Biermer have more recently directed attention.

[Footnote 60: My attention was accidentally called to Channing's observations in the Periscope of Hall's British-American Journal for 1845. Since then Musser, in the Med. News, Oct. 7, 1882, has given a valuable abstract of the paper.]

In Addison's monograph on the suprarenal capsules (1855) there is a brief but clear account of the disease, which he speaks of as follows: "For a long period I had from time to time met with a very remarkable form of general anæmia occurring without any discoverable cause whatever--cases in which there had been no previous loss of blood, no exhausting diarrhoea, no chlorosis, no purpura, no renal, splenic, miasmatic, glandular, strumous, or malignant disease. Accordingly, in speaking of this form of anæmia in clinical lectures, I, perhaps with little propriety, applied to it the term idiopathic, to distinguish it from cases in which there existed more or less evidence of some of the usual causes or concomitants of the anæmic state." As early as 1843 this acute observer had spoken in his clinics of this condition.[61]

[Footnote 61: McKenzie, S., Lancet, 1879, ii.]

{899} The physicians at Guy's appear to have been well acquainted with the disease, and in 1857 Wilks described cases under the heading "Idiopathic Fatty Degeneration." To the labors of Zurich professors we are indebted for much of our knowledge. That versatile clinicist Lebert, then at Zurich, published in 1853 cases of puerperal chlorosis, and we owe to him the excellent designation of essential as applied to these cases of anæmia (1858). It was in 1871-72 that the communications of Gusserow[62] and Biermer[63] aroused a very general interest in the disease. Gusserow's cases, like some of Channing's, were in connection with pregnancy. Biermer, thinking he was dealing with a previously unknown affection, gave it the name of progressive pernicious anæmia. In the past ten years the literature of this form of anæmia has enormously increased. In Germany, in addition to the articles in the encyclopædias (Ziemssen's, Eulenberg's) and innumerable contributions and dissertations, two important monographs have appeared by Müller (Zurich, 1877) and Eichorst (Leipzig, 1878). In France, Hayem, Lepine, and others have published important observations. In England, the Guy's Hospital physicians, Taylor and Pye-Smith, in the Hospital Reports (1878-83) have fully established Addison's claim to having given a clear account of the disease. Important contributions have been made by Stephen Mackenzie, Coupland, Bramwell, Bradbury, and others. In this country Pepper in 1875 brought the disease to the notice of the profession and suggested the name anæmatosis. Howard (R. P.) of Montreal at the Centennial Medical Congress (1876) gave a full account of the affection, the existence of which he had long recognized and taught. Musser[64] has reviewed the American literature, and has given a tabular synopsis of 39 cases which have been recorded in this country.

[Footnote 62: Archiv f. Gynäkologie, ii.]

[Footnote 63: Correspondenzblatt für Schweizerische Artze, 1872.]

[Footnote 64: Proceedings of Philadelphia County Med. Society, 1885.]

ETIOLOGY.--The disease is widely distributed, and there are no special geographical influences. In Germany and certain of the Swiss cantons--Zurich particularly--the cases seem to occur more frequently than in England or America. In this country it can scarcely be called one of the rare diseases, although up to January, 1885, Musser[65] could collect only 39 cases. During ten years in Canada I saw 16 cases, most of them with colleagues at Montreal.

[Footnote 65: Loc. cit.]

That bad hygienic conditions have much to do with the induction of the disease is shown by the records of Zurich and Berne, where the cases have been very numerous among the lower classes, who are hard worked, ill fed, and poorly housed. Possibly here other unknown causes may be at work, as the conditions which prevail in the Zurich canton are not unknown in other countries. In Ireland, where the peasants have poor food and wretched houses, the disease does not appear to be common. In the Montreal cases the subjects were chiefly of the upper or of the higher mechanic classes.

The age most subject to the disease is the adult period; cases are rare under twenty and over fifty. In Pye-Smith's table of 103 selected cases there were only 6 under fifteen years of age; 4 between fifteen and twenty; 29 between the twenty-first and thirtieth years; 26 cases between the thirty-first and fortieth years; 21 between the forty-first and fiftieth years; 13 between the fifty-first and sixtieth; and only 4 above sixty. The youngest case I have seen was in a girl of twenty, and oldest in a woman over sixty. The youngest case on record was at the fifth year.[66]

[Footnote 66: Quoted in Am. Journ. Med. Sci., Jan., 1885.]

Sex.--If we exclude all cases in women directly connected with the puerperal state, primary idiopathic anæmia is more frequent in men than in women. Of the 16 Montreal cases, 4 were dependent upon parturition, and of the remainder, 9 were in men and only 3 in women. But most of the {900} collected figures include the parturition cases, and the women are in excess; thus, of 93 cases from the Swiss clinics at Zurich and Berne, 67 were females. Eichorst's figures are 65 women and 30 men. Of 110 cases collected by Coupland, 56 were men and 54 women. In Pye-Smith's careful tabulation of 103 selected cases, 48 were men and 59 women.

As observed by Channing, Lebert, and Gusserow, pregnancy and parturition are important factors in the production of a grave form of anæmia. In the majority of cases the symptoms develop post-partum, often, but not necessarily, in consequence of loss of blood during delivery. Obstinate vomiting during pregnancy and prolonged lactation may bring about the same condition. Of 29 cases of this sort in Eichorst's table, in 19 the symptoms developed during pregnancy and in 10 after delivery.

Gastric and intestinal disturbance, dyspepsia, vomiting, and diarrhoea have occurred in a number of cases prior to the development of the anæmia.

In some instances loss of blood, chronic discharges, ulcers, or other sources of drain have been present.

In not a few cases there has been mental worry, grief, or fright. This has been specially noted by Wilks and Howard, and more recently by Curtin.[67] It does not seem probable that malaria has any predisposing influence.

[Footnote 67: "Nervous Shock as a Cause of Pernicious Anæmia," Med. Times, Philada., April 4, 1885.]

It is by no means always the ailing or delicate who are attacked; many of the cases have occurred in men previously strong and robust.

After excluding all these factors, which prevail in a considerable proportion, there still remain cases without, as Addison says, any discoverable cause whatever--cases to which in our present knowledge we may apply the term idiopathic. These may be primary, and the others, in which some one or other of the above-mentioned causes appears to have prevailed, secondary anæmias, the latter to be distinguished from a host of other sequential anæmias only by the fact of a progressive and pernicious course.

Of 91 observations collected by Eichorst, in 24 cases the disease appeared to have come on spontaneously, and 67 as the result of various causes: pregnancy and parturition, 29; digestive troubles, 24; loss of blood, etc., 7; bad hygienic conditions, 7.

SYMPTOMS.--The classical description of Addison must ever be quoted in this connection: "It makes its approach in so slow and insidious a manner that the patient can hardly fix a date to the earliest feeling of that languor which is shortly to become so extreme. The countenance gets pale, the whites of the eyes become pearly, the general frame flabby rather than wasted, the pulse perhaps large, but remarkably soft and compressible, and occasionally with a slight jerk, especially under the slightest excitement. There is an increasing indisposition to exertion, with an uncomfortable feeling of faintness or breathlessness in attempting it; the heart is readily made to palpitate; the whole surface of the body presents a blanched, smooth, and waxy appearance; the lips, gums, and tongue seem bloodless; the flabbiness of the solids increases; the appetite fails; extreme languor and faintness supervene; breathlessness and palpitations are produced by the most trifling exertion or emotion; some slight oedema is probably perceived about the ankles; the debility becomes extreme--the patient can no longer rise from his bed; the mind occasionally wanders; he falls into a prostrate and half-torpid state, and at length expires: nevertheless, to the very last, and after a sickness of several months' duration, the bulkiness of the general frame and the amount of obesity often present a most striking contrast to the failure and exhaustion observable in every other respect."[68]

[Footnote 68: Monograph on Disease of Suprarenal Capsules, p. 3.]

The mode of onset is variable: in many cases there are etiological {901} conditions, such as pregnancy, loss of blood, etc., which for weeks or months precede, and perhaps determine, the development of the anæmia. There may have been mental worry or shock, and after a prolonged period of ill-health the anæmic symptoms become marked. Failure of strength, lassitude and disinclination for exertion, with shortness of breath and palpitation and an increasing pallor, accompanied by headache, giddiness, and dyspepsia, are the symptoms for which the patient seeks advice.

The condition of the skin is remarkable in pronounced cases: the color is rarely a deep white or ashen, as in the pallor of fear or fainting or the bloodlessness from hemorrhage, but there is a peculiar lemon tint, a light straw-yellow or grayish-yellow color, which may be mistaken for a mild icterus. This is one of the most characteristic features of the disease.

The subcutaneous fat does not waste; on the contrary, the fatty panniculus may increase, and, as Addison remarked, there may be a bulkiness of the frame. Actual emaciation is very uncommon.

Slight oedema is present in the feet, particularly toward the close, and it may extend up the legs, but rarely reaches a high grade. Occasionally it may appear in the face and hands.

Cutaneous hemorrhages in the form of small petechiæ are liable to appear on the legs and arms, not often on the trunk.

The sweat secretion is not affected, but in several instances, as in other chronic affections where death is protracted, a cadaverous odor has been perceived from the skin or breath.

The blood, as expressed, often with difficulty, from the finger-tip, has not the rich color of health, but is pale, like a light claret. The corpuscles usually fill the drop, and we do not see, as in certain cachectic states, an extreme degree of hydræmia in which the red corpuscles do not entirely occupy the plasma. It is sometimes difficult to get a drop of blood from the finger-tip, and to do so the arm should hang by the side and may be squeezed from the shoulder downward to press the blood into the hand. The microscopical characters of the blood are as follows:

(1) The red cells present a great variation in size, and there can usually be seen (a) large giant forms, the megalocytes measuring 8, 11, or even 15 mm.: these are not often very numerous, and may show irregular foldings at the edges; (b) medium-sized disks, such as are usually found in the blood: these always predominate; (c) small round cells, microcytes, 6, 4, or even 2 mm. in diameter, and of a deep color. They are rarely absent in typical cases, though varying in number at different periods. The color of the large and medium-sized corpuscles may be much less intense than normal.

(2) In addition to the variation in size, the corpuscles show a remarkable irregularity in form--an irregularity which, so far as my observation goes, is never met with to the same extent in other conditions. They may be elongated and rod-like, scarcely recognizable as blood-disks. Balloon and kidney shapes are common. One end of a corpuscle may retain its shape, while the other is extended as a pointed or blunt process. The normal concavity may be lost on one side and deepened on the other. Many of the large forms are longer than broad, often quite ovoid, and with sinuous margins. The microcytes are either globular or present a pit-like depression on one surface. To this condition of irregularity of the corpuscles in size and form Quincke has given the name poikilocytosis ([Greek: poikilos], variously shaped). It possibly depends on an altered state of the serum; I have failed to produce it with dilution. The corpuscles in the blood of idiopathic anæmia do not form such well-defined rouleaux as in health.

(3) The colorless corpuscles may be relatively increased, but are usually diminished to some extent. They present no very special changes in form or stricture. Larger forms may occasionally occur, but I have not noted their {902} presence, specially the cases in which the marrow was found red and lymphoid after death. In two cases the majority of the corpuscles at several observations were smaller than normal. The amoeboid movements are active.

(4) In only two instances, in the cases I have examined, were nucleated red corpuscles present, and these very scanty. They have been noted by several observers. Ehrlich states[69] that they are present in all cases.

[Footnote 69: Berl. klin. Wochenschrift, 1880.]

(5) Schultze's granule masses, composed of the hæmatoblasts or blood-plates, are either absent or very scanty. In some cases not a trace of them could be found, and in others they are less abundant than in health. In this respect the blood offers a marked contrast to that of various cachectic states, and also to leukemia, in which the masses are sometimes very numerous. Leube,[70] however, has recorded a case in which they were abundant.

[Footnote 70: Ibid., 1879.]

(6) The fibrinous network between the corpuscles is thin and indistinct. The Cercomonas globulus and Cercomonas navicala, described by Klebs[71] as occurring in pernicious anæmia, are possibly peculiar to Prague.

[Footnote 71: Real Encyklopädie, art. "Flagellata."]

The reduction in the number of the red corpuscles is the special feature of the disease, the diminution reaching far below that met with after the most severe hemorrhage. Instead of a corpuscular richness of 5,000,000 per cubic millimeter, the number may be reduced to one-quarter, or even one-tenth. In the more extreme anæmia from hemorrhage, in cancer or in phthisis, the reduction rarely reaches as low as 1,500,000, while this figure is common in pernicious anæmia, and in advanced cases may sink below 1,000,000, or even to 500,000. This latter figure is exceptional. In only 2 cases have I counted the number so low as this. In a case of Quincke's the red were reduced to 143,000 per c.m., and, strange to say, the man recovered. Great variations may occur from month to month in the course of the disease. An increase in the number is not always associated with an improvement in the patient's condition.

The hæmoglobin is also greatly reduced, but not in proportion to the reduction in the red corpuscles. The relative coloration of the corpuscles is increased, and this seems as marked a feature in pernicious anæmia as the relative reduction is in chlorosis.[72] Owing to the fact that the hæmoglobin value of individual corpuscles is increased, the anæmia is never quite so intense as the number of corpuscles would appear to indicate.

[Footnote 72: Laache, Die Anämie, Christiania, 1883; Deutsche Medicin Wochenschrift, 1884, No. 43.]

The circulatory system presents many symptoms of importance. When the patient is recumbent and at rest, the heart's action is quiet, but on exertion or excitement the action becomes rapid, and there are palpitation, fluttering, and sometimes painful sensations in the cardiac region. Stairs are particularly trying to these patients. There may be slight enlargement of the heart, indicated by an increased area of visible pulsation, and an impulse in the third or fourth left intercostal space, near the sternum, is frequently seen. The hæmic or functional murmurs are usually present, variable in intensity and site, most often heard at the base and in both aortic and pulmonary areas, but also at the apex. Indeed, their variability is often puzzling; sometimes it would seem that there might be a murmur at each orifice, at another limited only to one; and for the bruit to be present at one examination and absent at the next is not uncommon. In several of Eichorst's cases there was a variable diastolic murmur at apex or base.

The larger arteries pulsate visibly--so much so that at times it suggests the water-hammer pulsation of aortic insufficiency. The carotid pulsation may be most evident, and still more so in the abdominal aorta, the throbbing of which may be very distressing to the patient. A systolic arterial murmur may be heard in all the arteries. The pulse is soft, compressible, usually {903} rapid (80 to 100 or over), depending a good deal on the position and state of excitement. One is sometimes surprised in these cases to find a full and at the same time very soft pulse. It may be dicrotic.

The venous hum is well marked, and is rarely absent except after prolonged rest in bed, when both cardiac and venous murmurs may disappear, to return at once on making the patient stand up. Channing, in the paper already referred to, speaks of the thin, scanty state of the blood, and yet notes the prominent appearance of the veins beneath the skin, particularly about the hands and wrists.

Hemorrhages occur very frequently. Epistaxis is most common, and may have preceded for years the onset of the grave anæmia. It may recur repeatedly and be a source of constant drain, or ultimately be the cause of death. From other mucous surfaces bleeding is not so common. I have seen one case in which there were for months repeated small hemorrhages from the bowels, and bleeding from the gums has been observed in several cases. The petechiæ on the skin have already been referred to. Retinal hemorrhages, as first noticed by Biermer, are very common. They are numerous and small, scattered around the disk. They are not peculiar to any special form, but are liable to occur in severe anæmia from any cause.

Respiratory symptoms are not prominent: a short cough may be present, but the only special feature is the shortness of breath, which is often early and troublesome, and depends on the condition of the blood, not of the lungs. There may be a very distressing and persistent sense of insufficient aëration (Pepper). Toward the close hydrothorax may develop.

The gastro-intestinal system is in the majority of cases more or less deranged. Dyspepsia may precede for years the anæmia, and may persist throughout the illness. There is loss of appetite, amounting sometimes to a positive repulsion toward all forms of nutriment. Nausea and vomiting are rarely absent throughout the illness, and there are some cases in which the gastric symptoms are so marked as to suggest a primary stomach lesion as the atrophy to which Fenwick[73] has called attention, or even arouse a suspicion of cancer.

[Footnote 73: Lancet, 1877, ii.]

Diarrhoea is also a frequent symptom, and in some cases hastens the fatal result. There may be melæna, and in Müller's monograph a case is given in which leucin and tyrosin were found in the stools.

The urine is pale, acid, and of low specific gravity. Occasionally it becomes darker in color. The urea may be diminished, but it has been found increased in some cases by Quincke, Eichorst, and Laache. The uric acid is more commonly increased, and the phosphoric acid. The percentage of iron has been found larger than normal. Albumen is rarely found. Peptones, leucin, and tyrosin may be present (Laache). Blood does not often occur.

Fever is not a constant symptom; some cases run their course without any elevation, but there is usually slight febrile reaction of an irregular, remittent type, an evening elevation of two or three degrees, and a morning remission to the normal standard. There may be a week or ten days of fever, and then a long spell without any. Toward the close there is commonly an elevation, occasionally depression, of temperature, as in one case reported by Müller in which it sank to 24.8° C.

COURSE.--In the majority of cases the disease runs a steadily downward course, well indicated by the terms progressive and pernicious. In almost every case periods of temporary improvement occur. Recovery is possible, and Pye-Smith[74] gives a summary of 20 undoubted cases which got well. The lactation and parturition cases stand a better chance of recovery than others. {904} The average course of the affection is from six to twelve months; there are rapid cases in which a fatal termination may be reached in a few months, and there are others which drag on for two, or even three, years, periods of improvement alternating with relapses. Death is usually by asthenia. It may be hastened by hemorrhage from the nose or bowels or by persistent vomiting or diarrhoea.

[Footnote 74: Guy's Hospital Reports, 1883.]

MORBID ANATOMY.--The body is not often emaciated; usually, indeed, the panniculus adiposus is well developed. The peculiar lemon tint of the skin is present in the majority of cases, and there may be petechiæ. The voluntary muscles may appear normal, but are often of an intense flesh color, more like horse muscle. In six cases the words "rich red color" and "remarkably deep red color" occur in my notes. In other instances they are pale. When the cavities are opened the general pallor of all the organs is most striking. The serous surfaces are smooth and glistening, and occasionally present ecchymoses. The amount of fluid may be increased. The mucous membranes are pale; minute hemorrhages are not uncommon.

The heart is in many cases large and flabby, in others normal, and in a few undersized. The pericardial fluid may be in excess, and the subpericardial fat is often increased. The flaccid relaxed state of the walls is very noticeable, and on opening the chambers the amount of blood is always very slight. In one case I could only obtain two drachms from the right heart, and between three and four from the left. There may be small clots entangled with the chordæ tendineæ of the valves. The muscle-substance is pale, of a faded-leaf, light-yellow color, and beneath the endocardium, particularly of the left side and of the papillæ, there are flaky spots (tabby mottling) of fatty degeneration. The peculiarities of general fatty degeneration of the heart are nowhere better seen than in these cases. The valves and orifices are usually normal. The intima of the aorta may show fatty changes. The smaller arteries and veins contain most of the blood.

The lungs are crepitant, pale, with a slight bloody oedema at the bases. The fluid expressed has often a yellowish tinge. Exudation into the pleural cavities is common. The air-passages do not offer any special changes.

The liver is of normal size, pale and generally fatty, not invariably; in none of Eichorst's cases was this a marked feature. Quincke and others have found the amount of iron increased.

The mucous membrane of the gastro-intestinal tract is pale, covered with a thin mucus, and may present ecchymoses. Post-mortem solution of the gastric mucosa is common, and I have seen oedema of it. Fatty degeneration of the cells of the peptic tubules is common, and they may be in an atrophic state, as well described by Fenwick.[75] Ecchymoses of the small and large bowel are common; ulceration is rare. In a few instances the lymphatic elements of the mucosa have been found swollen. Extensive atrophy of the mucosa has been found associated with degeneration of the nerve-elements, but these changes, as shown by the observations of Nothnagel[76] and Schleimpflug,[77] are not uncommon in many other conditions.[78]

[Footnote 75: Loc. cit.]

[Footnote 76: Beiträge zur Phy. u. Path. des Darms, Berlin, 1884.]

[Footnote 77: Zeitsch. f. klin. Med., ix., 1885.]

[Footnote 78: Sasaki, Virchow's Archiv, 96.]

The blood vascular organs have naturally received special attention. The spleen offers, as a rule, no important changes; the size is variable, rarely enlarged, occasionally reduced in size, but for the most part normal. The smallest I have seen was in one of Howard's cases, in which the organ weighed only one ounce and five drachms. In the 51 autopsies noted in Howard's paper the spleen was stated to be normal in 36 and enlarged in 13. Ten ounces is the heaviest I have seen. The spleen-tissue is moderately firm, of a light brown-red color. I have never noticed either the extreme softening of an acute splenic swelling or the hardness of chronic induration. {905} The histological characters present nothing special. Cells containing red corpuscles occur, but not in such numbers as in cases of acute splenic swelling from fever. I have seen the nucleated red corpuscles in several instances.

The lymph-glands are, as a rule, normal in size and appearance. In three instances I found them decidedly smaller than normal, and in two they had a rich deep-red color, and on section looked more like spleen-tissue than lymph-gland. Weigert has noted the same appearance.[79] In one of the cases there were nucleated red corpuscles in the glands, as has been observed by Rindfleisch in a case of rickets,[80] and more recently in tuberculosis.[81]

[Footnote 79: Virchow's Archiv, Bd. lxxix.]

[Footnote 80: Archiv f. Mikros. anatomie, Bd. xxiii.]

[Footnote 81: Med. News, xiv. No. 23.]

The fatty tissue of the long bones is in many instances replaced by a red marrow resembling that of the short bones of the adult and the entire osseous system of the infant. This was first noticed by Pepper in 1875,[82] and has since been frequently observed. The color is usually of a reddish-purple when fresh, becoming a bright red on exposure. Sometimes there is a grayish-red appearance. It may not be universally distributed in the long bones, and the change would appear to proceed from the trunk toward the periphery--a direction the reverse to that in which the red marrow of the child becomes fatty. In many cases the marrow has been found normal; in others, the change known as gelatinoid has been observed. In five Montreal cases I found the marrow of the long bones lymphoid, in one gelatinoid, and in two the long bones could not be examined. It must be borne in mind that the short and flat bones of the adult contain a red lymphoid marrow mixed with a variable amount of fat, in which nucleated red corpuscles can always be found.

[Footnote 82: American Journal of Medical Sciences, lxx.]

The brain and cord present an intensely anæmic appearance; the membranes are relaxed and oedematous, and petechiæ may exist. The convolutions are often wasted, and the amount of cerebro-spinal fluid increased. No important changes have been found in the substance.

The ganglia of the sympathetic system have been examined by Queckett in one of Addison's cases and found fatty. Wilks and others have found them normal. Brigidi[83] has described an increase in the interstitial tissue and pigmentation of the cells. In two instances I found nothing abnormal. Sasaki[84] has described marked degenerative changes in Auerbach's and Meissner's plexuses in two cases of pernicious anæmia.

[Footnote 83: London Med. Record, 1878.]

[Footnote 84: Loc. cit.]

The kidneys are usually pale and without special change beyond the fatty degeneration. Quincke has found the amount of iron increased. The suprarenals have in several instances been found very small. The sexual organs show no constant changes.

PATHOLOGY.--Under the general subject of Anæmia the pathology has been discussed at sufficient length. After excluding pregnancy, parturition, lactation, and inanition cases, as partaking more of the characters of secondary anæmia, we can recognize three groups of cases: First, those in which the bone-marrow has been found extensively affected--cases of anæmia medullaris; second, cases in which a primary atrophic change in the mucous membrane of the stomach appears to have been the starting-point of the trouble; and, third, cases in which after death no special changes have been found sufficient to explain the anæmia. To the latter the term idiopathic is applicable, and possibly they may be instances of hæmophthisis due to increased destruction of the corpuscles from causes unknown at present.

DIAGNOSIS.--A case in which anæmia comes on without obvious cause and without enlargement of the spleen, and progressively increases in spite of remedies, diet, change of air, etc., may be regarded as one of an idiopathic or essential character. If the case goes on to a fatal termination, the designation of pernicious is appropriate. I would place some reliance on the {906} microscopical examination of the blood, and would consider the presence of microcytes with great irregularity in the ordinary red corpuscles strong confirmatory evidence. The absence of wasting, the peculiar lemon tint of the skin, the occurrence of epistaxis and retinal hemorrhages, would render a diagnosis certain.

In that class of cases so well described by Fenwick,[85] Nothnagel,[86] and Nolen,[87] in which there has been an interstitial inflammation of the gastric mucosa and atrophy of the glands, the question has not yet been decided how far this condition is to be considered causal, and how far a part of the general disturbance of nutrition. The clinical picture may be identical with that of idiopathic anæmia, and in some of the cases the gastric symptoms have been so marked that the relation of the atrophy and the anæmia has evidently been that of cause and effect. And yet in these cases there does not appear to be the pronounced emaciation of inanition anæmia. In other instances the diarrhoea and chronic intestinal trouble may, with or without gastric participation, bring about a similar condition.

[Footnote 85: Loc. cit.]

[Footnote 86: Deutsches Archiv f. klin. Med., xxiv.]

[Footnote 87: Centralblatt f. d. Med. Wissenschaft., xx.]

Profound anæmia may arise during or after pregnancy, and a considerable proportion of the cases on record have been in this connection.

From ordinary cases of Hodgkin's disease, anæmia lymphatica, there could be no difficulty in making a diagnosis if the superficial glands were enlarged. In splenic anæmia, if the enlargement was not great, there might for a time be uncertainty, which the progressive increase of the organ would remove. Neither in anæmia splenica nor lymphatica are we so likely to meet with the microcytes or irregular corpuscles.

Chlorosis occurs chiefly in young girls, and is amenable to treatment.

From the various cachexias--malarial, syphilitic, metallic--the history will commonly afford grounds for a diagnosis, and in these states, as in latent cancer, the wasting is apt to be more pronounced than in essential anæmia. Cases of gastric cancer are occasionally met with which simulate closely pernicious anæmia, and the diagnosis may be doubtful for months.[88]

[Footnote 88: Richard Neale, Practitioner, 1883.]

The enteritis and hemorrhages caused by the presence of Anchylostoma duodenale in the intestines may produce an aggravated form of anæmia resembling closely the form under consideration. It prevails among the workers in mines and tunnels, hence the name miner's anæmia or anchylostomiasis. The diarrhoea and the detection of the ova or worms in the discharges would afford grounds for a diagnosis.[89]

[Footnote 89: Trans. of the International Med. Congress, London, 1881, vol. i. 437.]

The PROGNOSIS is unfavorable, particularly in those cases which have arisen without any cause or previous ill-health. In the cases arising from defective food, etc.--inanition anæmias--pregnancy, or lactation, the outlook is less grave. Of the 64 Zurich cases in Müller's monograph, 7 recovered, and of Quincke's 31 cases, 11 recovered. Pye-Smith gives a table of 20 recorded cases of recovery.[90] Great improvement may occur, or even recovery for a period of several years, after which the disease may recur and prove fatal. This was the history in a case under the care of Wilkins at the General Hospital, Montreal.

[Footnote 90: Loc. cit.]

TREATMENT.--The designation pernicious applied by Biermer indicates the hopeless character of the disease in perhaps a majority of the cases; of late the records happily show a considerable percentage of recoveries. Thus, Pye-Smith has collected 20 cases in which convalescence was established after severe and profound anæmia, belonging undoubtedly to the class here considered. The intractable nature of a case and the resistance to ordinary treatment are points which may first suggest to the practitioner the fact that he is dealing with a something more than simple anæmia.

{907} Hygienic and dietetic regulations are of the first importance. Cases appear to have got well with change of air and a better diet after resisting all ordinary means. In other instances no benefit whatever has been derived from residence at the sea or in the mountains. As a rule, the cases are best treated at home. The greatest care must be exercised in the regulation of the diet, which should be light and nutritious. So long as the digestion keeps tolerably active there is hope: anorexia, vomiting, and other dyspeptic symptoms are among the most troublesome and serious features. The bitter tonics, hydrochloric acid, and pepsin may be administered. But the stomach may fail absolutely and reject even the smallest amount of liquid food, and rectal alimentation must be employed. The gastric symptoms have been specially marked in cases in which there has been found post-mortem atrophy of the peptic glands. In certain of these cases the problem of feeding will tax to the uttermost the resources of the physician. Rectal injections of blood (fresh or dried), as recommended by A. H. Smith, I have found beneficial in several cases. Intestinal symptoms--diarrhoea, flatulence, and in some cases melæna--call for treatment.

Of medicines, arsenic is the most important, and in the form of Fowler's solution should be employed in small and increasing doses. We are indebted to Bramwell[91] for pointing out the great value of this medicine, and in certain cases it acts almost as a specific. In 8 of the 20 cases of recovery noted by Pye-Smith the improvement seemed due to the arsenic. Padley[92] has collected in the literature 48 cases treated without arsenic, of which 42 were fatal, while of 22 cases treated by arsenic 16 recovered, 2 improved, and only 4 proved fatal. The testimony of recent observers is very strongly in favor of this drug as the most efficacious we possess in this grave disease. The use should be continued long after the convalescence is apparently established; indeed, it should be given at intervals for many months after recovery, as there are dangers of relapse. There are cases which are not benefited by arsenic, even when well borne. Finlay[93] has recently reported a case which was cured by iron after the failure of arsenic.

[Footnote 91: Edinburgh Med. Journal, 1877.]

[Footnote 92: Lancet, 1883, ii.]

[Footnote 93: Lancet, 1885, i.]

Iron, as a rule, seems quite useless in the majority of these cases. I have frequently seen the percentage of red corpuscles gradually sink under its administration, and then rise in a remarkable way when the arsenic was employed. This is in curious contrast to the effect of this drug in the various secondary anæmias and chlorosis in which it is rightly regarded as a specific. The cases which are benefited may have a different etiology, and where the arsenic does not succeed some form of iron should be given, as Finlay's case, just mentioned, shows that there are instances where it cures after the failure of the arsenic.

Broadbent advises the use of manganese when the anæmia is associated with uterine or menstrual trouble. Phosphorus has been extensively employed, and occasionally with benefit.

When all remedies have been tried in vain the question of transfusion of blood arises. As a substitute for the intravenous transfusion the blood has been injected into the peritoneum: this has been practised in Italy with success.[94] The subcutaneous injection has also been used, and lately the inhalation of a spray of blood has been recommended.[95] In four or five instances intravenous injection has succeeded, but in the majority of cases it has proved useless. Von Ott's[96] interesting researches show that the injected blood-corpuscles and albuminous materials always undergo destruction in the blood, and a 6/10 per cent. solution of common salt seems to answer just as well, and is much more available and less dangerous.

[Footnote 94: Practitioner, vol. xxxi.; Ponfick, Berl. klin. Wochenschrift, 1879.]

[Footnote 95: Med. News, 1885, i.]

[Footnote 96: Virchow's Archiv, Bd. xciii.]

{908} The injection of milk, as first practised in cholera by my preceptors, Bovell and Hodder[97] of Toronto, has also been employed in anæmia (Pepper, Wulfberg).

[Footnote 97: Canadian Journal of Science, 1854.]

LEUKÆMIA.

DEFINITION.--A disease characterized by a great and persistent increase of the colorless corpuscles of the blood, associated with enlargement of the spleen, lymphatic elements, and bone-marrow.

SYNONYM.--Leucocythemia (Bennett).

HISTORY.--Our knowledge of this affection dates from the description of two cases by Craigie and Bennett in the October number of the Edinburgh Medical Journal for 1845. The altered state of the blood was thought to be due to the presence of pus--a suppuration of the blood. In the November number of Froriep's Notizen for 1845, Virchow described a case in which the proportion between the red and white corpuscles seemed reversed, and the blood had in consequence a grayish-white appearance. He attributed the condition to an increase in the colorless corpuscles. A case of Rokitansky's is referred to in this article. In 1846, Fuller described a case before the Medico-Chirurgical Society of London, in which the increase in the colorless corpuscles was noted during life and after death.

In the August and September numbers of Medicinische Zeitung des Vereins für Heilkunde (1846) Virchow reviewed these four cases, and insisted upon the fact that the colorless cells in the blood were not pus, and vindicated a place in pathology for the white blood-corpuscle. In the January number (1847) of the same journal he gives further cases of white blood which he had collected in the literature--cases of Bichat (1801), Velpeau (1827), Caventon (1828), Andral (1839), Barth (1834),[98] and several others--and discussed the conditions under which the colorless elements might increase and the relation of the spleen to the white cells. In the same year (1847), in the first volume of his Archiv, Virchow proposed the name leukæmia. Vogel in 1849 diagnosed a case during life.[99]

[Footnote 98: Donne (Cours de Microscope, 1844), who examined Barth's case, seems to have been the first to recognize that the colorless cells were blood- and not pus-corpuscles. See note by Gowers in Lancet, i., 1878.]

[Footnote 99: Virchow's Archiv, Bd. iii.]

Bennett in 1851 collected additional cases, and gave the name of leucocythemia to the disease, and in 1852 published a monograph entitled Leucocythemia; or, White-celled Blood, in Relation to the Physiology and Pathology of the Lymph-gland System. He claimed priority in the discovery of the condition, and for several years a lively paper war raged between the Edinburgh and the Berlin professors.

At this distance of time and place we can, now that the clouds of controversy have blown away, see the truth. Bennett certainly described cases before Virchow, but only in a manner similar to that in which Bichat, Velpeau, and others had previously done, and he distinctly stated his belief that the grayish-white color of the blood was due to pus. Virchow from the first grasped the idea that the altered state of the blood was due to an increase in the colorless cells, and he first suggested the relation between their increase and the condition of the spleen and lymph-glands, and he first gave a satisfactory name to the disease; so that, while acknowledging the great and valuable services of Bennett, we must, perforce, recognize the greater merit {909} of Virchow, and recognize his priority in the scientific description of the disease and in giving to it a suitable name. The further investigations of Virchow enabled a splenic and a lymphatic form to be recognized, and many years later Neumann[100] described the myelogenous variety.

[Footnote 100: Archiv der Heilkunde, Bd. xi.]

FORMS OF THE DISEASE.--According as the pathological changes are located in the spleen, lymph-glands, or marrow we speak of splenic, lymphatic, and medullary or myelogenous forms; but it is very exceptional for pure unmixed varieties to occur. More commonly, the spleen and marrow, or these with the lymph-glands, are involved. The disease may begin and make great progress in one of these regions, or be confined to it for months, before appearing elsewhere. The spleen is most often affected, and with it the marrow. According to many recent writers, the myelogenous form is the most general, and certainly the marrow is rarely found unchanged. The unmixed lymphatic variety is not of frequent occurrence. An intestinal form, characterized by swelling of the solitary and agminated lymph-glands and the general adenoid tissue of the bowel, has been described by Behier.[101] In a few instances the tonsillar and pharyngeal lymph-elements have been early, perhaps primarily affected, and Kaposi has recently recorded a case[102] under the name lymphoderma perniciosa, in which the lymphatic elements of the skin were first involved.

[Footnote 101: L'Union médicale, 1869.]

[Footnote 102: Wiener Med. Jahrbücher, 1885.]

ETIOLOGY.--We know scarcely anything of the causes of the disease, but it is usual to take into account certain factors which may possibly influence its production, such as climate and country, age, sex, etc.

Climate and Country.--The disease appears to be more common in temperate regions; not many instances are reported from the tropics. It does not appear to be often met with in India. It is, I think, more common in Europe than in this country. The determination of its prevalence is rendered difficult by the fact that many cases reported simply as enlarged spleen, without any examination of the blood, have possibly been leukæmia. It does not seem to be more common in the southern part of this continent.

Age.--No age appears exempt. Cases are recorded in infants of eight or ten weeks and in men of sixty-nine and seventy years of age. The youngest case I have seen was in a suckling of eight months. The majority of cases occur at the middle period of life, from thirty to forty. After the fiftieth year the cases diminish very much in number.

Sex.--Males are more prone to the affection than females, in the proportion of at least 2 to 1. Of 11 cases which I saw in Montreal, only 3 were in females; of 200 cases collected in the literature, 135 were in males and 65 in females (Birch-Hirschfeld[103]).

[Footnote 103: Lehrbuch der Path. Anatomie, 2te Auf., 1883.]

Social and sanitary conditions do not appear to have much influence, though the lower and middle classes furnish the majority of the cases. Mental worry and depression are specially mentioned as predisposing causes in some cases.

Previous Disease.--In women it has frequently been noticed that disturbance in the menstrual and sexual functions has preceded the onset of the disease. The climacteric period has the greatest number of cases, and in a few instances the disease had developed during pregnancy.

The hemorrhagic diathesis has been noted in many cases, and the patient may have been the subject of slight hemorrhages for years. In one case of Howard's[104] the lad had been subject to nose-bleeding as a child, and his mother and one sister had been much troubled in the same way.

[Footnote 104: Montreal Gen. Hosp. Reports, vol. i., 1880.]

Malaria.--On account of the frequency of chronic splenic tumor in malarial infection, inquiries are always carefully made in any suspected case as to the occurrence of intermittent fever. An intimate connection is believed by {910} certain writers to exist between the affections, and a few cases seem to have followed directly upon chronic malaria. In Mosler's statistics of 112 cases there were only 4 in which the sequence was well marked.[105] In Gowers' 150 cases there was a history of malaria in 30.[106] In the Montreal cases there was an account of malaria in 3 certainly--possibly in a fourth. In the reports of 33 American cases there were only 6 with a history of malarial attacks within twelve years from the date of the onset of leukæmia. Guiteras of Key West (now of Charleston, S.C.) states that it is a rare affection in the South. Schmidt of New Orleans writes me that it is not uncommon in Louisiana, but there are very few cases reported in Southern journals.

[Footnote 105: Die Leukæmie, Berlin, 1872.]

[Footnote 106: Reynolds's System, art. "Leucocythæmia."]

Syphilis appears to have been in a few cases closely connected with the onset of the disease.

Injury.--Many patients give an account of a blow or strain in lifting. In 3 cases which I have seen the patients laid great stress on this. One had received a kick in the side from a horse, and the two others had strained themselves in lifting. De Chapelle[107] has dealt specially with this feature in the etiology of the disease.

[Footnote 107: De la Leukémie dans ses Rapports avec la Traumatisme, Paris, 1881.]

Previously-existing splenic enlargement does not seem, as we might expect, to predispose to leukæmia. It is rare for a case of simple chronic hyperplasia of the spleen--from malaria, for instance--to terminate in leukæmia.

The disease occurs in the lower animals, and cases have been described in horses, dogs, oxen, cats, swine, dogs, and mice. The majority of cases have been in dogs.[108] A study of the comparative pathology of the disease has not thrown any light on the etiology.

[Footnote 108: Siedamgrotzky, Ueber die Leukæmie bei den Hausthieren, Leipzig, 1878; Bollinger, Virchow's Archiv, lix.; _London Med. Record_, vol. ii., 1874.]

SYMPTOMS.--A division of the disease into two or three stages has been made by some writers, but as no special regularity is observed in the sequence of events, we need only recognize a period of development, in which the disease gradually becomes established, and a final period of cachexia, when there are symptoms of profound blood-change and the viscera are involved.

The mode of onset is insidious. In the majority of cases there is failure in health and strength, and the patient seeks advice for progressive enlargement of the abdomen with dragging pain in the side, or for the shortness of breath, the enlarged lymph-glands, the pallor, or the various symptoms of anæmia, as headache, palpitation, and dizziness. Bleeding at the nose is common. Vomiting and diarrhoea may be early symptoms, and in a few cases oedema of the face and feet has been noted early in the disease. Occasionally the first symptoms to attract the attention of friends or physician are of a serious nature--a sudden hemorrhage, for example. In one of Howard's cases the lad had played lacrosse two days before the onset of the fatal hæmatemesis, and in another case, a girl, there was early and fatal hemorrhage from the stomach before the condition of splenic enlargement was suspected.

Digestive System.--Gastric symptoms are rarely absent in the form of oppression after eating, nausea, and vomiting; the latter may be an early and troublesome feature. The appetite is variable, and when the spleen is greatly enlarged the mechanical pressure is apt to cause uneasy feelings after eating.

Diarrhoea is common, and may come on very early in the disease (Case I.[109]), and it is a frequent cause of death. The stools are usually thin and catarrhal, not often dysenteric, but melæna occurs in many cases. The diarrhoea may be due to a dysenteric process in the colon (Case II.), and tenesmus may {911} be present. It has not been noted that the diarrhoea is more frequent when the lymph-glands of the intestines are involved.

[Footnote 109: These figures refer to Montreal cases, some of which I saw with my colleague, Palmer Howard, others with John Bell, Lachapelle, and G. T. Ross.]

The liver shows no alterations in the early stage, but as the disease advances it is almost invariably enlarged. Jaundice is not often present, but there may be recurrent attacks (Case II.), due either to catarrh of the ducts or to pressure of glands in the hilus. Ascites is a variable feature; a slight degree is not uncommon as part of a general dropsy dependent upon the blood-condition, but in some cases it is a prominent symptom and calls for frequent tappings (Case IX.). In some cases it is due to pressure of leukæmic growths in the branches of the portal vein or the liver, or of enlarged glands upon the trunk at the hilus. The ascites is not always hepatic; like the hæmatemesis and melæna, it may be of splenic origin and occur without any disturbance in the portal vein or liver. Leukæmic peritonitis has been met with.[110]

[Footnote 110: Willcocks, Proceedings of Conn. Med. Soc., 1874.]

Nervous System.--Headache, dizziness, and attacks of fainting are common, and due chiefly to the anæmia. In some cases the headache is severe and persistent. The intelligence is well preserved; only toward the close is there rambling delirium. Mental disturbance may occur, and in one case the patient committed suicide. Some writers speak of special sadness and moroseness. This I have never noticed; on the contrary, in most of the cases I have seen the patients seemed specially tranquil and resigned. Coma may come on suddenly from cerebral hemorrhage (Case X.).

Sleep is not usually disturbed; some patients doze incessantly.

Special Senses.--Weak vision is often complained of, due to the anæmia, sometimes to the leukæmic retinitis. Blindness rarely supervenes, even when the retinal changes are extensive. Marked intolerance of light may be present.

The condition of the retina is variable. There may be simply turbidity and swelling of the retina, with large and tortuous veins, or more commonly with the opacity there are hemorrhages, such as occur in profound anæmia from any cause. A peculiarity, however, of the extravasations in some cases of leukæmic retinitis is the appearance produced by the aggregation of colorless corpuscles, often in the centre of the hemorrhage, so that there is a yellow or white nucleus and a zone of red. The collections of colorless corpuscles may indeed have the characters of small leukæmic growths. In one case (XI.) throughout the retinæ were numerous small raised opaque white bodies one to two millimeters in diameter, some of them surrounded by rings of extravasation. There was no swelling of the disk.

Deafness has been frequently observed, and may appear early. It was specially noted in the cases of Edes,[111] Morrill,[112] Seguin,[113] and Pepper,[114] and DaCosta.[115] No satisfactory explanation has been given, and the suggestion that it is due to hemorrhage has not, so far as I know, been confirmed by autopsy. Noises in the ears may be very troublesome, and even be so bad as to disturb hearing and necessitate the writing of questions (Case XI.).

[Footnote 111: Boston Med. and Surg. Journal, 1871.]

[Footnote 112: Loc. cit.]

[Footnote 113: Archives of Scientific and Practical Medicine, New York, 1873.]

[Footnote 114: Med. and Surg. Reporter, 1883, 48.]

[Footnote 115: Ibid., 1874.]

Blood-vascular System.--In a well-marked case the blood-drop squeezed from the finger-tip is more or less turbid, of a reddish-brown or in extreme cases chocolate-brown color.

The blood should be examined in a thin layer, and for this purpose it is better to take a small than a large drop. A rough estimation of the proportion of white corpuscles can be much better obtained when a uniform thin layer is beneath the top cover. The red corpuscles, as a rule, present no striking changes, no special alterations in size or shape. Microcytes are {912} occasionally seen, and now and then larger forms, but the extreme variations of pernicious anæmia are rarely met with. They are reduced in number, but not often to a great extent. A reduction below 2,000,000 to the cubic millimeter has been exceptional in cases which I have examined. In only one did the number sink to 1,500,000 per c.m. Laache[116] has noted a case in which, with enlargement of the spleen and a ratio of white to red of 1:17, the number of red corpuscles was little if at all reduced.

[Footnote 116: Die Anämie, Christiania, 1883.]

The colorless corpuscles are enormously increased. Instead of eight to ten millions per c.m., as in normal blood, they may reach 500,000 per c.m. or even 700,000 per c.m. The ratio of white to red cells may be 1:20, 1:10, 1:4, or they may even equal or exceed the red. Without a proper apparatus (Gowers, Malassez, or Zeiss) an accurate estimate is impossible, and it is chiefly upon the rough-and-ready method that the statements are made of the white exceeding the red in numbers. It is very seldom indeed that this is the case, and even in extreme leukæmia the ratio does not often reach 1:3 or 1:2. In none of my observations did the ratio rise to 1:1; the highest was 1:2. Cases are on record in which the white have exceeded the red: Sörensen's,[117] where the red per c.m. were 470,000 and the white 680,000, and in an interesting observation of Fleischer and Penzoldt,[118] as a mean of 57 accurate counts, the ratio of white to red was 115:100. The corpuscles have the natural grayish-white appearance of leucocytes, but differ in certain points from normal white blood-cells. The variations in size are greater: in normal blood only a few may be seen less than 1/2800 or 1/3000 of an inch, but in leukæmia on a single slide there may be colorless cells with the extreme measurements of 1/2000 and 1/3500. In ordinary cases we meet with--(1) cells of the average size, about 1/2800 of an inch in diameter, like normal corpuscles, with two or three nuclei and fine granular protoplasm; (2) smaller forms, 1/3000 of an inch and under, with single nuclei, resembling rather lymph-cells, and they were believed by Virchow to indicate special involvement of the lymph-glands, but they are present in all forms, though possibly more prevalent in the lymphatic variety; (3) large forms, 1/2000 to 1/1500 of an inch, with bold nuclei and bearing a close resemblance to the marrow-cells. They are not always present, and are believed to originate in the marrow.

[Footnote 117: Virchow-Hirsch's Jahresber., 1874.]

[Footnote 118: Deutsches Archiv f. klin. Med., Bd. xxvi.]

Cafavy states[119] that the colorless corpuscles of leukæmia do not display active amoeboid changes, indicating thereby a diseased and enfeebled condition of protoplasm. I find a note made in Sanderson's laboratory in 1873 on the very sluggish and imperfect movements of the colorless corpuscles in a case of leukæmia in University College Hospital. In Case V. the note on one day is, "Active amoeboid changes," and in two other cases since Cafavy's paper I have seen the protoplasmic movements tolerably active, but not in all equally. Possibly the leucocytes from the marrow do not move so freely as the others; normal marrow-cells have very feeble amoeboid powers. Ehrlich[120] has observed that the number of leucocytes in leukæmic blood which contain granules reacting with eosin is very great, whereas in normal blood very few occur.

[Footnote 119: Lancet, ii., 1880.]

[Footnote 120: Zeitschrift f. klin. Med., Bd. i.]

Nucleated red blood-corpuscles, such as occur in the blood of the foetus and in the red marrow of the adult, have been found in leukæmic blood by Klebs, Mosler, and others. I have observed them in four cases. They are scanty, usually isolated, rarely more than one or two in a field; often, indeed, many fields must be searched before finding one. On two occasions (Case IX.) they might be called numerous--three or four in each field of the No. 9 immersion lens.

Schultze's granule-masses, the aggregations of the discoid hæmatoblasts, are {913} present in variable numbers, sometimes very numerous. I have examined slides in which they were absent. A curious mistake was made by a writer in the Lancet (1878, ii.) when he described these as a hitherto unnoticed feature of the blood in leukæmia.

The fibrin network which separates between the corpuscles is usually very thick and dense.

Peculiar crystals, elongated octahedra or spindles, of variable size and bright-white appearance, separate very commonly on a slide of leukæmic blood, particularly if kept surrounded with oil or paraffin for twenty-four hours. They are known as Charcot's crystals, and are identical with those which occur in the bone-marrow, in semen, and in sputum in some cases of bronchitic asthma. White of Boston described them well in 1859,[121] and believed they were produced by the separation of a neutral principle which he named leukosin. I can confirm Zenker's observation,[122] that they form sometimes in the colorless cells.

[Footnote 121: Boston Medical and Surg. Journal.]

[Footnote 122: Deutsches Archiv f. klin. Med., xviii.]

Leukæmic differs from ordinary blood, and from that of other anæmic or cachectic states, by the readiness with which the hæmoglobin crystallizes. Often if a slide is kept and prevented from evaporating by a rim of paraffin, beautiful plates of hæmoglobin will crystallize.

The pulse is always quickened--80 to 100, and in the final stages 110-130--usually soft and compressible, and not always small in volume. The heart's action is readily excited. A systolic murmur is not infrequent at the apex; basic hæmic murmurs are not so often heard as in anæmia, but a venous hum in the neck is generally present. The apex-beat of the heart may be pushed up an interspace by the enlarged spleen. Oedema of the ankles and feet from the feeble circulation is constantly met with, particularly toward the close, and there may be general anasarca. Effusion into the pleural cavities is not common.

Hemorrhages are among the most constant features of the disease, and may occur at any time, early or late, in the course. The tendency to bleeding is greater in this than in any of the allied affections. Epistaxis is the most frequent form, and may precede the development of the disease for months or years. Hæmatemesis may carry off a patient early (Case II.), or even before the nature of the trouble is suspected (Case VI.). Hemorrhage from the bowel is common. Hæmoptysis and hæmaturia are rare. Bleeding from the gums may be present (Cases V. and VII.). In women there may be profuse menstruation. Petechiæ on the skin are frequent; occasionally there are large extravasations beneath the skin or between the muscles. Hemorrhage into the brain may prove quickly fatal (Case X.), and the extravasations into the retinæ may impair vision.

The respiratory system offers few special symptoms. The shortness of breath on exertion is due in great part to the anæmia, and progressively increases with the advance of the disease. The free action of the diaphragm is hampered by the enlarged spleen. There may be cough from bronchitis, and toward the end signs of oedema at the bases of the lungs. Pneumonia is not uncommon as a final complication.

The temperature in the early stages presents very slight variations, but when the disease is advanced there is always fever of the remittent or of the continuous type. There is usually a morning remission, and an evening exacerbation which reaches 101° or 103°. Periods of pyrexia may alternate with prolonged intervals of freedom from fever. In some cases the febrile movement is very slight throughout the entire course.

Genito-urinary System.--The urine is usually normal in amount, pale, strongly acid, and its specific gravity above the normal. Considerable variations occur in individual cases. Sediments of lithates are very common. {914} The urea presents no constant changes; sometimes it is increased, at others diminished, the quantity depending probably on the food and the presence or absence of fever. The quantity of uric acid excreted seems always to be increased, due either to a lessening of the oxidation processes in consequence of the reduced number of red corpuscles, or, as Salkowski suggests, it stands in relation to the existing splenic tumor; but observers have not found the amount proportionately increased in other forms of splenic enlargement, and the cause of the constant increase is still doubtful. Hypoxanthine, lactic, formic, acetic, and hippuric acids have been found, but their presence is neither constant nor apparently of special import. Albumen may be present. Sugar is rare. Hæmaturia, as before observed, very seldom occurs. Cystitis may arise and be troublesome (Case XI.).

A curious symptom in connection with the generative system is priapism, of which a number of cases have been recorded. Edes[123] narrates the case of a boy of fifteen in whom obstinate priapism was the first symptom. Longuet[124] reports a case of six weeks' duration. Saltzer[125] mentions five cases, in one of which the condition persisted for seven weeks, and Peabody[126] gives a case in which it lasted six weeks. It is not definitely settled whether the priapism is due to thrombosis in the corpora cavernosa or to irritation of the nervi errigentes.

[Footnote 123: Boston Med. and Surg. Journ., 1871.]

[Footnote 124: Progrès méd., 1875.]

[Footnote 125: Berliner klin. Wochenschrift, 1879.]

[Footnote 126: New York Med. Journ., 1880, xxi.]

In women there are the usual menstrual irregularities consequent upon a grave constitutional disease. Occasionally the flow is excessive; more commonly it is interrupted altogether.

Blood-glandular System.--Slow increase in the volume of the spleen, causing a sense of weight in the left hypochondrium, is an early symptom in many cases. Patients do not usually come under observation until the enlargement is established and the organ can be felt below the costal border. Pain and tenderness over the organ are very common, though sometimes it is painless throughout. Palpation often elicits a creaking fremitus due to the rubbing together of the adhesions. The gradual enlargement causes an evident increase of girth in the lower thoracic and upper abdominal zones, and marked prominence of the left hypochondrium. The tumor extends to the right and downward, and may occupy a large portion of the abdomen, extending even to the pelvis. When there is no ascites the edge can be easily felt with the anterior notch or notches. The pressure of a large spleen causes distress after a full meal, and by its mechanical effect may even compress the bowels and produce fatal obstruction.[127] The effect upon the heart and respiration has already been noticed. The adhesions may interfere with the depression of the organ during a deep inspiration. The size varies in an inexplicable way, considering the indurated fibroid nature of the enlargement. It may be perceptibly larger after a meal.[128] A hemorrhage or free diarrhoea may reduce the size very much, as in Morrill's case.[129] A murmur may occasionally be heard, and an enlarged spleen has been known to pulsate.[130]

[Footnote 127: Collins, Brit. Med. Journ., 1882, i.]

[Footnote 128: Johnson, Lancet, 1870, Jan.]

[Footnote 129: Bost. Med. Journ., 1877.]

[Footnote 130: Gerhardt, Zeitschrift f. klin. Medicin, Berlin, Bd. iv.]

Lymphatic Glands.--In the great majority of cases the lymph-glands are but slightly if at all involved. Even when they are affected it is rare to see such large bunches as in Hodgkin's disease. When they are growing there may be pain and tenderness, and if large they may be a source of inconvenience, but severe pressure symptoms are not often witnessed. Enlargement of the glands in the superficial groups is readily detected, but the deep-seated collections in the mesentery and retro-peritoneum can rarely be palpated unless of considerable size. Mediastinal lymph-tumors in leukæmia are exceptional. In none of the cases I have seen were the lymph-glands {915} greatly enlarged. It is stated that in children the lymphatic variety is more common than in adults.

There may be tenderness over the bones, and in rare instances swelling, but unless the tenderness is marked and accompanied by some local expansion or softening, we cannot determine positively the existence of the myelogenous variety. The sternum, ribs, and flat bones are most often affected, and there may be great irregularity and deformities, as in a case I saw with Riess of Berlin. It is well to bear in mind that in perhaps the majority of persons there is a tender spot upon the sternum which may cause marked wincing when touched firmly. No reliance should be placed upon tenderness without swelling or softening. Such tenderness may exist, and post-mortem the marrow be found normal;[131] and, on the other hand, there may be extensive changes in the bone-marrow without any tenderness (Litten).

[Footnote 131: Deutsches Archiv f. klin. Med., xxvi.]

MORBID ANATOMY.--There may be extreme wasting. Dropsy of the feet is common, and ascites may be present.

A noteworthy feature is the full amount of blood in the heart and blood-vessels, usually in the form of large coagula. In one case (XI.) the weight of clots alone in the heart-chambers, not including what came from the veins, was 620 grammes. The portal, cerebral, pulmonary, and subcutaneous vessels were also greatly distended with clots. The portal vein just above the union of the branches measured eleven centimeters in circumference.

The blood is usually clotted in the heart and vessels, and the aggregation of the colorless corpuscles densely infiltrating the fibrinous clots and the serum gives a pus-like appearance, so that it has not infrequently happened, as in Virchow's memorable case, that the observer on opening the right auricle believed for the moment that he had cut into an abscess. The leukæmic clots often have a peculiar greenish color, and resemble somewhat the fat of the turtle. Similar coagula may fill the veins of the brain and abdominal viscera. The tendency of the white corpuscles to aggregate together, and the subsidence of the red to the lower part of the heart-chambers and vessels, may give an appearance of more intense leukæmia than actually exists. The reaction of the blood is usually acid. The chemical constitution has been carefully studied, but with no very satisfactory results. Hypoxanthine, lactic acid, leucin, tyrosin, a mucin-like body, and a gelatinous substance have been described, but none of them may be regarded as characteristic of the disease. The octahedral crystals are thought by some to be tyrosin,[132] but Schreiner[133] says they consist of the phosphate of an organic base, the composition of which is not yet settled.

[Footnote 132: Huber, Archiv der Heilkunde, Bd. xviii.]

[Footnote 133: Liebig's Annalen, cxciv.]

The specific gravity of the blood is lowered, 1036 to 1049. The water is increased. The fibrin in many observations has also been found increased; 4.8 per 1000 was the average of ten observations by Bennett. The albumen and the salts have not often been estimated. The former is stated to be diminished. The fatty bodies have been found in excess of the normal quantities.

The heart is often pushed up by the large spleen; the pericardium, more rarely the endocardium, may present ecchymoses, and the fluid may be in excess. In a few instances leukæmic growths have been met with. The chambers are usually distended, the walls soft, and a moderate grade of fatty change is very common. No special alteration has been met with in the blood-vessels. I have seen extensive fatty degeneration of the intima and small arteries.

In the great majority of cases the spleen is increased in size, but the shape is retained. It is usually of a deep violet-red color, and strong adhesions may unite it to the abdominal wall, diaphragm, or stomach. The capsule {916} may be greatly thickened, forming a firm fibro-cartilaginous investment. The vessels are enlarged, particularly the veins at the hilus. The weight may vary from two to eighteen pounds. The largest on record is given by Langley Browne[134]--18½ pounds. Six or seven pounds is an average weight. The length may vary from seven to twenty inches, and the breadth eight to twelve. The organ is in a condition of chronic hyperplasia--hard, firm, cuts with resistance, and displays a uniform reddish-brown surface on which the trabeculæ are more or less prominent. There may be hemorrhages or infarcts, and it is not uncommon to see regions of yellow or rusty-brown staining, indicating where an extravasation had occurred. As a rule, no trace of the Malpighian bodies can be seen. Grayish-white, circumscribed lymphoid tumors may occur throughout the organ, contrasting strongly with the reddish-brown matrix. The process of gradual enlargement is a simple hyperplasia. In the early stage, not often seen, there is swelling of the pulp, increase in the cell-elements, without the firmness and induration of the fully-developed leukæmic organ. Rupture may occur at this period from the intense hyperæmia. The Malpighian bodies are enlarged and prominent by their grayish-white color. A gradual and progressive induration results from the increase in the adenoid network and the fibrous trabeculæ. A section shows the enormous development of the fibrous elements. The cells may be scanty, only two or three in meshes, or, indeed, the reticulum may be so close that only a single cell is enclosed. As a rule, the hyperplasia extends over the whole organ, and the Malpighian bodies become involved and lose their distinctness. In only one of the cases which I have examined were they at all prominent. Leukæmic new growths in the spleen are rare.

[Footnote 134: Lancet, 1877, ii.]

Uncomplicated cases of the lymphatic form are very uncommon: usually they enlarge with the spleen, and in the majority of instances the hypertrophy is not extensive, scarcely ever reaching the high grade seen in Hodgkin's disease. The groups of cervical, axillary, mesenteric, and inguinal are most frequently affected; the bronchial and mediastinal but rarely. The bunches of glands are not usually larger than walnuts, moderately soft, isolated, movable; large matted groups do not often occur. They may vary a good deal in size during the course of the disease, often diminishing notably before death. In chronic cases they may become very indurated. The leukæmic lymphadenitis is a simple hyperplasia, and the soft glands may look, on section, of a normal gray color or may have a deep gray-red appearance. Hemorrhages may occur, and twice I have seen the enlarged glands deeply hyperæmic. Histologically, the appearance is very like a normal gland, only the lymph-spaces are more closely packed. In the harder glands the fibrous reticulum is much increased, the capsule thickened, and the section more grayish in color. Caseation or suppuration rarely occurs, and invasion of contiguous parts is most exceptional.

The tonsils and the lymph-follicles of the tongue, pharynx, and mouth have been found much enlarged.

The bone-marrow is usually the seat of important changes, which in some cases appear early and persist as very prominent features of the disease. The most constant alteration is a uniform substitution of a grayish-red or gray-green puriform-looking tissue for the normal red and fatty marrow of the long and short bones. The entire medulla may resemble the consistent matter which forms the core of an abscess, and the term pyoid applied to this condition by German authors well expresses the general characters. More rarely the marrow has a reddish-brown hue. The difference depends largely on the number of colorless corpuscles, which in the pyoid form are enormously increased, and there are but few red cells. Ponfick has met with dark-red, dense hemorrhagic infarctions in leukæmic marrow. The condition of the {917} bones is variable; usually, the compact and cancellated tissues appear normal, but the hard shell may be much thinned and expanded, the cancellæ widened, and the whole substance rendered spongy. In marked cases there may be localized swellings which are tender, and even yield, on firm pressure. The sternum and ribs are most frequently affected in this way. There are instances in which the bone-marrow has not been involved, and in one case there was osteo-sclerosis.[135] Histologically, the chief change is hyperplasia of the colorless marrow-cells, which in the pyoid variety compose the chief part of the tissue. They vary much in size and appearance. Three forms can usually be recognized: large granular cells with distinct nuclei; medium-sized cells, like colorless blood-corpuscles; and smaller forms, like lymph-cells, with large nuclei and a narrow zone of investing protoplasm. The red corpuscles and microcytes are in variable numbers. In one case the latter were very abundant. Nucleated red corpuscles are very constant elements. Corpuscles containing red blood-corpuscles are not so numerous as in ordinary red marrow, nor, as a rule, are the myeloplaques abundant. Charcot's crystals are always to be found--if not at first, when the marrow is quite fresh, certainly later, when decomposition has begun.

[Footnote 135: Heuck, Virchow's Archiv, lxxviii.]

The thymus is rarely affected, and even in children is not often swollen. A few cases of enlargement have been recorded.

The thyroid is even less frequently involved.

In one case the suprarenal capsules were large and swollen,[136] and in addition to the leukæmia there was bronzed skin. Hemorrhage, caseous degeneration, and in one instance rupture,[137] have been noted.

[Footnote 136: Barclay, Lancet, 1863, i.]

[Footnote 137: Fleischer and Penzoldt, loc. cit.]

In the digestive system the stomach rarely presents any changes other than catarrhal. Even when death has occurred from hæmatemesis the mucous membrane may be pale, without erosion, hemorrhage, or ulceration (Cases II. and VI.). In a few instances lymphatic growths have been described. In many cases the intestines have been the seat of leukæmic tumors which have originated in the solitary and agminated glands of Peyer. Occasionally the lymphoid infiltration is diffuse in the mucosa and not confined to the follicles. Ulceration may occur in the patches, and in a few cases the bowel lesions have been so pronounced that the term intestinal leukæmia seemed justifiable.[138] The cæcum and colon may also present these new growths, and in a few cases dysenteric processes have been observed (Case II.). The peritoneum has been found covered with small lymphoid growths. In Willcocks' case of lymphatic leukæmia[139] there were growths on the surface of the stomach and gastro-splenic omentum. Blood may be found in the cavity from rupture of the spleen. Ascitic fluid is common. Fibroid thickening, induration, and adhesions are very often met with, particularly in the neighborhood of the spleen.

[Footnote 138: Behier, loc. cit.]

[Footnote 139: Loc. cit.]

The liver is very commonly enlarged, pale, smooth, and retains the normal shape. It may be greatly increased in size, as in case of Walshe's, where it weighed 13½ pounds. The substance is usually firm, of a grayish-brown color, or even marbled. Two chief changes have been met with--a diffuse leukæmic infiltration and numerous small leukæmic tumors. The infiltration may be very slight, and not noticeable with the naked eye, or it may be in the form of irregular scattered areas of a yellowish-white appearance, not distinctly isolated, but merging into the hepatic tissue. When moderate, a section shows the columns of liver-cells to be separated by wide spaces occupied by leucocytes, which are partly within and partly outside of the capillaries. The accumulation of these elements produces atrophy of the liver-cells, and their aggregation and increase in certain regions produce the grayish-white areas, in the midst of which traces of liver-tissue may be found. {918} The defined leukæmic growths are small, not often attaining a large size, and may resemble tubercles. They are usually situated in the interlobular tissue, and consist of lymphoid cells in a well-defined reticulum, and they possibly have a different origin from the diffuse infiltrations.

Fatty degeneration of the liver-cells is a very common change.

The respiratory system is not often the seat of important lesions. Lymphoid growths have been found in the mucous membrane of the trachea and bronchi, and occasionally in the lungs, in which situation they may closely resemble tubercles, but differ from them in not tending to caseate or soften. Oedema of the bases of the lung is almost always found. Many patients are carried off by a low pneumonia. The greenish leukæmic clots projecting from the cut ends of the vessels may give a very curious appearance to the section of the lung. The pleural surfaces may be the seat of lymphoid growths.

The kidneys are usually pale, often enlarged, and show signs of parenchymatous swelling. The capillaries, like those of the liver, may be distended with leucocytes, and leukæmic tumors may occur, generally situated in the cortex and ranging in size from a pea to a cherry. In none of the cases I have examined were there any special changes in these organs beyond slight enlargement and filling of the capillaries with leucocytes.

The generative organs are usually normal. No changes have been found to account for the persistent priapism met with in certain cases.

The meninges of the brain, the veins, and sinuses, are often filled with grayish clots. Occasionally meningitis has been found, with exudation of lymph. The small vessels of the brain may be plugged with leucocytes, forming thrombi, from which softening results. Cerebral hemorrhage may prove rapidly fatal. In Case X. of the Montreal series the patient died suddenly, and without any premonition, with a huge apoplexy of the ventricles and posterior part of the hemispheres.

Leukæmic growths in the skin have been described.

The leukæmic tumors demand further consideration. They are not common. In 10 of the 11 Montreal cases careful post-mortem examinations were made, and in not one were there definite new growths. In Case I. there was diffuse leukæmic infiltration of the liver, the histological characters of which were carefully studied. In the 157 cases collected by Gowers[140] there were only 13 instances of leukæmic nodules in the liver, and 10 in the kidneys. They are still more uncommon in the lungs. In the spleen--unlike this organ in Hodgkin's disease--they are very rarely seen. The nodules consist of leucocytes in a meshwork of delicate reticular tissue. Their mode of origin has been much discussed. There can be no doubt, I think, that they are new growths of lymphoid tissue of local origin. Possibly they start from accumulations of colorless corpuscles which pass out of the capillaries. In the infiltration of the liver one sees diffuse collections which resemble new growths, but which have evidently resulted from the aggregation in and outside of the capillaries of enormous numbers of leucocytes, which cause the atrophy of the cells of the organ. Doubtless, they multiply in loco by a process of fission, and these aggregations may themselves be foci for the origin and development of colorless cells which pass into the blood-current and augment the number.[141] Quite recently Bizzozero has studied the development of these leukæmic new growths, and has shown clearly that the cells which compose them are in process of active fission.

[Footnote 140: Loc. cit.]

[Footnote 141: "On the Histology of Leucocythæmia," Canada Medical and Surgical Journal, 1876.]

The COURSE OF THE DISEASE is slow and chronic, a matter of months and years. There are exceptional instances in which the disease has proved fatal in a few weeks; this occurs sometimes in children,[142] but acute leukæmia is {919} very rare. In a table of 63 cases collected by Gowers, in which the date of the first symptoms was fixed with tolerable accuracy, the duration was less than one year in 13 cases; from one to two years in 16; from two to three years in 19; from three to four years in 9; from 4 to 5 years in 3; and five years and upward in 3 cases. The course is rarely uniform, but periods of improvement occur in which the fever subsides, the painful sensations in the abdomen diminish, the appetite improves, and the spleen reduces in volume. Such intervals, corresponding to the administration of certain drugs, are apt to lead to therapeutic errors. A patient may sometimes get about for months, and even attend to a light business, with an enormous spleen and a ratio of white to red corpuscles of 1 to 6 (Case VIII.). Hemorrhages, high fever, profuse diarrhoea, and the occurrence of dropsy shorten the course. Toward the close there is great muscular debility, and usually a wandering delirium.

[Footnote 142: Golitzinsky, Jahrb. f. Kinderheilkunde, 1860-61.]

In the majority of cases death is by asthenia--a gradually progressive weakness and ultimate failure of the heart. Diarrhoea and hemorrhage hasten the fatal result. A profuse hemorrhage may cut off a patient early or after the disease is well established. Cerebral hemorrhage was noticed in 6 of 60 cases in which Gowers was able to ascertain accurately the cause of death. A few are carried off by pleurisy or pneumonia or peritonitis after tapping.

Pyæmia and rupture of the spleen are mentioned as causes of death in some cases.

The DIAGNOSIS of leukæmia rests upon the determination of a great and persistent increase in the colorless elements of the blood. Cases of Hodgkin's disease and of splenic anæmia, almost identical in general features, can only be distinguished by an examination of the blood. I should say that in any case we can speak of the blood as leukæmia when the ratio of white to red cells falls below 1 to 50. Some writers hold that to determine leukæmia the ratio should be at least 1 to 20, but when the study of the variations in the proportion of the corpuscles in any case extends over weeks or months, we not uncommonly find that the ratio, which, at one observation may be 1 to 8, or 1 to 10, a week later may be 1 to 60 or 80, or even 150. Indeed, the state of the blood is a variable factor, and too close attention to it has diverted our minds from the broad features which this disease has in common with others. For practical clinical purposes we have to distinguish ordinary lieno-lymphatic leukæmia from--(1st) chronic malarial infection with splenic hypertrophy; (2d) from cases of non-malarial splenic enlargements with anæmia; (3d) from general lymphadenoma or Hodgkin's disease. The history in malarial cachexia, the absence of lymphatic enlargement, and the blood-condition will usually be sufficient for purposes of a diagnosis. Great increase in the white blood-corpuscles is not often seen in the chronic splenic tumor of malaria; indeed they may be much diminished in number. Toward the end in very chronic cases the clinical picture may be very similar: the large abdomen, possibly ascites, dropsy of the feet, and irregular fever may resemble closely splenic leukæmia, and the absence of an increase in the colorless corpuscles may be the only marked difference. From anæmia splenica there is still greater difficulty, and I have seen instances in which the absence of an excess of the colorless corpuscles in the blood formed the sole criterion: the hemorrhages, the dropsy of feet and abdomen, retinal extravasations, the general cachexia, and the fever were identical with those of leukæmia. Still greater may be the difficulty of separating certain cases of lymphatic leukæmia from general lymphadenoma or Hodgkin's disease; but in the latter affection the glandular enlargement is usually greater and altogether a more prominent feature, and the spleen is not so often increased in size. There may, however, be a considerable increase in the number of the white corpuscles, 1 to 150 or 1 to 100 red, and cases do occur which appear intermediate {920} or transitional in character, and upon which judgment must be reserved until the progress of the case decides the question.

Pure cases of myelogenous leukæmia are almost unknown; if the osseous symptoms are not marked the course is very like that of pernicious anæmia. Indeed, there are two interesting cases on record in which the progressive anæmia seemed to pass into leukæmia. In Litten's case[143] the patient presented the symptoms of profound anæmia, and five days before death the blood became markedly leukæmic. There was no enlargement of spleen or lymph-glands, but the bone-marrow was intensely leukæmic--i.e. of the pyoid form. In the case reported by Leube and Fleischer[144] the patient, aged thirty, four months after her confinement became anæmic and the left leg was swollen. Though at first only anæmic, subsequently the ratio of white to red corpuscles rose to 1 in 10. Gangrene of the leg supervened, necessitating amputation, from the effects of which she died. There was no affection of spleen or lymph-glands, but the marrow was of the red lymphoid variety. A gastric ulcer was also present. This was no doubt a case of post-partum anæmia aggravated by the presence of ulcer of the stomach, and the great interest of the case lies in the transition of the anæmia into leukæmia.

[Footnote 143: Berliner klin. Wochenschrift, 1877.]

[Footnote 144: Virchow's Archiv, lxxxiii.]

There are certain general conditions, accompanied by an increase in the colorless corpuscles, which must be distinguished from leukæmia. In suppuration there may be marked leucocytosis; so also in cancer and protracted cachectic states, as phthisis. In cases with large cancerous masses about the stomach and omentum, or where, as occasionally happens in chronic phthisis, there is a greatly enlarged amyloid spleen, if the white blood-corpuscles are much increased, care may be necessary to escape a mistake in diagnosis. In diphtheria the colorless elements may be much increased. Bouchat says that in some instances there may be an acute leukæmia.[145] In puerperal fever also the condition of leucocytosis is not uncommon.

[Footnote 145: Gazette des Hôpitaux, 1877.]

The PROGNOSIS is in the highest degree unfavorable, and in those cases, few, indeed, in number, in which there were symptoms like leukæmia and which disappeared under treatment, the doubt remains whether they were true examples of the disease. When once established, the spleen and glands enlarged, the hemorrhages and dropsies present, and the blood condition marked, death is the only termination to be expected. Specially unfavorable signs are a tendency to hemorrhage, persistent diarrhoea, early dropsy, rapid increase in the splenic tumor, great excess of colorless corpuscles, and high fever. Temporary improvement may occur for weeks or even months, and the white blood-corpuscles reduce in number, but such breaks are usually transient.

TREATMENT.--If, as some writers hold, chronic malarial poisoning is an important factor in the induction of leukæmia, we should take special pains with patients so affected, and endeavor by the use of quinine and arsenic to free the system and reduce the volume of the spleen. There certainly may be danger of the development of leukæmia in any case of chronic splenic tumor, though my own experience has been that in these cases the production of anæmia of high grade, without increase in the white blood-corpuscles, is more common. It is a mistake to suppose that anæmia always accompanies chronic splenic enlargement: it may persist for years with a percentage of red corpuscles little if at all below normal, but grave anæmia or leukæmia are probabilities to be dreaded.

In an early stage, when the spleen is moderately enlarged, the lymph-glands scarcely swollen, and the leucocytosis not intense, there is a hope that by the persistent use of quinine, iron, and arsenic a cure may be effected; but when the disease is fully established and the leukæmia marked, a recovery {921} is rarely if ever witnessed, and the treatment is largely palliative and symptomatic. To reduce the volume of the spleen various remedies are recommended, and so long as the organ is only moderately enlarged and hardened some of them may be beneficial. Quinine should be given a full and prolonged trial, as undoubtedly under its use the organ may reduce in size. As anæmia is almost always present, iron may be administered at the same time. That the quinine has any special influence over the production of the white corpuscles, as some think, I have not been able to satisfy myself. To be of use, it must be employed early and in large doses. Ergotin internally and by injection into the spleen has been recommended. I have not seen any permanent benefit from its use. Local measures, such as inunction of biniodide of mercury ointment over the spleen, the interrupted voltaic current, the application of cold, either ice or the cold douche, may be employed. Moderate reduction in the volume may be effected by these means--most effectually by the electricity and mercurial inunction.

Arsenic should always be given a trial, and pushed for several months in increasing doses. Several cases are reported in which the improvement lasted for many months. Direct injections into the spleen are also of service. Phosphorus, from which much was expected after the favorable reports of Broadbent and Wilson Fox, has not proved of much value. There are very curious remissions in the course of the disease which render therapeutical deductions somewhat fallacious. I have seen the most marked improvement occur without any special treatment: ascites and dyspnoea disappear, the white corpuscles decrease in number, and the patient from a bed-ridden, wretched condition get up, attend to light duties, and walk half a mile to hospital (Case IX.). In Case VIII. there were also during eighteen months remarkable variations, depending more on the state of the gastro-intestinal canal than the blood condition.

Transfusion has proved useless. Leukæmic blood to the amount of several ounces has been withdrawn and other healthy blood substituted.

Excision of the spleen has been frequently practised in leukæmia. Collier[146] gives a résumé of 16 cases, and concludes that it is a useless and unjustifiable operation, as all of them proved fatal. A successful case, however, is reported from Italy. If performed early, there is a possibility of success, but when the organ is enormously enlarged and the blood intensely leukæmic, the conditions are most unfavorable.

[Footnote 146: Lancet, 1882, i.]

Gastric symptoms and diarrhoea call for careful treatment, as the comfort of the patient depends largely on the condition of the primæ viæ. Hemorrhage is frequent, and is a dangerous symptom, particularly when it depends upon engorgement of the portal system, and calls for appropriate remedies. Purgatives are to be employed with caution. The dragging pain in the left hypochondrium, and the sense of weight and distension after eating, are very distressing, and the splenic pain may require sedatives. Inhalations of oxygen relieve the dyspnoea and have been found to check the progress of the disease.

HODGKIN'S DISEASE.

DEFINITION.--A disease characterized by progressive hyperplasia of the lymph-glands, sometimes also of the spleen, with anæmia and the development of secondary lymphatic growths in various parts of the body.

SYNONYMS.--Pseudo-leukæmia; General lymphadenoma; Malignant {922} lymphoma (Billroth); Lympho-sarcoma (Virchow); Adénie (Trousseau); Desmoid carcinoma (Wagner); Anæmia lymphatica (Wilks); Lymphatic cachexia (Mursick); Adenoid disease (Southey).

HISTORY.--Morgagni and other writers mention cases of enlargement of the lymph-glands proving fatal, but Hodgkin of Guy's Hospital first called special attention to the subject in a paper before the Medico-chirurgical Society of London,[147] entitled "On Some Morbid Appearances of the Absorbent Glands and Spleen." Some of the cases then described were undoubtedly examples of scrofulous glands, but four at least were instances of the disease which now bears his name; and at the meeting of the London Pathological Society in 1878, when a discussion on lymphatic disease took place, Wilks exhibited the original specimens collected by Hodgkin. Other cases were recorded in England by several observers, and in 1856, Wilks[148] reported several examples of enlarged lymph-glands with growths in the spleen associated with anæmia, but without any leukæmia; and again in 1865 this observer published additional cases,[149] and gave the name of Hodgkin's disease to the affection characterized by enlargement of the lymph-glands, growths in the spleen and other organs, and anæmia. The cases and discussions contained in the Transactions of the Pathological Society of London and Gowers' exhaustive article in Reynolds's System of Medicine embrace the most valuable of the English contributions. In Germany, Virchow described the cases under the term lympho-sarcoma, and in his work on tumors gave a full account of the histology. Billroth gave the term malignant lymphoma to these growths to distinguish them from local non-infective lympho-sarcomas. Cohnheim and Wunderlich used the term pseudo-leukæmia to express the distinction between these cases and leukæmic enlargements.

[Footnote 147: Transactions, vol. xvii., 1832.]

[Footnote 148: Guy's Hospital Reports, 3d Series, vol. ii.]

[Footnote 149: Ibid., vol. ix.]

In France, Trousseau described it under the term adénie, and Ranvier used the term lymph-adénie. In America many cases have been described, and one of the first and fullest analyses of recorded observations is by J. H. Hutchinson in the Transactions of the College of Physicians of Philadelphia, Series 3, vol. i.

ETIOLOGY.--No satisfactory etiological relations have been determined in the disease.

Age has an important predisposing influence. The majority of the cases are young persons. In Gowers' table of 100 cases, 30 were under twenty years, 34 between twenty and forty, and 36 above forty. Most of the cases I have seen have been in young adults.

Sex has a still more marked influence; at least three-fourths of all cases are in males, the proportion being considerably higher than in leukæmia--75 per cent. in Gowers' tables, and 40 out of 58 in Hutchinson's tables.[150]

[Footnote 150: Loc. cit.]

Heredity has in a few instances been adduced as a possible cause, but not, I think, on very reliable grounds. In two cases (II. and III.[151]) the patients were each a twin. It might be supposed that members of tuberculous families, or those who had suffered from scrofulous enlargements when young, would be more liable to the disease, but the cases in which such connection can be traced are very few in number.

[Footnote 151: These figures refer to cases of which I have notes.]

Antecedent syphilis has been noted in a few instances.

Exposure, intemperance, bad food, etc. are possible predisposing causes.

Local irritation, which so often produces lymphatic swellings, appears to stand occasionally in causal connection with the development of general lymphadenoma. Trousseau lays particular stress upon this, and gives instances in which chronic irritation of the skin, otorrhoea, chronic nasal or pharyngeal catarrh, irritation of a decayed tooth, gave rise to local gland swelling which preceded the general development of the disease. But this {923} is a comparatively rare affection, and think of the hundreds of instances met with of local lymphatic irritation!

SYMPTOMS.--Enlargement of the lymphatic glands in the neck, axillæ, or groins is the earliest symptom noticeable in the great majority of cases. This may be quite painless at first, and the patient seeks advice on account of the disfigurement or the inconvenience felt in adjusting the collar. Occasionally the anæmic and constitutional symptoms first attract attention. When the trouble begins in the deeper groups--bronchial, mesenteric, or retro-peritoneal--pressure effects are the first complaint, and there may be great obscurity and uncertainty about the nature of the case. Thus, the first symptom may be dyspnoea, with pain in the chest, or pain in the abdomen with swelling of the legs and shooting pains in the course of the nerves; or in rare cases symptoms of a totally different nature may be among the first to attract attention. Thus in J. H. Hutchinson's case there was paraplegia from pressure of a secondary growth, and the same was observed in a case which I dissected at the Montreal General Hospital (Case VI.). But such are very exceptional, and in the great majority swelling of the superficial glands is the earliest phenomenon. In rare instances the tonsils and pharyngeal adenoid tissue have been first affected.

Hemorrhage is not an early symptom. Epistaxis has been noted, but not with the frequency with which it occurs in leukæmia.

With the progressive enlargement of the glands the patient becomes anæmic, and finally cachexia is developed.

The Lymphatic System.--In an early stage it is difficult or impossible to distinguish the affection from syphilitic or scrofulous adenitis. The gradual increase in the size and the involvement of other groups, and the oncoming anæmia, will alone in certain cases render a decision possible. In the cervical group, in which the trouble usually begins, the chain of glands on one side becomes enlarged--perhaps only those just above the clavicle, or in some instances the posterior ones are also affected. They are isolated, movable, and not, as a rule, tender. Months, or even years (three years, Case VII.), may elapse before the enlargement becomes general or affects the other side. With their increase in size and number the separation between the glands, at first evident, disappears, and they form distinct groups or bunches. Thus the submaxillary set, those of the anterior triangle, and those of the posterior may form irregular aggregations of various sizes. Ultimately, huge tumors may develop which obliterate the neck, extending upon the shoulders and over the clavicles and sternum. When these grow inward, toward the trachea, great dyspnoea may be produced, and the pressure may be so extreme that tracheotomy must be performed.

The skin becomes involved, and ulcerates. Usually it is freely movable over the masses. The pharynx and oesophagus may be compressed, and occasionally the carotids. The submaxillary tumors may limit the movement of the jaws.

Next to the cervical, the axillary glands are most frequently involved. If small, no inconvenience is felt, but when large bunches occur there is great pain in moving the arms, and pressure upon the brachial or axillary veins may cause swelling of the limbs. The tumors may pass far out, almost to the nipple.

The inguinal glands are not so often involved. In only one of the ten cases which I have seen were they affected, but they may form large and even pendulous tumors, as well shown in the cases of Surgeon-Major Porter.[152]

[Footnote 152: Figured in Path. Soc. Trans., xxix.]

Of the internal glands, those of the thoracic cavity are most often attacked. The chain in the posterior mediastinum may be involved and surround the aorta or compress the gullet; or they may pass up the trachea to the {924} neck, and involve the thyroid (Case V.). When the bronchial group is enlarged there are signs of pressure on the tubes, dyspnoeal attacks, and serious implication of the lung (Case VI.) In the mediastinum there may be large masses covering the aorta, extending over the pericardium, and producing bulging of the sternum and ribs, perhaps pulsation, and ultimately erosion of the bones and outward projection of the tumors (Cases II. and III.). There may be considerable pressure upon the veins and obstruction to the flow in the superior cava and jugulars.

In the abdomen the mesenteric glands are often affected, and if the belly-walls are thin can be readily felt. The continuous chain of retro-peritoneal glands may be greatly enlarged, and extend from the diaphragm into the pelvis, surrounding the aorta, cava, and nerves. When the patient is thin there may be no difficulty in detecting these, but when there is an enormously thick panniculus the diagnosis may be impossible, as in Case I., in which intense lumbar and sacral pain and swelling of the legs were the only symptoms. The matting of organs in the pelvis caused by these growths may be a source of great difficulty in the diagnosis, as in a case in which I saw an eminent and careful surgeon open the abdomen to extirpate a uterus for fibroids, and found general lympho-sarcoma of the retro-peritoneal and pelvic glands.

It is probably in connection with affection of the abdominal glands that the bronzing of the skin occurs which is mentioned in a few instances. It was well marked in Case IV. of my series.

The glands present great variations in the rate of growth and there may be fluctuations from month to month. They may diminish rapidly, and almost disappear from a region to develop again in a few weeks. The enlargements may diminish very much before death.

The spleen does not present the almost constant enlargement of leukæmia, and in the majority of cases cannot be felt below the ribs. Moderate hyperplasia is common, but I have never seen the large splenic tumor. In some instances it has been found extending into the umbilical region, and if there are secondary lymphoid growths the surface may be very irregular.

The thyroid may be enlarged; it was so in Cases II. and IV., and in Case V. the growth in the glands of the neck involved the right lobe.

The thymus has also been found affected; indeed, the disease may, according to Virchow, sometimes begin in the gland.

Blood and Circulation.--The blood presents the characters of anæmia, and as a rule the more advanced the glandular trouble the greater the impoverishment. The red corpuscles are reduced in numbers one-half or even three-fourths, but never, in my experience, to the extent in pernicious anæmia. The lowest number per cubic millimeter which I have counted was in Case II., when on one occasion the numbers sank to 2,100,000 per c.m. There may be most advanced disease without great anæmia. In one case (IV.) with enormous enlargement of the cervical and axillary gland there were 4,250,000 to the c.m., and during his three weeks' stay in the hospital the numbers were never much reduced. So also in Case III. there was not profound anæmia to within two months of the patient's death.

The red corpuscles are usually uniform in size. I have never seen extreme poikilocytosis, though occasionally the microcytes have been numerous. The colorless corpuscles are not greatly increased, although there may be moderate leucocytosis, as in Case IV., in which the ratio of white to red kept about 1:150. A condition of actual leukæmia may be induced. The corpuscles may be smaller than usual, and present the characters of the blood in lymphatic leukæmia. I have not met with nucleated red corpuscles in any of the cases which I have examined.

The granule-masses of Schultze are in variable numbers.

{925} Cardiac weakness and palpitation are common, due chiefly to the anæmia. The mediastinal growths in some cases cause great embarrassment from pressure. Fatty heart-muscle is an almost constant sequence of the anæmia. The pulse is quickened--80-110, or, if much fever, 120-130. Hæmic murmurs may be heard at the base of the heart, and the venous hum at the root of the neck is often very distinct. Pressure of the tumors upon the nerves may influence the heart's action, and in one case in which sudden death took place it may have been due to interference with the innervation of the heart by pressure on the nerve-trunks.

Respiratory System.--Shortness of breath from the anæmia is common, particularly on exertion. When the tracheal and bronchial glands are affected urgent attacks of dyspnoea may occur and suffocation be induced. Pressure on the pneumogastric or recurrent laryngeal may cause hoarseness or aphonia. The gland-tumors may invade the lung, or there may be secondary growths. These are not usually large enough to induce symptoms. The shortness of breath may be caused by pleuritic effusion, which may be an early symptom and the one for which the patient is sent to hospital (Case X.). It is due to pressure on the azygos and intercostal veins.

Fever is observed in nearly all cases; even in the early stages slight elevation of temperature may be noted. When the disease is firmly established the fever is a marked feature. It may be of an irregular hectic type, with morning remissions--this is, I think, the most common--or it may be continuous, with an evening exacerbation. More rarely there are ague-like paroxysms, with rigor, hot and sweating stage (Case I.), and during these the fever may rise to 104° and glands may become more swollen. The range is never very great, rarely exceeding 103°.

Digestive System.--Difficulty in swallowing may result from the enlargement of the lymph-follicles at the base of the lungs and of the tonsils and pharyngeal adenoid tissue. This may be so great as to necessitate feeding with a tube. There may be early gastric trouble when the mesenteric and abdominal glands are first affected--dyspepsia, nausea, and vomiting. Secondary tumors of the stomach are not common. The loss of appetite and feeble digestion, prominent symptoms in so many cases, are largely due to the anæmia.

Diarrhoea is not met with so frequently as in leukæmia; it may come on toward the close and carry off the patient. New growths in the intestine may produce severe attacks and sometimes hemorrhage. Obstinate constipation may be the result of pressure.

The liver is rarely enlarged, and there are not often hepatic symptoms. The new growths do not produce irregularity in the enlargement. Pressure of enlarged glands at the hilus may cause jaundice and ascites.

Genito-urinary System.--The urine is usually clear and presents no striking changes. Reaction acid; albumen may be present. The testicles may be the seat of secondary growths.

Nervous System.--Headache, giddiness, and noises in the ear are common, and are dependent upon the anæmic state. Southey[153] has noticed delirium and coma in some cases.

[Footnote 153: Barth. Hospital Reports, vol. ix.]

Special Senses.--Deafness is not uncommon, caused by pressure of the large glands in the neck or by the growth of adenoid tissue about the pharynx, closing the Eustachian tube. Inequality of the pupils has been noted, from pressure of a gland on the sympathetic. Retinal hemorrhages are uncommon.

Skin.--There may be definite secondary lymphatic tumors apart from direct infiltration by continuity.[154] Bronzing may occur (Case IV.). Papular rashes may be very troublesome. Subcutaneous oedema of feet and eyelids may occur when the anæmia is very profound.

[Footnote 154: Greenfield, Path. Soc., xxvii.]

{926} MORBID ANATOMY.--The Lymph-glands.--Virchow made the division into the hard and soft varieties, the difference depending on the proportion between the cells and the adenoid reticulum. Where the cells predominate the growth is soft--may be semi-fluctuating--but when the stroma is much hypertrophied the glands are hard, firm, and feel like organs in a state of chronic induration. The great majority of the cases are of the soft variety. When first affected the glands may be hard, and as the development proceeds become less consistent; but there are cases in which they maintain their firmness and solidity throughout.

When examined in the early stage the individual glands are more or less isolated, perhaps not larger than almonds or walnuts, adherent by their capsules, but readily separated and movable. Even when death has been caused, some groups may generally be found in this state, as it is rare for all to be equally developed. When advanced, the glands fuse together, distinction is lost between them, and the bunch may form a large tumor the size of an orange or even a cocoanut. When of moderate size the section may show normal-looking gland-substance, and the distinction between cortical and medullary portions may be well preserved. When much enlarged the section has usually a grayish-white appearance, smooth, and of variable consistence, either firm and dry or soft and juicy. The vascularity is not often marked, and extravasation and areas of congestion are not seen so frequently as in some actively-growing neoplasms of the lymph-glands.

The capsules are thinned, and may disappear in the fusion of contiguous glands, traces being seen on the section as strands of connective tissue. About large groups the capsular tissues may be much condensed, forming a very firm investment. The growth may perforate the capsule and invade contiguous parts--muscle, skin, or the solid organs.

The chief changes which the tumors may undergo are fibroid induration, suppuration, and caseation. The gradual increase of the stroma may give a high degree of density, and the gland on section may present a smooth, glistening appearance. Suppuration is most frequently seen when the growth reaches the skin; it may point and an abscess discharge. In the deep glands the formation of pus is not often met with. Caseation is extremely rare. Hemorrhages may take place from rupture of the thin-walled vessels.

The chief characters of the lesions in the different groups have been dealt with in the section on Symptoms. The superficial glands are most often attacked, and the cervical or axillary may form huge masses before there are any signs of internal trouble. The superficial and deep cervical groups may be uniformly affected, the muscles lifted and wasted, and vessels and trachea surrounded by a solid mass. Sometimes all distinction between the tissues is lost, and the carotids run in the midst of the new growth, which may extend far out beneath the trapezius and down into the chest or over the clavicle on to the outside. When the neck is not primarily affected the groups are more isolated, and can be traced as chains of enlarged glands along the trachea and the carotids continuous with those of the axillæ and mediastinum.

The axillary group is next involved in the order of frequency, and the masses when large grow out under the pectorals and back beneath the scapulæ and high into the fossa, compressing the axillary vessels and causing great swelling of the arm. In Case VII. the growth infiltrated the neighboring muscles and eroded the humerus and neck of the scapula, perforated the blade, and exuded on its outer surface. Though an enormous mass, the vessels were not infiltrated, and only moderately compressed. The inguinal glands when very large may obstruct the femoral artery and vein, and seriously interfere with the circulation in the legs.

{927} Of the internal groups, those of the thorax are most often affected, and we may have the chain in the posterior mediastinum along the aorta and the sides of the trachea and gullet, and along them pass into the neck (Case V.), or the bronchial group may be primarily attacked, with the formation of a great bunch at the fork and numerous small masses along each bronchus at the root of the lung, which may be extensively involved (Case VI.); or those of the anterior mediastinum beneath the sternum may be affected, with the production of large masses extending over the pericardium and passing even to the diaphragm. In these cases bulging of the sternum and ribs, with erosion and perforation, may occur. In Case II. the sternum was completely destroyed to a level with the fourth rib. The heart may be pushed aside and the aorta and its branches completely surrounded by growths (Cases II. and VI.). It is remarkable in these cases that great vessels do not suffer more from compression. When the abdominal glands are involved, the retro-peritoneal are most frequently enlarged, and form a continuous chain from the diaphragm to the internal rings on either side of the aorta and its branches, extending into the pelvis. Pressure effects are not common, but they may compress the ureter, causing hydronephrosis, the sacral and lumbar nerves, the iliac veins, and, as in the case I mentioned, may adhere to the broad ligaments and uterus in such a way as to deceive the most skilled gynæcologist. The mesenteric glands may present slight enlargement, but in my experience they are but little affected, even when the retro-peritoneal are of large size. When the glands at the portal fissure are involved they may compress the vein and duct. Phelps of Chateaugay, N.Y., sent me a specimen in which the glands of this region formed two huge masses the size of cocoanuts, and, so far as I could ascertain, they were primary lympho-adenomatous growths. The possibility of ovarian disease had been discussed by several consultants.

The chief change is an increase of the cells with or without thickening of the reticulum. The cells correspond to ordinary lymph-corpuscles; some may be a little larger, with darker granules and more pronounced nuclei. Giant cells are frequently met with, more often in the small glands. I have not seen them in the large soft tumors. In the early stage there may be simple hyperplasia and the relations of the lymph-paths are maintained, but when the glands are much developed the normal arrangement is disturbed and they cannot be injected. The reticulum varies much; in the very soft form it is expanded and can scarcely be found; the substance may be semi-diffluent. The firmer the structure the more evident is it, and in the hard forms the network of fibres in whose meshes the cells are enclosed can be distinctly seen and by pencilling very clearly brought out. It is not merely a thickening of pre-existing fibres, but probably there is a new development of adenoid tissue. In some cases of advanced fibroid change very few cells can be seen. The vessels passing to the glands are sometimes dilated.

Spleen.--In about 75 per cent. this organ is hypertrophied or presents lymphoid growths (Gowers). The enlargement is not often great, rarely approximating the colossal size of the leukæmic organ. It is due to either simple hyperplasia or to the presence of the new growths, sometimes to both. In the 75 cases of enlarged spleen new growths occurred in 56 (Gowers). Of the 38 cases in Hutchinson's table, 27 presented the splenic tumors. These are grayish-white bodies, ranging in size from a small pea to a walnut or larger, scattered irregularly through the substance, usually rounded in outline, but in some instances irregularly shaped. They contrast by color strongly with the red spleen-pulp. The numbers may vary from one or two to many dozens, the spleen-substance being a mere remnant between them. These masses often resemble the lymph-glands in appearance and consistence. {928} They are not encapsulated, but in immediate contact with the spleen-tissue. They originate from the Malpighian corpuscles, and may be regarded as the enlarged and developed lymph-elements in the spleen. The larger ones probably arise from the fusion of several small ones. When uniform in size and scattered throughout the organ, they may resemble coarse tubercles, but the absence of any caseation may serve to distinguish them. Their histological characters are those of the glands, lymph-corpuscles in a fibrous reticulum; the consistence depends on the preponderating element.

Amyloid degeneration was found by Gowers in two cases in the growths.

The thymus has been found involved in the mediastinal growths, and is occasionally affected primarily. The thyroid may be attacked by the cervical tumors.

The suprarenals may contain secondary growths. In Case VII. both were extensively involved.

The medulla of the long bones has been found converted into red lymphoid marrow, and in a few instances into the pyoid variety met with in leukæmia. It has been found normal in other cases.

Digestive System.--In the mouth and pharynx the lymphatic elements are very commonly affected when the cervical glands are enlarged, sometimes independently. The tonsils may form large masses, and with the follicles at the root of the tongue and at the pharynx produce great obstruction. Sloughing may occur. In the gullet and stomach secondary tumors have occasionally been seen. In Case VII. there was a flat elevated mass at the cardia beginning to ulcerate.

The small intestines may be extensively involved; the glands of Peyer enlarged and even ulcerated. In Case VII. there were over twenty ulcers in the jejunum and ileum, ranging in size from a split pea to a bean, edges elevated and indurated and the bases sloughing. The large intestines may be secondarily affected, the intertubular adenoid tissue be greatly developed and compress the crypts of Lieberkühn, and lead to thickening of the mucosa.

The liver is often enlarged, and presents scattered lymphoid tumors, rarely larger than a pea, of a white or yellow-white color, and may be readily mistaken for tubercles. They are most common beneath the capsule and in the interlobular tissue. A diffuse interacinous growth may also occur. Cirrhosis has been observed in the vicinity of the growths, and fatty degeneration.

The pancreas may be the seat of secondary masses.

Genito-urinary System.--The kidneys are very often the seat of new growths, usually small and of a character similar to those in the spleen and liver. When the disease is very rapid the tumors may be large and very vascular. The texture of the kidney is usually soft, and parenchymatous change is common. The testicles may also be the seat of adenoid growths; this was the case in one of Hodgkin's patients.

The Respiratory System.--Growths in the trachea are rare. The lungs are frequently affected, either by the direct invasion at the root from the bronchial glands (Case V.), or by numerous scattered nodules through the substance. They develop about the bronchi, and may reach the size of marbles. Intense bronchitis, oedema, and congestion may be secondary changes induced by pressure on the bronchi or trachea.

The serous membranes occasionally present lymphoid growths. Pleural effusion is not uncommon.

The heart presents no very constant changes. When the anæmia is profound it may be very fatty. It may be compressed by mediastinal growths, and has been found much atrophied. Lymphoid growths may occur in it.

The Nervous System.--The brain itself is rarely affected, but growths have been found in the dura mater. In Case VI. a secondary mass compressed the spinal cord, as in Hutchinson's case, producing paraplegia.

{929} The skin may be the seat of adenoid growths, as in Greenfield's case.[155] The growing tumors may involve it (Case IV.), and ulceration may occur.

[Footnote 155: Loc. cit.]

COURSE, DURATION, AND TERMINATION.--Trousseau and other French writers have divided the disease into different stages--the latent and period of early development, the period of generalization, and the cachectic state; but the course of the disease is very variable, and depends much upon the position of the glandular enlargements, the rapidity of development of secondary growths, and also the constitutional peculiarities of the patient. Early and rapid growth in the mediastinal groups may produce pressure effects, and cause death before any marked anæmia--much less cachexia or the development of secondary masses in important organs, as the cord, may prove quickly fatal. In some cases the glandular enlargement rapidly spreads, and group after group is involved in the space of a few months; in others there may be hyperplasia of a single set, as the cervical on one side, for months, or even years, before the glands on the other side or in other regions become involved. The most acute cases may run a course in three or four months, the most chronic in as many years. Periods of quiescence are not uncommon, and the tumors may not only cease to grow, but actually diminish, or even disappear in a region, and this without any special treatment.

The mode of death is commonly by asthenia; cachexia is gradually developed, the anæmia becomes more profound, and finally, with local or even general dropsy, the end comes from heart failure. Very frequently the patient is cut off before grave constitutional disturbance is established, particularly by asphyxia from the pressure of enlarged glands on the trachea and bronchi or occlusion of the pharynx. Hemorrhage and diarrhoea, such common symptoms in leukæmia, are rarely seen. Coma has been the cause of death in a few cases. Oedema of the lungs, pneumonia, extensive pleuritic effusions, may hasten, and in some instances cause, the fatal result.

The DIAGNOSIS is in most cases easy; in others time alone will decide the true nature of the glandular enlargement. Of the chronic forms of adenitis which are liable to be confounded, the scrofulous is the most common. The points to be attended to in the diagnosis are--the age; scrofulous glands affecting chiefly the young and individuals presenting other signs of the so-called scrofulous habit, or there may be a well-marked family history of phthisis. In the question of age, however, it is to be remembered that there is a condition known as adult or senile scrofula, in which there may be general enlargement of the glands. Of all groups the cervical are most frequently involved in scrofula, and the submaxillary set more often than those of the anterior and posterior triangles, while in Hodgkin's disease the latter are usually affected first. The enlargement in scrofula is rapid at first, and may last for years in a group without extending; the bunches are often, even when small, welded together, and, most important of all, they tend to suppurate--a feature scarcely ever seen in true lymphadenosis. Size is an uncertain criterion. I have seen masses of scrofulous glands in the neck as large as two fists and without suppuration. A single large bunch in the neck, particularly if submaxillary, persisting for over a year or eighteen months without involvement, however slight, of the glands in the same or the opposite side or in the axillæ, is almost certainly not malignant lymphoma. On the other hand, a group of slowly-enlarging glands in the anterior cervical triangle, with gradual affection of those of the opposite side of the axillæ, particularly if in a person between twenty and thirty and becoming anæmic, would render the suspicion of Hodgkin's disease strongly probable.

In connection with this it may be mentioned that occasionally in acute {930} phthisis there may be great swelling of the glands, from a growth of miliary tubercles in them. A case of the kind was admitted into my wards in the General Hospital, Montreal: a man aged twenty-four, with great swelling of the cervical glands in both sides, tonsillitis, and sloughing pharyngitis, irregular fever, and diarrhoea, and for a time the case was believed to be one of Hodgkin's disease.

PATHOLOGY.--Local benign lymphomata occur, identical in histological characters with the tumors of Hodgkin's disease, and differing only in the absence of any tendency to extend in the neighborhood or to generalize. They are not uncommon about the neck, may grow slowly, and last for years.

The lymphatic growths of leukæmia are not in any essential particular different from those of Hodgkin's disease, and the diagnosis rests upon the examination of the blood. There are, however, certain broad differences when any considerable number of cases of the two diseases are compared. Thus the lymphatic element in leukæmia is less pronounced, the splenic and medullary forms predominate; in Hodgkin's disease exactly the reverse prevails. It is rare in leukæmia for the internal glands to be much involved, and patients do not often die from the pressure effects of the tumors. The hemorrhages so common in leukæmia, and the diarrhoea, are rare symptoms. The bone-marrow is more generally affected, and, lastly, the tendency to generalize seems greater in the growths of Hodgkin's disease.

From other forms of malignant growths in the lymph-glands there may be difficulty in the diagnosis, and even a microscopical examination may not serve to make the distinction.

Thus there is a true lympho-sarcoma, a small-celled growth of the lymph-glands, which must be distinguished, though it is hard in some cases, from the general lymphadenoma. The distinctions laid down by some writers, such as a special tendency to attack contiguous parts, and a more general distribution of the metastatic growths, will not hold, as we have seen that cases of lymphadenosis or Hodgkin's disease may attack neighboring structures, and the secondary tumors, though preferably in lymphatic textures, may occur in every organ. In the retro-peritoneum, for example, true lympho-sarcoma is not uncommon, forming large tumors which may press forward the viscera and produce a very prominent mass in the abdomen. They are not uncommon in children, and with renal sarcomas make up three-fourths of the abdominal growths of early life. But they may occur in adults and attain large size, involving adjacent organs, such as the kidneys, or, as in a case I saw a short time since, grow into the colon and cause death by gradual hemorrhage. These are local growths as regards the lymphatic system, not involving distant glands, and not often, indeed, producing metastasis.

We may recognize in the lymphatic glands--1st, the local benign growth which seems nothing more than hypertrophy, lymphadenoma, and which may persist for years; 2d, a local malignant growth, lympho-sarcoma, which invades contiguous structures and may be followed by metastasis, but there is not general involvement of the lymphatic tissues; and 3d, there is a generalized lymphoma involving groups of glands in succession, and the adenoid tissue throughout the body, usually accompanied by anæmia alone, in which case we term it Hodgkin's disease--sometimes by an excess of colorless corpuscles as well, when we call the affection lymphatic leukæmia.

PROGNOSIS.--When established sufficiently to make a sure diagnosis, the prognosis is in the great majority of cases bad; true examples of the disease rarely if ever recover. A hopeful prognosis may be given in those cases in which only a few glands are involved, and where there is any suspicion of a scrofulous habit or where the enlargement has persisted for years without {931} extending. The presence of profound anæmia, the existence of swelling in distant groups and in internal glands, are grave indications. High, irregular fever, rapid growth, and the development of cachexia are symptoms of the full establishment of the disease. The physician must not be deceived by intervals of improvement, with perhaps subsidence of the glandular swelling in places. Such breaks in the onward progress are not uncommon.

TREATMENT.--When small and localized, the question of the removal of the glands may be raised. If they persist after appropriate remedies, and if there is not grave anæmia, and other groups and the spleen are not affected, excision should certainly be performed. Circumscribed lymphadenoma, particularly of the neck, may exist for years before the glands in other regions become involved; and in such cases removal affords the best guarantee that the disease will not extend.

Local applications are of doubtful benefit. I have never seen any permanent improvement follow the persistent use of iodine, biniodide of mercury ointment, or friction with oil. Galvano-puncture has not been successful, and the same may be said of the various substances injected into the glands--iodine, arsenic, chromic acid, etc.

Internally, iodine and iodide of potassium have been extensively used, but without much benefit. Quinine, iron, and cod-liver oil are useful as tonics, but have no influence on the size of the tumors. Arsenic is the only medicine which has seemed to me of positive value, and under its use I have seen the gland-tumors decrease greatly in size. It should be given in increasing doses until some of the unpleasant effects of the drug are manifested, when a return should be made to a small dose, and again gradually increase. When well borne, large doses, 20 or 25 minims, of the liquor arsenicalis should be taken three times a day for many weeks. In two cases with moderate enlargement of the cervical and axillary glands the progress of the disease seemed arrested, and the glands certainly became smaller and softer. In the history of these cases the patients will often speak of changes in the volume of the gland quite uninfluenced by any treatment; and these fluctuations must be taken into account in estimating the value of a drug; but, making due allowance for this, the beneficial effects of the arsenic are unquestionable when given early in large doses and the administration kept up for months. Many recent writers have borne testimony to this, among them Karewski,[156] who reports three recoveries.

[Footnote 156: Berl. klin. Wochenschrift, 1884, 17 and 18.]

Phosphorus has been of service in the hands of Gowers and Broadbent, and when arsenic is not well borne it should be tried.

Change of air and scene has benefited some cases. The patient's strength must be supported by every possible means; fortunately, gastro-intestinal disturbance is not so marked as in leukæmia, and even with most extensive and progressive enlargement of many groups of glands the appetite may be good and the digestion excellent.

When the glands of the neck compress the trachea, or when the lymphoid elements of the tonsils and pharynx obstruct the orifice of the glottis, tracheotomy may be necessary.

HÆMOPHILIA.

DEFINITION.--An hereditary or congenital fault of constitution, characterized by a tendency to bleeding, spontaneous or traumatic, and often associated with swelling of the joints.

{932} SYNONYMS.--Hæmatophilia; Hereditary hæmorrhage; Hæmorrhagic diathesis; Idiosyncrasia hæmorrhagica. Ger. Bluterkrankheit, Blutsucht; Fr. Hémophilie. The term bleeder is applied to a patient.

CLASSIFICATION.--In this article the congenital or hereditary disease will alone be considered, to the exclusion of cases of transient hemorrhagic diathesis, the hemorrhages of scurvy, fevers, anæmia, purpura simplex, and purpura hæmorrhagica.

HISTORY.--So far as is known, the classical writers make no mention of the disease, though in the Pharsalia of Lucan there is a passage, quoted by Legg,[157] which well describes the hemorrhagic diathesis. The first positive reference is in the writings of Alzaharvi, a physician of Cordova who died in 1107 A.D. A doubtful case is mentioned by Benedictus in 1539, who relates the history of a barber who bled to death from slight wounds of the nose caused by clipping the hairs. Hochstetter described a case in 1674 to which Virchow has called attention.[158] Legg[159] found a well-recorded case by Banyer in the Philosophical Transactions (1743). Fordyce in 1784 described a Northamptonshire family the members of which suffered from hemorrhages.[160] With brief references to the disease by two German writers in 1793 and 1798, these scanty materials comprise the facts known at the beginning of this century.

[Footnote 157: Hæmophilia, London, 1872.]

[Footnote 158: Virchow's Archiv, Bd. xxviii.]

[Footnote 159: Loc. cit.]

[Footnote 160: Fragmenta Chirurgica et Medica, London, 1784.]

To American physicians belongs the credit of the full recognition and description of the disease and the discovery of its remarkable hereditary nature.

Otto[161] gave an account of a New England family members of which had been bleeders for several generations. He also referred to a Maryland family observed by Rush. Otto appears to have been the first to note the immunity of females in bleeder families, and their tendency to transmit the disposition. In the Philadelphia Medical Museum, vol. i., 1805, a letter of E. H. Smith is published, written in 1794, in which he gives an account of a boy affected with the disease. Hay[162] reported the Appleton-Swain families of Reading--one of the most remarkable histories ever published of the disease. In 1817 the Buel Brothers described the Collins family,[163] and Coates[164] a family in Delaware county, Pa. Hughes[165] and Gould[166] also described notable examples. Holton, Harris, and Dunn have studied other American bleeder families, and a brief record of the local literature of the subject will be found at the end of this article.

[Footnote 161: Medical Repository, New York, 1803, vol. vi.]

[Footnote 162: New England Medical Journal, 1813, vol. ii.]

[Footnote 163: Transactions of the Medical and Physical Society of New York, 1817.]

[Footnote 164: North American Medical and Surgical Journal, Philada., vol. vi., 1828.]

[Footnote 165: Transylvania Journal, 1831, vol. iv., and American Journal Med. Sciences, 1833, vol. xxi.]

[Footnote 166: Boston Medical and Surgical Journal, 1857.]

In Germany, Nasse (1820), Rieken (1829), Schönlein, Canstatt, Wachsmuth, Lange, Virchow, and others added greatly to our knowledge of the disease. Grandidier published a monograph in 1855, a new edition of which in 1877[167] contains a most exhaustive account of the disease and a statistical résumé of all cases to date. In England the disease has not attracted much attention. Legg published an important monograph in 1872, and many papers of value are scattered through the Transactions and journals.

[Footnote 167: Die Hämophilie, Leipzig, Zweite Auflage, 1877.]

In France the articles in the encyclopedias and a few theses--of which Gavoy's (1861) and Simon's (1874) are the most important--comprise the chief literature.

ETIOLOGY.--The disposition is, in the majority of cases, hereditary, but there may be a spontaneous origin, the disease appearing in the child of a family in which no previous cases had occurred. Nothing is known of the {933} conditions under which the disease may thus arise in a healthy stock. Many of such cases die early, but others live and may become the starting-points of new bleeder families. In the history of sixty families Grandidier[168] found statements of this mode of origin of the affection.

[Footnote 168: Op. cit., p. 136.]

The two most interesting features in the etiology relate to sex and heredity. The disease is much more common in males than females, the proportion being variously estimated at 11 to 1, or even 13 to 1. In 64 bleeder families, in 5 were sons and daughters alike affected; in 27 all the sons were bleeders; and in 6 of these there were no daughters.

There is no disease with so marked a tendency to transmission, and it may appear in four or five generations in succession. In the Appleton-Swain family of Reading, Mass., there have been cases since the early part of the last century, and F. F. Brown of that town writes me that cases still occur in the descendants.[169] Legg gives a chart of the Clitherow family, in which it has existed for the past two hundred years.[170]

[Footnote 169: The last case Brown has been able to ascertain was in a lad, Warren Coburn, aged seventeen, who died about twelve years ago. His mother's brother was a bleeder, and died of hemorrhage from a slight scalp wound after having been brought to death's door on three or four other occasions by trivial wounds. Mrs. Coburn was a daughter of Daniel Hart, whose wife was a Norton. Her mother was a Bacheller and a granddaughter of Oliver Appleton's daughter. This lad is an instance of the transmission of the disposition to the seventh generation within a period of two hundred years. Brown further states that there do not appear to be in the vicinity of Reading any Appleton or Swain families in which bleeders exist. As the tendency is chiefly transmitted through the female members of a family, who lose the patronymic by marriage, it is often difficult to trace the relationship. I think if we had fuller genealogical details we should find that several of the bleeder families now thought to be distinct belonged to the same stock.]

[Footnote 170: St. Barth. Hospital Reports, 1881.]

YEATON. | +----------+-------------+---------+---------+----------+ | | | | | | Son, bleeder. Daughter. Daughter. Daughter. Daughter. Daughter. | | | | | | | | | | +----------+-----+ | | | | | | | | | | Son, bleeder. Three daughters. | | | | | | | | | Son, bleeder. | | | | | | | | +------------+-----------+ | | | | | | | | | Son, bleeder. Daughter; Daughter. | | | children not bleeders. | | | | | | +-----------+-----------------+----+ | | | | | | | Son, bleeder. Daughter. Daughter. | | | | | | Son, bleeder. +-----+-----+ | | | | | | One son Four daughters. | | bled to death. | | | | +-----------+----------+----------+----------+ | | | | | | Son, bleeder. Daughter. Daughter. Daughter. | | | | | Twin boys, Son, not Son, not | bleeders. a bleeder. a bleeder. | | +--------------+-----------+----+ | | | Son, bleeder. Son, bleeder. Daughter.

In the celebrated bleeder families of Tenna, Switzerland, five generations have been affected. The modes of transmission are as follows: (1) Father {934} to son, grandson, etc. This is rare, but instances are on record. (2) Father not a bleeder, but of bleeder stock, transmits the tendency to son--very uncommon. (3) Father to daughter, granddaughter, etc.--not common. The daughters of a bleeder are usually free, though their brothers may be affected. (4) Mother a bleeder, transmits to sons and daughters. (5) Mother not a bleeder, but daughter of one, transmits to her sons, the daughters remaining free, but their sons affected. This is the most common mode of inheritance. Atavism by transmission through the female line is almost the rule, and the daughters of a bleeder, though healthy and free from any tendency, are almost certain to transmit the disposition to their male offspring. The 657 cases analyzed by Grandidier occurred in two hundred families. The chief facts of heredity are well illustrated by the preceding chart of the Yeaton family, given by Gould in the Boston Medical and Surgical Journal, 1857.

The Anglo-Germanic nations appear especially prone to the disease. Of 194 families in Grandidier's table, 154 were of the Teutonic stock. Records of the disease among the Latin races are rare. Jews are probably not more liable than other people, but the rite of circumcision gives an unusual opportunity for its manifestation at an early age.

The age at which the bleeding tendency first appears was determined by Grandidier in 113 cases as follows: in 63 during the first year; in 17 during the second, and up to the end of the second year in 93. It is rare for the first manifestation to occur after the twelfth year, and there was only one case in which the first bleeding appeared after the fifteenth year.

The constitution and temperament of bleeders, about which the older writers had much to say, probably present no peculiar characteristics. Some persons claim to be able to recognize bleeders even before they have manifested any tendency to hemorrhage. They are usually fresh, healthy-looking persons, with fine, soft skins, through which the superficial veins may show with more than usual distinctness. A division of cases into erethetic and atonic forms has been made by Wachsmuth and Grandidier. The mental activity of bleeders has been noted to be above the average, due, doubtless, to the fact that the liability to bleed from slight blows and cuts has made sedentary and studious habits preferred to out-of-door employments and amusements.

Families in all conditions of life are affected. Much interest was excited in the disease in England from the fact that the late Prince Leopold was a sufferer.

Climate appears to have an influence in determining attacks. Cold, damp, changeable weather is favorable, while a residence in a warm, equable climate diminishes the tendency in a very marked manner. Some patients have an extraordinary susceptibility to changes in the weather.

All observers have noted the great fertility of bleeder families. Those first born seem less liable to bleed than subsequent ones.

SYMPTOMS.--The existence of the defect of constitution may not be suspected until an uncontrollable hemorrhage follows some trivial injury or operation, or a spontaneous bleeding may occur and present great or insuperable difficulties in its arrest. The symptoms usually occur in the first years of life, and in the great majority of cases, as mentioned above, the first bleeding occurs before the fifth year. The symptoms may be grouped under three divisions (Legg, Grandidier): external bleedings, spontaneous and traumatic; interstitial bleedings, petechiæ, and ecchymoses; and the joint affections. Legg recognizes three grades of the disease. The first and most severe is characterized by bleedings of every kind, external and internal, and by troublesome joint affections: this form is most often seen in men. The second grade is less severe; there are spontaneous hemorrhages from the mucous surfaces, but no traumatic bleeding or ecchymoses and no joint {935} troubles: this form is most often seen in women. The third and lowest degree is when there is a tendency simply to ecchymoses; no dangerous bleedings occur: this form is often seen in members of bleeder families, and if in women the menstruation may be early and profuse.

External Bleedings.--The spontaneous bleedings may occur from the skin, the mucous, and in rare instances the serous, membranes. There are frequently preliminary symptoms--prodromata--such as flushing, fulness of the head, and throbbing of the arteries--signs of so-called plethora; often there is irritability of temper, but sometimes, in children, extra cheerfulness has been observed. The localities affected and the frequency are shown by the following analysis of 334 cases by Grandidier: Epistaxis, 169 times; from the mouth, 43; stomach, 15; bowels, 36; urethra, 16; lungs, 17; cerebral hemorrhage, 2; skin of head, 4; tongue and finger-tips, 4 each; tear-papilla, 3; eyelids, 2; external ear, 5; female generative organs, 10; ulcer of skin, 2; navel (long healed), 2. An odd situation for spontaneous bleeding is mentioned by Townsend,[171] in which a child bled to death from the scrotum. In many cases these spontaneous hemorrhages prove fatal--most frequently the epistaxis. The traumatic bleeding may result from blows, cuts, scratches, etc., and the blood may be effused into the tissues or discharged externally. Fatal hemorrhages have occurred from the following wounds: blow on head, 11 times; slight scratches on skin or abrasion of dermis; laceration of the frænum of the lip, slight cut (two lines deep) in a duel wound; bite of the tongue (7 cases); fall on the mouth; blow on the nose; blow of a stone on the finger; cut in paring the nail; fall on the head with meningeal hemorrhage (2 cases, brothers); and rupture of the hymen on the wedding-night.

[Footnote 171: Boston Med. and Surg. Journal, lv.]

After operations, trivial and severe, many fatal cases have occurred, and the statistics of the same author give the following: cutting of the frænum linguæ, 1; leeching, 5; venesection, 4; blister, 2; extraction of tooth, 12; circumcision, 8; cutting umbilical cord, 4; vaccination, 2; fistula, stone, ligation of carotid, of radial, of ulnar, of femoral arteries, amputation of arm and of thigh, 1 each; phimosis, 2. Leeching, extraction of teeth, and circumcision are most dangerous operations in bleeders.

The bleeding is always a capillary oozing, and the vessels are not seen. It may last for hours, or even many days and weeks, and the amount of blood lost may be enormous. Epistaxis may be fatal in twenty-four hours. In Coates' case a medical student lost half a gallon of blood in twenty-four hours, and in the ten days which the bleeding continued it was estimated that he lost about three gallons.

The healing of a wound in a bleeder may take place rapidly, either with or without suppuration. When the hemorrhage is large or prolonged, severe anæmia follows, from which, as a rule, the patients recover with remarkable rapidity.

The interstitial hemorrhages--petechiæ, ecchymoses, hæmatoma--may be spontaneous or the result of injuries. The petechiæ occur most frequently in the skin, particularly of parts distant from the heart--the legs and arms, less often the face. On the mucous and serous surfaces they are less common. They resemble ordinary purpuric spots, and crops may come out with symptoms of swelling and pain in the joints. Large extravasations--hæmatoma--are most frequently of traumatic origin and may follow the slightest blow, as in a case of Sir Wm. Jenner's, in which from the fall of a rubber ball on the thigh an enormous extravasation took place between the knee and trochanter.[172] They are blue, black, or reddish-black at first, and in their absorption go through the various changes in color which we notice in a bruise. These blood-tumors may occasionally arise spontaneously.

[Footnote 172: Legg, etc., p. 68.]

The arthritic affections in hæmophilia are very remarkable, and so {936} common as to form prominent features in the disease. There may be simple pain in and about the joints, or swelling with redness and signs of intense inflammation. The attacks may come on suddenly with fever, resembling closely acute rheumatism. The large joints are usually affected, the knees most often, then the elbows, ankles, and shoulders. There may be repeated attacks, and at last great crippling and deformity. The small joints are rarely affected. In cold, damp weather the attacks are most common; occasionally they follow traumatism. In addition to the joint troubles, bleeders suffer much with irregular pains in the limbs, particularly during change of weather, or these pains with arthritis may usher in an attack of hemorrhage.

Many other irregular symptoms are described in the monographs, some of which have no intimate relation with the disease. The anæmia has, of course, all the features of the traumatic form. Digestive troubles, after the bleeding, are common, and are due to the anæmia. The Buel Brothers[173] mention that in two of their cases the patients showed a marked inclination to eat sand and earth. Children with the hemorrhagic tendency pass through the ordinary diseases of infancy like others. Whooping cough is very liable to cause epistaxis. Rheumatism and scrofula are said to be common in bleeder families.

[Footnote 173: Op. cit.]

The blood in bleeder cases is, as a rule, normal, so far as our present means of investigation enable us to decide. When a hemorrhage has continued for some time, it is thin and watery, but at the beginning of the bleeding the blood is usually rich in corpuscles and fibrin and coagulates firmly. The salts have been found increased in quantity. No change has been noted in the corpuscles, the number of which is stated by several observers to be increased. Prior to a hemorrhage there may be, according to some writers, a state of plethora or increase in the total quantity of blood, and the tolerance of the loss, so much greater in bleeders than in ordinary persons, is adduced in support of this view.

MORBID ANATOMY.--Not many changes other than those of profound anæmia have been found in the bodies of bleeders. An unusual thinness of the walls of the vessels, first noted by Bladgen in 1817,[174] has been met with in a number of cases; in a few instances hypertrophy of the heart; in others a rounded foetal shape of the organ. Within the past few years careful microscopical examination has been made of the tissues and blood-vessels of bleeders. Kidd[175] found degeneration of the muscle-fibres of the middle coat of the arteries, and the endothelium of the small arteries, veins, and capillaries was swollen, proliferated, and some of the small veins were blocked with the products. Legg[176] reports a case in which Klein made a most careful examination with negative results, and he stated that of six such examinations which had heretofore been made, in only one case (Kidd's) were important changes found. At the same meeting of the London Pathological Society, Theodore Ackland also reported a case with negative results as regards histological changes.

[Footnote 174: Medico-Chirur. Transactions.]

[Footnote 175: Medico-Chirurgical Society's Transactions, vol. lxi.]

[Footnote 176: Lancet, Oct. 27, 1884.]

The joint changes have been studied in a number of cases. Hemorrhage has been found in and about the capsule, and the acute swelling may be due largely to it, as was shown in Hutchinson's case,[177] in which he aspirated the joint. When it lasts any time, there is great staining of the cartilages and discoloration. There may be inflammation of the synovial fringes and erosion and destruction of the articular surfaces (Legg).

[Footnote 177: Trans. State Med. Soc. N.Y., 1877.]

The PATHOLOGY of the disease is unknown. No doubt two circumstances combine in hæmophilia--congenital fragibility of the vessels and a defect in coagulability of the blood--but whereon these depend we are as yet entirely ignorant. There is no evidence of the nature of the anatomical changes in {937} the vessels which permits of their ready laceration, and none on the nature of the alteration of the blood which prevents the normal thrombus formation in a wound; and in the absence of information on these points theories must necessarily be unsatisfactory, and their discussion, in a work of this practical nature, profitless.

The DIAGNOSIS presents no difficulty in members of a bleeder family, in whom slight joint trouble and petechiæ are as much manifestations of the disease as the more severe hemorrhages. In a large majority of cases the tendency becomes manifest at an early date. The spontaneous umbilical hemorrhages of infants are, as a rule, to be excluded, being dependent upon, or associated with, jaundice or syphilis or a mycosis (Weigert[178]). The hemorrhagic diathesis may develop in children or members of a healthy family and prove fatal, and the question in such cases always comes up, Are they instances of hæmophilia? There seems to be a desire to limit this term to cases of an hereditary nature only; but when a child shows a marked tendency to multiple hemorrhages, spontaneous or traumatic, which tendency persists and is not merely transitory, and particularly if there are joint troubles, I think that under these circumstances we have a genuine case of hæmophilia; and such a child, if he--it is more likely to be a male--survives and marries, may be the founder of a bleeder family. These are the congenital in contradistinction to the hereditary cases. In the histories of the bleeder families we frequently come back to the origin in a person born of a healthy stock in which there have been no hemorrhagic tendencies. On the other hand, single severe uncontrollable hemorrhages in children or adults are not to be ranked as hæmophilia unless there have been other features pointing to the existence of the diathesis. The literature abounds in cases of this kind, many of which are described as hæmophilia. In doubtful cases it is very difficult to decide, as in a case of Forscheimer brought before the Academy of Medicine of Cincinnati.[179] In the review of American literature we have excluded all cases in which the hereditary or congenital characters were not well marked.

[Footnote 178: Cohnheim's Pathologie, i. 382.]

[Footnote 179: Cincinnati Lancet and Clinic, 1884.]

It may be useful to put down here for the guidance of the practitioner the varieties of bleeding commonly met with, and which must not be confounded with hæmophilia:

(1) The umbilical hemorrhages of infants, due to jaundice or to syphilis hæmorrhagica neonatorum, etc.

(2) Purpura simplex, seen often in debilitated, rarely in healthy, children, usually confined to the legs, and in some cases I have seen it associated with rheumatic pains or swellings in the knees and ankles.

(3) Peliosis rheumatica, an affection which in the large interstitial hemorrhages and the joint swellings touches hæmophilia in a curious way. It too may show itself in several members of the same family.

(4) Purpura hæmorrhagica, Morbus maculosus Werlhöfii, a grave disease, characterized by extensive cutaneous ecchymoses, mucous hemorrhages, but not dependent on any local disease, or, so far as is known, on any specific poison. The bleedings in scurvy may be mentioned here, but there could be little difficulty in determining their nature.

(5) Infective purpura, due to the action of some specific poison--small-pox, measles, scarlet fever, cerebro-spinal fever, etc. The hemorrhages may be cutaneous and trivial, or may be in the most aggravated form of interstitial and mucous bleedings, as seen, for example, in black small-pox.

(6) Toxic purpura, as in snake-bites and many poisons, such as phosphorus.

(7) Simple hemorrhagic diathesis, under which may be included those cases in which, without any hereditary disposition or previous hemorrhagic history, there is a tendency to uncontrollable hemorrhage from a slight wound.

{938} (8) Hæmatidrosis, bloody sweats, which occur usually in hysterical or epileptic females, and are in rare instances accompanied with mucous hemorrhages.

In considering the PROGNOSIS it is well to remember that the patients rarely die in the first bleeding. The younger the individual the worse is the outlook. As above stated, the attacks are most frequent under five years of age, and of 152 boys the subject of the disease, 81 died before the termination of the seventh year (Grandidier). Legg, however, states that it is rarely fatal in the first year. The longer a bleeder lives, the greater the chance of his outlasting the tendency; but that it may persist to the end of a long life, and then prove fatal, is shown by the case of old Oliver Appleton, the first recorded American bleeder, who died at an advanced age of hemorrhage from a bedsore and from the urethra. A bleeder may have years of existence, in which the tendency seems lessened or even absent. The prognosis is always worse in a boy than in a girl. In the latter menstruation is sometimes early and excessive, but, happily, in the female members of hæmophilic families neither this function nor the act of parturition bring with them special dangers.

TREATMENT.--The prophylaxis is all-important. The members of a bleeder family, particularly the boys, must be guarded from injury as much as possible, and operations of all kinds must be avoided, except when life itself is in jeopardy. The extraction of a tooth should be absolutely prohibited. Occupations must be sought which will give the least possible risk of injury. Daughters of bleeder families should not be permitted to marry, as it is through them that the tendency is chiefly propagated, and, even if not bleeders themselves, some of their male children are certain to be affected. The question of the marriage of male bleeders is more difficult to decide, but in any case where the tendency is marked it should be prohibited.

When an injury or wound has occurred, absolute rest, cleansing the wound, and compression should first be tried. If in a favorable locality pressure on the artery may be employed, failing in this, the various styptics may be used. In epistaxis, ice, tannin, and gallic acid may be tried before plugging.

Internally, ergot seems to have been of use in several cases. Otto[180] speaks of the value of sulphate of soda in purgative doses. The perchloride of iron, 30-40 minim doses, every two hours, is advised by Legg, with a purge of sulphate of soda if there is no bleeding from the bowels. Venesection has been resorted to in several instances. Transfusion has been employed, but without benefit. The diet should be light and supporting. After the attacks the patients should take iron and cod-liver oil until the health seems restored. When possible, a residence in the South during the winter is advisable, as most cases are aggravated by the cold weather, and in any case care must be taken to protect patients against cold and wet.

[Footnote 180: Loc. cit.]

The joint troubles must be treated on general principles.

AMERICAN LITERATURE OF HÆMOPHILIA.

Buel: Transact. of the Med.-Physic. Society of New York, vol. i., 1817; 1 F., 4 cases.

Coates: North Am. Med. and Surgical Journal, Philada., 1828, vi. p. 37; 1 F., 5 cases.

Dunn: Am. Journal Med. Sciences, 1883, vol. lxxxv. p. 68; 4 F.

Felt: History of Ipswich, 1834--Appleton family referred to.

Gould: Boston Med. and Surgical Journal, 1857, p. 500; 1 F., 11 cases.

Harris: Philada. Med. Times, 1872; 2 F., 7 cases.

Hay: New England Journal of Med. and Surgery, 1813, vol. ii. p. 221; 1 F., 15 or 16 cases (accurate number rather difficult to make out).

{939} Holton: Am. Journal of Med. Sciences, April, 1874; 1 F., 7 cases.

Hughes: Transylvania Med. Journal, 1831, vol. iv. p. 518, and Am. Journal Med. Sciences, 1833, vol. xxi. p. 543; 1 F., many cases.

Hutchinson: Trans. State Med. Society of New York, 1877, p. 208.

Otto: Medical Repository, 1803, vol. vi.; 3 F., 8 cases.

Pepper: Philada. Med. Times, 1881, vol. xii. p. 109; 1 case--Lancaster county family described by Dunn.

Sewell: Med. Chronicle, Montreal, 1857, vol. iv.; 2 F., 4 or 5 cases.

Smith: Philadelphia Medical Museum, 1801, vol. i. p. 284.

Traneus: St. Louis Med. and Surgical Journal, 1870, p. 535; 1 F., 4 cases.

Townsend: Boston Med. and Surgical Journal, vol. lv. p. 447; 1 F., 3 cases.

ADDISON'S DISEASE.

DEFINITION.--A constitutional affection characterized by asthenia without emaciation, a depressed circulation, gastric irritability, and usually pigmentation of the skin. In the majority of cases it is associated with a fibro-caseous degeneration of the suprarenal capsules, and in many there are changes in the abdominal sympathetic system.

SYNONYMS.--Morbus Addisonii; Bronzed-skin disease. Fr. Maladie d'Addison, Maladie bronzée; Ger. Addisonische Krankheit.

HISTORY.--In the Halle Hospital Reports for 1823 Schötte describes a case, and one is also given by Bright in vol. ii. of his Medical Reports, 1831. A few other instances are also on record before 1855, when Addison published his monograph On the Constitutional and Local Effects of Disease of the Suprarenal Capsules, from which we may date our knowledge of the affection. Following close upon the work of Addison numerous observations were made in England, where the disease appears to be more common than elsewhere. Wilks of Guy's Hospital,[181] and Greenhow of the Middlesex Hospital, may be mentioned among those who in England have specially studied the disease, and the latter published an important monograph in 1875.[182] In France, besides numerous minor contributions, the exhaustive articles in the encyclopædias have been the most important publications. In Germany the monograph of Averbeck (1869) and the abstracts of Meissner in Schmidt's Jahrbücher may be specially mentioned. Virchow, Griesinger, Oppolzer, Bamberger, and others have made valuable contributions. Recently Burger[183] has published a small monograph. In other European centres contributions have been made, among which may be mentioned that of Schmidt of Amsterdam, who brought forward cases in support of the view that the disease was an affection of the sympathetic ganglion. In America the first cases were reported by Ranking[184] and Taylor.[185]

[Footnote 181: In numerous communications in Guy's Hospital Reports and Trans. Path. Society.]

[Footnote 182: "On Addison's Disease," Croonian Lectures.]

[Footnote 183: Die Nebeunieren und der Morbus Addison, Berlin, 1883.]

[Footnote 184: Am. Journ. Med. Sci., 1856.]

[Footnote 185: New York Med. Journal, 1856.]

ETIOLOGY.--The causation of the disease is unknown. Cases are more frequent in hospital than in private practice. Males are more often attacked than females; the proportion in Jaccoud's table[186] is 79 to 48, and in Greenhow's[187] analysis of 183 good cases, 119 were males and 64 females. Under ten and over fifty years of age the disease is very uncommon; the majority of the cases occur between the twentieth and the fortieth year. Greenhow {940} has called attention to the fact that in a number of instances the disease appears to have followed an injury, such as a blow upon the abdomen or back, and in several cases caries of the spine has preceded the attack. He refers also to the greater frequency of the disease in the laboring classes and those exposed to injury from over-exertion. The disease does not seem to be more prevalent among members of phthisical families, although the morbid process in the glands has been regarded as of a tuberculous nature, and it is common for other tuberculous lesions to occur in the course of the disease.

[Footnote 186: Dictionnaire de Médecine.]

[Footnote 187: Op. cit.]

The disease is rare in America--apparently much more so than in England.

SYMPTOMS.--In the words of Addison, the leading and characteristic symptoms are: "Anæmia, general languor and debility, remarkable feebleness of the heart's action, irritability of the stomach, and a peculiar change of color in the skin occurring in connection with a diseased condition of the suprarenal capsules."

Although, perhaps, not the most essential, the symptoms pertaining to the skin are in the majority of cases the most prominent, and have given rise to the names bronzed skin, melasma suprarenale, etc. which have been applied to the disease. A gradual increase in the pigment of the rete mucosum, either patchy or diffuse, causes a gradual discoloration, which may ultimately reach such a degree that a previously blonde individual may have the aspect of a Malay or a mulatto. The grades of coloration may range from a light yellow to a deep brown, or even black. In some instances there is a greenish-brown tinge, to which the term bronzed is peculiarly applicable. In typical cases it is diffuse over the whole surface, but as a rule deeper on exposed parts, face, neck, and hands, and also in those regions where the normal pigmentation is most intense, nipples, scrotum, and penis, or in the vicinity of cicatrices or regions of chronic irritation. It is usually first noticed on the face, either diffuse or in spots, and the extension may be rapid or gradual, in many instances not reaching a high grade and not becoming universal. It may be absent, and is not to be regarded--as was formerly the case--as an essential feature of the disease. Patches of leucoderma may occur in connection with the pigmentation, as beautifully delineated in Pl. xi. of Addison's monograph. The pigmentation is not confined to the skin, but may extend to the mucous surfaces--mouth, conjunctivæ, vagina. In the mouth the patches may be as dark as in the dog; they are usually scattered, often on the margins of the lips and on the edges and under surface of the tongue and on the cheeks. The conjunctivæ are less often affected. The vagina may be very deeply pigmented. An intensification of the choroidal pigment has been observed. In some cases a patchy pigmentation of the serous membranes has been found, and is figured in one of Addison's original plates, and pigmentation of the nails, hair, and teeth may also occur. A variation has been observed in the intensity of the coloration with the general health of the patient. The discoloration rarely precedes the general symptoms, but more usually follows the asthenia.

Some observers have noted a peculiar odor of the breath and from the skin, particularly during the last few days of life.

Anæmia of a moderate degree may exist, but it is not, as often stated, a constant symptom. Greenhow states that "there is no real anæmia, the blood being often rich in red corpuscles, even in excess, and there is no increase in the white." No special alterations in the appearance of the corpuscles have been noted. In some instances free pigment has been found.[188] In a case recently at the hospital of the University of Pennsylvania, Hughes found the number of red corpuscles over five millions per cubic millimeter, and there were free pigment-granules in the blood.

[Footnote 188: Corput, Gazette hébdomadaire, 1863.]

Hemorrhages are rare; extravasations into the retinæ have not, so far as I {941} can ascertain, been observed, nor are there often the other common features of anæmia.

The pulse is frequent and small, the heart's action weak--sounds clear; a venous murmur may sometimes be heard. In some cases there appears to be a special enfeeblement of the heart and a liability to fainting attacks, and without any warning a fatal syncope may occur. Cold feet and hands result from the weak circulation, and may be a most annoying symptom.

Symptoms in connection with the respiratory system are not common. There may be dyspnoea, and the complication of phthisis may give rise to all the features of that disease. There may, however, be extensive lung trouble with but few symptoms. The temperature is rarely elevated, more often it is subnormal.

Gastric disturbances are very common--anorexia, nausea, vomiting--particularly toward the close, but they may be early and prominent features, persisting in spite of all remedies and proving the most formidable symptoms of the malady. They appear to be of nervous origin, and not referable to changes in the organ itself. It is doubtful if the case reported by Gilliam,[189] in which there was degeneration of the gastric mucosa, was Addison's disease. The state of the bowels is variable; constipation is more frequent than the normal condition. Diarrhoea is common, and may come on suddenly without obvious cause, and is a not infrequent cause of death.

[Footnote 189: Phil. Med. and Surg. Reporter, xxiv.]

The urine is usually pale, free from albumen, not often increased in amount. It is interesting to note, in connection with the involvement of the abdominal sympathetic, that in a few cases there has been polyuria. The nitrogenous elements may be greatly reduced, the urea to 13-20 grammes daily, and the amount of indican may be increased as much as 64-75 milligrammes in 1000 c.c. (Samuel). In one case Thudichum found the urinary pigments greatly reduced in amount, the uromelanin not amounting to more than one-twelfth the normal quantity. A recent observation of Nothnagel is of interest.[190] In a patient aged twenty, who had the typical symptoms of the disease for two years, death took place by coma and the condition of acetonuria was determined.

[Footnote 190: Zeitschrift für klin. Med., Bd. ix.]

The symptoms connected with the nervous system are the most prominent in the disease, and are more constant than the anæmia or the bronzing. The most marked is a depression and enfeeblement of the nervous forces, a profound asthenia out of all proportion to the general condition. The patients complain of a lack of energy, mental and bodily; the least exertion is an effort, and there is a feeling of tire and weariness with which the facial expression is quite in keeping. The fainting fits, giddiness, noises in the ears, may also be due to faulty innervation, as they occur in cases in which the anæmia is by no means advanced. Headache, lumbar and abdominal pains are frequent, and in a considerable proportion of cases there is tenderness on pressure in the lumbar region. With the advance of the disease the prostration becomes more marked, the patient remains in the recumbent posture, the voice gets weak and small, the intelligence dulled, and occasionally there is delirium. Head symptoms may suddenly supervene, and death by coma or convulsions cut short the progress even early in the disease (Pye-Smith). In Jaccoud's series convulsions were noted in 19 cases.

The disease may be said to be invariably fatal, but the course presents many variations. The majority of cases die within eighteen months of the first onset of the symptoms. B. Fenwick, in an analysis of 30 recent cases,[191] calls attention to the fact that when bronzing does not occur the course is more rapid. Thus the average duration of the non-bronzed cases was only 4.8 months, while for bronzed ones it was 23.6 months. There are acute cases {942} in which, with great weakness, vomiting, and diarrhoea, the fatal end may occur in a few weeks. Some of these rapid cases resemble typhus. Syncopal attacks, coma, or convulsions cut short not a few cases. In a few instances it is much prolonged--six years (Niemeyer) or even ten years (Greenhow). Whether recovery ever takes place is doubtful. Finney[192] has reported an apparently genuine case which got well. Some French observers (Potain) think that recovery takes place more often than is supposed. Sir Wm. Gull mentioned a case of recovery.[193] Periods of improvement lasting many months may occur.

[Footnote 191: Path. Soc. Trans., vol. xxxiii., London.]

[Footnote 192: Dublin Med. Journ., April, 1882.]

[Footnote 193: Int. Med. Congress (London) Transactions, vol. ii.]

MORBID ANATOMY.--The panniculus adiposus and subperitoneal fat may be in normal quantity. There is rarely great emaciation, nor are the organs blanched and bloodless. The most constant lesion is in the suprarenal organs, which present a caseo-fibrous change, more rarely simple atrophy or other alterations. So frequent is the caseo-fibrous condition that some writers (Wilks) hold that it is the specific lesion of the disease. The organs are enlarged--may weigh several ounces each. The capsules are thickened, and may present caseous or even calcareous masses. The normal shape of the gland is lost, and it forms an irregular nodular mass closely adherent to contiguous parts--liver, kidney, and cava on the right side, kidney, spleen, and often pancreas, on the left. There is usually a good deal of fibrous thickening and matting in the vicinity, and the adhesions to adjacent structures may be very strong. The peritoneum often shows patches of fibroid induration. On section the diseased organ cuts with great resistance, and to the touch has an almost cartilaginous hardness. The exposed surface shows caseous masses of a yellow or grayish-white color, varying in size from a pea to a walnut, imbedded in a grayish semi-translucent fibrous tissue, pale when first cut, becoming reddish on exposure. These caseous masses may undergo softening or calcification, and pockets of pus are not uncommon. Definite small miliary granulations are not often seen, though nodular grayish-yellow bodies the size of small peas may occur. The strands of fibrous tissue which separate and enclose the caseous masses have often a very peculiar translucent, infiltrated appearance. When the cheesy lumps are small, the amount of this tissue is considerable and gives a remarkable character to the section. Wilks has described a case in which this tissue made up the entire mass. The substance of the gland is usually destroyed. The vessels and nerves can be traced to the organs where they become imbedded in the fibrous tissue.

Histologically, the soft translucent tissue consists chiefly of spindle-shaped fibre-cells, and in firmer older parts of ordinary fibrous stroma. In the immediate neighborhood of the cheesy masses there are round corpuscles--about the size of or a little larger than white blood-cells--imbedded in a fine reticulum of fibres. Giant-cells are sometimes found, but they have not been common elements in the specimens which I have examined. The caseous substance consists of granular débris in which the remains of cells and fibres can be seen. In coarse and microscopical features the lesion resembles closely local tubercular affections. The extension is by a small-celled growth, which gradually invades the adjacent parts, extending peripherally as the central portions caseate. Distinct miliary granulations are not often met with. The relation of this local growth to tuberculosis is a very interesting question. It is usually regarded as a scrofulous or tuberculous process, to which in its general features it quite conforms. I have been interested in ascertaining whether the bacillus tuberculosis existed or not in the local lesion. In Cohnheim's laboratory Karl Hüber kindly gave me an opportunity of examining the adrenals in two cases, in only one of which were the {943} bacilli evident. Since then I have re-examined the fibro-caseous tissue in Ross's case,[194] which was a most typical one, the suprarenals alone involved, and in the recent case reported by Pepper,[195] and in neither have I been able to demonstrate bacilli. Future examinations must decide whether the local affection is inflammatory or whether it belongs to the infective granulomata.

[Footnote 194: Can. Med. Assoc. Trans., vol. i., 1877.]

[Footnote 195: Phila. Med. Times, 1885.]

That other alterations may occur in cases of Addison's disease appears well established, though some still regard the caseo-fibrous change essential and specific. Atrophy of one or both glands has been frequently seen. Jaccoud gives 7 cases in his tables. Good recent cases have been described by W. B. Hadden,[196] Hebb,[197] and Goodhart.[198] The atrophy is due to a chronic interstitial process similar to cirrhosis of the liver. Hadden[199] states that the lesion is identical with that in the thyroid gland in myxoedema.

[Footnote 196: British Medical Journal, 1885.]

[Footnote 197: Lancet, 1883, i.]

[Footnote 198: Path. Soc. Trans., 1882.]

[Footnote 199: Loc. cit.]

Absence of one or both the capsules has been noted by Legg, Spender, Borland[200] and Hubbard.[201]

[Footnote 200: Boston Med. and Surg. Journal, 1867.]

[Footnote 201: Proceedings of Conn. Med. Society, 1868-71.]

Cancer of the adrenals, by no means uncommon as a secondary process, rarely produces any special symptoms; but there are cases which are difficult to exclude from the category of Addison's disease. Jaccoud gives several, and in the case of Edes, often quoted,[202] the asthenia and discoloration may have been due to the capsular affection, but there was also extensive peritoneal cancer.

[Footnote 202: Boston Med. and Surg. Journal, 1878.]

By far the most constant morbid change after that in the adrenals is a more or less widely distributed tuberculosis, particularly of the lungs. A very considerable proportion of the cases are complicated with chronic phthisis. Regarding the disease of the suprarenals as primary, the general tuberculous affection may be secondary; and it is just in these organs, as Weigert has shown, that the veins are apt to be perforated by tubercles and systemic infection induced. The retro-peritoneal and mesenteric lymph-glands may also be tuberculous. Ulcers of the ileum may occur, and swelling of Peyer's glands and the solitary elements in the bowels is very common. In Ross's case there were numerous lymphoid infiltrations of the mucosa of the stomach, chiefly about the pylorus and cardia. The changes in the skin are confined to an increase of the pigment in the cells of the rete mucosum, most pronounced in the deeper layers and in the deeper parts in the connective-tissue cells of the papillæ and subcutaneous tissues. The condition is not to be distinguished from a deeply-pigmented scrotum or from the dark skin of the negro. The pigment resembles the ordinary coloring matter of the skin, but is possibly different from it in containing no iron.[203] Nothnagel has made[204] an exceedingly interesting study of the pigmentation in Addison's disease, and concludes that it is identical in distribution with that in the skin of the dark races; that it does not originate in the cells of the rete mucosum, but is elaborated in deeper cells, about the vessels of the cornium, and transported by them to the more superficial layers--a mode which recent observations seem to show is the normal one; and, lastly, that it is a process induced through the nervous system in some way as yet unknown.

[Footnote 203: Arnold, Virchow's Archiv, xxxv.]

[Footnote 204: Loc. cit., Bd. ix.]

The spleen has been found enlarged. The thymus gland may also persist or be much larger than normal. In Ross's case it weighed six ounces. The heart and blood-vessels do not present any constant changes: the heart has been found small in some cases. Venous engorgement of the abdominal viscera has been noted in a few cases, but it is not a common feature. It was not present in two typical cases which I have examined.

{944} In the nervous system the condition of the abdominal sympathetic has received special attention, and in a number of cases definite changes have been met with, chiefly of a sclerotic or chronic nature and intimately associated with the fibroid induration about the capsules. The nerve-cells of the semilunar ganglia are described as degenerated, deeply pigmented, and often present a new growth of connective tissue about and between the cells. There are at least thirty or more cases in which such alterations have been found. In some instances the medulla of the nerves passing from the ganglia has been found wasted and the fibres in a state of fatty degeneration. In some cases these parts have been found normal (Foa,[205] Huber,[206] Hebb,[207] and Hadden[208]). In a most typical case under Ross at the Montreal General Hospital, I could find no differences in the cells and nerves, comparing them with those of a woman dead on the same day of heart disease. More recently, I have examined a case for Pepper in which the right semilunar ganglion was imbedded in the sclerotic tissue of the right adrenal; the nerve-cells were undergoing atrophy from compression; and there were fatty changes and degenerations in the nerves connected with this ganglion. The left was uninvolved, and the cells and fibres appeared normal.

[Footnote 205: Virchow-Hirsch, 1879.]

[Footnote 206: Virchow's Archiv, 86.]

[Footnote 207: Lancet, 1883, i.]

[Footnote 208: Loc. cit.]

Jacquet has described pigmentary changes in the ganglia of the cord as well as in those of the abdomen, and Guermonprez[209] alterations in the brain similar to those of senile dementia. At the Congress in 1881 at London, Semmola of Naples showed a figure illustrative of degeneration of the ganglia of the abdomen, and also an infiltration of leucocytes in the neighborhood of the central canal of the cord, from a case of Addison's disease without affection of the adrenals.

[Footnote 209: Quoted by Burger, loc. cit.]

PATHOLOGY.--The suprarenal organs are usually grouped with the blood-vascular organs. From the number of nerve-fibres--sympathetic, pneumogastric, and even phrenic--passing to the medullary part, and from the presence of cells resembling nerve-corpuscles, Leydig and others have thought that this portion belonged to the nervous system. We know absolutely nothing of their functions. They do not appear to be essential to life, but may be removed, crushed, or destroyed with impunity, though the operation is not without danger from their close proximity to important structures. They are sometimes congenitally absent. They are proportionately larger during foetal life, but they do not appear to atrophy as age advances; indeed, it would appear from the observation of Mattei (Jaccoud) that they augment in volume with increasing years. Their chemistry has attracted much attention. Vulpian has described a material which gives a green, blue, or black color with perchloride of iron, and with oxidizing substances a rose-red; and the same observer found also hippuric and taurocholic acids. Leucin, margarin, myeline (Segilsohn), and a special coloring matter (Arnold), have been described. Henle has pointed out that the central part in the horse became of a rich brown with bichromate of potash from the reduction of the brown oxide of chromium. MacMunn's[210] observations on the spectroscopic appearance of the pigment of the suprarenals point to these glands as in some way concerned with the transformation of the effete coloring matters of the body.

[Footnote 210: Paper read before the Physiological Society of London, Journal of Am. Med. Assoc., 1885, March 21.]

An immense number of experiments have been made with a view of ascertaining the function of these bodies, and extirpations, crushings, etc. have been made--among others by Brown-Séquard,[211] Gratiolet,[212] Phillipeaux,[213] Harley,[214] Nothnagel,[215] the general result of which appears to be that they are not {945} important organs and that they have no influence in the production of pigment. Recently, Tizzoni[216] has stated--as Brown-Séquard had done--that pigmentation followed extirpation in the rabbit; but there is a large amount of negative evidence by most careful observers; as, for example, Nothnagel, who found no changes in 153 animals in which he had destroyed the suprarenals.

[Footnote 211: Archives générale, 1858.]

[Footnote 212: Ibid., 1856, ii.]

[Footnote 213: Ibid., 1858.]

[Footnote 214: Med.-Chir. Review, vol. xxi.]

[Footnote 215: Zeitsch. f. klin. Med., Bd. i., 1879.]

[Footnote 216: Lancet, 1884, ii.]

Various attempts have been made to explain the phenomena of the disease, to two or three of which we shall refer:

1st. That the disease is directly dependent upon destruction of the capsules and consequent abnegation of their functions. This was the view of Addison, and it appeared to be supported by the experiments of Brown-Séquard (performed shortly after the publication of Addison's memoir), who held that after extirpation of the glands pigment accumulated in the blood; which he explained on the supposition that their function was the disposal of a material in the blood readily converted into pigment. Subsequent experiments appear to have demonstrated conclusively that, like the spleen, the adrenals are not necessary to life, and that no important changes occur after their removal, or even after the induction of caseous and fibroid induration (Nothnagel). A much stronger argument against this view is found in the fact that cases have been reported in which the capsules presented little or no change.[217] Taylor[218] held that the pigmentation was induced by destruction of the cortical part of the organs, and the general nervous phenomena by involvement of the central part, which has such close relation with the nerve-structures. This view has again been advanced by B. Fenwick.[219]

[Footnote 217: Care must be exercised in the examination of apparently normal capsules. There may be extensive small-celled infiltration and destruction of the gland-elements without either reduction or increase in size.]

[Footnote 218: Loc. cit.]

[Footnote 219: Path. Soc. Trans., xxxiii., 1882.]

2d. That it is an affection of the abdominal sympathetic system, induced, most commonly, by capsular disease, but also by other chronic affections which implicate the solar plexus and its ganglia. Addison hinted at this explanation, and had the ganglia examined in one of his cases, but Schmidt of Amsterdam (1859) was the first to point out the possible connection and to record a case. Many corroborative observations have since been made, and this view has the support of the leading authorities. The changes which have been met with are very varied--fibroid thickening of the sheaths with atrophy of the nerve-tubes, fatty degeneration and wasting, excessive pigmentation of the cells, myxomatous degeneration of the stroma of the semilunar ganglia, and in a few instances there have been changes in the spinal cord. The chronic caseo-fibrous process in the capsules seems specially prone to involve contiguous tissues, and the close proximity of the semilunar ganglia renders them more liable to be attacked by the sclerotic process than in other affections in the vicinity, such as aneurism or tumors. According to this view, the symptoms of Addison's disease are to be regarded as the expression of a severe nutrition disturbance caused by a morbid state of the sympathetic ganglia, or, as Semmola puts it, the entire affection, beginning with disturbance of digestion and running its course with asthenia, low temperature, and marked debility in the oxidation and nutritive processes, is a pathological demonstration of the physiological functions of the sympathetic ganglia. The pigmentation may have its origin in changes in the trophic nerves, and the pronounced debility is the outcome of the disturbed chemical activity in the tissue-elements. It is, in short, a disease of the nervous system of organic life. Greenhow, who is a strong advocate for this view, also thinks that the circulatory, respiratory, and digestive symptoms may in part be due to implication of the pneumogastrics, the peripheral branches of which are frequently {946} involved in the thickened tissues about the capsules. The feeble action of the heart, small pulse, the nausea, vomiting, and the gasping respiration, may arise reflexly from irritation of these branches.

There are about thirty cases on record in which changes have been found in the sympathetic system. Riesel[220] compares the symptoms of Addison's disease with those which follow extirpation of the semilunar ganglia in animals. There is a paralysis of the vaso-motor nerves of the abdominal viscera, induced either by degeneration of the ganglia or reflexly by irritation, and consequently the blood accumulates in these parts, and there is a corresponding spanæmia of other organs, which explains the weak circulation, anæmia and the heart symptoms, fainting, and loss of energy. Recently this theory has been advocated by F. P. Henry.[221]

[Footnote 220: Deutsches Archiv f. klin. Med., Bd. vii.]

[Footnote 221: Philada. Med. Times, 1885, No. 452.]

The occasional occurrence of pigmentation of the skin in abdominal tuberculosis, retro-peritoneal tumors, cancer of pancreas, and in uterine irritation lends support to this view.

The weak points of this view are--the doubtful nature of the changes in the ganglia and the nerves in many cases. Mere increase of the normal pigment, slight fatty degeneration or swelling, so often recorded, should not be regarded as important, for they occur under a variety of conditions. Of positive swelling and redness of the ganglia, fibroid atrophy with destruction of nerve-cells and degeneration of the nerve-fibres, there can be no doubt, but about less marked alterations opinions will differ whether they are truly morbid or not. The fact that in certain well-observed cases the ganglia and nerves were found normal is hard to reconcile with a theory that the disease is an affection of the abdominal sympathetic. Burger states[222] that there are nine cases in which changes could not be found, and there are the recent cases of Huber,[223] Hebb,[224] Foa,[225] and Hadden.[226]

[Footnote 222: Loc. cit.]

[Footnote 223: Virchow's Archiv, Bd. lxxxviii.]

[Footnote 224: Lancet, 1883.]

[Footnote 225: Virchow-Hirsch, 1879.]

[Footnote 226: Brit. Med. Journ., 1885, i.]

Hale White's recent observations,[227] as well as those of Saundby,[228] on the histological changes in the sympathetic clearly show that many of the changes which have been described in cases of Addison's disease are common in other affections, and have probably no direct association with the characteristic symptoms of the malady.

[Footnote 227: Ibid.]

[Footnote 228: Ibid., 1883, i.]

Then, again, the absence of the characteristic symptoms of Addison's disease in so many cases in which the matting and implication of the nerves seems quite as great as in capsular disease. In aneurism of the abdominal aorta in the neighborhood of the coeliac axis the tissues in the vicinity may be indurated and cicatricial, the semilunar ganglia compressed, and the nerve-fibres atrophied, without bronzing and without the constitutional symptoms. Cases, too, of retro-peritoneal cancer rarely induce pigmentation, though in some instances--as in a case of Paget's (Geo.),[229] in which there was extensive lymphadenosis with involvement of the abdominal sympathetic--the bronzing may be intense. Induration about the pancreas and stomach in cancer has induced the same change, and recently Jürgens has recorded a case of aneurism[230] of the abdominal aorta with symptoms of Addison's disease and degeneration of the sympathetic nerves.

[Footnote 229: Lancet, 1879, i.]

[Footnote 230: Berliner klin. Woch., March, 1885.]

3d. That the essence of the disease is to be sought in some injurious agent--a poison introduced from without or possibly arising within the body as a result of faulty metabolism. There is not the slightest evidence for the existence of any such specific poison, which Averbeck, in his monograph, brings forward to account for the anæmia and the local disease in the capsules.

A more plausible theory, one closely related to the first one mentioned, is {947} that the blood is gradually poisoned by the retention of some material the destruction or alteration of which it is the function of the adrenals to effect. The disease is in this view analogous to chronic uræmia.

The relation of affections of the thyroid gland to myxoedema and cretinism, and the experimental production of these conditions by the removal of the thyroid, have widened our view of the importance of the ductless glands. It is interesting to note the analogy between myxoedema and Addison's disease. In both there are distinct histological changes in the tissues--in one an increase in the mucin, in the other an increase in the pigment--and in both marked nervous phenomena: mental dulness, a progressive dementia in myxoedema, a profound asthenia in Addison's disease. We regarded the thyroid as unimportant to life until the experience of surgeons and extirpation in monkeys by Horsley demonstrated that abolition of its function was followed by a serious train of symptoms; and perhaps the experimental removal of the suprarenals in monkeys--so much more closely allied to man than the animals hitherto experimented upon--may demonstrate that these little bodies are also not without their influence upon health.

Although the view of disturbed innervation consequent upon involvement of the abdominal sympathetic meets the case, theoretically, better than any other, and is at present widely held, yet there are signs of a return to the old view of Addison, which has been so consistently advocated by Wilks.[231] The data are not yet forthcoming for a final decision of the question, but it is possible that future investigations may establish the truth of Addison's view, that suspension of the function of the glands is the essential factor in the causation of the disease. That the sympathetic may be normal in genuine cases, and again that all the symptoms of the disease may occur without affection of the adrenals, are, however, facts difficult to harmonize with either theory.

[Footnote 231: Discussions at Pathological Society of London, session 1884-85.]

DIAGNOSIS.--It is of the first importance to remember that an increase in the pigment of the skin is by no means confined to Addison's disease, and, on the other hand, that the constitutional symptoms may be present without a trace of bronzing; and in their absence a positive diagnosis cannot be made. The conditions which give rise to a deepening of the color of the skin are--(1) Abdominal growths, tubercle, cancer, lymphoma. The patches of pigmentation in such cases are usually scattered, most often about the face and forehead. Occasionally the pigmentation may be deep and extensive, as in one case I saw of abdominal tuberculosis believed to be Addison's disease. Guéneau de Mussey[232] has called special attention to the frequency of this complication in chronic tuberculous peritonitis. Pigmentation may also be on the mucous surfaces in these cases. (2) Pregnancy, in which the discoloration is usually limited to the face, the so-called masque des femmes enceinte, and which, it is to be remembered, does not always disappear with the pregnancy. Chronic uterine disease, especially fibro-myoma, is a very common cause of patchy melasma. (3) Hepatic disease, which may induce definite pigmentation as well as the yellow-brown color of jaundice. Overworked persons of constipated habit and sluggish livers may present a patchy staining about the face and forehead. (4) The vagabond's discoloration, caused by the irritation of lice and dirt, may reach a high grade, and has been mistaken in several instances for the pigmentation of Addison's disease. (5) In rare instances there may be deep discoloration of the skin in connection with melanotic cancer--so deep and general that it has been confounded with melasma suprarenale. Wagner,[233] Wickham Legg,[234] and Falls[235] have {948} described remarkable cases of the kind. The occurrence of melano-sarcoma of the choroid or skin should render the diagnosis in these cases easy enough, but if deep seated a difficulty might readily occur.

[Footnote 232: Étude sur la Pigmentation de la Face dans la Tuberculose abdominaire, Paris, 1879.]

[Footnote 233: Archiv der Heilkunde, Bd. v.]

[Footnote 234: Path. Soc. Trans., London, vol. xxxv., 1884.]

[Footnote 235: Philada. Med. Times, 1883.]

It must be borne in mind that there are cases without bronzing, in which the profound asthenia and gastric symptoms are the prominent features, and, as mentioned above, these cases seem to run a very acute course. Indeed, they have been mistaken for typhus.

TREATMENT.--As cure is out of the question, the treatment is symptomatic and directed to the avoidance of certain perils associated with the disease. We have no means of checking the progress of the capsular affection. Pepper advises counter-irritation, and in the early stages the cautery may be used. Rest of mind and body must be enjoined, and the dangers of exertion and exhaustion set before the patient. Even in the early stage fatal syncope may occur.[236] The sense of weakness and tire at times becomes greatly aggravated, and may deepen into attacks of the most profound asthenia, during which the patient should be strictly confined to bed. It is in these paroxysms that special dangers occur. General tonic measures must be employed for the support of the strength. When there is anæmia, iron may be given, and Greenhow speaks of the good effects of the citrate or perchloride given with glycerin. Arsenic, strychnia, phosphorus, have been found useful in individual cases. Galvanism has been used, but without much benefit. The paroxysms of profound asthenia call for stimulants--wine, brandy, and ammonia. The gastro-intestinal symptoms require the most careful treatment. Bismuth, hydrocyanic acid, creasote, soda-water, ice, and champagne will be found useful in allaying the vomiting and irritability of stomach, but in some cases these symptoms prove most intractable. Purgative medicines must be given with very great caution on account of the liability to profuse diarrhoea and serious collapse. The constipation, which may be obstinate, is best treated by mild enemata. The greatest care should be exercised in the diet, which should be plain and easily digested. Though the vomiting is not directly dependent upon the state of the stomach, yet indigestible food and irregularities in eating may induce the gastric attacks. When there is much irritability of the stomach the patients seem to do best on a strict milk diet.

[Footnote 236: Quite recently an active professional man consulted me for bronzing of the face and hands, and he had had one fainting spell. With the concurrence of Pepper he was advised to give up business for a year and live quietly abroad. His general condition was so good and the pigmentation so limited that there seemed just a possibility that it was not Addison's disease. He went home and prepared to follow out our advice, but a second sudden attack of syncope proved fatal.]

{949} OTHER DISEASES OF SUPRARENAL BODIES.

ANOMALIES.--There may be four glands, two on each side. More commonly, there are small supplementary organs--glandulæ succenturiatæ--situated in the neighborhood, seldom reaching the size of a pea. Grawitz has recently shown that many of the small adenomas of the kidney are in reality minute portions of suprarenal tissue which have become included in the course of the development of these organs. Fusion of the two glands has been observed (Klebs). They may be absent.[237]

[Footnote 237: Defect of adrenals is very rare. There are not a few observations in which it is stated that the right gland was absent. Now, if the examination is not made with care, and particularly if the liver is removed first, the right gland may be taken away with it closely lodged in the fossa suprarenalis, and so escape observation. Time and again have I directed the attention of the student making the autopsy to the right adrenal on the under surface of the liver.]

It is curious how liable the suprarenals are to anomalies in position or form in connection with defective development of the brain and cord. In anencephalous monsters the glands may be absent or very small.[238] In one instance I found them normal in size, but they were below, not above, the kidneys.

[Footnote 238: Lomer, Virchow's Archiv, Bd. xc.; Weigert, ibid., Bd. c.]

ATROPHY.--Extreme wasting may be met with as an accidental circumstance: there may be only a trace of gland-tissue left. Several such specimens have been found in association with Addison's disease. There may be an interstitial growth of fibrous tissue, cirrhosis, with shrinking of the organ. More often the glands are larger and harder in connection with the cyanotic induration of heart disease. It is stated by some writers that the adrenals of the negro are larger than those of the European races--a statement which I have not been able to confirm in several observations.

APOPLEXY.--In the new-born and young children congestion is not infrequent. Hemorrhage into the central medullary substance is by no means uncommon, either on one side or bilateral. The amount may be considerable, and the glands greatly distended, forming large tumors.

INFLAMMATION.--Suppuration is rare except in connection with the caseo-fibrous change already described as specially associated with Addison's disease. Abscesses in the vicinity, as from caries of the spine, may involve one or both capsules.

DEGENERATIONS.--Fatty changes are very common, particularly in the cortical layer, which then has a light-yellow color, instead of the normal dark gray-red. Yellow oil-drops appear to be normal constituents of the cells of the cortex.

Amyloid degeneration may occur, but only in connection with similar changes in other organs. The glands are enlarged, very firm, and the medullary part translucent. The iodine reaction shows it to be limited to the fibrous septa and blood-vessels.

The brown pigment of the intermediate zone, zona reticularis, may be greatly increased. Normally in man, the amount is very variable, and the deeper color may be due to congestion of the blood-vessels.

CYSTS with serous or hemorrhagic contents are occasionally found, chiefly in the cortical part. They may be multiple. Hydatid cysts have been met with.

TUMORS are not very uncommon. Cancer may attack them primarily, but more often they are involved in secondary growths after carcinoma of stomach or other organs. They are not infrequently affected in cancer of the kidneys {950} by direct extension of the growth. Sarcomas are also not uncommon, and may form large masses the size of the foetal head. They may be melanotic.

These varied pathological conditions are not usually associated with any special or distinctive symptoms, and in the great majority of cases have been unsuspected during life. The organs may be totally destroyed without inducing any of the phenomena of Addison's disease. In a few cases, however, bronzing of the skin has been met with.

{951}

DISEASES OF THE SPLEEN.

BY I. E. ATKINSON, M.D.

Morbid processes affecting the spleen have been and remain involved in great obscurity. Older writers, who were accustomed to reach their conclusions in great measure through the observation of symptoms alone, were obliged in the absence of anything like correct knowledge of anatomy, physiology, and pathology to supply from the imagination most of their theories of disease. Untrammelled by the bonds of accurate investigation and ignorant of pathological anatomy, they found no difficulty in ascribing to various parts and organs peculiar groups of symptoms, both physical and moral; and for a number of these the spleen was held responsible. We now know that many of the symptoms thus supposed to indicate splenic disease depend upon alterations in other parts of the body, and may be observed in persons possessing perfectly healthy spleens. But while we have learned that symptoms formerly supposed to depend upon splenic disorder may, in reality, have nothing to do with this organ, we still remain ignorant of many of the real symptoms of splenic disease, as well as of many of the morbid conditions that induce them. Such knowledge as we have, however, is based upon comparisons of symptomatology with dead-house revelations and the experience of the laboratory, and, while as yet imperfect, cannot fail to increase under modern methods of research.

In order to begin the study of diseases of the spleen in an intelligent manner it is manifestly necessary to have some settled ideas regarding its anatomy and physiology. No apology is needed, therefore, for the brief anatomical and physiological descriptions that follow.

The spleen is the largest of the ductless glands, and is situated in the left hypochondriac region. It is of a dark slate or bluish-gray color, and often of wrinkled appearance. It is of soft, friable structure. It rests between the stomach, diaphragm, and left kidney, and in form resembles a flattened oval. It extends from the level of the eleventh rib, beginning one or two centimeters distant from the vertebral column, downward and forward to a position about four centimeters from the point of the eleventh rib (Lushka). It is separated from the ninth, tenth, and eleventh ribs by the diaphragm. It presents two surfaces--one external and convex, facing the diaphragm; the other internal and concave, applied to the cardiac end of the stomach. The hilum divides the internal portion into two parts by a deep fissure, which marks the line of attachment of the gastro-splenic omentum. The larger and anterior part is bound to the fundus of the stomach by delicate areolar tissue, and the posterior and smaller portion to the left pillar of the diaphragm and the left suprarenal capsule. The upper portion is connected with the diaphragm by peritoneum forming a suspensory ligament. The bottom of the hilum is perforated by a number of openings for the transmission of blood-vessels, nerves, and lymphatics. The anterior border of the organ is notched and thinner than the posterior border. The pointed lower end touches the splenic flexure of the transverse colon and rests upon the costo-colic ligament. {952} The spleen varies in size and weight within wide limits. Its average weight in adults is 250 grams, its length from 11 to 13 centimeters, and its thickness from 4 to 6 centimeters (Orth). Its volume is from 150 to 180 cubic centimeters. According to Gray, the proportionate weight of this organ to that of the whole body varies from 1:320 to 1:400, gradually diminishing until old age, when the proportion becomes as 1:700.

In the vicinity of the spleen are often found a number of small bodies similar to it in structure. These are known as accessory spleens, and are usually situated in the gastro-splenic or in the greater omentum. The attachments of the viscus are not very close, and much variation in size and position is possible.

Except at the hilum the peritoneum forms everywhere one of the coverings of the spleen. Its peculiar sheath or capsule is composed of fibro-elastic tissue of a whitish color, prolongations of which extend into the substance of the organ and form the trabeculæ that constitute its supporting framework and sheaths for blood-vessels and nerves. A close meshwork is thus created in which are contained the splenic vessels and pulp. This fibrous coat and these trabeculæ contain involuntary muscular fibres. These, with the elastic fibres, provide for the changes in size that the organ undergoes. When incised, the normal spleen presents a reddish-brown color, and its substance may be readily broken down with the finger into a pulp. This pulp consists of a mass of branched intercommunicating connective-tissue corpuscles of different sizes, within the substance of which remains of red blood-corpuscles may often be detected. The interstices of these cells are filled with blood. The very large splenic artery enters the spleen by numerous branches, ramifying within the trabecular sheaths and terminating in pencils of minute size.

The external coats of the smaller arteries are converted into lymphoid tissue, which, suddenly expanding here and there, forms the bodies known as the Malpighian follicles, which are supplied with capillary vessels, and which may often be distinguished by the naked eye as points of whitish color, sometimes attaining the size of pinheads. These small arteries end in capillaries, which, according to Müller, gradually lose their cylindrical character and emerge into a system of connective-tissue corpuscles, inosculating with the corpuscles of the splenic pulp in such a manner that the blood passes into the pulp-tissue freely, and is gradually brought to the veins by the transition of this tissue into that of the blood-vascular system. The splenic lymphatics originate in the arterial sheaths and in the trabeculæ. In the former case they accompany the blood-vessels; in the latter, they communicate with a superficial network in the corpuscle. All join at the hilum and enter the neighboring lymphatic glands. The splenic nerves are from the right and left semi-lunar ganglions and right pneumogastric nerve. They accompany the branches of the splenic artery, and have been traced deeply into the tissue of the organ.

It is perfectly established that under normal conditions the volume of the spleen may vary considerably, and especially during the act of digestion, and that this does not occur through simple engorgement of the vessels. The very important experiments of Roy show that, in cats and dogs at least, the splenic circulation does not depend upon the ordinary blood-pressure, but is carried on "chiefly, if not exclusively, by a rhythmic contraction of the muscles contained in the capsule and trabeculæ of the organ."[1] This rhythmic contraction and expansion Roy observed to occur with great regularity at the rate of about sixty contractions an hour, with extremes of rapidity of rhythm of forty-six seconds for the most rapid and two minutes three seconds for the slowest. He also observed that stimulation of the central end {953} of a cut sensory nerve, or of the medulla oblongata, or of the peripheral ends of both splanchnics and both vagi, causes a rapid contraction of the spleen. Unsatisfactory as is our knowledge of splenic physiology and of its exact relations to the maintenance of life (for that the spleen is not the seat of a peculiar and exclusive function has been demonstrated by the survival of individuals after extirpation of the organ), at present certain theories of its nature find pretty general acceptance. Thus, it is considered that in the lymphoid tissue of the blood-vessels and Malpighian corpuscles leucocytes are produced--that the cells of the splenic pulp appear to take red blood-corpuscles into their interior, where their disintegration takes place. There are not sufficient grounds for believing that in the spleen red blood-corpuscles are formed. Recent observations of Tizzoni, Crédé, and Zesas have led them to the conclusion that they are made in the spleen; but Bizzozero and others deny that this occurs except after serious hemorrhage.

[Footnote 1: Journal of Physiology, vol. iii., 3 and 4, p. 203.]

It is impossible to detect by palpation any part of a healthy spleen. Its area may be approximately defined by percussion alone, though even by this method it is not always easy to determine its position and size. Loomis advises that the patient be placed upon his right side in order to facilitate the examination. The anterior border of the spleen is then "readily determined by the tympanitic resonance of the stomach and intestines. Inferiorly, where the organ comes into contact with the kidney, it is difficult, and often impossible, to determine its boundary. Its superior border corresponds to the line which marks the change from flatness to pulmonary resonance." The vagueness of these directions is necessitated by the difficulties of the subject, the splenic outlines being liable to frequent variations. Schuster and Mosler give excellent reasons for prosecuting the investigation with the patient in the right semi-supine position.

Acute Congestion of the Spleen.

Except within the physiological limits already referred to, acute congestion of the spleen never occurs as a primary process. Under pathological conditions it is known to take place under a great variety of circumstances, principally, however, in connection with those states of the system in which disease is supposed to depend upon some specific principle or germ. To a minor extent it is probable that splenic congestion accompanies nearly all febrile conditions, and from the border-lands of health to that highest and most intense degree of hyperæmia by which the organ acquires a volume and prominence that have caused it to be designated as acute splenic tumor, all gradations may be observed, though in many instances these may be so slight as to be incapable of recognition clinically, and are only brought to our knowledge through necroscopic examination. The congestion becomes most marked in the course of the acute specific fevers. In typhus and typhoid fevers, in small-pox, scarlatina, diphtheria, in epidemic cerebro-spinal meningitis, in acute tuberculosis, in erysipelas, puerperal fever, in conditions of blood-poisoning and in malarial fevers, more especially those of more severe type, it reaches its highest development. According to Friedreich, a form of pneumonia (differing from ordinary croupous pneumonia in its serpiginous course), acute coryza, and acute pharyngitis and tonsillitis are accompanied by enlargement of the spleen in consequence of the septic nature of these disorders. During the fever of secondary syphilis a splenic enlargement purely hyperæmic in character may sometimes be detected. Similar conditions are occasionally observed in a number of other affections. This tendency of the spleen to active congestion is to be accounted for by its peculiar anatomical structure, whereby unusual facilities for hyperæmia are {954} afforded, more especially in the infective fevers, in the course of which the organic germs which are supposed to constitute their essential principles collect in the pulp, and by their accumulation and multiplication serve to excite a more or less intense determination of blood to the part, the organisms themselves being taken up by the leucocytes and connective-tissue corpuscles composing the pulp. We can thus account for the multitudes of these organisms to be found in the splenic pulp after various infective disorders, as in relapsing fever as observed by Ponfick, in pyæmia by Birch-Hirschfeld, and in splenic fever of animals by various observers. The less intense degrees of congestion occurring during the various specific fevers and in many simple febrile disturbances are usually so slight as not to attract attention. When the hyperæmia has been unduly prolonged, as more especially occurs as a result of chronic malarial poisoning, leucocythæmia, pseudo-leucocythæmia, or Hodgkin's disease, there is a well-pronounced tendency toward permanent structural changes and the development of hypertrophy.

SYMPTOMATOLOGY.--Milder degrees of congestion do not, generally, reveal their existence by symptoms, and those of more pronounced character give for the most part signs that are vague and nearly obscured by the more prominent features of the pathological processes that occasion or accompany the splenic changes. It may happen that acute splenic tumor of considerable size may be quite painless. It has been objected, indeed, that when pain accompanies splenic enlargements it is not attributable to any sensibility of the spleen itself, but to the participation of the investing peritoneum in the morbid action or to the dragging of the enlarged organ upon the parts with which it is connected (Mosler). Patients, however, will often complain of a dull, aching pain and a sensation of weight in the left hypochondrium. Occasionally, this pain may be severe and lancinating or may extend to the shoulder. Headache and various digestive disorders--anorexia, vomiting, flatulence, and diarrhoea--may prove distressing accompaniments. Other symptoms, such as melæna, voracious appetite, vertigo, extreme anæmia with its various concomitants, etc., belong rather to conditions of protracted congestion where new formation and true hypertrophy have been developed.

It is evident that it will often be extremely difficult, and sometimes even impossible, to determine the extent to which symptoms are occasioned by the splenic congestion or by the general affection to which it owes its origin. Mosler declares that he is nearly always able to detect during the cold stage of intermittent fever a peculiar murmur over the splenic region and upward and downward in the abdominal region, which he attributes to the contraction of the splenic artery. This murmur he has not been able to perceive in chronic splenic tumors.[2]

[Footnote 2: Ziemssen's Cyclop., vol. viii. p. 468.]

The normal splenic area can only be defined by percussion, and congestion to a not insignificant extent may occur without revealing itself by other symptoms than increase of the extent of percussion dulness. When the organ projects beyond the margin of the ribs and can be felt by the fingers of the examiner, it is enlarged, unless the patient is the subject of displaced or of wandering spleen. But whether the enlargement be due to hyperæmia simply or to hypertrophy can only be determined by a consideration of all the concomitant circumstances. Unless under the influence of chronic irritation or as a result of mechanical hyperæmia, congestions of the spleen are commonly of sudden development and of transitory duration. In ordinary inflammations, such as pleurisy, etc., the degree of congestion is so slight as to be unnoticeable; but as an epiphenomenon of the various specific fevers the enlargement occurs rapidly and acquires a prominent interest in many cases. Acute splenic tumor, for example, is almost of constant occurrence during the course of typhoid fever, and, according to Friedreich, its presence may {955} be ascertained some days before the specific symptoms of the disease have declared themselves. A similar early development has been claimed for it in diphtheria and other affections. The congested spleen of typhoid fever and of relapsing fever, however, differs from that of most other acute disorders in returning to its normal dimensions much more slowly; and it is important to remember that until the splenic tumor has disappeared there is reason to believe the danger of relapse still imminent. In most cases the enlargement disappears pari passu with the disorder that occasioned it. In malarial fevers and in septic diseases the splenic tumor may acquire excessive dimensions. Acute splenic tumor, however, never attains the dimensions often encountered in chronic congestion and hypertrophy.

PATHOLOGY AND PATHOLOGICAL ANATOMY.--Simple splenic congestion presents at first no anatomical features differing from purely physiological hyperæmia. There is simply more blood in the dilated vessels and vascular spaces, and consequently in the viscus, than is usual. Very soon, however, there is hyperplasia of the cells of the pulp. Enlargement, tension of the capsule, and diminished consistency of the spleen appear. The color will depend upon the condition of the capsule, being most dark and blue when this is thinnest. In high grades of congestion the parenchyma upon section will be found distended and semi-diffluent, and after acute malarial fever (pernicious remittent fever), the organ may resemble a bag of half-liquid pulp. Softening in varying degree may be found after acute congestion from whatever cause. In the congestions due to some infective processes at least additional factors are introduced, although as yet definite knowledge of their exact pathogenetic influence has not been attained. The observations connecting minute organisms with the origin of these affections have been so elaborate, so carefully and conscientiously reported, extend over such wide and varied fields, that it is difficult to refuse to place reliance in them. It seems that in a number of affections the presence of these microscopic organisms is constant and essential, and that the splenic congestion that accompanies them is a direct result of their presence in the spleen itself. The micro-organisms will be found infesting the cells of the pulp, and, so far as we have definite knowledge, they show peculiar characteristics according to the particular infectious disease to which the patient succumbed. While the conditions in acute splenic tumor are identical with those of inflammation, and in the affections properly designated as septic, should the life of the patient have been sufficiently prolonged, may be found to have led to the formation of embolic centres with hemorrhagic infarctions and abscess, in infectious diseases not septic they do not prove equal to the production of suppuration. Where the action is acute, resolution will speedily follow the subsidence of the febrile process. But in prolonged hyperæmia new formation will be developed, and the enormous collection of leucocytes will give a reddish-gray color to the organ. This change will also be sometimes observed in the spleens of those in whom the infectious diseases have run a more protracted course.

DIAGNOSIS.--Acute splenic tumor, if at all pronounced, may usually be diagnosticated without much difficulty. The development of an enlargement in the splenic region, with pain and tenderness to pressure, during the course of any acute febrile disease will nearly always indicate splenic hyperæmia. It may sometimes be difficult to determine whether the tumor may not have existed prior to the invasion of the present malady. In such cases one must have recourse to the previous history of the patient, or, failing in this, must observe the behavior of the tumor upon the subsidence of the general affection.

PROGNOSIS.--The prognosis of acute congestion and acute splenic tumor will depend rather upon the exciting cause. When of simple origin it is of but insignificant importance. Even in specific fevers the spleen will in most {956} instances return to its normal volume upon the establishment of convalescence. Rupture of the spleen has been known to occur in congestion from severe malarial fever, but this is a most rare accident in the absence of traumatic influences. The congestion may become chronic, and frequently does become so, in cases where the stimulus continues to exert an influence upon the spleen, as is done in chronic malarial poisoning.

TREATMENT.--The transitory hyperæmia of a brief malarial attack or of any ordinary febrile seizure will disappear with its exciting cause, and will require no special treatment. For the acute congestions of most specific fevers but little is to be done except through attention to the general condition: it is only when pain and discomfort in the splenic region are sufficient to attract the attention of the patient that measures for the relief of the congestion will be necessary. In that most common exciting cause of it, malarial fever, patients will often complain bitterly of the pain in the left hypochondrium for some time after the febrile attack has been overcome. In such cases it may be pretty safely concluded that the poisonous influence of the malaria has not been entirely overcome, and the proper employment of quinine and other derivatives of Peruvian bark, and bitter tonics, will undoubtedly prove most serviceable. In very many cases benefit may be derived from local applications. Experiment has clearly shown that the stimulation of the splenic nerves is capable of effecting a notable reduction in the bulk of the organ. Clinical experience gives similar proofs, and cold effusions, evaporating lotions, etc. will sometimes secure prompt unloading of the spleen; indeed, Mosler considers that there is danger in treating the acute splenic tumor of typhus fever of inducing unfavorable changes by the too sudden reduction of its bulk by local applications. The use of stimulating applications to the splenic region will also prove beneficial in many cases. Among the most valuable of these will be found the tincture of iodine.

Chronic Congestion and Enlargement of the Spleen.

Within narrow limits there may be simple increase in the size of the spleen from hyperæmia, without alteration of the relations between its structural parts. The common results, however, of hyperæmia of long standing are overgrowth of the elements of the reticulum, with new formation of connective tissue and hyperplasia of the pulp-tissue. This condition of chronic enlargement or hypertrophy of the spleen may develop as a result of chronic active hyperæmia or through passive or mechanical engorgement of the portal system. Chronic active hyperæmia of the spleen is in much the greater number of instances caused by chronic malarial poisoning. It also occurs as a cause or a result of leucocythæmia and of pseudo-leucocythæmia or Hodgkin's disease, and is always associated with more or less true hypertrophy of the structural elements of the organ. Enlargement from the above-mentioned causes constitutes the vast majority of those abnormalities generally designated as chronic splenic tumor. In persons living in malarious countries, and subjected for prolonged periods to the intoxicating influence, the peculiar splenic enlargement tends to become chronic. After the earlier attacks the spleen returns more or less promptly to its normal dimensions. Usually it is only after repeated attacks of intermittent or remittent fevers, and often only after exposure to the malarious influence for years, that the splenic tumor becomes established as a permanent disorder and assumes the characteristics that have secured for it the popular denomination ague-cake. Persons living in the localities referred to may develop this enlargement without ever having had unequivocal attacks of malarial fever. They will betray, however, the effects of the poisoning by malarial neuralgias and {957} neuroses or by a well-marked periodicity in the course of simple maladies, or they will exhibit its effects by the peculiar facies and by general paludal cachexia. Under these conditions the splenic enlargement sometimes attains enormous proportions.

Splenic enlargement of considerable extent may result from mechanical hyperæmia of the portal circulation from cirrhosis of the liver. It is, however, certainly not a necessary consequence of cirrhosis, since this may exist to a pronounced degree and yet the spleen remain normal--a condition that is probably favored by extensive distribution of muscular and elastic fibres to the viscus, that enable it to a great extent to regulate its own circulation. On the other hand, the spleen may be atrophied by a fibrotic contraction of its trabeculæ, the result of long-standing hyperplasia. Chronic engorgement and enlargement of the spleen may also result from mechanical obstruction to the systemic venous circulation, especially that due to insufficiency of the mitral valve, whereby obstruction to the portal circulation arises secondarily. (The ulcerative endocarditis of septic origin is associated with splenic congestion, which is, however, always of the acute active variety, and complicated for the most part with embolic abscess and hemorrhagic infarction.)

SYMPTOMATOLOGY.--Long-continued or frequently-recurring attacks of splenic hyperæmia, occurring under the stimulus of chronic malarial poisoning or of leucocythæmia or pseudo-leucocythæmia, will ultimately induce those structural changes that result in new formation. Enlargements from the two latter diseases will be more appropriately considered elsewhere. After repeated attacks of remittent or intermittent fever or other forms of malarial intoxication the symptoms of acute will gradually merge into those of chronic congestion. They will usually prevail to a more intense degree. The dragging weight of the tumor will excite pain, and may render rest upon the right side too uncomfortable to be indulged in. Hemorrhage from the stomach and bowels may occur, and at times will be excessive. The patient may be reduced to an extreme degree by the profuse and repeated losses of blood. In the intervals of the malarial attacks the temperature will be unelevated, and the pulse may be slow and irregular, though oftener feeble and rapid. All the symptoms will be, however, commingled with those from other causes. Those of malarial cachexia will sometimes be very pronounced. The pale, sallow complexion, the pallid lips, the extreme anæmia and generally unhealthy aspect, and the general symptoms accompanying such states, the history of miasmatic fevers, of characteristic neuralgias, etc., will generally be present. Oedema may be observed, but will usually be hydræmic in origin. Anomalous symptoms due to the systemic condition will be often developed when the enlargement arises from other than malarial causes.

Under the influence of the latter cause the spleen may acquire many times its normal dimensions, and may easily be felt below the border of the ribs, where its irregularly curving and notched border will serve to identify it. The tumor sometimes becomes so large that it reveals its presence by causing a bulging and asymmetry appreciable by the patient. Here, however, congestion will have been supplanted by hypertrophy. The tumor may vary greatly in size. It may fill the left part of the abdominal cavity, reaching to the pubes and distending the belly-wall with its dense enlargement, dull upon percussion, and perhaps moving within narrow limits under the hand of the examiner. This tumor may attain a size and weight many times greater than the normal. Hypertrophy once established, it may remain more or less pronounced for years, directly occasioning unimportant symptoms. It is difficult to determine the exact influence exerted by these tumors upon the duration of life.

PATHOLOGICAL ANATOMY.--In simple hypertrophy there is both hyperplasia of the pulp and of the trabecular connective tissue. The spleen is {958} enlarged, sometimes to an extreme degree, equalling fifteen or sixteen times its normal weight.[3] Such enlargement is not observed in any other form of splenic disorder, excepting in some rare cases of leucocythæmia and tumor. Its density is also increased. The capsule is thickened, and adhesions to the surrounding parts may be quite intimate. The color of the surface is darker than normal. Upon section the structure appears dense, smooth, of a dark color (from deposit of pigment), and showing to the naked eye great increase of the trabecular tissue. The pigmentation more especially observed in malarial intoxication occurs in the intervascular cords of the pulp (Rindfleisch), where it can be seen as black, flaky masses of hæmatin (the origin of melanæmia). According to Friedreich,[4] there may be a circumscribed splenic hypertrophy, consisting of little points of granulation imbedded in the pulp. In ordinary diffuse hypertrophy all the elements are involved, though the trabeculæ show the greatest increase and encroach more or less upon the pulp. The Malpighian corpuscles may show little or no enlargement. The processes are indistinguishable from those of chronic inflammation. In hypertrophy from obstructed portal circulation the organ will be dark red and very full of blood. It sometimes happens that obstructive hypertrophy terminates in fibrotic contraction, when the connective tissue will be found to have almost completely crowded out the pulp.

[Footnote 3: Hertz, Ziemssen's Cyc., vol. ii.]

[Footnote 4: Virchow's Archiv, xxiii., 1865; Ziemssen's Cyc., viii., Mosler.]

DIAGNOSIS.--Decided enlargement will usually be recognized with but little difficulty. A tumor in the left hypochondrium, occupying and transgressing the normal splenic boundaries, will probably be of splenic origin. Occasionally enlargement may be simulated by a spleen of normal size displaced downward by intra-thoracic growths or effusions or by that remarkable abnormality known as wandering spleen. The course of the primary affection in the one case, and the free movability of the organ in the other, will suffice generally to guard against error. Rarely, the tumor may be due to cancer of the stomach, enlargement of the left kidney or of the left lobe of the liver, omental tumors, fecal accumulations in the colon, or ovarian tumors. The concomitant symptoms will suffice to distinguish cancer of the cardiac end of the stomach. Percussion will reveal the presence of subjacent gases, and palpation will detect the greater hardness of the gastric tumor. Enlargement of the left kidney may be due to cancer, abscess, or other causes, and may simulate splenic hypertrophy. The renal tumor may be traced farther backward, and will not present the characteristic outline of the spleen. The clinical history and symptoms will here, again, prevent error. Omental tumor is usually separated from the splenic region by an area of resonance. Enlarged liver may be traced toward the right side of the body, becoming more noticeable as the spleen is receded from. Fecal accumulation may closely resemble splenic tumor, as it does other abdominal enlargements. The doughy consistency of enlarged spleen may be like that of the fecal mass, but one may often permanently alter the shape of the latter by the pressure of the fingers, and in any case doubt may be dispelled by the use of purgatives. Ovarian tumors may be traced into the pelvis, as may also, for the most part, fibro-cystic and fibroid tumors of the uterus and its appendages.

On the other hand, recognition of splenic tumors may be prevented by gaseous distension of the stomach and bowels, by abdominal dropsy, diffuse or encysted, by fecal distension of the colon, and may, indeed, be impossible until these conditions have been remedied. Enlargement of the spleen from simple hyperplasia must also be distinguished from other forms of splenic enlargement--from splenitis, from lardaceous degeneration, from tumors, from leukæmia and pseudo-leukæmia, from syphilitic and tuberculous {959} spleen, etc. In such cases the diagnosis will rather depend upon concomitant symptoms than upon the physical characters of the enlarged organ. Percussion and palpation will not seldom enable one to determine the presence of tumor (cancer), hydatids, etc. Pressure will often serve to elicit expressions of great tenderness in splenitis; enlargements with fluid contents will be revealed by fluctuation. In the greater number of cases where the enlargement is evident, but is without distinguishing characteristics, the general condition of the patient and the history of his illness will disclose its true nature. Lardaceous degeneration will have been anteceded by prolonged suppuration, by tubercle, by scrofula, or by syphilis, and will generally be associated with the same processes in other parts. Syphilitic disease may be indicated by the history of the patient, though in this case, of course, lardaceous degeneration could only with difficulty be excluded. Tubercle, rarely giving rise to an appreciable tumor, can only be conjecturally diagnosticated from the history and general condition of the patient. The condition of the blood and of the lymphatic system in leukæmia and pseudo-leukæmia will suffice to determine the nature of the splenic enlargement. The ague-cake of chronic malarial poisoning is usually accompanied by a degree of cachexia, as is shown in the earthy pallor of the complexion. This is often sufficient to enable one to discriminate between several forms of enlargement, for it differs from the intense pallor of leukæmia by its sallow hue, and is not at all like the hue of the complexion in lardaceous disease. The cancerous cachexia, it is true, may closely resemble it, but here the history and symptoms assist in avoiding mistakes.

PROGNOSIS.--When the hyperplastic processes have amounted to true connective-tissue formation, a complete return to normal conditions will not occur after the removal of the stimulus. The permanence of the enlargement will be proportionate to the extent of organization of the hyperplastic elements. In ague-cake some reduction in size will follow the exhaustion of the malarial influence, though the spleen probably never ceases to be appreciable as a distinct enlargement. At the same time, the enlarged organ may not, of itself, exert any specially unfavorable effect upon its bearer. Not a few persons will live for years with it, and eventually die from other causes. It may be assumed, however, that the presence of ague-cake is indicative of profound malarial cachexia, by which the powers of life are much less resistant to unfavorable influences. It may be said, in a general way, that the larger the spleen the less favorable is the prognosis. It should be remembered that a considerable proportion of persons suffering from leucocythæmia have also suffered from chronic malarial poisoning, and that the enlarged spleen of this affection may possibly have begun its morbid course under the influence of malaria.

TREATMENT.--In passive congestion relief is often secured through the use of remedies that diminish portal engorgement or enable the heart to find compensation for a damaged mitral valve--conditions in which the splenic disorder is really an unimportant concomitant. In the enlargement that has for its cause chronic malarial intoxication cinchona and its alkaloids are preferable to all other remedies, not only in arresting the new growth otherwise progressive under the stimulus of the poison, but by neutralizing the latter and facilitating the absorption of the hyperplastic elements that have not already become converted into more highly-developed tissue. To effect these objects the agents must be given in fair doses (twenty grains of sulphate of quinia daily) until the malarial cachexia shall have been overcome--until the bulk of the enlarged spleen shall have been reduced to the smallest possible proportions. To bring about the desired result the treatment may have to be continued during several months, occasionally suspended upon the supervention of symptoms of cinchonism. A drug of deserved repute {960} (probably through its anti-malarial influence) is arsenic. This should be given for protracted periods. Many remedies possessing anti-malarial properties have also been recommended and employed in these conditions. Eucalyptus and eucalyptol have recently been used with promising results, though the sanguine expectations of some will hardly be realized. Iron, preferably as a sulphate or as the tincture of the chloride, is invaluable in correcting the profound anæmia always present in these cases, though its influence in reducing the splenic bulk immediately is, at best, doubtful. Remedies competent to reduce hepatic and portal engorgement will often prove beneficial. Salines and vegetable cathartics may more especially be employed, but the use of mercurials, except for occasional administration, is almost universally condemned as productive of evil consequences.

Local Treatment.--The systematic application of cold by effusion or by ice-bags will at times undoubtedly reduce the size of an enlarged spleen. Alleviation will often be afforded by solutions of nitric acid to the splenic region, and counter-irritants are of occasional service, either by means of the tincture of iodine persistently employed or by blistering fluids or plasters. These, however, should be used with great caution in debilitated subjects, as gangrene has been known to follow their application. Mosler thinks that the practice of injecting tincture of iodine, carbolic acid, etc. into the substance of the spleen is sufficiently promising to justify further experiment. The continuous electric current and electrolysis have also been recently recommended as of advantage in reducing the splenic bulk. In cases of excessive enlargement, where accompanying or consequent cachexia threatens to end in death, extirpation of the spleen has been advised and practised. While the removal of the leucocythæmic spleen is so constantly followed by death that the operation cannot be considered justifiable, it seems that the spleen enlarged from other causes may sometimes be removed with safety. In the Lancet of Feb. 11, 1882, Herbert Collier tabulates all (until then) known cases of removal of the spleen for disease, 29 in number: 16 of these operations were upon leukæmic subjects, and had a fatal termination; 8 of the remaining cases recovered. Crédé[5] concludes from an analysis of 30 cases of extirpation of splenic tumor that the adult spleen may be removed without detriment; that its removal causes temporary derangement of the blood-making function; and that this is compensated for by activity of the thyroid body and red marrow of the bones. As bearing further upon the question of the practicability of splenectomy, should surgical art succeed in reducing the dangers immediately dependent upon the operation, are the highly interesting experiments of Tizzoni[6] and Griffini,[7] wherein extirpation of the spleen in dogs was followed by reproduction of true splenic tissue.

[Footnote 5: Centralbl. f. d. med. Wissensch., June 23, 1883.]

[Footnote 6: Arch. Ital. de Biologie, 1883, iii. 2, and i. 1.]

[Footnote 7: Ibid., 1883, iii. 2.]

In chronic congestion and enlargement of the spleen from malarial poisoning the removal of the patient to a non-malarious locality will always materially assist in the recovery of health.

Hemorrhagic Infarction of the Spleen.

The investigations of Virchow, and more recently of Cohnheim, into the pathogenesis and pathology of hemorrhagic infarction have afforded an easily intelligible explanation of the causes of the frequency of this morbid process in the spleen. A moment's reference to the anatomy of the splenic blood-vessels will show that the conditions most favorable to the production of hemorrhagic infarction in the presence of an exciting cause are here afforded. Instead of terminating in a capillary network with free and abundant {961} anastomoses, the splenic arteries end in fine pencils, opening, not into capillaries leading to venous radicles, but into vascular spaces in which traces of both afferent and efferent blood-vessels gradually become effaced. These arterioles have no other vascular communications than with the small arteries, the terminal extremities of which they are. This arrangement may be very perfectly demonstrated in injected spleens where the material has been imperfectly driven through the vascular system of the organ, so that wedge-shaped areas of successful injection become sharply defined. This distribution of the blood-vessels renders the area supplied by each almost completely dependent upon it for efficient nutrition, and almost certain to become structurally altered if its lumen should become in any manner obstructed. To this arrangement of the arteries and arterioles upon one side is added, upon the other, a valveless condition of the splenic veins, whereby regurgitation may readily occur. We have here, therefore, evidently conditions most favorable to the development of hemorrhagic infarction.

The process through which hemorrhagic infarction occurs has been definitely observed by Cohnheim. The area of the distribution of the obstructed artery or arteriole, receiving no blood-supply from anastomosing branches, undergoes disintegration. The walls of the blood-vessels as far as the nearest communicating branch participate in the process of disorganization. After a while a backward movement of the blood-current begins in the nearest still pervious vessels, and is continued into the obstructed vessels, through whose disintegrating walls the blood escapes and the hemorrhagic infarction is established. The future course of the infarct depends almost entirely upon the nature of the causes that brought it about.

In the spleen, as in other organs, the causes of hemorrhagic infarction may be widely different, though an essential condition of each is that it be competent to produce plugging of the blood-vessel. The most important cause is probably ulcerative endocarditis, in the course of which minute fragments of the endocardium or of the vegetations that have formed upon it, especially of the neighborhood of the valves, in consequence of inflammation, constitute the emboli. The plugs largely consist of fibrinous matter enveloping colonies of micrococci, or they may be derived from detached portions of thrombi, or from solid particles that may have in any way gained access to the circulatory current, as from endarteritis, from atheroma, primary emboli in the pulmonary circulation, etc.

Hemorrhagic infarction has also been described by Ponfick[8] as occurring in relapsing fever and originating in the veins, and not to be referred to any of the already-mentioned causes. It is thrombotic in origin, and due to some peculiarities of the morbid processes of the affection.

[Footnote 8: Virchow's Archiv, Bd. lx.; Mosler, Ziemssen's Cyclop., viii. p. 443.]

SYMPTOMATOLOGY.--Hemorrhagic infarction of the spleen, as such, reveals its presence by no signs during life. Its importance depends almost entirely upon the nature of its exciting cause. When this is of simple origin there is hardly ever any deleterious influence exerted upon the health of the individual. That hemorrhagic infarction was present in any given case can only be ascertained by the evidences of it discoverable after death. Rarely by its presence localized inflammation and abscess may be excited. Far different, however, is the result where the embolic material has been derived from an ulcerative endocarditis or other septic centre. In this event the infarction serves surely as the starting-point for metastatic abscess.

PATHOLOGICAL ANATOMY.--Hemorrhagic infarctions of the spleen may vary in number from one to many, and in size from that of a large shot to a bulk nearly equal to that of the spleen itself. They are usually situated at the surface of the organ in a wedge-shaped distribution, the base looking toward the capsule and causing a slight projection, the apex pointing toward {962} the deeper portions. Infarctions, however, may also occasionally occur in the central parts of the spleen. A definite wedge-shape may be destroyed by the coalescence of several neighboring infarcts.

The appearance and density of the infarction will depend very much upon its age. When recent it is of a dark-red color, of firm consistency, and of homogeneous aspect, and is surrounded by a zone of hyperæmia. As it grows older the dark color gradually fades to a paler hue, in consequence of the absorption of the color-elements of the hemorrhage, and a yellowish shade appears, from fatty degeneration of the cellular constituents. With the fading in color the infarction decreases in size; contractions and scar-formations are developed, later to become converted into bands of dense fibrous tissue. Occasionally complete fatty metamorphosis of the cellular elements may ensue and caseation of the infarct take place. The caseous mass may soften and form a cavity, or may ultimately undergo calcareous degeneration. Not very infrequently one may detect at necroscopic examinations of spleens these calcareous nodules, equal to shot or peas in size, witnesses of the bygone metamorphoses of which we are speaking. When, instead of being of simple origin, the infarct is the result of septic changes, the course is different. Coincident with or immediately preceding the hemorrhagic infarction inflammatory symptoms will develop around the embolic masses (consisting principally of fibrinous material imprisoning multitudes of micrococci), and metastatic abscess rapidly becomes established. Pus will then be commingled with the softening mass, and the microscope will reveal the swarming organisms. In the latter event the changes of the hemorrhagic infarction are much more rapid than in simple infarction, when they may be very protracted.

Splenitis.

Although it is impossible to separate acute splenic tumor and chronic splenic enlargement from the processes of inflammation, for practical purposes it is convenient to consider as splenitis only those morbid conditions in which the tendency is toward suppuration. Simple idiopathic splenitis is undoubtedly very rare, and, although formerly its symptoms were described with great detail, most recent writers are content to acknowledge an almost complete ignorance of them. Indeed, splenic abscess is often detected after death when it had not even been suspected during life.

Diffuse Splenic Abscess.--In the rare cases of idiopathic splenic inflammation the exciting cause will commonly have been a fall or blow or other violence by which the spleen has been injured, or it may have followed chronic malarial poisoning or an extension of inflammation from the capsule or neighboring parts.

SYMPTOMATOLOGY.--The rarity of this affection makes accurate description of its symptoms almost impossible. Mosler has never seen it. The descriptions of it are based, at best, upon observation of but few cases. Its onset may be sudden; more commonly it is insidious, the patient complaining of weight and dull pain in the left hypochondrium, irradiating to the left shoulder. The presence of pain depends upon the participation of the capsule in the process. Cough and dyspnoea may be present, and febrile phenomena are constantly to be observed. Vomiting, want of appetite, furred tongue, etc. will be noticeable. After a time a tumor will be detected that will, at first, almost certainly show no sign of fluctuation. Coincidently with the development of the tumor a small degree of ascites and of anasarca of the lower extremities may appear.

Up to this point the presence of abscess may only be conjectured, and indeed throughout its entire course it usually escapes positive identification. {963} Fluctuation may, however, be detected, and from its location and concomitant symptoms may reasonably be ascribed to a splenic abscess. The fluctuating tumor has been known to fill the whole abdominal cavity from epigastrium to pubes. Grisolle reports such a case where the tumor presented the appearance of ascites. In this form of splenic abscess the progress is generally insidious. Under symptoms of hectic fever, wasting, etc. the physical signs of splenic enlargement are gradually manifested until the presence of fluid may be determined. After months of suffering the patient will expire from exhaustion or from the consequences of rupture of the abscess into the abdominal or pleural cavity or into the lungs, lighting up rapidly-fatal inflammation; or, discharging into the bowel or stomach or through the abdominal wall, the abscess may temporarily improve and allow a short prolongation of a wretched life. In the event, however, of an escape of pus from the body, as through the abdominal wall, bowel, etc., recovery is possible in a very small proportion of cases. Wardell has seen such a case discharging through the abdominal parietes. Zweifel has met a similar condition. Nasse has known of recovery after the pus had been expectorated, and Webb, after discharge into the intestine. Occasionally, splenic abscess may become encapsulated and undergo caseous metamorphosis, when it may become inactive, ultimately cicatrize, or become calcareous.

PATHOLOGICAL ANATOMY.--In abscess of the spleen, when of small size, a non-metastatic origin may be recognized by the absence of micrococci from its purulent contents and of concomitant signs of blood-poisoning. When not spontaneously arrested, these abscesses attain a size not equalled by metastatic splenic abscess. The splenic substance will then be reduced to a semi-fluid or fluid mass of reddish pus enclosed within a pyogenic membrane. In extreme cases all traces of true splenic pulp and trabeculæ will be obliterated; but when the inflammatory action is less intense the trabeculæ will extend in all directions through the abscess cavity. The capsule, thickened and indurated, will have formed adhesions or will have entirely disappeared before the advancing wall of the abscess.

Embolic Abscess.

It has been shown that hemorrhagic infarction in the spleen is the result of an embolic obstruction of the splenic blood-vessels. If the embolus be simply a detached portion of an aseptic clot or fibrinous vegetation or of atheromatous degeneration, the subsequent changes will be those characteristic of the involution of hemorrhagic infarction. Under exceptional circumstances and from not understood causes inflammation and abscess may follow. These, however, are to be reckoned among the rare results of simple hemorrhagic infarction of the spleen. Altogether more frequently the embolus is derived from the ulcerative endocarditis of septic origin or from other septic centre, and consists of congeries of micro-organisms, themselves the infecting agents or the vehicles of the poison that lights up the characteristic morbid processes. A colony of these micro-organisms, lodged in and occluding splenic arteries, by the irritation of their presence and by their multiplication excite the inflammatory processes that accompany and follow the hemorrhagic infarction. Embolic splenic abscess is, then, nearly constantly a secondary result of conditions of blood-poisoning, and as such can only play a subservient part in the train of pathological events in which all parts reached by the blood-supply may be engaged. The vascular distribution in the spleen is such as to afford exceptionally favorable opportunities for the development of metastatic abscesses, and in a large proportion of spleens of those who have died from blood-poisoning they will be detected. They are rarely {964} present without the appearance of similar changes in other organs, and there is, therefore, but little difficulty in attributing them to their true cause.

SYMPTOMATOLOGY.--Unless inflammation of the splenic capsule be excited, these abscesses give rise to no pain, neither do they (except rarely) produce discoverable splenic enlargement as distinct from the general splenic enlargement always present in septic fever. Their course is usually brief, in consequence of the usually acute course of the disease that occasions them. When, in chronic pyæmia, splenic embolic abscess may develop more slowly, exceptionally palpable fluctuating tumor becomes manifest.

Fever, with all the accompanying phenomena of blood-poisoning, is present in these cases, and commonly masks any splenic alteration that might otherwise become apparent. Embolic abscess should always be suspected in blood-poisoning, though in most cases its detection could have but little influence in determining treatment.

PATHOLOGICAL ANATOMY.--Embolic abscess may develop from a hemorrhagic infarction, in which case the necrotic central mass is surrounded by a zone of inflammation which rapidly converts the whole area into a broken-down, reddish, purulent, semi-fluid matter. If the abscess supervene without the occurrence of hemorrhagic infarction, its situation is still nearly always peripheral, the wedge-shaped embolic area pointing toward the centre. It varies in size from that of a pinhead to that of a pea and larger. It consists of a necrotic centre composed of pus-cells and detritus, a surrounding mass of exudation, and a circumscribing border of hyperæmia. Microscopic examination will usually reveal swarms of micrococci. In the progress of the abscess the whole mass becomes converted into a grumous brownish fluid. The peritoneum rarely participates in the activity of the inflammation, but may form deposits of lymph over the seats of the abscesses.

Mosler[9] summarizes Ponfick's description of a peculiar splenic inflammatory process resulting from relapsing fever. It differs from ordinary embolic abscess in being limited to the splenic venous system. It may equal two-thirds of the entire spleen in bulk. It resembles in appearance embolic abscess, but the arteries remain pervious. These abscesses may heal or may enlarge and peritonitis may be excited. The possibility of their originating in a venous thrombosis is entertained by Ponfick. A peculiar inflammatory condition of the follicular tissue of the spleen has also been described by Ponfick as a result of relapsing fever.

[Footnote 9: Ziemssen's Cyclop., vol. iii.]

DIAGNOSIS.--The diagnosis of splenic abscess presents very often great difficulties, and is frequently quite impossible. In ordinary embolic abscess a diagnosis cannot be made with certainty. The existence of pyæmia with enlargement and pain would make it probable that splenic abscess had formed. In the larger abscesses of malarial, traumatic, or unknown origin the detection of a fluctuating tumor in the region of the spleen will suggest its true cause, but examination of the contents will alone clear up the diagnosis between the real disease and hydatid tumors, nephritic and perinephritic accumulations of fluids, etc. Even where the contents of the cavity are purulent, it will often be impossible to decide upon their splenic origin unless in the event of portions of the splenic tissue escaping at the orifice of the abscess. In cases of constant and increasing pain and tenderness in the splenic region, with enlargement, associated with general failure of health, splenic abscess may be suspected, and an exploratory puncture with the aspirating-needle may not only be justifiable, but imperatively called for. In all cases it must be remembered that splenic abscess of this character is a most rare disease.

PROGNOSIS.--Splenic abscess usually terminates fatally. The life-destroying influence, however, is not exerted through the spleen itself, for this may {965} be converted into a simple bag of semi-fluid contents, with complete destruction of all its tissue, and yet danger is to be apprehended only from the effects of suppuration or of rupture into the closed cavities or from peritonitis, etc. Of itself, embolic abscess rarely excites alarming symptoms, because, being usually of septic origin, the stress of the general condition is thrown more upon the whole body, or upon a number of its parts, of which the spleen is not the most important.

TREATMENT.--Treatment should be directed more toward prophylaxis than toward cure. In those congestions and hyperplasias that may result in abscess the remedies indicated for these conditions should be actively employed. The application of ice to the splenic region, of counter-irritants, the use of local bloodletting, the unloading of the intestinal circulation by saline purgatives, the proper employment of quinine, etc. in chronic malarial poisoning, seasonably adapted, may prevent the formation of abscess. In the event of fluctuation declaring itself, evacuation under antiseptic precautions should be practised; ordinarily, the most effective general treatment is that directed against the primary disease.

Perisplenitis.

Inflammation of the splenic capsule is a more common affection than clinical observation would lead one to suppose. It consists of a more or less localized splenic peritonitis, and its lesions are often found at the necropsy when its existence had not been suspected during life.

ETIOLOGY.--Its commonest cause is the extension of inflammation from neighboring parts. Chronic ulcer of the stomach may be the origin of chronic perisplenitis, leading to the formation of dense inflammatory deposits. Persons who have long suffered from miasmatic poisoning frequently develop strong adhesions between the spleen and diaphragm. And from the same cause the spleen may become closely adherent to the neighboring viscera. Chronic enteritis, perinephritic inflammation, and the like may excite it. It has been shown that the pain in splenic affections is nearly always due to the capsulitis present; and it is probable that much pain in the splenic region, stitches in the side, etc. are really the results of this inflammation. It can only be conjectured that in given cases one has to do with perisplenitis. Almost all that is known about it comes from the dead-house.

PATHOLOGICAL ANATOMY.--The simplest post-mortem signs of bygone perisplenitis are the unusually dense fibrous adhesions between the spleen and surrounding parts. These may vary within wide limits. Exceptionally, the spleen will be found intimately adherent to surrounding parts throughout, and can only be separated from them by tearing it away. Under these circumstances, mostly in chronic malarial subjects, the capsule will be uniformly much thickened and sac-like. The splenic tissue may be reduced to a tarry, semi-fluid pulp that oozes through the lacerated walls. Sometimes the capsule of the spleen will show localized thickenings of dense cartilage-like consistency, usually on the convex surface. According to Wilks and Moxon (p. 487), "section shows them to be laminated parallel to the surface, and the microscope reveals a fibrinous structure, the fibres being arranged in dense areolated lamellæ." The same authors consider these to be among the most decisive evidences of chronic alcoholism. They may become calcified (Orth). It is not unlikely that they may often be the effects of syphilis. They undoubtedly often occur in syphilitic subjects. The interest attaching to them is entirely a pathological one, as the affection is never detected during life, and as they probably exert no influence whatever upon the duration of life or even upon the well-being of their bearer.

{966} Lardaceous Spleen.

The spleen is more liable to lardaceous or amyloid disease than any other organ of the body. And, although in the further course of the degeneration other organs and tissues inevitably become implicated (unless the patient die of some intercurrent affection), the spleen may in the earlier stages be alone involved. In 58 cases of lardaceous disease compiled from the records of the London Hospital, the spleen was the only organ in which the degeneration was detected in 28 cases, while it remained unaffected in only 10 cases.[10]

[Footnote 10: Turner, Transactions Patholog. Soc. Lond., vol. xxx.]

The tendency of lardaceous disease toward generalization shows that it is under systemic and not local influence, though whether this influence is exerted in depositing preformed albuminoid material in the affected parts (infiltration), or in bringing about a special alteration in situ (degeneration), is even yet not definitely decided. Upon the one hand, the infiltration theory is upheld by Rindfleisch, Billroth, and others, while Fehr, Kyber, Cohnheim, and others consider it to be a result of tissue-metamorphosis. Cohnheim concludes that the infiltration theory could only be accepted upon the presumption that the lardaceous material is not a soluble but a corpuscular substance, or that it is only deposited in consequence of some acquired predisposition of the part. He regards the process as a local degeneration due to general causes in which the lardaceous material is derived from the pre-existing albumen of the tissues. According to Virchow and Kyber, there is brought to the tissue whose nutrition is somehow lowered a substance, between which and a malarial substance formed in loco an intimate combination occurs, the result being lardaceous material (Ziegler).

This form of degeneration involves the spleen in one or both of two ways. It may appear as scattered points throughout the splenic substance, corresponding to the Malpighian bodies and presenting a resemblance to grains of boiled sago, or in a diffused manner, constituting true lardaceous spleen, in which the entire organ appears to be involved.

ETIOLOGY.--As in lardaceous disease of other parts, by far the most common causes of its development in the spleen are prolonged suppuration, especially of bone, the suppurative processes of phthisis pulmonalis and of scrofulosis. The next most frequent causative influence is syphilis, whether accompanied by prolonged suppuration or by the cachexia so often observed in this disorder. Chronic malarial poisoning, chronic diarrhoea, chronic alcoholism, and occasionally the less-rapidly fatal malignant new growths, may induce the degeneration. Exceptionally, it has been observed where no other general disturbance of nutrition had existed. The various causes of lardaceous degeneration have in common one feature, chronicity, though Mosler quotes from Cohnheim instances where lardaceous spleen was discovered in one case five months after joint injuries had been received, and in another four months after a compound fracture of the right leg.

SYMPTOMATOLOGY.--Lardaceous disease of the spleen is usually associated with similar disease of other organs--the liver, kidneys, stomach, intestines, heart, etc.--and its symptoms are so frequently accompanied by those of the affection that has given origin to it that it must always be difficult to distinguish them as attributable to the condition of the spleen itself. Profound anæmia with an appearance of cachexia is always present in advanced cases. Milder cases may reveal themselves by no signs. The symptoms arising from other parts implicated in the degeneration may completely mask those depending upon the spleen. When the stomach is involved, vomiting and hæmatemesis even to a fatal termination may occur, or uncontrollable diarrhoea from intestinal changes may supervene. Splenic enlargement is not {967} unusually accompanied by enlargement of the liver. Ascites, however, is always a rare accompaniment.

Rarely, the spleen attains enormous size, and may then occasion sensations of weight and tension, and occasionally acute pain from implication of the capsule in inflammatory action. When the organ can be felt through the abdominal walls it will generally be hardened, painless, and with its boundaries much thicker and rounder than normal.

PATHOLOGICAL ANATOMY.--As has been already remarked, lardaceous disease of the spleen is observed in two forms. In both the spleen is enlarged and hardened. Its structure presents a tough, waxy consistence, and the organ has entirely lost its friability. In sago spleen, light-brown or grayish waxy bodies are scattered throughout the splenic structure. The pulp may remain quite healthy, or it may also be involved. These sago-like bodies correspond to the enlarged and lardaceous Malpighian corpuscles, and stand out with some prominence from the general surface. They may vary in size from that of a pinhead to that of a small pea. The color of the spleen may shade from a pale fawn color to a reddish-brown. In many cases where the parenchyma is involved there will be exhibited scattered areas of semi-transparent, wax-like material.

In the diffusely lardaceous spleen the organ is enlarged throughout, pitting to pressure, and upon section presenting a waxy, semi-translucent appearance, usually of a reddish-gray, but sometimes of a deep-red, color. Instead of a pulpy, easily broken-down condition of the splenic parenchyma, there will be found a dense tissue that can be cut into tough, glistening slices. Minor degrees of the change cannot be readily detected by the unaided eye, and even in advanced cases the judgment will often be at fault. Under these, and in fact under all circumstances a correct conclusion as to the nature of a given change can only be reached after the employment of reagents that exert peculiar influences over the lardaceous material. The action of iodine upon this material is quite characteristic. If a watery solution of iodine with iodide of potassium be applied to the cut surface of the suspected organ, the normal portions will be stained a yellowish color, while those parts that have undergone lardaceous degeneration will assume a rich mahogany red or brown, which will become violet or purple upon addition of sulphuric acid. This latter reaction is not constant, and may usually be omitted. Cornil has recently proposed as a test a solution of methyl-aniline-violet, which possesses the property of staining lardaceous matter red, while ordinary tissues will be stained a deep, bright blue. This reaction possesses the advantage of being permanent and very delicate, and on that account preferable for microscopic examination of specimens. According to Cohnheim, this reagent enables one to distinguish commencing lardaceous change.

In lardaceous disease of the Malpighian corpuscles the alteration will be found to begin in the arterial twig to which the corpuscle is attached, soon extending to the entire tissue of the corpuscle, which it causes to enlarge considerably. When the splenic pulp is attacked it is said to be the vessels of the pulp that are first involved. It is held by most pathologists (Virchow, Kyber, etc.) that the change is chiefly seated in the muscular coat of the small arteries, but that the intima is also very frequently affected, and that occasionally all the coats are involved. Thence the degeneration spreads to the cells and nuclei of the splenic tissue. Later investigations, however, seem to make it probable that the lardaceous degeneration is mostly limited to the connective-tissue trabeculæ and walls of the venous sinuses; that the pulp-cells are for the most part not implicated, but that they disappear in consequence of the pressure of the ever-increasing lardaceous material and the consequent anæmia (Cohnheim, Ziegler).

DIAGNOSIS.--This will depend more upon the history and concomitant {968} symptoms and general condition of the patient than upon any positive evidence to be gained by special reference to the spleen. In a patient predisposed to lardaceous degeneration by any of the influences enumerated above the presumption in favor of splenic lardaceous disease is strong if, in addition to splenic enlargement, there is evidence of hypertrophy of the liver and albuminuria, indications of the participation of other organs in the process, and an anæmic and cachectic appearance of the individual always observed in advanced degrees of the degeneration.

PROGNOSIS.--The prognosis is almost always unfavorable, not so much on account of the splenic condition as from the general depreciation of the powers of life. The disorder being progressive, the tendency is toward death by complications resulting from degenerations of other organs. And yet it seems quite probable that mild grades of lardaceous degeneration may be entirely recovered from occasionally; but this will be almost invariably in cases where the spleen alone is implicated. At all events, when not advanced it may be long held in abeyance. The duration of the disease generally is indefinite and may cover a space of years.

TREATMENT.--The treatment of lardaceous degeneration of the spleen will consist rather in combating its exciting causes than in efforts directed toward the condition of the spleen itself. It may, however, be possible to effect some good by resorting to remedies supposed to be useful in subduing ordinary splenic enlargement.

Echinococcus of the Spleen.

Echinococci invade the human body in the United States far less frequently than in many other countries, where the canine race occupies much closer relations with man (as in Iceland). The echinococci are the larval forms of Tænia echinococcus, a tape-worm of minute size inhabiting the intestinal tract of the genus Canis, more especially that of the dog. The ova of the tæniæ are voided in countless numbers in the feces of their hosts. Still unhatched or in an embryonic form, they are thence conveyed through the medium of water or otherwise to the stomach of man, whence the embryos (scolices) escape into the tissues and develop into ordinary hydatid cysts. Rare as is this affection in the human body, it is relatively extremely uncommon as implicating the spleen, and recorded instances of its occurrence are not numerous. Hydatids of the spleen may coexist with those of other parts, and in occasional instances are said to be secondary to these. They are commonly encountered about the middle period of life, and appear to affect the sexes in equal proportions.

In cases of multiple hydatid cysts in different parts of the body it has been asserted, upon the one hand, that a single older cyst serves as the parent cyst, germs from which become transplanted in other localities through the blood. This view receives some support from the fact that one cyst, usually seated in the liver, is commonly much larger than the others. An objection to its universal acceptance, however, as pointed out by Budd, is that it is very difficult to imagine that a germ from a larger cyst can travel through the portal vein, against the current, toward the spleen, mesentery, etc., to form a secondary cyst. On the other hand, it seems likely that an individual exposed to infection by the echinococcus would be liable to ingest many scolices at one time or on repeated occasions, and that the differences in development depend upon varying degrees of assimilative power on the part of the parasite and of the conditions of its environment.

SYMPTOMATOLOGY.--Whether echinococcus of the spleen will betray symptoms of its presence depends upon varied circumstances. Small cysts, {969} certainly, may occasion no signs, subjective or objective. Cysts may even attain very large dimensions without exciting discomfort to their bearer, and may consequently escape detection. Pain may precede the appearance of a tumor, but will be irregular and paroxysmal, increasing in severity with the growth of the cyst. The most constant annoyance, however, is that occasioned by the size and weight of the enlargement. The patient may detect its presence accidentally, or his attention may first be directed to it by his medical attendant. He may give a history of its growth during a number of years without its having occasioned more than passing uneasiness.

The tumor may exceptionally attain a large size, nearly filling the left side of the abdominal cavity. It may encroach upon the area of the thoracic cavity. Upon examination, the tumor, when of sufficient size, will be rounded, not resembling the appearance of a simply enlarged spleen. Fluctuation will be detected, and occasionally the peculiar hydatid thrill, upon the diagnostic importance of which great stress has been placed. This, however, is a very inconstant sign, and in the majority of cases is not to be discovered. Frerichs only found it where the sac was not tense and contained other vesicles. A peritoneal friction sound may sometimes be detected by the ear placed over the region of the tumor. These cysts differ from other fluctuating tumors in being of very slow growth, remaining almost without change for years, and in exciting no constitutional reaction, unless, as is quite possible, inflammation of the sac is developed, when rigors, hectic, and other symptoms indicative of suppurative inflammation will be observed. Pressure of the tumor upon the stomach may excite anorexia, vomiting, epigastric uneasiness, and gastric catarrh. If the pressure is exerted upon the portal vein or vena cava, dropsy may result; if upon the bowel, constipation may be produced.

It is possible for the development of the cyst to be arrested through the death of the echinococcus. This may occur if it is of small size. Its walls may then become calcareous, and the mass will cease to exert any injurious influence upon the host. In other cases, as a result of inflammation, rupture will take place, and the contents of the cyst, with the characteristic formations, will escape into the peritoneal, pericardial, or pleural cavities, or into the alimentary tract, the urinary passages, or even into the vena cava; or they may be discharged through the body-wall. In any of these events a fatal termination is almost inevitable. Rupture may also occur in an unaltered cyst from any sudden or excessive violence. Death will usually speedily ensue from collapse or as a result of inflammation of the peritoneum. Finally, complete recovery will sometimes be secured through treatment.

DIAGNOSIS.--Echinococcus of the spleen presents no characteristic symptoms. When the tumor is small and escapes observation, or when the fluid nature of its contents cannot be recognized, its existence cannot be determined. In larger tumors the hydatid thrill will, when present, assist the observer, and the presence of fluctuation will of course serve to exclude all solid enlargements of the spleen from consideration. Abscess will differ in its shorter course, its rapid increase in size, and its inflammatory symptoms, the general condition contrasting with the excellent condition of health usually observed in simple hydatid tumor. The diagnosis will become greatly obscured in the event of inflammation of the cyst. Certainty can only be attained through an exploratory puncture and examination of the contents of the cysts. These will consist of a clear, non-albuminous fluid, rich in sodium chloride, and revealing the echinococcus scolices and hooks and membranous shreds when examined under the microscope. Doubt may arise where inflammatory changes have made the fluid albuminous and where the scolices and hooklets have been destroyed or do not accompany the escaped fluid.

{970} MORBID ANATOMY.--The spleen may be almost destroyed by the hydatid cysts, which, usually single, may exist in large numbers. According to Wardell,[11] "they are seldom found in the pulp, usually in the gastro-splenic epiploon or in the cysts constituted of the serous investment." The cysts consist of a thick fibrous investment and an inner parenchymatous layer, from which the little heads develop in tiny vesicles. Compound systems, one enclosed within the other, are thus formed, varying from the size of a pea to that of a marble, and even very much larger. The cysts may undergo atheromatous or calcareous degeneration. In these cases the echinococci are destroyed, and the mass becomes encapsulated in a calcareous envelope and remains quiescent. The microscope will reveal the remains of the echinococci, even after long periods. Where rupture has taken place the rent in the cyst will have allowed characteristic matters to escape into the communicating parts, where they may be detected.

[Footnote 11: Reynolds's System of Medicine, vol. v.]

The PROGNOSIS of echinococcus of the spleen is always serious, usually most unfavorable. The best results are observed in those cases where, the cyst being small, spontaneous arrest of development has occurred. Puncture of the cyst and partial evacuation of its contents, when practicable, increase what would otherwise be almost hopeless chances of ultimate recovery in cysts of moderate and large size.

TREATMENT.--The only treatment that promises good results is the evacuation of the cyst fluid. Murchison recommends the removal of the fluid with a very small trocar, whereby the admission of air into the cavity is avoided. The withdrawal of the fluid is sufficient to destroy the life of the parasite, and in favorable cases to secure the degenerative changes of which mention has been made. The adoption of antiseptic precautions will undoubtedly increase the chances of recovery. Unfortunately, a certain number of cases will run into suppuration, when all the dangers of suppurating cavities have to be encountered, and must be treated in the usual way. Various injections into the cyst-cavity have been recommended, but they do not seem to afford better results than simple evacuation. These will probably most successfully be employed in cases where the cyst has formed inflammatory adhesions to the skin, which may be effected through the external application of caustic agents capable of exciting inflammatory changes in the deeper parts (Vienna paste, etc.). Injections may be then made through incisions carried into the cyst, without danger of exposing the peritoneal cavity. Internal medication, except for general purposes, has no efficacy in the treatment of these tumors.

Syphilis of the Spleen.

The spleen is not very frequently affected by syphilis. Nevertheless, this viscus may become the seat of syphilitic disorder during either its early or late phases. It has even been asserted by Weil that the spleen may become enlarged in the interval between the appearance of the primary sore and the first cutaneous eruption. Whatever changes the spleen may undergo during the course of early syphilis are essentially of the simple congestive type, and are comparable to the acute splenic enlargements of the ordinary specific fevers; certainly, no essentially syphilitic changes can be detected at this stage. In fact, throughout the whole secondary period the splenic derangement is of the nature of simple hyperplasia. In the later stages of syphilis there is a more permanent enlargement of the spleen, due to a chronic interstitial inflammation that should be distinguished from that very much more common result of old syphilis, lardaceous degeneration. The histological characteristics of these enlargements are not known to differ essentially from the simple chronic enlargements of the spleen already considered.

{971} It is only toward the end of the secondary period, and during tertiary syphilis and in inherited syphilis, that products essentially syphilitic can be recognized. Gummy infiltrations and tumors of the spleen have been observed by a few writers--not, however, clinically, but for the most part in the dead-house. These tumors are found scattered throughout the substance of the organ, but most commonly near its surface. They vary in number within not very wide limits, and in size from that of a pinhead to that of a pea or larger. They may be sharply circumscribed (but not encapsulated) or more diffused. The portions of the spleen affected become changed by the syphilitic material into grayish-red, homogeneous masses in recent cases. At a later stage they are "gray or grayish-yellow, homogeneous, somewhat dry, tough, almost cheesy."[12] The spleen under these circumstances is, as a whole, somewhat enlarged.[13] Gummy tumors of the spleen may be confounded with tubercle and old hemorrhagic infarction.

[Footnote 12: Wagner, Mosler, Ziemssen's Cyclop., vol. viii. p. 485, Am. ed.]

[Footnote 13: Gold, Viertelj. f. Derm. und Syph., 1880, p. 463.]

There is a form of circumscribed enlargement from new growth that is sometimes observed in the spleens of syphilitics, and which is probably of syphilitic origin, producing changes similar to certain forms already described as a variety of perisplenitis. It is situated at the surface of the spleen, and consists of hard whitish or pale-yellow plates but slightly elevated above the normal level, but of considerable superficial extent. When incised, these plates remind one of cartilage.

Splenic enlargements are common in the subjects of inherited syphilis. According to Cornil, infants syphilitic by inheritance have very frequently enlarged spleens, the capsule being inflamed and thickened and the splenic tissue abnormally hard. The organ may thus become sufficiently enlarged to be detected by palpation. Sée considers that enlargement of the spleen is present in one-fourth of all cases of inherited syphilis, and Haslund reports splenic enlargement in 58 of 154 necropsies of such infants.

The clinical signs of syphilitic spleen are almost beyond recognition, if indeed they can be said to exist. Circumstances of growth, etc. may excite the suspicion that a given splenic tumor may be syphilitic. Jullien, it is true, describes symptoms of splenic syphilis, but his views do not seem to be well founded.

TREATMENT.--In recent enlargements therapeutics may effect much in reducing the tumor, and the facility with which its reduction is effected will afford a valuable indication of the success of treatment. Gummy tumors are probably within the reach of antisyphilitic treatment, and it is not unlikely that some of the shrunken, indurated areas often detected post-mortem, and usually ascribed to infarctions, are in reality due to the cicatricial remnants of old gummata. Chronic diffuse splenic enlargements of syphilitic origin are but little influenced by treatment.

Rupture of the Spleen.

The peculiar texture of the spleen renders it especially liable to rupture--more so than any of the other abdominal viscera. By far the most common cause of splenic rupture is external violence from blows, kicks, falls, squeezing force, and wounds incised or punctured. It may be the direct result of the injury, or the rent may be made by the penetration of broken ribs or of foreign bodies. The rupture may even occur spontaneously from causes located within the organ itself. It has been previously observed that in the enlargement accompanying the acute infectious fevers, malarial fever, etc., while the distension of the capsule renders the spleen tense and elastic, {972} section through its substance will often reveal a semi-diffluent condition, the exact nature of which is not well understood, but which undoubtedly originates in excessive vascularity. This occurs especially in malarial fever and typhus. Rupture may here take place spontaneously, or, as is commonly the case, a very slight degree of violence is sufficient to produce it: a wrench, the effort to preserve a disturbed equilibrium, an otherwise insignificant blow, may determine the lesion. Pregnancy and the puerperal state may be the predisposing causes to the accident, and vomiting has been known to produce it. It has also been known to follow the softening and breaking down of a hemorrhagic infarction or the rupture of varices and aneurism. The normal spleen is only with the greatest rarity subjected to a degree of violence sufficient to rupture it, while in countries where enlargement of the spleen is of common occurrence, as from malaria, the accident occurs more frequently.

SYMPTOMATOLOGY AND COURSE.--When the rupture is of traumatic origin there may be no marks of external violence: the symptoms usually are those that follow sudden and great losses of blood, faintness, pallor following intense pain in the splenic region, frequency and weakness of pulse, sighing, coldness of the extremities, and the rapidly developing signs of profound prostration. A fatal termination usually quickly follows the rupture. Where the hemorrhage is not immediately great the patient may not succumb at once, but may live for hours, even days--nay, may even recover, as has occurred in the experience of some observers. Wilks and Moxon saw a case of splenic laceration where five ounces of laminated clot in process of absorption were found lying upon the spleen, death having occurred eighteen days after the accident in consequence of abscess of the brain. In cases where rupture has taken place, perhaps from very slight violence, in a spleen enlarged and softened from disease, the above-mentioned symptoms may have been preceded by pain and a sense of weariness in the splenic region, and by distinguishable enlargement of the organ.

PATHOLOGICAL ANATOMY.--Except in injuries caused by the penetration of foreign bodies or fractured ribs the rupture will usually be linear, and either straight, curved, angular, or stellate. If the rupture have occurred spontaneously it will probably be single, but in the event of its following violence it will most often have resulted at several places. In cases of traumatic splenic rupture in persons suffering from chronic malarial poisoning, Konaraloff[14] invariably found the rents in the lower portion of the organ, the greater ones on the outer surface, the smaller ones mostly on the inner surface near the hilum. They were widely gaping and deep. In ruptures consequent upon disease alone or slight violence to a diseased organ the spleen will usually be found enlarged, sometimes to three or four times its normal volume, with its substance softened and of a cherry-red color. In such cases signs of bruising or injury to the integument will not usually be discoverable. Splenic hemorrhage has been known to occur from the rupture of varices and aneurism, in which case characteristic appearances have been found after death. After death from rupture of the spleen the abdominal cavity will be more or less filled with blood, dark and coagulated. Though the contrary has been held, it is doubtful if multiple rupture of the spleen can be regarded as certainly indicative of a traumatic origin.

[Footnote 14: Lond. Med. Rec., No. 97, 1883, p. 259.]

Tubercle of the Spleen.

Tubercle not unfrequently attacks the spleen, but only as secondary to general tuberculosis. Wilks and Moxon indeed think the larger nodules of tubercle may be primary, but there seems to be no evidence in support {973} of this opinion. As a symptom of general tuberculosis, splenic enlargement from congestion, simply and quite without any specific deposit, is observed as a form of acute splenic tumor. It is at the later stages of general tuberculosis that distinct deposits of tubercle are formed in the spleen, and these are consequently almost always crude. They are generally scattered throughout the pulp, and, according to Billroth, they but rarely affect the Malpighian corpuscles. They are of very small size, and may be present in great numbers; their color is grayish and they are translucent, and only the largest show the yellow tinge of commencing fatty degeneration. According to Orth, they are not always easily distinguishable from the Malpighian bodies. Occasionally, and especially in scrofulous children, larger nodules are formed by the confluence of several tubercles that may equal a pea in size and present numerous yellow points of caseation.

It is usually impossible to diagnosticate the existence of splenic tubercle during life. After death the general splenic tissue will be darkened from hyperæmia and the tubercles surrounded by a vascular halo. When incised the tubercles will stand out from the tissue in which they are imbedded, unlike the Malpighian bodies, and when exposed to a stream of water the latter will disappear, while the tubercles will remain unaffected.

Tumors of the Spleen.

The spleen is very rarely invaded by new growths other than those already mentioned, and then almost exclusively either from direct extension from other parts or by metastasis. In pseudo-leukæmia or Hodgkin's disease the spleen is usually enlarged by a hyperplastic process quite like that of leukæmia. In that variety of this disease that has been called lympho-sarcoma, in which the spleen is invaded subsequently to the implication of the lymphatic glands, especially those of the cervical region, the Malpighian follicles may become enlarged, and even attain the size of walnuts. They contain spindle-cells and connective tissue. The trabeculæ likewise participate in the enlargement. Apart from the hyperplastic follicles thus occurring and also seen in leukæmia, small-pox, scarlatina, etc., lymphoma has been observed by Virchow, Weichselbaum, and others. The tumors consist of bright grayish-red or reddish, not sharply defined, nodules projecting from the dark-red mass of the spleen. Primary sarcoma is said to have been observed in the spleen, but malignant tumors of this organ are usually secondary growths, and even thus occurring are exceedingly rare. They are soft and very rapidly-growing sarcomata and carcinomata. As a rule, they depend upon malignant disease of the liver or abdominal glands through metastasis or by extension of growth. They sometimes grow with almost incredible rapidity. The symptoms are very obscure, and the presence of the malignant infiltration cannot be detected unless hard nodulated masses are formed, which become perceptible through the abdominal wall, as in hepatic cancer. The prognosis is always bad, and depends generally upon the existence of splenic cancer only in so far as this indicates the dissemination of the primary affection and becomes the forerunner of the cancerous cachexia. Fibroma and angioma have also been encountered in the spleen: they are both exceedingly rare. The latter has been known as a pulsating tumor (Langhans).

{974}

DISEASES OF THE THYROID GLAND.

BY D. HAYES AGNEW, M.D., LL.D.

The thyroid body occupies a very important position in the neck, being closely related to the larynx, the trachea, the carotid blood-vessels, the pneumogastric, sympathetic, and recurrent laryngeal nerves. These relations render quite intelligible the phenomena which are so frequently present when the gland becomes the subject of disease. It is richly supplied with blood-vessels from the external carotids and the subclavian arteries.

Notwithstanding the obscurity which enshrouds the physiological function of the gland, there are good reasons for supposing that its office in the animal economy is not an unimportant one: indeed, its presence, not in the vertebrata alone, but also in birds, reptiles, and fishes, tends to strengthen this conclusion. The experiments of Zesas appear to show that the thyroid body plays an important rôle in regulating the supply of blood to the brain, and also of supplementing the work of the spleen. The place, therefore, of the gland in the body as an appendage to the vascular system appears to be well chosen.

Congenital absence of the thyroid body is uncommon, though it has been noted by a few writers. Curtin[1] met with one case in which the gland was replaced by a mass of fat. Possibly in this instance the fat was the result of a morbid change in the thyroid, and not an evidence of the latter having never been present. Beach[2] furnishes another case where on dissection no trace of the gland could be found. Hyrtl speaks of the isthmus being frequently absent--a fact observed by other anatomists.

[Footnote 1: Lancet, 1850, vol. ii. p. 25.]

[Footnote 2: Medical Times and Gazette, May 30, 1884, p. 603.]

Goitre.

Various names have been employed by different writers to designate enlargements of the thyroid body. Among these may be named bronchocele, tracheocele, thyrophraxia, Derbyshire neck, struma, and goitre. Among English-speaking people the disease is generally spoken of as goitre or Derbyshire neck.

Hypertrophy of the gland may be either general or partial; when general--that is to say, involving the entire body--the term symmetrical or bilateral is employed to designate the enlargement; when confined to a single lobe, it is said to be asymmetrical or unilateral. Not unfrequently limited portions or small areas of one lobe only are affected, causing irregularities or nodosities which may be readily detected by the eye or the touch.

SYMPTOMS.--The earliest evidence of bilateral goitre is the appearance of an unusual fulness and breadth of the lower part of the neck or that part between the sternum and the larynx. This fulness extends laterally under the sterno-cleido-mastoid muscles, partially effacing the suprasternal fossa, {975} and is entirely unattended by pain, heat, redness, or other sign of inflammation. When the disease is unilateral, the swelling is seen to extend from the side of the trachea and larynx outward under the sterno-cleido muscle. The tumor, in consequence of its attachment to the trachea, follows the movements of the latter, and hence will be seen to rise and fall during the act of swallowing or of deglutition.

The progress of the enlargement varies greatly in different cases. After its first appearance it may remain quiescent for years, scarcely causing any change in the appearance of the neck which could be deemed a deformity; in other instances the growth will be progressive, attaining to the size of a goose egg, when it may again remain stationary. It is not common in the United States to meet with those excessive hypertrophies of the thyroid so common in Switzerland, where the gland extends up behind the ears, outward to the margins of the trapezii muscles, and hangs down in front of the sternum a large pendulous mass and imparting a most hideous appearance to the patient.

Pressure Symptoms and the Attendant Phenomena.--It is very remarkable to what a degree hypertrophy of the thyroid may reach without giving rise to any marked functional disturbances. This is due, no doubt, to the character of the enlargement, the cystic and vascular causing less inconvenience than the fibrous or more solid varieties. The pressure symptoms which may ensue are--first, difficulty of respiration. This is likely to follow when the central portion of the gland enlarges in common with the lateral masses, thereby causing pressure directly upon the trachea. This pressure may result in softening, and even complete absorption, of one or more of the rings of the trachea. An irritative cough may appear in the course of the hypertrophy, which is to be referred to the encroachment by the gland on the pneumogastric nerve. Hoarseness and a peculiar croaking voice are also sometimes witnessed, indicating the contact of the tumor with one or both recurrent laryngeal nerves.

Redness of the skin and elevation of temperature on one side of the neck are occasionally present, and sometimes accompanied by dilatation of the pupil of the eye corresponding to the affected side. These symptoms result from pressure upon the sympathetic nerve, and may exist in either unilateral or bilateral goitre. When associated with the latter form of the disease, the sides of the tumor will be found asymmetrical.

GEOGRAPHICAL DISTRIBUTION.--Goitre is met with in all parts of the world. There are, however, localities in which it prevails to a remarkable extent, assuming, indeed, the importance of an epidemic disease. In some portions of Switzerland, as in Savoy and in the Tyrol, there are villages in which scarcely a single inhabitant escapes. The disease is very common in Piedmont and in all deep valleys of the Alps, the Pyrenees, the Apennines, and about the foot-hills of the Cordilleras. In the valley of the Maurienne, Larrey states, nearly all the residents were subjects of goitre. According to the government reports in Piedmont and Savoy, there are 22,371 persons afflicted with bronchocele. There is a notable prevalence of the disease at Schlettstadt on the Rhine. In France the districts where the largest number of cases of goitre is observed are St. Aubin and Rosieux. These places, with others less noteworthy in the same country, it is estimated, furnish not less than 500,000 cases of the disease. In the government of Irkoutsh, which is drained by the sources of the Lena and its tributaries, there were in 1870, according to Hachine, as many as 3400 persons laboring under goitre. Among the inhabitants of Siberia antecedent to the conquest by Russia the disease was scarcely known. Its prevalence after this event was attributed to the habit adopted by the Russians of living in heated and uncleanly rooms, altogether unlike the Siberians, who spend most of their time in the open air. {976} Humboldt speaks of goitre being so common in Honda and Moussa, towns contiguous to the Magdalena River, that very few of their inhabitants escaped the disease.

In England the counties of Derbyshire, Surrey, Nottingham, and Norfolk furnish a large number of cases. In this country New Hampshire, Connecticut, Vermont, and New York are the States which supply the most examples of goitre. In Lower Canada goitre is also quite common.

In Switzerland the disease is frequently associated with mental imbecility (cretinism), though it is not at all established that between the two there exists any necessary connection, as cretinism is often met with in persons free from goitre, and the latter in those whose intellectual powers are unimpaired. Indeed, it has been observed by Burns, that in some countries where goitre is very prevalent cretinism is exceptionally rare; nevertheless, the observations of Lemon and the experiments of Horsley are of a character to leave the relation between the two still an open question.

CAUSES.--The causes of goitre are quite obscure. The disease is in some way associated with countries the topographical features of which consist in high mountains and deep valleys. In illustration of this fact we have only to cite the great prevalence of the disease in Switzerland, in the central mountainous parts of Asia, on the Himalayas and the Andes, as also in the mountains of Brazil. In Europe it may be said that goitre is much more common in the south and south-west countries than in the north and north-west. Sea-coasts are generally exempt from the disease. Bardeleben during the many years in which he acted as chief of the surgical clinic at Greifswald saw only two cases of goitre.

The use of glacier- or snow-water has been charged with the production of this evil, containing as it does large quantities of carbonic acid and other matters not generally found in pure potable water. In opposition to this view we are able to present the testimony of Captain Gerard that in those portions of the Himalayas where the inhabitants for a number of months in each year drink snow-water goitre is really less frequently observed than among those who live at the foot-hills of the same region. This coincides with what Lebert states, that if water from the regions of ice and snow constitutes a cause of goitre, then we should expect to find the disease increasing more and more as the glaciers are approached, when, really, just the reverse is the case, the subjects of such enlargements being seen in greater numbers at the bottom of valleys than in the more elevated regions. The Polar expeditions of Lenstake and Kolleweg, undertaken in the years 1868 and 1870, also contradict the supposed connection between goitre and ice-water, as not a case of the disease was reported, notwithstanding the men drank nothing else; and in Sumatra, where snow is never seen, goitre is quite common. Nor is there any satisfactory evidence that lime- or magnesia-water, also charged with exerting a determining influence in the causation of goitre, has anything to do with its existence. The testimony of Humboldt as to the rareness of the affection at Mariquita, where the water is strongly impregnated with lime salts, and my own observation that throughout the Pequea and Conestoga valleys, both limestone districts, goitre seldom occurs, are inimical to such a theory. From St. Maurice to Martiny in Wallis, Lebert speaks of goitre being very common, notwithstanding the absence of lime formation.

That water, however, does become the medium for certain materials which, taken into the system, produce enlargements of the thyroid, is unquestionably true. In corroboration of this statement we have two notable facts recorded by Frank, who says that at Rheims, where goitre was very common, quite one-half of the tumors disappeared after the source of the old water-supply was abandoned and the town supplied by a branch from the river Verle. {977} And again at Stenseifen, near Schmideberg, where goitre prevailed as an endemic, the disease disappeared on the closing of a fountain which furnished water to the inhabitants of the place.

Atmospheric causes have also been invoked in order to shed light on the production of goitre. Thus it is said that the common occurrence of the latter in very deep valleys, so overshadowed by the dense foliage of timber as to prevent a proper interchange or circulation of air, is favorable to this theory; yet as against this view we have the statement of Humboldt, who says that on the plateaus of Bogota, which are swept by constant currents of air and are quite sterile in vegetation, goitre is common.

That local or geological conditions do exist which are directly concerned in the development of endemic goitre cannot be gainsaid, and these of so active a nature that persons coming from remote districts into such goitrous centres and entirely free from all enlargements of the gland, are liable to suffer in common with the native born. Not only so, but, as has been observed by Virchow, even domestic animals in such localities become subjects of the disease.

The very careful study of this subject by Labour of Newcastle, England, furnishes strong evidence that water passing through calcareous soils alone had little if anything to do with goitre, but when such soils were impregnated with ferruginous and earthy salts the geological conditions were present for developing the disease.

Enlargement of the thyroid body is occasionally seen as one of the late manifestations of syphilis, usually bilateral and attaining in some instances a great size.

Gestation is another and not an uncommon cause of goitre, the tumor appearing in the last months of pregnancy or immediately after parturition. Three cases clearly traceable to the above cause are under the writer's care while penning this article. It is in such cases that the tumors sometimes grow with frightful rapidity. Roberts reports three cases in primiparæ, all of which ran an acute course and terminated fatally by asphyxia.

In Graves' or Basedow's disease goitre forms one of the elements in the morbid circle, and when thus associated may be regarded as a neurosis.

VARIETIES.--Goitre appears under different forms, and not unfrequently one variety is transformed into another. The following classification, resting on a pathological basis, will be adopted, namely--Follicular; Gelatinous; Cystic; Fibrous; Vascular.

In follicular goitre there is a proliferation, both in the cell-elements of the follicles and in the connective tissue constituting their walls. This general hyperplasia of the normal histological components of the gland constitutes a tumor which, for a time at least, remains quite soft and compressible, even communicating to the touch the sensation of fluctuation. The tendency, however, of the growth is not to remain long in this condition, but to become more firm and even hard to the feel.

The fibrous is often a transformation from the follicular goitre, an advanced stage in the life-history of the latter. There occurs a new formation of interstitial connective tissue, which by its accumulation and encroachment upon the follicles lessens, and finally obliterates, them to a degree which converts the gland into a fibroma. It is rare, however, to find this metamorphosis general. Generally the change is limited to portions of the thyroid, and accordingly the tumor in this variety of the disease is found hard, knotty, and incompressible at different points corresponding to the sclerosed portions. The vascularity of the fibrous variety is quite insignificant in those portions of the gland which have been the subject of this morbid change, though in other parts there is a liberal supply of blood-vessels.

Vascular goitre may also be a transformation from the follicular variety, in {978} which, with an increased hyperplasia of the follicular elements of the gland, there is a new formation of blood-vessels taking the place of the connective tissue present in the fibrous form of goitre. When the arterial element predominates, the vessels will be found to be very much dilated and anastamosing freely. These goitres are compressible, have a soft, spongy feel, sometimes pulsate, and on auscultation disclose a distinct bruit, hence the term aneurismal goitre often applied to such. In other instances the venous element predominates, when the swelling will, as in the arterial variety, be compressible and communicate to the ear a well-marked blowing sound or murmur. As the superficial veins, in common with the deep ones, are enlarged and tortuous, the surface of the tumor will often exhibit at different points a bluish appearance. In two instances, and in females of a highly-wrought nervous temperament, I have known the vascular goitre to enlarge in a few minutes to wellnigh twice its usual size, threatening the patient with suffocation for the time, and almost as quickly subside after a free emesis.

In gelatinoid goitre the follicles of the gland are distended so as to form large cavities filled with a gelatinoid- or colloid-looking substance, the product of the enclosed cells. As the distension of the follicles progresses the vascularity of the gland becomes notably less, the vessels being obliterated by the pressure. This tumor may attain a very great size, is much firmer than the vascular goitre, and to the touch has a doughy feel.

Cystic goitre is rarely such in the beginning of its history, being often an advanced stage of the follicular variety. In the transition the compartments of the latter undergo enlargement, their normal cell-contents being replaced by an albuminoid transudation from the vessels of the follicles. This process continuing, the interfollicular connective tissue disappears--a mechanical result caused by pressure. Still later, and from this cause, the walls of the adjoining follicles suffer a similar fate, and as these melt away larger cavities are formed, until at length the whole interior of the gland is converted into a number of loculi, and in some rare instances into one great sac. The gelatinoid or colloid goitre may undergo a similar transformation, and much in the same way. The fluid contents of cystic goitre vary in their physical properties as also in their chemical constitution. Generally the substance contained in the cysts is rich in albumen, has a ropy appearance resembling somewhat the white of an egg, and to the feel is viscous or unctuous, similar to that of the synovial secretion. Sometimes it is dark, resembling coffee-grounds--a condition due to the decomposition of extravasated blood derived from ruptured blood-vessels belonging to the gland. Crystals of cholesterin are also present, formed by fatty degeneration of the cells of the follicles, and mingled with a variable amount of sodium chloride. The cystic goitre is soft and fluctuating, and often grows to a large size.

* * * * *

The blood-vessels of goitre are not exempt from pathological changes, but frequently become the subjects of atheromatous and amyloid changes.

Carcinoma and Sarcoma of the Thyroid Gland.

Malignant growths of the thyroid body are comparatively rare, and when present are accompanied by symptoms sufficiently significant to differentiate them from those which are benign. In both carcinoma and sarcoma the increase of the tumor is rapid; the surface veins become very distinct, and the enlargement is general, affecting the entire gland. In addition to the above phenomena, the evil effect resulting from pressure is sooner realized and more pronounced than in goitre, and in a short time the generalization of the disease becomes apparent in the loss of flesh and strength. Should {979} the tumor be a carcinoma, there will likely follow the infection of those lymph-glands in nearest relation to the neoplasm.

EVIL EFFECTS OF GOITRE.--In this country, though goitre may grow to a large size, it is not common for patients to suffer any inconvenience other than that which results from the unsightly appearance of the tumor; hence life is not seriously imperilled by the disease. Occasionally, however, there are exceptional instances in which unpleasant and even troublesome symptoms are developed. Among these may be mentioned alteration of voice or a slight aphonia in consequence of pressure by the tumor on the recurrent laryngeal nerve. An irritating cough may also exist, and when no evidence of pulmonary trouble is present it must be referred to pressure upon the pneumogastric nerve. Dyspnoea when present results usually from pressure upon the trachea. It has been observed that when this pressure is long continued, particularly in cases of vascular goitre, some of the rings of the trachea gradually disappear, leaving only a membranous tube, which may collapse and cause the sudden death of the patient.

Hiccough and diaphragmatic spasms have also occurred when the enlargement of the gland extended laterally, in consequence of pressure on the phrenic nerve. In addition to the above phenomena there is often experienced in goitre severe neuralgic pains on the side of the neck, in the ear, and over the back of the head, and indeed in the course of any of the branches of the cervical plexus of nerves.

Occasionally I have seen a red blush of the integument on the side of the neck, answering to the largest portion of tumor, accompanied by increased heat, doubtless from the growth encroaching on the sympathetic nerve.

TREATMENT.--The treatment of goitre may be divided into constitutional and local. Too often the management of the disease is conducted in an empirical manner, every variety being subjected to the same routine of remedies. No greater mistake can be made. To attain any satisfactory success it is absolutely necessary that a correct diagnosis of the composition of the tumor shall be known. In follicular and in fibrous goitre much may be anticipated from constitutional and local measures. Those remedies which possess the property of inducing retrograde changes of structure and their subsequent absorption are the ones to be selected for administration, and among these iodine and its combinations rank highest. The compound solution of iodine, the iodide of potash, and the iodide of iron, all have their therapeutical adaptiveness. The earlier treatment is commenced the more hopeful will be the prognosis. If the patient is in all other respects in good health, and especially is somewhat fleshy or given to obesity, the compound solution of iodine should of preference be selected. At first the dose should be small, in order to test the tolerance of the stomach, not exceeding five or six drops three times a day, taken in some sweetened water, orange syrup, or curaçoa, and always about one hour after meals. Every two or three days the dose may be increased one or two drops until eighteen or twenty are taken, beyond which it is not desirable to go. It is in these forms of goitre that the burned sponge (spongia usta) was at one time very generally used as an internal remedy, half a drachm to a drachm being taken twice or thrice daily. As the virtue of the article was due to the iodine it contained, it must necessarily be inferior to the solution of the same substance.

In addition to the constitutional treatment the local use of alterative ointments will be indicated, the best of these being iodoform, iodide of lead, and iodide of mercury. Iodoform will be found most efficient employed in the following formula:

Rx. Iodoform, drachm iss; Benzoated lard, ounce j.

This ointment is to be rubbed into the goitre for fifteen or twenty minutes {980} morning and evening, after which a piece of lint smeared with the same should be laid over the tumor, covered with oiled silk, and retained in position by a strip of muslin. If the officinal iodide-of-lead ointment be used, it will be desirable to lessen its strength by the addition of a little simple cerate, as it is liable to cause severe irritation of the skin when thoroughly applied, thus neutralizing in a great measure the value of the application. Whatever unguent is selected, the application will be best made before an open fire.

There are several natural waters which can at the same time with the other treatment be taken with advantage, their efficiency being due to the iodine which they contain. The most valuable of these are Adelheid's Quelle and Wildegger. A glass of either can be drank morning and evening. If after two or three months' continuous treatment under the plan described no impression is made on the disease, or in the event of the iodine acting unpleasantly by causing symptoms of iodism, the iodide of potash should be substituted, administering three times a day from five to twenty grains of the salt dissolved in water and syrup, and well diluted.

Boinet has proposed the mixture of iodine with the food as a very satisfactory mode of introducing the drug into the system; and I suppose that it was on the strength of this suggestion that Michaud, with a view to protect the garrison of Étiennes against the prevailing goitre, ordered iodine to be baked in the soldiers' bread. In cases of goitre associated with a pale, anæmic state of the system it will often be found necessary to alternate, for a time, the remedies already directed with iodide of iron and cod-liver oil.

In follicular and fibrous goitres which prove rebellious to the plan of treatment detailed a resort may be had to injections. From eight to twenty drops of the tincture of iodine should be introduced deep into the substance of the gland by the hypodermic syringe. This procedure can be repeated every three or four days, selecting at each operation a different section of the gland, at the same time carefully watching the effect produced. Any marked elevation of temperature, local or general, accompanied by pain or stiffness of the neck, is the signal for suspending temporarily this form of medication. The favorable signs following injections are the shrinking and increasing hardness of the tumor; and so long as these processes continue progressive no repetition of injections will be necessary.

Electrolysis constitutes another therapeutic resource, applicable not only to the treatment of follicular and fibrous, but also to the vascular, goitre. This agent has been favorably employed by Chvostek of Vienna, and to some extent in this country by Baird and others. The current used by Chvostek was one from a Siemens battery of thirteen elements and strong enough to cause a moderate degree of burning. The time consumed at each sitting is not to exceed five minutes, during which the points of application must be frequently changed.

In vascular goitre, iodine, either internally or locally, effects little good. Ergot is to be preferred. From ten to twenty drops of the fluid extract should be given internally three times a day, with injections of the same amount and used in the same general manner as has been directed for the iodine.

Recently I have been using injections of carbolic acid in vascular goitre, and thus far with the most promising results. Four or five drops of a solution of the crystals of the acid dissolved in glycerin, using no more of the latter than will be barely sufficient to liquefy the crystals, should be deposited by means of the hypodermic syringe deep into different portions of the gland at intervals of four or five days. On the withdrawal of the instrument the puncture can be covered with a strip of rubber adhesive plaster. The acid when thus employed causes the tumor to shrink and become hard.

{981} Gelatinous and cystic goitres are quite intractable to constitutional remedies. They require to be attacked locally. Bonnet has tried caustic potash and chloride of zinc. The applications were made over the front wall of the tumor, and in some instances to the inner surface of the sac. The results were not of a kind to make the method a popular one. Iodine and alcohol have also been thrown into the parenchyma of the gland, and with a like unsatisfactory effect. Setons have had numerous trials. The method is an old one, having been used by Celsus, and revived from time to time by Quadi of Naples, Hutchinson, Kennedy, and Stanton. The object in using the seton is to develop in the tumor a destructive inflammation and suppuration. Any one who has witnessed a case of acute suppuration in the thyroid gland will not be anxious to repeat the experience. The purulent products are profuse, highly offensive, and tax severely the powers of the general system; and to these disadvantages may be added the risks of sloughing, hemorrhage, and septic poisoning.

The treatment which promises most in gelatinous and cystic goitre is either that practised by Gosselin or that by Morrell Mackenzie of London. The plan of Gosselin is to make a very small incision in the skin over the front of the tumor, in order to lessen the resistance to the introduction of a small trocar and canula, through the latter of which, after evacuating the cyst and washing it out with tepid water, he injects the tincture of iodine (fluidrachm j). This injection is allowed to remain about five minutes. Should its discharge be followed by a flow of blood, a second and even a third injection is made before withdrawing the canula. This operation does not materially differ from that practised by V. Dumreicher, except that this practitioner emptied the cyst with an aspirator previous to washing out the sac and injecting the iodine. The method of Mackenzie, however, has succeeded so well in practice that it is to be preferred both for efficiency and safety. In this plan perchloride of iron is substituted for iodine. One part of the iron is mixed with four parts of water, and after partially emptying the cyst with a trocar and canula at its most dependent part the fluid (fluidrachm j-fluidrachm ij) is thrown into the sac by a syringe. The canula is now plugged with a stopper that the injection may be retained. After three days the stopper is removed and the contents of the sac are allowed to flow out. In case the discharge proves to be bloody or serous, the injection is repeated; if, on the contrary, it exhibits signs of pus the iron solution is withheld, but the canula is permitted to remain, that free drainage may be maintained until the goitre has been destroyed by suppuration. During the presence of the instrument the affected part of the neck is covered by a flaxseed-meal poultice.

In gelatinous goitre, when the tumor is multilocular, after tapping and before injecting, I introduce through the canula a plunger, and by pushing it in different directions through the interior of the tumor break up the separating walls of the cysts, and thus open a way for the better diffusion of the injecting material. The plan of Mackenzie, destroying as it does the tumor by a slow chronic form of suppuration, and at the same time draining away the pus as it forms, greatly lessens the risk which might otherwise arise from diffused suppuration, bleeding, or sloughing. At the Copenhagen Congress, Mackenzie stated that he had by the method described treated 193 cases of goitre with only 2 fatal cases, the latter being those of a fibro-cystic form.

In making a comparison between the relative safety of perchloride of iron and of iodine as injections in goitre, the great superiority of the former over the latter is well brought out in the cases collected and analyzed by Schwalbe, 106 in number, for the cure of which iodine was used, death following in 5 cases and diffused suppuration in 22 cases.

When all measures fail to control the growth of a goitre, and the life of the patient is jeopardized from the effects of pressure, the case ceases to be {982} a medical one and must be relegated to the domain of surgery. Fortunately, the necessity for operation rarely occurs. It may be remarked, in closing this article, that the excision of the gland has been followed in several instances by evils greater than those for which the operation was performed. The experiments of Zesas and Horsley on lower animals, and the observations of Kocher after the removal of the thyroid in man, place the question of extirpation of goitre among the unsettled problems of surgery.

{983}

SIMPLE LYMPHANGITIS.

BY SAMUEL C. BUSEY, M.D.

ANATOMY AND PHYSIOLOGY.--The pathological relations of the absorbent system are important, because of their direct connection with the morbid processes and structural changes taking place in a variety of diseases; therefore, before discussing the subject of lymphangitis, a brief reference to the anatomy and physiology of the lymphatic system is necessary.

The lymphatic system consists of large and capillary vessels, interstitial spaces or juice-tracks, lacteals, follicles, and glands. The serous cavities are also considered lymph-chambers, and the loose cellular tissue is a vast chambered lymphatic sac communicating with lymphatic vessels. The larger vessels are divided into two classes--the superficial, which in the subcutaneous tissue accompany the veins, while in the solid viscera they lie under the capsule, and in the tubular viscera under the serous membrane; and the deep-seated vessels, which accompany the deep-seated blood-vessels, ramify through the interior of the organ in the solid viscera, and emerge at the hilus; while in the tubular viscera they lie in the submucosa, and by free anastomosis form plexuses. There is no communication between these two sets of vessels, except in the solid viscera and in the glands which may be common to both sets. Between the vessels of each set there is, however, a free anastomosis, by which large-meshed plexuses are formed. In consequence of these peculiar arrangements each set may be separately diseased, and inflammation may spread rapidly from vessel to vessel of the same set.

The lymph-capillaries are arranged in networks which lie in the meshes of the plexuses of the blood-capillaries, from which they are separated by intervening tissue-elements. Their walls consist of a single layer of endothelium resting upon elastic tissue. In their continuity they are sinuous, and are provided with an incomplete valvular arrangement.

The large vessels have three coats, not unlike the coats of the veins, and are provided with numerous valves. These valves are the more abundant in the superficial vessels, and the intervals between them grow gradually less as they approach the glands.

The whole lymph vascular system terminates either in the right or left thoracic duct.

The origin of the lymphatics has not been definitely settled. It has been demonstrated that lymph circulates in the connective-tissue interstices, and it seems to have been established that these spaces are lymph reservoirs, discharging through lymph-capillaries. It is admitted that the capillaries commence either in closely-meshed networks or lacunar spaces. Plexuses of lymphatic capillaries, corresponding with the distribution of the blood-capillaries, lie under the endothelium of the serous membranes, and are in open communication with the serous cavities through the stomata. The stomata vera are either the openings of lymph-channels communicating directly with lymph-capillaries, or discontinuities between the cells of the surface, leading {984} into superficial lymph-sinuses. The pseudo-stomata are the interstitial or intercellular cement substance, and represent the communication of the lymph canalicular system with the free surface of serous membranes.

Lymph-follicles consist of a reticulum of connective tissue, the meshes of which are crowded with cells, thus forming patches in the submucous or subserous tissue. Around these patches there is a plexus of lymph-capillaries.

Lymphatic glands are round or oval bodies situated in the course of the lymphatic and lacteal vessels. They are composed of follicular tissue, trabeculæ, and lymph-tracts, all enclosed in a capsule. No doubt exists in regard to a channel of communication between the afferent and efferent vessels through a complex system of lymph-paths which communicate more freely with the afferent than with the efferent vessels. They are very vascular.

Every lymphatic vessel passes through one or more glands before reaching the trunks. Before penetrating the peripheric fascia of a gland these vessels divide into a number of smaller ones, which are distributed upon the surface of the cortical portion, and empty directly into the superficial lymph-sinuses. A number of vessels emerge from each gland, but they are less numerous and larger than the afferent vessels. The lymph is poured through the afferent vessels into the lymph-spaces of the cortical alveoli, and thence into the channels of the medullary substance, from which it escapes, enriched in corpuscular elements, into the efferent tubes. The current of fluid passing through such a complex structure must necessarily be retarded. This relation of the glands to the lymph-current is, moreover, especially interesting in its pathological significance. Whatever enters the lymph may, if small enough, pass through the glands and be swept along with the current, but the structure of the gland is, in a mechanical sense, a filtering apparatus, interrupting the free current of the fluid and retaining the coarser particles. The lymph in passing through the glands derives constituents not previously possessed, but, nevertheless, the retention of elements which for a time might arrest the dissemination of hurtful material may eventually convert the gland into a new source of infection. This fact is illustrated in the history of malignant growths.

Perhaps the most interesting consideration connected with this relation of the lymph-glands to the fluid passing through them is presented by the anatomical arrangement of the chyle-vessels and the mesenteric glands. The lacteals, commencing as the central efferent vessels of the intestinal villi, pass between the folds of the mesentery, through several tiers of mesenteric glands, and, uniting into one or more trunks, terminate in the receptaculum chyli. During digestion these vessels are full of chyle, and during the intervals of digestion they convey lymph.

The lymphatic system may be considered an appendage of the blood vascular system. By the blood the tissues are supplied with nutriment and oxygen. By both the blood and lymph the surplus and waste are conveyed away. The current of the lymph is in a reverse direction to that of the blood-supply. The lymphatic vascular system receives through its rootlets, which are distributed through the tissues, the surplus transudation from the arterial capillaries, the products of tissue-waste and transformation, and the chyle, and empties its contents into the great venous trunks near their termini. It therefore performs the double function of absorption from without and absorption from within. In other words, it introduces into the blood the material from both the food and the air which is required for the sustenance and repair of the tissues, and conveys away the unassimilated surplus, waste, and effete material.

The forces concerned in the locomotion of the lymph are numerous. Recklinghausen believes the movement of the lymph to be mainly due to the difference between the arterial and venous blood-pressure. The greater this {985} difference the more rapid its current. The lymph canalicular system is not in vascular continuity with the blood-capillaries, and consequently the force of blood-pressure can only be communicated to the column of lymph by the passage of the plasmatic fluid into the lymphatic system by peripheral transudation and endosmosis. These are favored by the single homogeneous walls of the lymphatic plexuses and the enormous absorbing surface. These forces are essentially vis a tergo, for the difference between the arterial and venous blood-pressure is the excess of the former over the latter. To these must be added other factors, not less important or necessary, derived from the contractility of the walls of the lymphatic vessels, from the compression of the surrounding and contiguous parts, from the movements of respiration, and from the absorption of chyle. Besides these, the slowness of the movement of the lymph as compared with the rapidity of the arterial and venous blood-currents; the varying amount of pressure in the lymph vascular system, and the absence of distension in a normal condition; the entrance of the lymphatic trunks into the veins near the confluence of large branches, where the venous blood-pressure is almost inappreciable and the current is most rapid; the marked effect of active muscular movement in accelerating the flow of lymph; and the contractility of the vascular walls,--are all conditions which cannot be omitted from a consideration of the forces concerned in the locomotion of the lymph.

The supply of valves is very abundant, and they are always more numerous where pressure from surrounding and contiguous parts is most effective, though not infrequently most irregular in its operation, and consequently where isolation of small sections of the column of the fluid is most needed. The valves prevent regurgitation only so far as the superimposed column of fluid is insufficient to impair their integrity, or where there is no solution of the continuity of the vascular walls, and distension is within the limits of ordinary and normal extensibility. In cases of lymphangiectasis it is not usually necessary to look beyond the nearest neighboring and connected gland for the cause of such distension. Nature has increased the number of valves in the afferent vessels as they approach the glands, as well to modify and direct the flow as to prevent regurgitation; but if from any cause the passage of the lymph through the glands is obstructed or prevented, dilatation of the afferent vessels will ensue as a consequence. Valvular insufficiency and dilatation may exist in opposite relations to each other, either as cause or effect. The dilatation of a vessel may result from thinning or loss of contractility of its walls, caused by increased resistance to the onward movement of the fluid, and by the lesser extensibility of the intima than of the adventitia.

Lymphatic varices usually have their beginning in the vessels and extend to the plexuses, but the plexuses may be alone affected. Varicosities always extend backward from the point where the flow of the contained lymph is arrested, and may result from a repletion of each proximal intervalvular section with valvular incompetency.

The propulsive power of the heart diminishes with increased distance, due to increased friction and increasing resistance from flexures, bendings, and anastomoses, but chiefly from the increased carrying capacity of the vascular subdivisions. Hence, as the current of the lymph is in reverse relation to the capacity of the vessels, flowing, as does the venous blood, from subdivisions into trunks of diminished aggregate capacity, the velocity of the current of the lymph should be faster in the trunkal vessels than in the subdivisions. Such is the fact, though farther removed from the left heart and peripheral plasmatic circulation; and yet it is much slower in the thoracic duct than the blood-current in the venæ cavæ, which are not supplied with valves. The movement of the venous blood is in a measure due to cardiac and arterial contraction, but that force is least where the current is most rapid--in the {986} venæ cavæ. The increased rapidity of the venous blood-current as it approaches the heart must, therefore, be derived from some other source; and it is equally manifest that the velocity of the venous blood in the terminal trunks is transmitted to the column of lymph and chyle flowing from the thoracic duct into the blood-channels.

The foregoing reference to the anatomy and physiology of the absorbent system shows very conclusively the importance of its pathological relations. It is certainly concerned in the morbid processes of a variety of diseases. But not less important is the fact that it is the main channel for the diffusion of infections throughout the body. Disease may be conveyed by the lymph from a single focus to many and distant parts, whilst the intervening channel of communication may remain free from injury. Along the course of the current every gland may become an additional focus, intensifying the infectiveness of the noxious material and increasing the area of its diffusion. This is alike true of poisons introduced from without and of those originating in the system.

SYNONYM.--Angioleucitis.

DEFINITION.--Lymphangitis may be either simple or septic. As a rule, the disease is localized, but may, especially when induced by some septic poison, be widely diffused, implicating extensive areas of lymphatic tissue and extending to contiguous structures.

Simple lymphangitis may be either reticular or tubular. In the former the fine capillary network or plexus is involved; in the latter the trunkal vessels are inflamed. Very frequently both forms exist at the same time.

ETIOLOGY.--Simple lymphangitis may be either idiopathic or traumatic. It is, however, rarely spontaneous. External irritation, such as solar rays, pressure, and friction, may set up a superficial inflammation, though usually there is some form of injury--a wound, scratch, sprain, contusion, abrasion, prick, or sting of an insect. The graver forms are caused by neighboring inflammation, suppuration, and ulceration. The products of these morbid changes are absorbed and conveyed along the vessels. The inflammation may be continuous along the course of the vessel, or separated from the origin of the morbid product by an area of intervening healthy tissue. Absorption of the secretions and parenchymatous fluids of inflamed parts is an active and frequent agency in the causation of lymphangitis. It may also be caused by contiguous inflamed tissue and by obstruction of the current of the lymph. Lymph-thrombosis, from whatever cause produced, may excite inflammation at the locality of formation, which is usually in the immediate vicinity of a valve, or the thrombi may disintegrate or undergo puriform liquefaction, and thus extend and diffuse the inflammation.

Slight pricks, scratches, and abrasions, which in themselves are so trifling as not to attract attention, may admit irritating substances from without. This is a frequent cause among medical men, whose hands and fingers are constantly exposed to irritating and ichorous discharges.

Localized lymphangitis is frequently set up by specific kinds of irritation. The adenitis and periglandular inflammations in cases of scarlet fever and diphtheria are familiar illustrations. The indurated glands in syphilis and suppurating buboes in chancroid exhibit the different effects of the virus of these forms of disease. The lymphatics of the solid viscera are often inflamed when the organ is the seat of disease. Pelvic cellulitis, if not in itself a lymphangitis, may be the starting-point of a severe and extensive inflammation of the absorbents, occasionally involving both the superficial and deep-seated vessels along one or both thighs.

Age and constitution are recognized factors. Lymphangitis is more frequent in the young, and is much more easily excited in the strumous and persons in a low state of health. Unhygienic conditions predispose to its development.

{987} Lymphangitis may also find its cause in excessive exercise of function, paralysis of vessels, mechanical obstruction to the lymph-stream, lodgment of particles of cancerous or tuberculous matter in the vessels, compression from cicatrices, indurated connective tissue, tumors, diseased glands, stasis in large veins, and regurgitant heart affections.

SYMPTOMATOLOGY.--Reticular lymphangitis is characterized by rapidly-increasing localized redness, attended with a burning, throbbing pain, and usually quickly implicates the skin and its capillaries. Oedema to a greater or less extent may soon ensue, which, when present, increases the pain. Fever may or may not be present, depending in some measure upon the extent, intensity, and cause of the inflammation and upon individual peculiarities. Erythema usually represents a reticular lymphangitis with hyperæmia of the skin and its capillaries, and erythema nodosum is the same associated with lymphatic oedema. Any trivial injury may induce this form of inflammation, such as a prick or the sting of an insect, which in extent, duration, and intensity will vary with the cause, nature of the poison introduced, location, and susceptibility of the sufferer.

Tubular lymphangitis is usually a much more serious form of the disease. When the vessels of the superficial set are involved, wavy or straight irregularly reddened lines are seen along the course of the vessels, extending from the point of beginning to a single gland or ganglion, which is usually tender and enlarged. These lines feel like hard, knotted cords. The inflammation may be limited by the first tier of glands, or it may extend to one or more distant ganglia. From the inflamed gland the disease may be conveyed along the connecting branches of the deeper set of vessels, and both sets may become involved. The inflammation may also extend through the intervening tissues from the superficial to the deeper-seated vessels. When both sets are involved, the disease assumes a graver form and the symptoms are aggravated. The pain becomes more acute, and the swelling is greatly increased and more diffused. Fever may or may not be present, and is usually moderate when the inflammation is confined to the superficial vessels, but when the deeper set is implicated it often commences with a rigor and is usually considerable. When the deeper set is alone affected the red wavy, knotted lines cannot be seen, but may, unless the oedema is great, be felt. The parts are swelled, indurated, and stiffened, due in the acute stage to increased saturation of the tissues, and in the chronic stage to hypertrophy of the connective tissue. When the oedema is great the covering integument presents a glossy, shining appearance.

PATHOLOGY AND MORBID ANATOMY.--In lymphangitis the adventitia of the vessels and surrounding connective tissue are chiefly affected. The external coat is thickened, injected, and infiltrated with cells. The intima becomes opaque and is stripped of its endothelium. The lymph coagulates in the interior of inflamed vessels and blocks up the channel. These thrombi may become organized and permanently obliterate the lumen of the vessel, or they may liquefy or suppurate. Their products may enter the circulation and cause septicæmia or pyæmia. In a few instances the clots have undergone calcareous degeneration. In some instances coagula are found independently of any disease of the coats of the vessels. In such cases the coagulation has been caused by the entrance of some foreign material into the lymph-stream. The thickening and relaxation of the coats of the vessels lead to dilatation, and consequently to slowing of the current and stasis of lymph. From this may result the serious consequences of an extensive lymphangiectasia, which may involve either or both the superficial and deeper vessels of a large area or an entire extremity. In such cases enormous development of the adipose tissue usually takes place, not infrequently associated with rupture of the dilated radicals and exhaustive periodic discharges of lymph. In most of the {988} cases of lymphangiectasia and lymphorrhagia the fluid, which either accumulates in the affected area or is discharged through the ruptured orifices, presents the physical characteristics and appearance of chyle, due to the quantity of fat it contains. In some cases the fluid at first discharged is serous, and gradually changes, as the flow continues, to a chylous or milk-like fluid. In these cases there is also a tendency to frequently-recurring attacks of an erysipelatous or elephantoid inflammation. This predisposition is traceable to the structural changes produced by the previous inflammation, traumatism, or thrombosis. Inflammation and lymph-thrombosis are the pathological processes which usually cause circumscribed narrowing or complete occlusion of lymph-channels; and within the area from which the narrowed or occluded vessels originate there is lymph-stasis, dilatation of trunkal vessels, and oedema of the tissues. Lymphangitis may also cause adhesion of the internal surfaces of the vessel, fibroid transformation or calcification of their coats, and suppuration.

The alterations which take place in the lymph consist chiefly of an increased proportion of fibrin, the addition of numerous cell-elements, not unlike endothelial cells, white and occasionally red blood-corpuscles, lymphoid cells, granular matter, and a varying quantity of albumen and fat, which in a measure must owe their presence to pathological processes affecting the intima and to transformation of the inflammatory products.

All forms of inflammation of the lymphatic vessels exhibit a tendency to extend to the connective tissue. Cellulitis is almost a constant accompaniment of lymphangitis. In other cases the inflammation and consequent thrombosis and obstruction of the lymph-stream produce oedema and saturation of the tissues. Hyperplasia and sclerosis of the connective tissue follow.

Adenitis is characterized by swelling, congestion, and hardness. If resolution takes place, as is usual in all forms of simple lymphangitis, the gland or ganglion will be restored to its normal condition, though not infrequently some enlargement and firmness will remain for a considerable time, which favor recurrences from very trivial causes. It often happens, however, that structural changes occur. Exudation and suppuration may take place. Suppuration begins in the centre, and sooner or later the whole gland-structure is converted into a pus-cavity. Buboes are usually associated with periglandular abscesses. In fact, the latter are very frequently present when the glands do not suppurate, but have assumed a condition of chronic or subacute inflammation, which subsides very slowly and is subject to recurring acute exacerbations from some continuous or repeated irritation. Glands may be devastated or rendered wholly or partially impermeable, thus forming permanent and irremediable obstacles to the lymph-stream. Inflamed and swollen glands are not necessarily impermeable, but the flow of the lymph through them is undoubtedly impeded. The subacute or chronically inflamed glands may become adherent to and imbedded in a mass of indurated connective tissue, and may finally undergo calcareous or caseous degeneration.

Lymphangitis sometimes extends by contiguity of tissue to the synovial membrane of joints, most frequently the knee-joint. So likewise may synovitis and other joint affections set up a lymphangitis. In either case the tendency to suppuration is imminent.

DIAGNOSIS.--The diagnosis of the forms of simple lymphangitis is very easy. The red, wavy, corded, and irregularly-knotted lines following the course of lymphatic vessels readily distinguish it from phlebitis. These lines lead to a gland, which soon also becomes tender and swollen. Oedema soon takes place. An inflamed lymphatic vessel is much smaller and more tender to the touch than an inflamed vein, and usually lies between the injured locality and an inflamed gland. Fever is more constantly present and higher than in phlebitis.

{989} Reticular lymphangitis is usually a circumscribed inflammation, with more or less oedema, located in the region of a lymphatic network. It invades the integumental structures. It is not necessary to distinguish it from an erythema, for the latter can scarcely ever be present without implication of the lymphatic radicles. Tubular lymphangitis and lymphangiectasia, which are so frequently associated conditions and attended with oedema, present objective appearances very similar to those present in oedema from phlebectasis. Phlebectasis is excluded by the absence of pain, of dilatation of the superficial vein, and of changed color, and of a single hard cord along the course of the varicose vein; by the non-appearance of oedema in the neighborhood of the ankle and on the dorsum of the foot during the earlier stages of the disease, and its gradual extension upward. The infiltration in phlebectasis results from increased transudation in consequence of increased blood-pressure in the venous radicles, and their dilatation, or from interrupted venous circulation. The accumulated fluid is consequently watery, poor in solid constituents, and the resulting swelling presents all the characteristics of ordinary oedema. Absorption may be normal or perhaps increased, and with rest of the limb the intumescence will probably diminish or disappear. In consequence of the poverty of the transuded fluid the changes in nutrition are very slow, and the enlargement partakes more of the nature of an anasarca than of an hypertrophy; and, finally, phlebectasis is usually connected with some constitutional affection or distant local disease, and attacks the most distal parts, where the circulation is least supported by the muscles. Lymphangiectasis is most often found in circumscribed localities where the networks of lymph-capillaries are most numerously distributed. The swelling is more diffused, and is not in the form of single hard cords. It is more resistant, and the color of the surface is unchanged. It usually extends downward, and is not so much influenced by continued rest and posture. The accumulated fluid results from diminished absorption or interrupted lymph-circulation, and consists of the normal pre-existing parenchymatous fluids, the nutritive juices continually conveyed thither, and the fluids consumed by the functions of the parts saturated with organic débris. It is, however, more abundantly supplied with organic elements from both progressive and retrogressive metamorphosis. It also contains more albumen and fibrinous substances than the accumulated fluid in phlebectasis and ordinary oedema. The swelling or enlargement is formed of more consistent, coagulable, and partly organizable material, possesses greater consistence, and is nearly compact to the touch, which increases as the fluid undergoes the changes due to its retention in the parts. The development is peculiar, and not altogether unlike phlegmasia. The pus-formations which sometimes ensue partake of the nature of cold abscesses, and are located in the connective tissue. The pus-formations in phlebectasis usually begin in the venous thrombi within the dilated and enlarged veins, are associated with acute symptoms, and result, usually, in purulent absorption.

In view of later anatomical and pathological researches, it must be admitted that phlegmasia dolens is occasionally a lymphangitis, having its origin in inflammation of the vessels or areolar tissue. Some pathologists have advanced the theory that, as seen in lying-in women, it is a parametritis commencing in the cellular tissue in the immediate vicinity of the womb and extending to remoter parts. The writer saw recently, in consultation with J. Taber Johnson, a case of puerperal pelvic cellulitis associated with a firm, resistant, diffuse, painful, and tender swelling involving the inner aspect of both thighs, and extending from the groin on each side downward below the middle third of the thigh. The pelvic inflammation appeared first in the left iliac fossa, and was associated with the swelling before described on the thigh. This subsided, and was immediately followed by a similar condition {990} in the right iliac fossa, accompanied by a precisely similar intumescence on the right thigh. At no time could any enlarged, hard, or corded veins be discovered. The swellings presented the usual objective and tactile characteristics of those inflammatory affections so frequently supervening within areas abundantly supplied with lymph networks, in communication with the original lymphangitis and lymph-thrombosis. In this case the swellings were located in a region specially rich in lymph capillary networks. With the subsidence of the pelvic cellulitis the thigh intumescence on either side gradually disappeared.

Tubular lymphangitis is readily distinguished from erysipelas by the presence of the knotted and corded lymphatic vessels. Reticular lymphangitis is characterized by fine, closely-arranged red lines limited to a circumscribed area, and is usually associated with and starts from some injury. In erysipelas the redness is uniform. It does not follow the course of the lymphatic vessels, nor extend from a wound in the direction of and to a gland or ganglion of glands. The fever is usually higher and of longer duration. The inflamed surface is marked by the appearance of blebs.

PROGNOSIS.--Simple lymphangitis is usually unattended with danger unless complicated with suppurating arthritis. The disease, as a rule, runs a rapid course to recovery. It is more favorable the nearer the inflammation lies to the surface.

TREATMENT.--The treatment is both constitutional and local. The first indication is to remove the cause. The wound should be cleansed and disinfected. For this purpose solutions of carbolic or acetic acid may be employed, or it may be cauterized with caustic potash or chloride of zinc. The fever should be controlled by the employment of antipyretics. One or more full doses of the sulphate or hydrochlorate of quinia, administered at shorter or longer intervals according to the quantity given at each dose and the intensity of the fever, may be sufficient. Antipyrin is a very valuable remedy. It will reduce the fever more speedily and decidedly than the salts of quinia. If the fever is reduced and kept under control by the judicious administration of this remedy in moderate doses, the tendency of the inflammation to extend is very greatly diminished, and may be arrested. Its antipyretic effect is, however, less durable than that of the salts of quinia, but is unattended with the cerebral disturbances usually associated with the employment of quinia salts. The bowels should be kept solvent by the use of saline cathartics. The diet should be restricted during the pyrexial stage. After the acute stage has passed, tonics and improved diet may become necessary; especially will this be the case in those previously debilitated. In healthy, robust subjects it is not probable, under proper and prompt treatment, that the disease will continue long enough to endanger convalescence by serious exhaustion. When needed, iron, cod-liver oil, and the salts of quinia may be resorted to. But, after all, a good appetite and a sufficient supply of nutritious and easily-digested foods constitute the best and most available tonics. Rest of the affected part is very important, and the posture should be such as to remove pressure and relieve tension.

In the beginning of the acute stage cold applications may be employed, but, as a rule, the local treatment should be confined to the assiduous application of hot soothing and emollient fomentations, to which opium or belladonna may be added. By these means the tension of the swollen and inflamed parts, and consequently the pain, are assuaged. It is rarely necessary to employ internally any anodyne to relieve the pain; but in occasional cases, occurring in persons keenly susceptible to pain, an opiate or some less powerful anodyne may be administered. Some advise the local abstraction of blood by leeching, but it is admissible only when the pain is very acute and confined to a limited and defined area. After the subsidence {991} of the fever and acute inflammatory stage the remaining oedema and indurations may be treated with the local application of the tincture of iodine, inunction with mercurial ointment, bandaging, massage, and rest.

For the oedematous condition, which is sometimes very persistent, pressure is the most available and potential remedy. This should be secured by systematic bandaging either with a flannel or an elastic bandage. In such cases passive movement and massage or kneading of the part constitute an important and valuable auxiliary to pressure.

To allay itching, which is sometimes almost intolerable even after the acute inflammation has subsided, the part may be painted with a solution of nitrate of silver or collodion. If these fail, an alcoholic solution of benzoic acid, twenty grains to the ounce, may be employed.

If suppuration takes place, the abscess should be promptly and effectually incised. It should be thoroughly evacuated and dressed antiseptically. When this occurs a more or less tonic and supporting treatment is necessary. Iron, cod-liver oil, quinia, and stimulants may be, according to circumstances, administered. The devastating effects of suppurating cavities should be controlled by the liberal use of the appropriate remedies to arrest exhaustion and to rebuild waste.

In occasional instances the initial stage, consentaneous with the receipt of the injury, such as the sting of an insect, is marked by violent shock and threatening collapse. The writer has witnessed two such cases occurring in robust, healthy men stung by honey-bees on the forearm, where great exhaustion and alarming collapse, with violent retching, profuse diarrhoea, and agonizing pain, were accompanied by rapidly-developed inflammation and swelling at the locality of the puncture. In such cases the free administration of alcoholic stimulants seems imperatively demanded.

The general plan of treatment of acute simple lymphangitis is antiphlogistic, by the employment of remedies to reduce inflammation and promote resolution. The danger of suppuration should not be overlooked or underestimated. A single suppurating focus may widely diffuse disease and impair the entire organism. A single and apparently trivial inflammation of lymphatic tissue may be the initial stage of a fatal pyæmia or septicæmia.

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INDEX TO VOLUME III.

A.

Abdominal aneurism, 821 viscera, lesions, in catarrhal pneumonia, 358

Abscess, diffuse splenic, 962 embolic, of spleen, 963 of the lung, 296 of the mediastinal space, 861 termination of croupous pneumonia in, 311, 332

Abscesses, seat and nature, in suppurative endocarditis, 604

Accidents during tracheotomy, 156

Acephalocysts, expectoration of, in pulmonary hydatids, 469

Aconite, locally, in chronic laryngitis, 127 use, in exophthalmic goitre, 767

Acupuncture, use, in thoracic aneurism, 820

Acute general diseases, resemblance of croupous pneumonia to, 317 miliary tuberculosis, 472

ADDISON'S DISEASE, 939 Definition, synonyms, and history, 939 Diagnosis, 947 Duration, 941 Etiology, 939 Morbid anatomy, 942 Nervous system, lesions, 944 Spleen, lesions, 943 Suprarenal capsules, lesions, 942, 943 Pathology, 944 Theories regarding origin, 945-947 Symptoms, 940 Anæmia and hemorrhages, 940 Bronzing of skin, seat and characters, 940 Dyspnoea, 941 Gastro-intestinal disorders, 941 Nervous symptoms, 941 Pain, characters and seat, 941 Pulse in, 941 Urine, condition, 941 Treatment, 948

Adductors of vocal cords, paralysis of, 81

Adenitis, in lymphangitis, 988

Adherent pericardium, 785

Adhesions, pericardial, seat and characters, 785

Adults, grave form of catarrhal pneumonia in, 360

Adventitious products of the heart, 637

Ægophony, significance, in pleurisy, 510

Aërial fistula, following tracheotomy, 163

After-treatment of tracheotomy, 159

Agaricus, use, in pulmonary phthisis, 438

Age, influence on aortic obstruction, 655 on causation of acute catarrhal laryngitis, 93 of acute miliary tuberculosis, 478 of angina pectoris, 759 of aortic regurgitation, 655 of asthma, 190 of bronchitis, 157 of cardiac thrombosis, 722 of catarrhal pneumonia, 353 of croupous pneumonia, 314 of exophthalmic goitre, 764 of fatty degeneration of the heart, 613 of fibroid phthisis, 441 of fibro-serous pleurisy, 492 of gangrene of lung, 301 of hæmoptysis, 275 of hay asthma, 212 of Hodgkin's disease, 922 of laryngismus stridulus, 70 of leukæmia, 909 of mediastinal tumors, 871 of mitral regurgitation, 671 of mitral stenosis, 666 of pernicious anæmia, 899 of phthisis, 396 of pneumothorax, 576 of pseudo-membranous laryngitis, 101 of purulent pleurisy, 540 of simple lymphangitis, 986 of thoracic aneurism, 802

Air, compressed, use, in bronchial asthma, 208 moist, use, in acute catarrhal laryngitis, 97 rarefied, exhalation into, in emphysema, 246

Albuminoid expectoration following thoracentesis, 535

Alcohol, abuse, influence on causation of chronic laryngitis, 121 of the caisson disease, 858 influence on causation of fatty cardiac degeneration, 612 use, in acute miliary tuberculosis, 481 in bronchial asthma, 205 in catarrhal pneumonia, 370 in croupous pneumonia, 348, 349, 351 in endocarditis, 651 in gangrene of the lung, 305 in parenchymatous degeneration of the heart-muscle, 611 in pseudo-membranous laryngitis, 108 in pulmonary phthisis, 435

Alcoholism, influence on causation of chronic myocarditis, 607 of pleurisy, 493 of croupous pneumonia, 314

Alkalies, use, in pseudo-membranous laryngitis, 105 in rheumatic pericarditis, 783 in prevention and treatment of pulmonary embolism, 389, 390

Alkaline sprays, use, in chronic laryngitis, 125, 127

Allen's nasal forceps, 54

Altitude, influence on causation of hæmoptysis, 277, 278

Alum, use, in laryngismus stridulus, 73

Ammonium, carbonate, use, in cardiac thrombosis, 745 in croupous pneumonia, 349 in prevention of pulmonary embolism, 389 and chloride of, use, in catarrhal pneumonia, 370, 371 chloride, use, in chronic laryngitis, 124, 125

Amphoric respiration in pulmonary phthisis, 417

Amyl nitrite, use, in angina pectoris, 760 in bronchial asthma, 204 in chronic endarteritis of the coronary artery, 830 in fatty cardiac degeneration, 616

Amyloid degeneration of heart-muscle, 616 of suprarenal bodies, 949

ANÆMIA, 887 Albumen, continuous loss of, influence on causation, 887 Blood, changes in, 890, 891 Bone, spleen, lymph-glands, enlargement of, and relation to production of blood-corpuscles, 888-894 Hemorrhage, influence on causation, 887 Inanition, influence on causation, 889 Toxic causes of, 889

Anæmia in Addison's disease, 940 in exophthalmic goitre, 763 in pulmonary phthisis, 406

ANÆMIA, PROGRESSIVE PERNICIOUS, 898 Course, 903 Definition and history, 898 Diagnosis, 905 Etiology, 899 Age and sex, influence on causation, 899 Hygiene, bad, influence on causation, 899 Loss of blood, chronic discharges, etc., 900 Mental worry and anxiety, 900 Pregnancy and parturition, 900 Morbid anatomy, 904 Bones, changes in, 905 Lymph-glands, changes in, 905 Spleen, changes in, 905 Pathology, 905 Prognosis, 906 Symptoms, 900 Blood and blood-corpuscles, changes in, 901 Gastro-intestinal disorders, 903 Hæmic heart-murmurs, 902 Hemorrhages in, 901-903 Oedema in, 901 Onset, mode of, 900 Skin, changes and color of, 901 Temperature, 903 Urine, changes in, 903 Treatment, 906 Arsenic, use, 907 Diet in, 907 Iron, use, 907 Milk, injection of, 908 Transfusion of blood, 907

Anæmic necrosis of heart-muscle, 610

Anæsthesia of larynx, 65

Anæsthetics, use, in laryngismus stridulus, 73

Anatomy of tracheal region, 146, 147

ANEURISM, ABDOMINAL, 821 Diagnosis, 822 Symptoms, 821 Treatment, 822 Compression of aorta, good results of, 822

Aneurism, diagnosis of, from mediastinal tumors, 876

ANEURISM, THORACIC, 801 Definition, 801 Diagnosis, 814 From abscess, 814 From tumors, 814 Duration, 815 Etiology, 802 Age and sex, influence on causation, 802, 803 Occupation, influence on causation, 803 Syphilis and gout, influence on causation, 803 Morbid anatomy, 801, 802 Symptoms, 803 Auscultation in, 811 Bone, signs of pressure upon, 807 Bruit, characters, 811 Cyanosis and oedema, 807 Dysphagia in, 806 Dyspnoea in, 805 Frémissement cataire, frequency, 808 Inspection, 807 Localization of tumors, 812 Myosis in, 805 Of varicose form, 813 Oral whiff of Drummond, significance, 812 Pain, characters, 804 Palpation in, 808 Percussion in, 812 Physical signs in, 807 Pressure signs, 804-807 Pulse, peculiarities of, 808-810 Thrill in pulse, 809 Veins, signs of pressure upon, 807 Voice, modifications of, 806 Terminations, 815 Treatment, 816-820 Acupuncture, use, 820 Barwell's operation of ligation, 818, 819 Ergotin, hypodermic use, 816 Electrolysis, method of applying, 819, 820 Opiates, use, 817 Potassium iodide, 818 Pressure, use, 816 Starvation method, 816 Tufnell's method of rest and diet, 816, 817 Wire, introduction of, into sac, 816

Aneurism of the coeliac axis, 841 of the coronary artery, 830 of the heart, 636 of the hepatic artery, 840 of the interior mesenteric artery, 839 of the superior mesenteric artery, 836 of the pulmonary artery, 833

Aneurismal form of hæmoptysis, 284

Angina, in anæmic necrosis of heart-muscle, 610

ANGINA PECTORIS, 755 Death, cause of, 760 Definition, 755 Diagnosis, 757 Etiology, 758 Morbid anatomy, 758 Prognosis, 759 Symptoms, 755-757 Treatment, 760 Amyl nitrite, use, 760 Chalybeates, use, 760 Digitalis and nux vomica, 761 Opium and morphia, use, 760 Preventive, 760 Stimulants, 760

Angina pectoris in aortic regurgitation, 661

Anginoid attacks in chronic myocarditis, 608, 609

Anomalies, congenital, of heart and great vessels, 687 of blood-vessels of tracheal region, 147 of suprarenal bodies, 949

Ante-mortem heart-clots, character, 737

Anthracosis, appearance of lungs in, 458

Antimony, use, in bronchitis, 179, 180 in croupous pneumonia, 347

Antipyrin, use, in acute miliary tuberculosis, 480, 481 in simple lymphangitis, 990

Antiseptics, use, in croupous pneumonia, 352

Antispasmodics, use, in functional heart disease, 754 in laryngeal oedema, 116 in laryngismus stridulus, 73 in spasm of the glottis, 74

Anxiety, in cardiac thrombosis, 731

Aorta, atheroma of, 800 disease of, influence on causation of hypertrophy of the heart, 620 diseases of, 800 occlusion of, 824, 825 perforation of, 824 rupture of, 823 stenosis of, 825

Aortic arch, localization of aneurism of, 812 conus, defects of, in cyanosis, 708 obstruction, 654 regurgitation, 659 stenosis and regurgitation, treatment, 683 trunk, narrowing, in cyanosis, 708 and mitral orifices, defects of, in cardiac malformations, 690

Aortitis, acute, 800

Apex-beat, in dilatation of the heart, 634 in hypertrophy of the heart, 625, 627 normal position of, 654 significance of position of, in diagnosis of functional heart disease, 750

Apex of lung, tendency to tuberculous deposit in, 408

Aphonia, in paralysis of adductors of vocal cords, 82 in pulmonary phthisis, 403

Apomorphia, use, in catarrhal pneumonia, 371 in acute catarrhal laryngitis, 97, 98

Apoplexy of suprarenal bodies, 949 pulmonary, 293

Appetite, impaired, in pulmonary phthisis, 406

Arch of aorta, localization of aneurisms of, 812

Arsenic, use, in acute miliary tuberculosis, 482 in Addison's disease, 948 in atrophic nasal catarrh, 49 in bronchial asthma, 207 in carcinoma of larynx, 131 in chronic congestion and enlargement of the spleen, 959 in chronic laryngitis, 125 in dilatation of the heart, 636 in Hodgkin's disease, 931 in leukæmia, 921 in pernicious anæmia, 907 in pulmonary phthisis, 436

Arterio-sclerosis of the coronary artery, 828 of the pulmonary artery, 833

Artery, coronary, diseases of, 828 hepatic, aneurism of, 840 pulmonary, diseases of, 833 inferior mesenteric, diseases of, 834 superior mesenteric, diseases of, 836

Arytenoideus, paralysis of, 84

Aspiration in pericardial effusion, 776, 780 of the pleura, dangers of, 596 history, etc., 593-596

Aspirators in thoracentesis, varieties, 530, 532

Asthenic pneumonia, treatment, 351

ASTHMA, BRONCHIAL, 184 Definition, 184 Diagnosis, 198 From dyspnoea of bronchitis and cardiac disease, 198 of laryngeal affections, 199 From embolism of pulmonary artery, 200 From emphysema, 198 From spasm of diaphragm, 199 Duration, 189 Etiology, 190 Age and sex, influence on causation, 190 Cold and damp, influence on causation, 192 Enlarged bronchial glands, 191 Heredity, influence on causation, 190 Pollen of plants, vapors, gases, etc., 192 Uterine, nasal, and stomachic irritation, 193 History, 184 Morbid anatomy, 197 Pathology, 193-197 Prognosis, 200 Sequelæ, 189 Synonyms, 184 Symptoms and course, 185 of intervals, 184 paroxysms, description, frequency, and time of onset, 185-187 heart-circulation, state of, during, 188 physical signs of, 187, 188 Physiognomy of asthmatics, 186, 190 Treatment, 201 Hygienic and dietetic, 206 Locality, change of, 206 Of intervals, 206 Of paroxysms, 201 Use of arsenic, 207 of belladonna and stramonium, 203 of chloroform, 202 of cigarettes, medicated, 203, 207 of compressed air, 208 of electricity, 205 of emetics, 204 of lobelia and tobacco, 204 of morphia and chloral hydrate, 201, 202 of nitrite of amyl, 204 of nitro-glycerin, 208 of potassium bromide, 204 iodide, 207 nitrate, 203 of stimulants, 205

Asthma complicating emphysema, 239 hay, 210

Astringents, use, in chronic laryngitis, 125, 126 in laryngeal oedema, 116

Atelectasis, influence on causation of bronchial dilatation, 228

Atelectasis. See Lung, Collapse of.

Atheroma of the aorta, 800 of the coronary artery, 828 of the pulmonary artery, 833

Atmospheric causes of goitre, 977

Atomizer, use, in hyper- and paræsthesia of the larynx, 64

Atresia of the pulmonary artery, 702

Atropia, use, in profuse expectoration of bronchiectasis, 231 in pulmonary phthisis, 438 in the caisson disease, 858

Atrophic form of chronic nasal catarrh, 47 lobar emphysema, 248

Atrophy of suprarenal bodies, 949 of the heart, 618

Auricles of the heart, hypertrophy of, 627

Auriculo-ventricular orifice and tricuspid valve, defects of, 689 rings, condition, in cardiac dilatation, 633

Auscultation during paroxysm of asthma, 187 of mediastinal tumors, 874 in bronchial dilatation, 229 in bronchitis, 170-174 in cardiac malformation, 710, 711 thrombosis, 728 valvular disease, 657, 663, 668, 673, 675, 677, 680 in catarrhal pneumonia, 359, 360, 362, 363 in collapse of the lung, 253 in croupous pneumonia, 335, 337, 338 in emphysema, 238 in endocarditis, 648 in fibro-serous pleurisy, 507-510 in hydrothorax, 572 in mediastinal abscess, 862 in pericarditis, 775 in pneumothorax, 579 in pulmonary phthisis, 412-418 in purulent pleurisy, 543, 544 in pyo-pneumothorax, 545 in thoracic aneurism, 811

Auscultatory percussion in fibro-serous pleurisy, 503

Auto-laryngoscopy, 29

Axillary glands, enlargement of, in Hodgkin's disease, 926

B.

Bacelli's sign of pleurisy, 510, 517, 543

Bacillus tuberculosis, relation of, to acute miliary tuberculosis, 477 to hæmoptysis, 279, 280 to pulmonary phthisis, 398

Balfour's treatment of aneurism, 818

Balsams, use, in chronic bronchitis, 182

Bandage, use, in phlegmasia dolens and lymphangitis, 848, 991

Barrel-shaped chest of emphysema, 237

Barwell's operation for cure of thoracic aneurism, 818

Basedow's disease. See Exophthalmic Goitre.

Baths, cold, use, in bronchial asthma, 206 in croupous pneumonia, 349 hot, use, in laryngismus stridulus, 73

Belladonna, use, in pulmonary phthisis, 438 and stramonium, use, in bronchial asthma, 203

Bellocq's canula, use, in epistaxis, 52

Benign form of pulmonary embolism, symptoms, 382 growths of the larynx, 128 tumors of the trachea, 140

Benzoin, use, in chronic laryngitis, 124, 126

Bilious pneumonia, 334

Binaural stethoscope, use, in auscultation, 412

Black sputa of pitmen, 455, 459

Blaud's pills, use, in chlorosis, 896

Bleeder families, 933

Bleeding in heart disease, question of, 686

Bleedings, seat and amount, in hæmophilia, 935

Blisters, use, in acute myocarditis, 606 in capillary bronchitis, 180 in chronic phlebitis, 848 in pericardial effusion, 784 in pleurisy, 521 in thoracic aneurism, 817

Blood changes in, in croupous pneumonia, 313 in hæmoptysis, 287 in Hodgkin's disease, 924 in leukæmia, 911, 915 in pernicious anæmia, 901 condition of, in chlorosis, 894 in hæmophilia, 936 diseases of the, 882

Blood-corpuscles, changes in, in pernicious anæmia, 901 relation of spleen, lymph-gland, and bone-marrow to production, 890, 891

Blood-glandular system, diseases of, 882

Bloodletting, local and general, in pulmonary congestion and oedema, 263, 264

Blood-vessels, pulmonary, changes in, in emphysema, 243 relation of, to miliary tubercles, 474, 475

Bone-marrow, hyperplasia of, in anæmia, 892 influence on blood-formation, 885 lesions, in leukæmia, 916 in pernicious anæmia, 905

Bones, pressure upon, in thoracic aneurism, 807

Bowditch's connection with history of thoracentesis, 591-595

Brain, lesions, in croupous pneumonia, 313 in pernicious anæmia, 905 and membranes, lesions, in catarrhal pneumonia, 358 in leukæmia, 918

Breath, fetid, in chronic pharyngitis, 122

Breathing, in collapse of lung, 252

Bright's disease, complicating phthisis, 407 influence on causation of pericarditis, 771 of congestion and oedema of the lungs, 259

Bromides, use, in exophthalmic goitre, 767

Bronchi, diseases of, 164

Bronchial asthma, 184 breathing, in pleurisy, 508 catarrh, complicating emphysema, 247 influence on causation of collapse of lung, 251 glands, enlargement of, in croupous pneumonia, 313 lesions, in bronchitis, 175, 176 in catarrhal pneumonia, 357 in pneumonokoniosis, 457 lesions of syphilis of the lungs, 451 respiration in croupous pneumonia, 337

BRONCHIAL TUBES, DILATATION OF (Bronchiectasis), 227 Definition, history, and etiology, 227 Diagnosis and prognosis, 230 Morbid anatomy, 230 Symptoms, 228 Treatment, 230

BRONCHITIS, 164 Definition, 164 Diagnosis, 176 From phthisis, 177 From pneumonia, 176 Of chronic form, from emphysema, 177 Etiology, 164 Age and sex, influence on causation, 165 Cold and damp, season, etc., 166-168 Exciting causes, 168 Predisposing causes, 165 History, 164 Morbid anatomy, 175 Mortality, 165, 177 Prognosis, 177 Synonyms, 164 Symptoms--acute form, 169 Capillary form, 171 Cough, characters, 171 Dyspnoea in, 171 Physical signs of, 171 Chronic form, 174 Cough and expectoration, characters of, 174 Mechanical form, 170 Pseudo-membranous form, 173 Rheumatic form, 172 Treatment, 178 Of acute and capillary forms, 178-180 Antimony, use, 180 Counter-irritation, 178 Emetics, 180 Expectorants, 179 Quinia, use, 179 Venesection, 178 Of chronic form, 181 Alteratives, 182 Change of climate, 183 Compressed air, 183 Diet, 181 Inhalations, 182 Iron, use, 182 Of pseudo-membranous form, 180 Of rheumatic form, 180

Bronchitis and pneumonia, influence on causation of phthisis, 394 complicating emphysema, 239 tracheotomy, 162 of acute infectious diseases, influence on causation of catarrhal pneumonia, 354

Broncho-vesicular respiration, characters and significance of, 412

Brown atrophy of heart-muscle, 616 induration of lungs, 256

Bruit, in thoracic aneurism, 811

C.

Caffeine, use, in dilatation of the heart, 635

CAISSON DISEASE, 854 Definition, 854 Duration, 855 Etiology, 857 Morbid anatomy, 855 Pathology, 855 Symptoms, 854 Headache, vertigo, and coma, 855 Nausea and vomiting, 854 Pain, seat and characters, 854 Paralyses, 854, 855 Treatment, 858 Atropia, use, 858 Compressed air, 859 Ergot, use, 859 Morphia, use, 858 Of paralysis, 859

Calcareous degeneration of the heart-muscle, 616

Calcification of the vein, 852

Calcium sulphide, use, in acute phlebitis, 846

Canulas, tracheotomy, 151, 152

Cancer of adrenals in Addison's disease, 943 of the heart, 639 of the lungs, 460 of the pericardium, 792 of the pleura, 583 of the veins, 853

Capillary bronchitis, 171 emboli of lungs, effects, 385 vessels, relation to miliary tubercles, 475

Caput Medusæ, 849

Carbolic acid, danger of, in injections into pleural cavity, 561 use, in abscess of lung, 300 in gangrene of lung, 305 injections, in goitre, 980 and iodine, injections, in pericardial effusions, 795

Carcinoma of the larynx, 128 of the mediastinum, seat and characters, 869 of the nasal passages, 55 of the thyroid gland, 978 of the trachea, 141

Cardiac action, irregular, in fatty degeneration of the heart, 615 disease influence on causation of chronic splenic enlargement, 957 hæmoptysis, symptoms, 285 hypertrophy, relation to adherent pericardium, 786 murmurs, relation to valvular disease, 651 sedatives, use, in hypertrophy of the heart, 630

CARDIAC THROMBOSIS, 718 Complications and sequelæ, 733 Definition, 718 Diagnosis, 740 From dyspnoeic uræmia, 742 laryngeal affections, 743 nervous shock of acute endocarditis, 744 pulmonary embolism, 743 Duration and terminations, 732 Etiology, 721 Age and sex, influence on causation, 722 Mechanical causes, 723 Vital or pathological causes, 724 Endocarditis, influence on causation, 725 History, 719 Morbid anatomy and pathology, 734 Of ancient clots, 737 cadaveric and terminal clots, 735 Physical characters of clots, 735-740 Prognosis, 744 Synonyms, 718 Symptoms, 726 Blowing murmur of Bouillaud, significance, 730 Dyspnoea, 730 Mental condition, 731 Pain, 730 Physical signs, 727 Physiognomy in, 730 Pulse, characters, 729 Syncope, 730 Treatment, 745 Alkalies, as solvents, use, 745 Ammonium carbonate and liquid ammonia, use, 745 Counter-irritation, 746 Digitalis and nux vomica, use, 746 Intravenous injections of ammonia, 745 Rest, value, 746 Sodium bicarbonate, use, 745 Stimulants, use, 746

Cardicentesis, 798

Caseated morbid products, influence on causation of pulmonary phthisis, 400

Caseous pneumonia following pleurisy, 514 pus, influence on causation of acute miliary tuberculosis, 473

Casts of bronchi, in pseudo-membranous bronchitis, 176

Catarrh, chronic nasal, 42

Catarrhal pneumonia in children, symptoms, 359 relation of, to collapse of lung, 354, 355 tendency, influence on causation of hæmoptysis, 275

Catheterization of larynx in true croup, 107

Cavernous form of hæmoptysis, 284

Cavities, diagnosis of, in pulmonary phthisis, 416 tubercular, injection of, 439, 440

Cell-walls, changes in, as a cause of emphysema, 334

Cerebral anæmia, in aortic obstruction, 656 disturbance in functional heart-disease, 749 hyperæmia in tricuspid regurgitation, 649

Cerebral symptoms in cardiac thrombosis, 731 of croupous pneumonia, 329 of pericarditis, 774

Chest, alterations of, in pleuritic effusions, 497, 498 changes in, in emphysema, 236, 237

Cheyne-Stokes breathing in fatty degeneration of the heart, 615

Children, catarrhal pneumonia in, 359

Chills in croupous pneumonia, 320 in pleurisy, 494 in purulent pleurisy, 542

Chloral hydrate, use, in bronchial asthma, 202 in catarrhal pneumonia, 372

Chlorides, diminution of, in croupous pneumonia, 330

Chloroform, use, in bronchial asthma, 202

Chlorosis, 894 Definition and etiology, 894 Morbid anatomy, 894 Symptoms, 895 Treatment, 896

Chondritis of the larynx, 117

Chorea of the larynx, 76

Chronic bronchitis, 174 influence on causation of bronchiectasis, 228 congestion and enlargement of the spleen, 956 endarteritis of the coronary artery, 828 of the pulmonary artery, 833 interstitial pneumonia, 391, 440 lobular emphysema, 233 myocarditis, 607 pericarditis, 784 phlebitis, 848 purulent pleurisy, symptoms, 342

Cigarettes, medicated, use, in bronchial asthma, 203, 207

Circumscribed pleurisies, 545

Cirrhosis of the liver, influence on causation of splenic enlargement, 957 of lung, displacement of heart by, 603

Classification of hay asthma, 221 of pleurisy, 454 of pneumonokoniosis, 454 of pulmonary embolism, 373

Climate, change of, in acute laryngitis, 96 in chronic bronchitis, 183 influence on frequency of hæmoptysis, 277

Climatic treatment of pulmonary phthisis, 427

Clothing, proper, for phthisical patients, 433, 434

Clots, ancient or ante-mortem, of heart, characters, 737 cadaveric, in cardiac thrombosis, 735 terminal, in cardiac thrombosis, 735

Clubbing of fingers in cyanosis and cardiac malformations, 711

Cocaine, use, in chronic laryngitis, 127 in coryza, 42 in epiglottic ulceration, 112 in hyper- and paræsthesia of the larynx, 65 in morbid growths of the larynx, 131

Codeia, use, in bronchitis, 180, 182 in cough of miliary tuberculosis, 480

Cod-liver oil, use, in acute miliary tuberculosis, 482 in atrophic nasal catarrh, 49 in chronic bronchitis, 182 in chronic laryngitis, 125 in pulmonary phthisis, 434 in purulent pleurisy, 549 in ulceration of trachea, 139 in vesicular emphysema, 245

Coeliac axis, aneurism of, 841 diseases of, 841

Coffee, use, in bronchial asthma, 205 black, use, in cardiac thrombosis, 746

Colchicum, use, in rheumatic bronchitis, 181

Cold applications in epistaxis, 51 influence on causation of congestion and oedema of the lungs, 258 of pericarditis, 770 of perichondritis and chondritis of larynx, 117 use, in catarrhal pneumonia, 371 in pericarditis, 783 in reduction of temperature in croupous pneumonia, 349 in simple lymphangitis, 990 and damp, influence on causation of asthma, 192 of bronchitis, 166 of croupous pneumonia, 315 of fibro-serous pleurisy, 491 and moisture, influence on causation of acute catarrhal laryngitis, 93

Collapse of lung, 250

Color of ante-mortem heart-clots, 739

Columnæ carneæ, lesions, in chronic myocarditis, 607

Communicability of pulmonary phthisis, 396

Complications after tracheotomy, 161 of acute coryza, 41 of cancer of the lungs, 464 of cardiac thrombosis, 733 of catarrhal pneumonia, 364 of emphysema, 239 of fibro-serous pleurisy, 512 of mediastinal abscess, 864 of pulmonary phthisis, 400

Compressed air, use, in bronchial asthma, 208 in chronic bronchitis, 183 in emphysema, 245

Compression in treatment of abdominal aneurism, 823

Congenital anomalies of the heart and great vessels, 687 malpositions of the heart, 601

Congestion, acute, of spleen, 953 and enlargement of the spleen, chronic, 956 and oedema of the lungs, 258

Congestive form of hæmoptysis, 283

Contagiousness of acute miliary tuberculosis, 472 of pseudo-membranous laryngitis, 102 of pulmonary phthisis, 396-400

Conus arteriosus dexter, obstruction with open ventricular septum in cyanosis, 703

Convallaria, use, in dilatation of the heart, 635

Convulsions, in croupous pneumonia, 329 in pseudo-membranous laryngitis, 102

CORONARY ARTERY, DISEASES OF, 828 Chronic Endarteritis (Arterio-sclerosis; Atheroma), 828 Diagnosis and prognosis, 829, 830 Etiology and symptoms, 828 Pathology, 829 Treatment, 830 Aneurism of, 830 Embolism of, 831 Embolism and thrombosis of, 831 Obliterating endarteritis of, 830 Occlusion of, 831 Rupture of, 833 Thrombosis of, 832

Corpuscles of the blood, changes in, in Hodgkin's disease, 924 in leukæmia, 912 in pernicious anæmia, 901

Coryza, acute, 41

Cough in acute catarrhal laryngitis, 94 in asthma, 188 in bronchial dilatation, 228 in capillary bronchitis, 171 in cardiac malformations and cyanosis, 710 in catarrhal pneumonia, 358-361, 363 in chronic bronchitis, 174 pharyngitis, 122 in croupous pneumonia, 322 in emphysema, 236 in fibro-serous pleurisy, 495 in hydatids of pleura, 585 in laryngismus stridulus, 71 in mitral regurgitation, 671 stenosis, 667 in morbid growths of the trachea, 140 in pseudo-membranous laryngitis, 102 in pulmonary congestion in oedema, 260 phthisis, 400 treatment, 436 in purulent pleurisy, 542 in thoracic aneurism, 806 nervous, 71

Counter-irritation in acute bronchitis, 178 in atelectasis, 255 in cardiac thrombosis, 745, 746 in catarrhal pneumonia, 369 in croupous pneumonia, 347 in pericarditis, 783

Course of anæsthesia of the larynx, 67 of cardiac thrombosis, 732 of fibro-serous pleurisy, 510 of hyperæsthesia of the larynx, 163 of hypertrophy of the heart, 621 of laryngismus stridulus, 71 of leukæmia, 818 of pernicious anæmia, 903 of pulmonary congestion and oedema, 261

Crepitant râle of croupous pneumonia, 335

Crico-arytenoid muscles, hysterical paralysis of, 83

Cricotomy, 148, 156

Critical phenomena in croupous pneumonia, 331

Croup, false. See Laryngismus Stridulus.

Croupous pneumonia, 307

Cubebs, use, in chronic laryngitis, 124

Cyanosis, admixture theory of origin, 712 congestive theory of origin, 714 in cardiac malformation, 709 in fibroid phthisis, 442 in fibro-serous pleurisy, 496 in mitral regurgitation, 671 and congenital anomalies of the heart and great vessels, 687

Cysts, fibrinous, in cardiac thrombosis, 738 hydatid, of lungs, number and seat, 467 of suprarenal bodies, 949 of the heart, 637

Cystic goitre, 978

D.

Dangers of thoracentesis, 534

Death, cause of, in angina pectoris, 760 in croupous pneumonia, 345 in leukæmia, 919 in pericarditis, 783 in pulmonary embolism, 380, 381 in thoracentesis, 536, 537 in valvular heart disease, 681 mode of, in cardiac thrombosis, 732 in Hodgkin's disease, 929

Decubitus in fibro-serous pleurisy, 495

Definition of acute miliary tuberculosis, 472 of Addison's disease, 939 of angina pectoris, 755 of anæsthesia of larynx, 65 of bronchitis, 164 of bronchial asthma, 184 dilatation, 227 of brown induration of lungs, 256 of cancer of the lung, 460 of cardiac thrombosis, 718 of catarrhal pneumonia, 353 of chronic laryngitis, 121 nasal catarrh, 42 of collapse of the lung, 250 of congestion and oedema of lungs, 258 of croupous pneumonia, 307 of dilatation of the heart, 630 of endocarditis, 639 of emphysema, 232 of epistaxis, 50 of gangrene of the lung, 301 of hæmophilia, 931 of hæmoptysis, 266 of hæmothorax, 582 of hay asthma, 210 of Hodgkin's disease, 921 of hydrothorax, 570 of hyperæsthesia of the larynx, 62 of hypertrophy of the heart, 619 of laryngeal oedema, 112 of leukæmia, 908 of lymphangitis, 986 of mediastinal tumors, 864 of morbid growths of larynx, 128 of trachea, 139 of pericarditis, 169 of perichondritis and chondritis of the larynx, 117 of pernicious anæmia, 898 of pleurisy, 483 of pneumonokoniosis, 454 of pneumothorax, 573 of pulmonary abscess, 296 embolism, 373 hydatids, 466 phthisis, 391 of purulent pleurisy, 539 of simple tracheitis, 133 of spasm of the glottis in adults, 74 of stenosis of trachea, 142 of syphilis of the lung, 447 of the caisson disease, 854 of thoracic aneurism, 801

Deflected septum in chronic nasal catarrh, 44

Degenerations of heart-muscle, 609-616 of the suprarenal bodies, 949 of the veins, 852

Dermoid cysts of the mediastinum, 870

Delirium in croupous pneumonia, 329

Dentition, influence on causation of laryngismus stridulus, 70

Depressing influences, influence on causation of croupous pneumonia, 315

Diagnosis of abdominal aneurism, 823 of abscess of the lung, 299 of acute and chronic bronchitis, 176 of acute catarrhal laryngitis, 95 of acute congestion of spleen, 955 of acute miliary tuberculosis, 480 of acute myocarditis, 606 of acute phlebitis, 846 of Addison's disease, 947 of adherent pericardium, 788 of anæsthesia of larynx, 66 of aneurism of the coeliac axis, 842 of angina pectoris, 757 of aortic obstruction, 657 regurgitation, 664 of asthma, 198 of atrophic emphysema, 249 of bronchial dilatation, 230 of cancer of the lung, 464 of the pleura, 584 of cardiac thrombosis, 740-744 of catarrhal pneumonia, 365 of chronic congestion and enlargement of the spleen, 958 endarteritis of the coronary artery, 829 laryngitis, 124 myocarditis, 609 of collapse of the lung, 254 of coryza, 41 of croupous pneumonia, 339 of cyanosis, 709 of dilatation of the heart, 634 of echinococcus of the spleen, 969 of embolic splenic abscess, 964 of embolism of the coronary artery, 832 of the superior mesenteric artery, 838 of endocarditis, 650 of epiglottic affections, 109-112 of exophthalmic goitre, 763 of fatty cardiac degeneration, 615 infiltration of the heart, 612 of fibroid phthisis, 443 of functional heart disease, 749-752 of gangrene of the lung, 304 of hæmophilia, 937 of hæmoptysis, 289 of hæmothorax, 582 of hay asthma, 221 of hemorrhagic pleurisy, 568 of Hodgkin's disease, 929 of hydatids of the pleura, 585 of hydrothorax, 572 of hyperæsthesia and paræsthesia of the larynx, 64 of hypertrophic lobar emphysema, 243 of hypertrophy of the heart, 627 of interlobular emphysema, 249 of lardaceous spleen, 967 of laryngeal oedema, 115 of laryngismus stridulus, 72 of leukæmia, 919 of mediastinal abscess, 863 tumors, 876 of mitral regurgitation, 674 stenosis, 669 of morbid growths of the larynx, 130 of the trachea, 141 of paralysis of adductors of vocal cords, 83, 85 of tensors of vocal cords, 85, 86 of pseudo-membranous laryngitis, 103 of pericardial effusion, 778 of pericarditis, 776 of pernicious anæmia, 905 of pleurisy, 514 of pneumonokoniosis, 459 of pneumothorax, 580 of pulmonary apoplexy, 294 congestion and oedema, 262 embolism, 387 hydatids, 469 phthisis, 410 regurgitation, 677 stenosis, 676 of purulent pleurisy, 543 of simple lymphangitis, 988 tracheitis, 134 of spasm of the glottis in adults, 75 of stenosis of the aorta, 827 of the trachea, 142 of syphilis of the lungs, 453 of thoracic aneurism, 815 of thrombosis of the coronary artery, 832 of tricuspid stenosis, 677

Diaphoretics, use, in laryngeal oedema, 116 in pulmonary abscess, 264

Diaphragm, displacement of, in pleurisy, 497, 498, 507

Diaphragmatic pleurisy, 563

Diarrhoea in Hodgkin's disease, 925 in leukæmia, 910 in pernicious anæmia, 903 in pulmonary phthisis, 406 treatment, 439

Diathesis, the tubercular, 477

Diet after tracheotomy, 161 in acute miliary tuberculosis, 481 in Addison's disease, 948 in bronchial asthma, 206 in cardiac valvular disease, 683, 685 in catarrhal pneumonia, 369, 370 in croupous pneumonia, 348 in collapse of the lung, 256 in endocarditis, 651 in fatty degeneration of the heart, 616 in hay asthma, 224 in pericarditis, 783 in pernicious anæmia, 907 in pseudo-membranous laryngitis, 108 in simple lymphangitis, 990 restricted, in thoracic aneurism, 817

Dietetic treatment of pulmonary phthisis, 431

Digestive disorders in functional heart disease, 749 influence on causation of pernicious anæmia, 900

Digitalis, use, in acute myocarditis, 606 in angina pectoris, 761 in aortic disease, 684 in chronic endarteritis of the coronary artery, 830 in croupous pneumonia, 349 in dilatation of the heart, 635 in exophthalmic goitre, 767 in fatty degeneration of the heart, 616 in functional disease of the heart, 754 in hypertrophy of the heart, 630 in mitral disease, 685 in pericarditis, 783 in pulmonary congestion and oedema, 263 in vesicular emphysema, 247, 248

Dilatation of the pulmonary artery, 833 of the bronchial tubes, 227 of the heart, 630 of the trachea, 143 of the veins, 849

Diphtheria, influence on causation of anæsthesia of the larynx, 66 paralysis of the larynx, 80 of the trachea, 136

Displacement of adjacent organs in pleurisy, 504 of the heart in pneumothorax, 577

Displacements of the heart, 601-604

Disseminated form of catarrhal pneumonia, lesions, 357

Diverticular dilatation of trachea, 143

Double pleurisy, 562 pneumonia, prognosis, 343

Drainage of pleural cavity, methods of, 552-562

Dropsy in aortic regurgitation, 661 in mitral regurgitation, 672 of emphysema, treatment, 247 time of appearance in tricuspid regurgitation, 679

Drummond's oral whiff in aneurism, 812

Ductus arteriosus Botalli, defects of, in cardiac malformation, 691

Duration of anæsthesia of the larynx, 67 of asthma, 189 of cancer of the lungs, 463 of cardiac thrombosis, 732 of catarrhal pneumonia, 368 of fibro-serous pleurisy, 511 of Hodgkin's disease, 929 of laryngismus stridulus, 71 of life in cardiac malformations and cyanosis, 711 of mediastinal abscess, 863 tumors, 875 of pulmonary phthisis, 424 of stenosis of the aorta, 825 of the caisson disease, 855 of thoracic aneurism, 815

Durham's tracheotomy canula, 151

Dysphagia in chronic pharyngitis, 122 in hysterical affections of the glottis, 83 in inflammation of the epiglottis, 110 in laryngeal oedema, 114 in mediastinal tumors, 872, 873 in morbid growths of larynx, 129 in perichondritis and chondritis of the larynx, 118 in thoracic aneurism, 806

Dysphonia in morbid growths of larynx, 129 in perichondritis and chondritis of the larynx, 118 in pulmonary phthisis, 408

Dyspnoea in acute catarrhal laryngitis, 94 in Addison's disease, 941 in angina pectoris, 756 in aortic regurgitation, 661 in cardiac thrombosis, 730 in catarrhal pneumonia, 359, 360, 363 in chronic pharyngitis, 122 in croupous pneumonia, 321 in cyanosis and cardiac malformation, 710 in dilatation of trachea, 144 in fatty infiltration of the heart, 612 in fibro-serous pleurisy, 493, 495 in Hodgkin's disease, 925 in hydatids of pleura, 585 in hydrothorax, 571 in hypertrophy of the heart, 626 in laryngeal oedema, 114 in leukæmia, 913 in mediastinal tumors, 872 in mitral regurgitation, 671 stenosis, 667 in morbid growths of the larynx, 129 in paralysis of abductors of vocal cords, 88 in pernicious anæmia, 903 in pneumothorax, 578 in pulmonary embolism, 379-381 in stenosis of the trachea, 143 in thoracic aneurism, 805

E.

Echinococcus of the spleen, 968

Effects of cardiac hypertrophy, 626 of pulmonary embolism, 383

Effusions, characters, in purulent pleurisy, 540, 541 of fibro-serous pleurisy, 487-491 of pericarditis, 772

Elaterium, use, in hydrothorax, 572

Electric illuminator, use, in laryngoscopy, 24

Electricity, use, in anæsthesia of the larynx, 68 in angina pectoris, 761 in bronchial asthma, 205 in paralysis of the larynx, 90

Electrolysis, use, in goitre, 980 in thoracic aneurism, 819

Embolic abscess of the spleen, 963

Embolism and thrombosis of coronary artery, 831 of pulmonary artery, 835 complicating cardiac thrombosis, 733 from aortic obstruction, 656 influence on causation of gangrene of the lung, 302 of inferior mesenteric artery, 839 of pulmonary artery distinguished from asthma, 200 of superior mesenteric artery, 836 relation to acute myocarditis, 604 symptoms of, in endocarditis, 647

Emetics, use, in acute catarrhal laryngitis, 97 in catarrhal pneumonia, 371 in collapse of the lung, 255 in pulmonary congestion, 263 in pseudo-membranous laryngitis, 106

EMPHYSEMA, 232 Definition and history, 232 Varieties, 232 Interlobular or Extra-vesicular Emphysema, 249 Vesicular Emphysema, 232 Acute lobular form, 232 Symptoms and treatment, 233 Atrophic lobar form, 248 Symptoms and treatment, 248, 249 Chronic lobular form, 233 Hypertrophic lobar form, 233 Complications, 239 Diagnosis, 243 Duration, 242 Etiology, 234 Changes in alveolar wall, influence on causation, 234 Expiratory and inspiratory theories of causation, 235, 236 Heredity, influence on causation, 234 Morbid anatomy, 242 Prognosis, 244 Symptoms, 236 Cough and dyspnoea, 236 Chest, shape of, 237 Physical signs, 236-238 Respiration, peculiarities of, 238 Treatment, 245 Cod-liver oil, use, 245 Compressed air, use, 245, 246 Digitalis, use, 247 Expectorants, use, 246 Expiration into expired air, 246 Iron, use, 245 Potassium, iodide, 246 Quinia hydrobromate, hypodermatically, 247 Strychnia, use, 245

Emphysema after tracheotomy, 162 distinguished from asthma, 198 following asthma, 189

Empyema, pulsating, 596 See Pleurisy, Purulent.

Enchondroma of the mediastinum, 871

Encysted pleurisies, 545, 546

Endarteritis, obliterating, of the coronary artery, 830 of the pulmonary artery, 833 of the superior mesenteric artery, 839

ENDOCARDITIS, 639 Definition, 639 Diagnosis, 649 From aortitis, 650 From pericarditis, 649 Etiology, 645 Acute and chronic Bright's disease, 646 Acute rheumatism, 645, 646 Pyæmia, puerperal fever, the specific fevers, etc., 646 History, 639 Morbid anatomy, 640-645 Of acute exudative form, 640 Of interstitial form, 643 Of ulcerative form, 642 Prognosis, 650 Symptoms, 646 Dyspnoea, 647 Mitral murmurs, frequency and characters of, 648 Of exudative form, 647 Of interstitial form, 647 Of ulcerative form, 647 Pain in, 647 Physical signs, 648, 649 Physiognomy, 647 Pulse, characters, 647 Tricuspid and aortic murmurs, characters, 649 Treatment, 650 Iron, use, 651 Opium, use, 651 Rest, value, 651 Stimulants, use, 651

Endocarditis, influence on causation of cardiac thrombosis, 725 ulcerative, influence on causation of splenic infarction, 961

Engorgement stage of croupous pneumonia, 308

Enlargement of the spleen, chronic, 951, 956 in lardaceous disease, 967 in syphilis, 971

Epigastric pulsation in mitral disease, 672 in tricuspid disease, 679

Epiglottis, erosion of, 110 treatment, 111 inflammation of, 109, 110 ulceration of, 111 symptoms and treatment, 112

Epistaxis, 50-52 in croupous pneumonia, 331

Ergot, use, in epistaxis, 51 in embolism of superior mesenteric artery, 839 in hæmophilia, 938 in hæmoptysis, 291 in morbid growths of larynx, 131

Ergotin, use, in aneurism, 816 in exophthalmic goitre, 766 in hæmoptysis of heart disease, 685 in hæmothorax, 583 in pulmonary phthisis, 437

Erosion of epiglottis, 110

Eruptive fevers, influence on causation of pericarditis, 771 of pleurisy, 493

Erysipelas of the trachea, 136

Ether, use, in pneumothorax, 582

Etiology of acute catarrhal laryngitis, 93 miliary tuberculosis, 473 splenic congestion, 953 of Addison's disease, 939 of anæsthesia of the larynx, 65 of aneurism of the coeliac axis, 841 of the coronary artery, 830 thoracic, 802, 803 of aortic obstruction, 655 regurgitation, 660 of asthma, 190 of atheroma of the aorta, 800 of atrophic lobar emphysema, 252 of bronchial dilatation, 227 of bronchitis, 164 of brown induration of the lungs, 256 of cancer of the lungs, 460 of cardiac malformation, 694 thrombosis, 721 of catarrhal pneumonia, 353 of chronic congestion and enlargement of spleen, 956 endarteritis of the coronary artery, 828 laryngitis, 121 of collapse of the lung, 250 of congestion and oedema of the lungs, 258 of croupous pneumonia, 324 of dilatation of the heart, 631 of the veins, 849 of embolism of the coronary artery, 831 of emphysema, 234 of endocarditis, 645 of epistaxis, 50 of exophthalmic goitre, 764 of fatty degeneration of the heart, 612 of fibroid phthisis, 440 of fibro-serous pleurisy, 491 of functional heart disease, 752 of gangrene of the lung, 301 of goitre, 976 of hæmophilia, 932 of hæmoptysis, 272 of hæmothorax, 582 of hay asthma, 212 of hemorrhagic pleurisy, 565 of Hodgkin's disease, 922 of hydrothorax, 570 of hyperæsthesia of the larynx, 62 of hypertrophy of the heart, 619 of hysterical affections of the glottis, 83 of lardaceous spleen, 966 of laryngeal oedema, 113 of laryngismus stridulus, 70 of leukæmia, 909 of lymphangitis, 986 of mediastinal abscess, 861 tumors, 871 of mitral regurgitation, 671 stenosis, 666 of morbid growths of the larynx, 127 of the trachea, 139 of paræsthesia of the larynx, 63 of paralysis of abductors of vocal cords, 87 of adductors of vocal cords, 81 of constrictors of larynx, 80 of tensors of vocal cords, 85, 86 of the whole larynx, 79 of pericarditis, 769 of perichondritis and chondritis of larynx, 117 of perisplenitis, 965 of pernicious anæmia, 899 of pneumonokoniosis, 454 of pneumothorax, 573 of pseudo-membranous laryngitis, 101 of pulmonary abscess, 296 apoplexy, 293 embolism, 374 hydatids, 466 phthisis, 394 stenosis, 675 of purulent pleurisy, 539 of spasm of the glottis in adults, 74 of stenosis of the aorta, 826 of the trachea, 142 of syphilis of the lung, 447 of the caisson disease, 857 of tricuspid regurgitation, 678

Eucalyptol, use, in bronchial dilatation, 231

Evil effects of goitre, 979

Exciting causes of asthma, 191 of bronchitis, 168 of gangrene of the lung, 302 of hay asthma, 214

Excision of the spleen, 960 of the sternum in mediastinal abscess, 863 of the thyroid gland, 981

Exercise, importance, in pulmonary phthisis, 432, 433 in chronic bronchitis, 183

EXOPHTHALMIC GOITRE (Graves' Disease; Basedow's Disease), 761 Definition, 761 Diagnosis, 763 Etiology, 764 Morbid anatomy, 764 Prognosis, 765 Symptoms, 762 Dyspnoea, 763 Digestive disorders, 763 Eyeball, protuberance of, 762 Increased heart-action, 762 Thyroid body, enlargement of, 762 Treatment, 765 Aconite, use, 766 Digitalis, use, 767 Ergot, hypodermically, 766 Ice-bag to præcordiæ, 767 Iron, use, 766, 767 Iodine, use, 766 Hydropathic packing and the needle-bath, 766 Galvanization, 767 Of exophthalmia, 766 Opiates, use, 766

Expectorants, use, in bronchitis, 179 in simple tracheitis, 135 in pulmonary phthisis, 436

Expectoration, albuminoid, following thoracentesis, 535 characters in, in acute catarrhal laryngitis, 79 in asthma, 188 in bronchial dilatation, 228 in capillary bronchitis, 171 in catarrhal pneumonia, 359-361 in croupous pneumonia, 322 in chronic bronchitis, 174 in fibroid phthisis, 441

Expectorations, characters in fibro-serous pleurisy, 496 in gangrene of the lung, 303 in pulmonary congestion and oedema, 260 in pulmonary phthisis, 401 in simple tracheitis, 133, 134 of acephalocysts in pulmonary hydatids, 469

Expiratory movement in asthmatic paroxysm, 186 theory of origin of emphysema, 235

Exploratory puncture in mediastinal abscess, 863 value, in diagnosis of pleurisy, 518 of purulent pleurisy, 543, 548

Extra-pulmonary hæmoptysis, 285

Exudations of fibro-serous pleurisy, characters, 486

Exudative endocarditis, acute, 640

Eyeball, protuberance of, in exophthalmic goitre, 640

F.

Faintings in Addison's disease, 941

False membranes of true croup, nature, 100 seat and character, in purulent pleurisy, 541

Fatality of Addison's disease, 941

Fatty degeneration of the heart, 612 of the veins, 852 infiltration of the heart, 611

Fevers, influence on causation of dilatation of the heart, 632

Fibroid heart, 607 phthisis, influence on causation of bronchial dilatation, 228

Fibroma of nasal passages, 55

Fibromata of trachea, frequency, 140

Fibro-serous pleurisy, 484

Fibrous goitre, 977

Fistula, aërial, following tracheotomy, 163 in phthisical persons, treatment of, 439

Fistulæ, pleuro-bronchial, seat and characters in purulent pleurisy, 542

Fistules, pericardial, 796

Flatness, level of, pleuritic effusions, 487, 491, 500

Fluctuation in pulmonary hydatids, 468

Flush of pneumonia, 328

Follicular goitre, 977 and fibrous goitre, treatment, 979, 980

Fomentations, use, in phlebitis, 846

Fragility of pulmonary vessels as a cause of hæmoptysis, 275

Frémissement in pulmonary hydatids, 468 cataire in thoracic aneurism, 808

Friction sounds in fibro-serous pleurisy, 507-509 in pericarditis, 775, 777

Functional heart disorders, 747

G.

Gallic acid, use, in epistaxis, 51 in hæmoptysis, 291

Gangrene of the lung, 301 influence on causation of pneumothorax, 575 complicating catarrhal pneumonia, 364 termination of croupous pneumonia in, 332

Gastric pneumonia, 334

Gastro-intestinal canal, lesions, in catarrhal pneumonia, 358 in croupous pneumonia, 313 in Hodgkin's disease, 928 in leukæmia, 917 in pernicious anæmia, 904 disorders in abdominal aneurism, 821 in Addison's disease, 941 in catarrhal pneumonia, 360, 362 in croupous pneumonia, 330 in endocarditis putrida, 647 in functional heart disease, 749 in Hodgkin's disease, 925 in leukæmia, 910 in mitral regurgitation, 671 in pernicious anæmia, 903 in pulmonary phthisis, 406 in tricuspid regurgitation, 679

Galvanism, use, in Addison's disease, 948

Galvanization, use, in exophthalmic goitre, 767

Galvano-cautery knife, use, in tracheotomy, 150 snare, use, for removing nasal growths, 56 use, for removal of nasal hypertrophies in hay asthma, 224 in chronic nasal catarrh, 44, 45, 47, 48, 50 in epistaxis, 51

Gelatinous goitre, 978 treatment, 981

General diseases, influence on causation of phthisis, 396

Geographical distribution of goitre, 975 of hay asthma, 218

Gestation, influence on causation of goitre, 977

Giddiness in Addison's disease, 941

Glacier- and ice-water, influence on causation of goitre, 976

Glands, bronchial lesions of, in bronchitis, 175

Glottis, hysterical affections of, 83 spasm of, in adults, 74, 75

GOITRE, 974 Definition, 974 Etiology, 976 Atmospheric causes, 977 Gestation and syphilis, influence on causation, 977 Glacier- and ice-water, influence on causation, 976 Geographical distribution, 975 Symptoms, 974 Treatment, 979 Electrolysis, use, 980 Ergot, use, 980 Excision of gland, 982 Injections, use, 989, 981 Iodides of lead and mercury, locally, 980 Iodine, use, 979-981 Iodoform, use, 979 local, 979 Natural mineral waters, use, 980 Of follicular and fibrous form, 979 Of gelatinoid or cystic form, 981 Of vascular form, 980 Syrup of iodide of iron, 979-981 Tincture of iron, injections, 981 Varieties, 977

Goitre, exophthalmic, 761

Gold, chloride of, use, in epiglottic erosion and ulceration, 111, 112

Gout, influence on causation of aortic regurgitation, 660 of thoracic aneurism, 803

Granulations, exuberant, complicating tracheotomy, 162

Grave form of pulmonary embolism, 380

Graves' disease. See Exophthalmic Goitre.

Great vessels, malformations of, 690

Gray hepatization stage of croupous pneumonia, lesions, 310

Gummy tumors of the spleen, 971

Gummata of the lung, 449, 450

H.

Hæmatemesis, distinguished from hæmoptysis, 289

Hæmopericardium, 788, 789

HÆMOPHILIA, 931 Classification, synonyms, and history, 932 Definition, 931 Diagnosis, 937 Etiology, 932 Age and sex, influence on causation, 933 Heredity, causation, 932 Morbid anatomy, 936 Pathology, 936 Prognosis, 938 Symptoms, 934-936 Blood in, 936 External bleedings, seat, 935 Interstitial bleedings, seat and characters, 935 Joints, affections of, 935, 936 Treatment, 938 Diet, 938 Ergot and iron, use, 938 Prophylaxis, 938

HÆMOPTYSIS, 266 Definition, 266 Diagnosis, 289 From hæmatemesis, 289 Etiology, 272 Age, influence on causation, 275 Bacillus tuberculosis, relation of, to, 279, 280 Catarrhal predisposition, influence on causation, 275 Exciting causes, 278 Fragility of blood-vessels, influence on causation, 275 Heredity, influence on causation, 272-275 Injury, influence on causation, 279 Pregnancy, influence on causation, 278 Sex, influence on causation, 276 Season, climate, etc., influence on causation, 277, 278 History, 266-272 Mortality, 290 Pathology and morbid anatomy, 286 Aneurisms of pulmonary artery, appearance of, 287 Heart, changes in, 288 Of cardiac hæmoptysis, 288 Of pulmonary infarction, 288 Seat of, and changes in hemorrhages, 288 Prognosis, 290 Synonyms, 266 Symptoms, 281 Frequency of attacks, 284 Of aortic aneurism discharging into air-passages, 285 Of cavernous form, 284 Of extra-pulmonary form, 285 Of hemorrhagic infarction and cardiac form, 285, 286 Of simple, congestive, and ulcerative forms, 283, 284 Physical signs, 282 Treatment, 291, 292 Absolute quiet, necessity of, 291 Astringent inhalations, 291 Ergot and turpentine, use, 291 Gallic acid, use, 291 Ice, use, 291 Ipecacuanha, use, 292 Opium, use, 291, 292 Quinia for fever following, 292

Hæmoptysis in hypertrophy of the heart, 627 in pulmonary phthisis, 401 influence on causation of pulmonary phthisis, 395

HÆMOTHORAX, 582 Etiology and pathology, 582 Symptoms, 582 Treatment, 583

HAY ASTHMA, 210 Classification, 221 Definition, 210 Diagnosis, 221 Etiology, 212 Age, sex, and heredity, influence on causation, 212, 213 Certain plants and grasses, 215, 216 Dust and animal parasites, 216 Exciting causes, 214 Heat and dryness, 214, 215 Occupation and temperament, 213, 214 Pollen theory of origin, 216-218 Predisposing causes, 212 Geographical distribution, 218 History, 210 Prognosis, 222 Symptoms and course, 218-221 Treatment, 222 Diet, 224 Climate, change of, 224 Galvanism, 224 Nasal hypertrophies, removal of, 224, 225 Nasal injections, use, 224 Quinia, use, 224

Headache and vertigo in mitral regurgitation, 672 in acute congestion of spleen, 954 in croupous pneumonia, 329 in Hodgkin's disease, 925 in leukæmia, 911

Head-reflector, use in laryngoscopy, 22

Heart and circulation, effect of asthmatic paroxysm upon, 188

HEART AND GREAT VESSELS, MALFORMATIONS OF, 687 Diagnosis, 709 Duration of life in, 709 Etiology, 692 Defects of arterial outlet of right ventricle, the most frequent primary cause, 694 Narrowing of pulmonary artery and patency of septum ventriculorum, theories of origin of, 697-702 Development of foetal heart, relation to course, 698, 700 Malformation affecting primarily left side, 707-709 Narrowing of aortic trunk, 708 Stenosis of the conus, 708 Affecting primarily the right side, 702-706 Of conus arteriosus dexter, with open ventricular septum, 703 Of pulmonary artery, combined stenosis, and atresia of, 706 Of pulmonary artery, closure of, with perfect ventricular septum, 702 Of pulmonary artery, stenosis of, with open ventricular septum, 706 Symptoms, 709 Clubbing of fingers and toes, 711 Cyanosis, 709 Dyspnoea and cough, 710 Physical signs, 710 Temperature in, 710

Heart and lung, disease, influence on causation of pulmonary embolism, 375 aneurism of, 636 atrophy of, 618 cancer of, 637 changes in, in emphysema, 240 clot, as a cause of death in croupous pneumonia, 343 condition of, in hæmoptysis, 288 cysts of, 637

HEART, DILATATION OF, 630 Definition, 630 Diagnosis, 634 Etiology, 631 Morbid anatomy, 633 Prognosis, 635 Symptoms, 634 Treatment, 635 Caffeine, use, 635 Convallaria, use, 635 Digitalis, use, 635 Rest, value of, 635

Heart disease, death from, following thoracentesis, 536 displacements of heart from, 602 influence on causation of congestion of the lungs, 258 influence on causation of hydrothorax, 570 diseases of the substance of, 601

HEART, DISPLACEMENTS OF, 602 From abdominal disease, 604 From changes in chest-wall, 602 From cirrhosis of lung, 603 From disease of pleura, 498, 504, 603 From heart disease, 602 From mediastinal tumors, 603 From pericardial effusions, 602 In pneumothorax, 577

HEART, FATTY DEGENERATION OF, 612 Diagnosis and prognosis, 615 Etiology, 612 Age and sex, influence on causation, 613 Cardiac hypertrophy, influence on causation, 613 Mineral and alcoholic poisoning, 612 Morbid anatomy, 613, 614 Symptoms, 614 Physical signs, 615 Pulse in, 615 Treatment, 616 Amyl nitrite, use, 616 Digitalis, use, 616 Iron and vegetable tonics, 616

HEART, FATTY INFILTRATION OF, 611 Diagnosis, 612 Etiology, 611 Symptoms and treatment, 612

HEART, FUNCTIONAL DISORDERS OF, 747 Diagnosis, 749 Etiology, 750 Morbid anatomy, 752 Prognosis, 753 Symptoms, 748 Cerebral disturbances, 749 Digestive disturbances, 749 Infrequency of intermittence of heart's action, 748 Palpitation, 747 Paroxysms, characters, and frequency of, 748 Treatment, 753 Aconite, use, 754 Alcohol, use, 755 Antispasmodics, use, 753, 754 Digitalis, use, 754 Opium and morphia, use, 754 Preventive, 754 Tonics, chalybeate, use, 754

HEART, HYPERTROPHY OF, 619 Definition, 619 Diagnosis, 627 Etiology, 619 Disturbed innervation, influence on causation, 619 Kidney disease, 621 Mechanical causes, 620 Morbid anatomy, 624 Prognosis, 629 Symptoms, 624 Dyspnoea, 626, 627 Physical signs, 625-627 Pulse, characters, 625, 627 Sensation, uneasy cardiac, 626, 627 Treatment, 630 Digitalis, use, 630 Sedatives, use, 630 Varieties, 619

Heart, lesions of, in Hodgkin's disease, 928 in interstitial endocarditis, 644, 645 in pernicious anæmia, 904 malpositions of, 601 murmur, cause of, in pleurisy, 510 muscle, amyloid degeneration of, 616 anæmic necrosis of, 610 brown atrophy of, 616 calcareous degeneration of, 616 degenerations of, 609-616 hyaline degeneration of, 616 parenchymatous degenerations of, 610 neuroses of, 747 normal positions of, 601, 602 palpitation of. See Heart, Functional Disorders of. parasites of, 637 rupture of, spontaneous, 617

Heart's action, increase of, in exophthalmic goitre, 762 mechanism of, 652

Heart, sarcoma of, 637 sounds, in adherent pericardium, 788 in pericarditis, 776 syphilis of, 637 tubercle of, 637

HEART, VALVULAR DISEASES OF, AND CARDIAC MURMURS, 651 Definition, 651 History, 651 Murmurs, 654 Aortic Obstruction or Stenosis, 654 Diagnosis, 657 Etiology, 655 Morbid anatomy, 654 Symptoms, 656 Cerebral anæmia, 656 Cerebral and other embolisms, 656 Murmurs, characters, 657 Physical signs, 657 Pulse, characters, 657 Aortic Regurgitation or Insufficiency, 659 Diagnosis, 664 Etiology, 659 Morbid anatomy, 659 Symptoms, 659 Carotid pulsation, 661, 662 Pain, characters, 661 Physical signs, 662 Pulse, characters, 661 Mitral Regurgitation, 669 Diagnosis, 674 Etiology, 671 Morbid anatomy, 669 Symptoms, 671 Cough and expectoration, 671 Cyanosis and physiognomy, 671 Digestive disorders, 671 Dropsy, occurrence of, 672 Headache, vertigo, etc., 672 Murmurs, seat and characters, 673 Physical signs, 672 Pulse, characters, 672 Mitral Stenosis, 665 Diagnosis, 669 Etiology, 666 Morbid anatomy, 665 Symptoms, 667 Hæmoptysis, 667 Murmurs, characters, 668 Pain, 667 Physical signs, 668 Pulmonary congestion, cough, etc., 667 Pulse, characters, 667 Purring thrill, significance, 668 Pulmonary Obstruction, 674 Diagnosis, 676 Etiology, 675 Morbid anatomy, 675 Symptoms and physical signs, 675 Pulmonary Regurgitation, 676 Physical signs, 677 Tricuspid Regurgitation, 677 Diagnosis, 680 Etiology, 678 Morbid anatomy, 678 Symptoms, 679 Cerebral hyperæmia, 679 Jugular and epigastric pulsation, 679 Physical signs, 679 Prognosis in valvular heart disease, 680-683 Treatment, 683 Arsenic, use, 684, 685 Calomel and jalap, use, 685 Diet in, 683-686 Digitalis, use, 684, 685 Ergotin, 685, 686 Hygienic, 683, 684, 686 Iron, use, 684, 685 Nitrate of amyl, use, 684, 686 Of aortic disease, 683, 684 Of dropsy, 684, 685 Of hæmoptysis, 685 Of mitral disease, 685 Of tricuspid disease, 686 Opium and morphia, use, 684, 686 Quinia and strychnia, use, 684, 685 Rest, value, 683 Squill, juniper and cream of tartar, use, 685

Heat and dryness, influence on causation of hay asthma, 214 use, in laryngismus stridulus, 73

Hemorrhage and congestion in pulmonary embolism, 384 during and after tracheotomy, 158, 162 in croupous pneumonia, 331 influence on causation of anæmia, 887 intestinal, in embolism of the superior mesenteric artery, 837 seat, in hæmoptysis, 287

Hemorrhages in Addison's disease, 940 in leukæmia, 913 in pernicious anæmia, 903 in pulmonary phthisis, 401, 402 interstitial, of hæmophilia, 935 seat and amount, in hæmophilia, 935

Hemorrhagic infarction of spleen, 960 pleurisy, 565

Hemorrhoids from obstruction of portal vein, 850

Hepatic artery, aneurism of, 840

Hepatization of croupous pneumonia, lesions, 309

Heredity, influence on causation of acute catarrhal laryngitis, 93 of asthma, 190 of emphysema, 234 of epistaxis, 50 of hæmophilia, 934 of hæmoptysis, 272-275 of hay asthma, 212 of Hodgkin's disease, 922 of pulmonary phthisis, 395 on prognosis of phthisis, 423

Hernia of trachea, 143

Herpetic eruptions of croupous pneumonia, 328

Hiccough in goitre, 979

History of Addison's disease, 939 of bronchial asthma, 184 dilatation, 227 of bronchitis, 164 of brown induration of the lungs, 256 of cardiac murmurs, 651 thrombosis, 719 of collapse of the lung, 252 of congestion and oedema of the lungs, 258 of croupous pneumonia, 307 of cyanosis and cardiac malformations, 687 of emphysema, 232 of endocarditis, 639 of gangrene of the lung, 301 of hæmophilia, 932 of hæmoptysis, 266 of hay asthma, 210 of Hodgkin's disease, 922 of hydrothorax, 570 of the laryngoscope, 19 of leukæmia, 908 of pernicious anæmia, 898 of pleurisy, 483 of pneumonokoniosis, 454 of pneumothorax, 573 of pulmonary abscess, 296 embolism, 373 hydatids, 466 phthisis, 392, 394 of purulent pleurisy, 539 of the rhinoscope, 21 of syphilis of the lung, 447

Hoarseness in acute laryngitis, 94

HODGKIN'S DISEASE, 921 Course, duration, and termination, 929 Definition and synonyms, 921 Diagnosis, 929 Etiology, 922 Morbid anatomy, 926 Lymph-glands, lesions, 926, 927 Spleen, lesions, 927 Pathology and prognosis, 930 Symptoms, 923 Blood and circulation, changes in, 924 Digestive disorders, 925 Genito-urinary system, changes in, 925 Hæmic murmurs in, 925 Lymphatic glands, enlargement of, seat and characters, 923 Skin, changes in, 925 Special senses, modifications of, 925 Spleen, enlargement of, 925 Respiratory system, disorders, 925 Treatment, 931 Arsenic, use, 931 Local, 931 Iodine and potassium iodide, use, 931 Phosphorus, use, 931 Quinia, iron, and cod-liver oil, use, 931

Hoffmann's anodyne, use, in functional heart disease, 753

Hyaline degeneration of heart-muscle, 616

Hydatids of the pleura, 585 pulmonary, 466

Hydropathic packing in exophthalmic goitre, 766

Hydropericardium, 789, 790

HYDROTHORAX, 570 Diagnosis and prognosis, 572 Definition, etiology, and history, 570 Pathological anatomy and symptoms, 571 Treatment, 572

Hygienic treatment of croupous pneumonia, 347 of pernicious anæmia, 907 of pleurisy, 519 of valvular heart disease, 683-685

Hyoscyamia, use, in catarrhal pneumonia, 372

Hyoscyamus, use, in acute catarrhal laryngitis, 98

Hyperæsthesia of larynx, 62

Hyperplasia of cytogenic tissues, relation to increase of white blood-corpuscles, 893 of spleen, lymph-glands, and bone-marrow, influence on causation of anæmia, 890, 891

Hypertrophic lobar emphysema, 233 nasal catarrh, 44

Hypertrophy of auricles of the heart, 627 of erectile tissue in chronic nasal catarrh, 44 of the heart, 619

Hypophosphites, use, in acute miliary tuberculosis, 481 in emphysema, 245 in phthisis, 435

Hypostatic pneumonia. See Lungs, Congestion and Oedema of.

Hysteria, influence on causation of paræsthesia of the larynx, 64

Hysterical affections of the glottis, 83

I.

Ice, use, in acute catarrhal laryngitis, 97 in laryngeal oedema, 117 in pericarditis, 783 in pseudo-membranous laryngitis, 104

Iceland, frequency of hydatid disease in, 466

Idiosyncrasy, influence on causation of cardiac functional disease, 752

Image, the laryngeal, 30 the rhinoscopic, 39

Impulse, cardiac, in adherent pericardium, 787 in aortic obstruction, 657 regurgitation, 662 in mitral regurgitation, 672 stenosis, 668 in pericarditis, 774 in tricuspid regurgitation, 679 in dilatation of the heart, 634 in hypertrophy of the heart, 625, 627

Inanition, influence on causation of anæmia, 889

Incipient phthisis, diagnosis of, 411

Indications for paracentesis of the pericardium, 794 for thoracentesis, 521 for tracheotomy, 145

Infarction, hemorrhagic, of lungs, symptoms, 286 of spleen, 960 pulmonary, lesions of, 288 in pulmonary embolism, characters and seat, 384

Infectious fevers, influence on causation of acute interstitial myocarditis, 605

Inferior mesenteric artery, diseases of, 839 tracheotomy, 148, 155

Inflammation of the epiglottis, 109 of the mediastinum, 861 of suprarenal capsules, 949 of the veins, 843

Inflammatory theory of origin of cardiac malformations, 692

Inflation of lung in atelectasis, 253, 254

Infrequency of heart's action in functional disease, 748

Inhalations, astringent, in hæmoptysis, 291 in chronic bronchitis, 182 in fibroid phthisis, 444 in pseudo-membranous laryngitis, 106 in simple tracheitis, 135 in ulcer of trachea, 139

Injections, use, in chronic enlargement of the spleen, 960 in echinococcus of the spleen, 970 in goitre, 980, 981 into pericardial sac, 795 into pleural cavity in purulent pleurisy, 551, 553, 562 of arsenic into spleen in leukæmia, 921 of tubercular cavities, 439, 440

Injury, influence on causation of hæmoptysis, 279 of paralysis of the larynx, 79

Innervation, disturbed, influence on causation of hypertrophy of the heart, 619

Innominate aneurism, localization of, 812

Inoculability of tuberculous disease, 397

Inspection in bronchitis, 163 in cardiac malformations, 710 thrombosis, 729 valvular disease, 657, 662, 668, 672, 675, 677, 679 in catarrhal pneumonia, 360, 361 in croupous pneumonia, 335, 336, 338 in endocarditis, 648 in fibro-serous pleurisy, 497, 498 in hypertrophy of the heart, 625, 627 in mediastinal abscess, 862 tumors, 874 in pericarditis, 774 in pneumothorax, 578 in thoracic aneurism, 807

Inspiratory and expiratory theories of origin of emphysema, 235

Instruments necessary in tracheotomy, 149

Insufficiency, aortic, 659

Insufflator, use, in chronic laryngitis, 126

Intercostal spaces, bulging of, in pleuritic effusion, 497, 498, 507

Interlobular emphysema, 249 pleurisy, 564

Intermittence of heart's action, 748

Intermittent pneumonia, 334

Interstitial endocarditis, 643 myocarditis, acute, 605 pneumonia, chronic, 391, 440

Iodine, locally, in acute congestion of the spleen, 956 in chronic congestion and enlargement of the spleen, 960 inflammation of the epiglottis, 110 laryngitis, 126 in exophthalmic goitre, 766 in pulmonary phthisis, 435 injection of, in goitre, 980, 981 internal use, in goitre, 979, 980 test for lardaceous spleen, 968 use, in Hodgkin's disease, 931

Iodoform, use, in chronic epiglottic inflammation, 110 in chronic laryngitis, 125

Ipecacuanha, use, in acute catarrhal laryngitis, 98 in bronchitis, 180 in hæmoptysis, 292 in laryngismus stridulus, 73

Iron, perchloride, injection of, in goitre, 981 pernitrate, use, in epiglottic ulceration, 112 syrup of the iodide of, use, in goitre, 979 use, in Addison's disease, 948 in anæsthesia of the larynx, 68 in angina pectoris, 761 in chlorosis, 896 in chronic congestion of the spleen, 960 in dilatation of the heart, 636 in endocarditis, 651 in exophthalmic goitre, 766, 767 in fatty degeneration of the heart, 616 in functional heart disease, 755 in hæmophilia, 938 in paralysis of the larynx, 91 in passive pulmonary congestion, 263, 264 in pernicious anæmia, 907 in pulmonary phthisis, 436 in valvular heart disease, 684, 685 in vesicular emphysema, 245

Irregular cardiac action in fatty degeneration, 615

Irritable heart, 747

Irritants, influence on causation of pseudo-membranous croup, 101 to pulmonary tissue, influence on causation of phthisis, 394

Ischæmia of the heart, influence on causation of angina pectoris, 758

Itching of skin and mucous membranes in hay asthma, 220, 221

J.

Jaborandi, local use, in chronic laryngitis, 125 use, in fibro-serous pleurisy, 520, 521 in laryngeal oedema, 116

Jacquemet on causes of death in pulmonary embolism, 381

Jarvis' snare for removal of nasal polypi, 54

Jaundice in mitral regurgitation, 671

Joint affections of hæmophilia, 935

Joints, lesions of, in hæmophilia, 936

Jugular pulsation in tricuspid regurgitation, 679

K.

Kidney disease, influence on causation of cardiac hypertrophy, 621 of pleurisy, 493 of pulmonary embolism, 375

Kidneys, lesions, in Hodgkin's disease, 928 in leukæmia, 918 in pernicious anæmia, 905 state of, in pseudo-membranous laryngitis, 102

L.

Lactic acid, use, in pseudo-membranous laryngitis, 106

Lardaceous spleen, 966

Laryngeal image, the, 30-33

Laryngectomy in morbid growths of the larynx, 131

LARYNGITIS, ACUTE CATARRHAL (False Croup), 92 Diagnosis, 95 From diphtheritic laryngitis, 95 From membranous croup, 95 From tubercular laryngitis, 95 Duration, 94 Etiology, 93 Pathology, 92 Prognosis, 96 Symptoms, 93 Treatment, 96 Alkalies in, 97 Apomorphia in, 97, 98 Baths, cold and sea, in, 96 Emetics in, 98 Ice in, 97 Inhalations in, 97 Narcotics in, 98 Of oedema of glottis in, 98 Potassium chlorate in, 91 iodide in, 97 Silver nitrate in, 97, 99

LARYNGITIS, CHRONIC, 121 Definition, etiology, and synonyms, 121 Diagnosis, 123 Morbid anatomy, 122 Prognosis, 124 Symptoms, 121 Treatment, 124 Ammonium chloride, use, 124 Anodynes, 127 Arsenic and cod-liver oil, use, 125 Cocaine, use, 127 Cubebs, use, 124 Inhalations, use, 126 Insufflations, use, 126 Iodoform, use, 125 Respirators, use, 126 Tar, use, 125, 126 Tracheotomy in, 127

Laryngitis, chronic tubercular, 123 syphilitic, 123 complicating pulmonary phthisis, 403

LARYNGITIS, PSEUDO-MEMBRANOUS, 100 Complications, 103 Contagiousness, 101 Diagnosis, 103 From catarrhal laryngitis, 104 From general oedema of glottis, 104 Etiology, 101 Mortality, 103 Pathology, 100 Prognosis, 103 Symptoms, 101 Treatment, 104 Alkalies in, 105 Diet in, 107 Emetics in, 106 Ice in, 104 Inhalations in, 106 Lactic acid in, 106 Massage of larynx, 107 Mercury in, 104 Pilocarpine in, 106 Quinia in, 105, 108 Stimulants in, 108 Strychnia in, 108 Tracheotomy in, 107

Laryngoscope, description of, 21 history of, 19

Laryngoscopy and rhinoscopy, 19

LARYNGOSCOPY, ART OF, 25-29 description of the laryngeal image, 30-33 methods of illumination in, 23-25 obstacles to, 28, 29 position of observer, 26 position of patient in, 26 use of electric illuminator, 24 use of head-reflector in, 22

Laryngotomy, in morbid growths of the larynx, 31

Larynx, anæsthesia of, 65 treatment, 67

LARYNX, CHOREA OF, 76 Symptoms, 76 Treatment, 77 Diseases of, 109 Disorders of motion of, 68 Exalted action of, 69 Hyperæsthesia of, 62 Treatment, 64 Lepra of, 132 Lupus of, 132 Muscles of, 59 Nerves of, 60

LARYNX, MORBID GROWTHS OF, 127 Definition and etiology, 127 Morbid anatomy, 128 Prognosis and diagnosis, 130 Symptoms, 129 Treatment, 131 Cocaine, use, 131 Laryngectomy, 131 Laryngotomy in, 131

Larynx, muscles of, 59 nerves of, 60 neuroses of, 59

LARYNX, OEDEMA OF, 112 Definition and synonyms, 112 Diagnosis and morbid anatomy, 115 Prognosis, 116 Symptoms, 113 Treatment, 116 Antispasmodics, use, 116 Astringents, use, 116 Diaphoretics, use, 116 Jaborandi, use, 116 Ice, use, 117 Morphia, use, 116 Purgatives, use, 116 Scarification, 116 Tracheotomy, 117

LARYNX, PARÆSTHESIA OF, 63 Symptoms and treatment, 64 Paresis and paralysis of muscles of, 78 Paralysis of constrictors of, 80 Perversions of sensations of, 61

LARYNX, PERICHONDRITIS AND CHONDRITIS OF, 117 Definition and etiology, 117 Diagnosis and prognosis, 120 Morbid anatomy and symptoms, 118 Treatment, 121

LARYNX, SPASM OF, IN CHILDREN (Laryngismus Stridulus), 70 Course and duration, 71 Diagnosis, 72 From true croup, 72 From simple laryngitis, 72 Etiology, 70 Pathology, 71 Prognosis, 72 Symptoms, 70 Voice in, 71 Treatment, 73 Alum in, 73 Anæsthetics, 73 Antispasmodics in, 73 Baths, hot, in, 73 Emetics in, 73 Ipecacuanha, 73 Potassium bromide in, 73

Latent pneumonia, 334, 342

Laxatives, use, in pleuritic effusions, 520

Leeches, in acute bronchitis, 178

Left ventricles, hypertrophy of, 625

Lepra of the larynx, 132

Lesions of cancer of the lung, 460, 461 of chronic congestion of the spleen, 958 of croupous pneumonia in children, 312 of fibro-serous pleurisy, 485 of lungs in pneumonokoniosis, 457, 458 in pulmonary phthisis, 408, 410 of nervous system, in Addison's disease, 944 of pulmonary hydatids, 467 Seat in syphilis of the lung, 450

LEUKÆMIA, 908 Course, 918 Definition, synonym, and history, 908 Diagnosis, 919 Etiology, 909 Age and sex, influence on causation, 909 Climate, influence on causation, 909 Malarial and previous disease, causation, 909 Syphilis, influence on causation, 910 Morbid anatomy, 915 Blood, and heart-changes in, 915 Bone-marrow, changes in, 916 Lymphatic glands, changes in, 916 Leukæmic growths, characters of, 918 Spleen, changes in, 915 Prognosis, 920 Symptoms, 910 Blood-corpuscles, changes in, 911, 912 Digestive disorders, 910 Genito-urinary disorders, 913 Hemorrhages, seat and characters, 913 Lymphatic glands and spleen, enlargement of, 914 Nervous symptoms, 911 Pulse, characters, 913 Respiratory symptoms, 913 Special senses, modification of, 911 Treatment, 920 Arsenic, use, 921 Ergot, use, 921 Excision of spleen, 921 Iron, use, 921 Quinia, use, 921 Transfusion, 921

Ligation of carotid and subclavian arteries in thoracic aneurism, 818

Lime, use, in pseudo-membranous laryngitis, 105

Liver, changes in, in tricuspid regurgitation, 678, 679 displacement of, in pleurisy, 497, 507 enlargement of, in leukæmia, 911 influence on destruction of the blood, 885 lesions, in catarrhal pneumonia, 358 in Hodgkin's disease, 928 in leukæmia, 918 in mitral regurgitation, 670

Lobelia, use, in bronchial asthma, 204

Local treatment of chronic congestion and enlargement of the spleen, 960 of chronic laryngitis, 125 of epiglottic inflammation, 109, 110 ulceration, 112 of laryngeal oedema, 116 of simple lymphangitis, 990 of ulceration of trachea, 139

Locality, change of, in bronchial asthma, 206 choice of, in treatment of hay asthma, 223

Localization of thoracic aneurisms, 812

LUNG, ABSCESS OF, 296 Definition, history, etiology, and synonyms, 296 Diagnosis, 299 Pathology and morbid anatomy, 298 Prognosis, 300 Symptoms and course, 297 Treatment, 300

LUNGS, CANCER OF, 460 Definition, 460 Diagnosis, 464 Duration, 463 Etiology and morbid anatomy, 460 Prognosis, 465 Symptoms, 461

LUNG, COLLAPSE OF (Atelectasis), 250 Definition and history, 250 Diagnosis, 254 Etiology, 250 Age, influence on causation, 251 Bronchial catarrh, relation of, to, 250, 251 Mechanism of production, 251 Thoracic effusions, influence on production of, 252 Morbid anatomy, 253 Prognosis, 255 Symptoms, 252 Treatment, 255 Diet in, 256 Emetics, question of use, 255 Expectorants, use, 255 Of congenital form, 255

LUNGS, CONGESTION AND OEDEMA OF (Hypostatic Pneumonia), 258 Course and termination, 261 Definition, 258 Diagnosis, 262 Etiology, 258 History, 258 Morbid anatomy, 261 Prognosis, 262 Symptoms, 260 Treatment, 263 Of passive form, 263 Of pulmonary oedema, 264 Use of bloodletting, general and local, 263, 264 of diaphoretics, 264 of digitalis, 263 of emetics, 263 of iron in chronic form, 263, 264 of stimulants, 263 of quinia hydrobromate, hypodermatically, 264

Lung, displacement of, in pleurisy, 506

LUNG, GANGRENE OF, 301 Course and duration, 305 Definition, synonyms, and etiology, 301 Diagnosis and prognosis, 304 Pathology and morbid anatomy, 303, 304 Symptoms, 302 Treatment, 305

Lungs, appearance of, in congestion, 262 brown induration of, 256 changes in, in hæmoptysis, 287 condition of, in pneumothorax, 576 early lesions of, in pulmonary phthisis, 408-410 lesions of, in croupous pneumonia, 308-313 in Hodgkin's disease, 928 in leukæmia, 918 in pernicious anæmia, 904 in pneumonokoniosis, 457 syphilitic disease of, 447

Lung-tissue, gross and microscopic appearance of, in catarrhal pneumonia, 356, 357

Lupus of the larynx, 132

Lymph, mechanism of circulation of, 984, 985

LYMPHANGITIS, SIMPLE, 983 Definition, 986 Diagnosis, 988 Etiology, 986 Age, influence on causation, 986 Specific irritation, 986 Traumatism, influence on causation, 986 Pathology and morbid anatomy, 987 Prognosis, 990 Symptoms, 987 Oedema, 987 Of tubercular form, 987 Pain, characters, 987 Temperature, 987 Treatment, 990 Antipyrine, use, 990 Bandage, use, 991 Cold, locally, 990 Diet in, 990 Fomentations, use, 990 Iron, arsenic, and cod-liver oil, 990, 991 Local, 990 Quinia, use, 990 Rest, 990 Silver nitrate, locally, 990

Lymphatic glands, changes in, in leukæmia, 914, 916 enlargement of, in Hodgkin's disease, 923, 926 influence on blood-formation, 884 lesions, in pernicious anæmia, 905 relation to production of blood-corpuscles, 890 swelling of, in perichondritis of larynx, 118

Lymph-spaces, seat of miliary tuberculosis in, 475

Lymph-vessels, lesions, in lymphangitis, 987

Lympho-sarcoma of the mediastinum, 867

M.

Mackenzie's method of injecting goitre, 981

Malaria, influence on causation of acute splenic enlargement, 954 of lardaceous spleen, 966 of leukæmia, 909

Malformations of left side of heart, 707 of right side of heart, 702

Malignant tumors of trachea, 141

Malign growths of larynx, 128

Malpositions of the heart, 601

Marriage of bleeders, 938 of phthisical persons, 439

Marrow of bone, lesions, in leukæmia, 916

Massage of larynx in true croup, 107

Measles, influence on causation of acute miliary tuberculosis, 473

Mechanical bronchitis, 170 causes of cardiac thrombosis, 723 of collapse of the lung, 251

Median tracheotomy, 148, 155

Mediastinal pleurisy, 564

MEDIASTINUM, DISEASES OF, 861 Abscess of the Mediastinal Space, 861 Complications and terminations, 863 Diagnosis and prognosis, 863 Etiology, 861 Symptoms, 862 Treatment, 863 Inflammation of the Mediastinum, 861 Tumors of the Mediastinum, 863 Anatomy of the mediastinal space, 863 Definition, 863 Diagnosis, 876 From abscess, 877 From aneurism, 876 From chronic pneumonia, 879 From pericarditis, 878 From pleurisy, 878 Of anterior growths, 877 Of posterior growths, 878 Differentiation of malignant growths, 879 Duration, 875 Etiology, 871 Pathology and morbid anatomy, 865-871 Carcinoma, characters, seat, and method of growth, 869 Lympho-sarcoma, characters, seat, and method of growth, 867 Sarcoma, characters, seat, and method of growth, 865-867 Prognosis, 876 Symptoms, 871 Cyanosis and oedema, 873 Dyspnoea, peculiarities of, 872 Pain, characters and seat, 872 Physical signs, 873 Pressure symptoms, 872, 873 Treatment, 880 Donovan's solution, use, 881 Morphia, use, 880 Paracentesis, 880 Resection of sternum, 880

MELANÆMIA, 896 Definition and etiology, 896 Morbid anatomy, 897 Pigment, mode of origin, 897, 898

Membrane of pseudo-membranous laryngitis, nature, 100 seat, 101

Membranous exudation, nature of, in pseudo-membranous bronchitis, 176

Menstrual disorders in chlorosis, 894, 895

Menstruation in fibro-serous pleurisy, 497, 498

Mental emotion, influence in evoking paroxysms of angina pectoris, 456

Mercury, use, in pseudo-membranous laryngitis, 104

MESENTERIC ARTERY, INFERIOR, DISEASES OF, 839 Aneurism, 839 Embolism, 839, 840

MESENTERIC ARTERY, SUPERIOR, DISEASES OF, 836-839 Aneurism, 836 Embolism, 836-839 Endarteritis, 839 Thrombosis, 839

Metallic tinkling in pneumothorax, 579

Meteorological conditions as a cause of bronchitis, 168

Miliary tubercles, physical characters of, 474 tuberculosis, acute, 472

Mineral and coal-dust, influence on causation of pneumonokoniosis, 455 poisoning, influence on causation of asthma, 191 of fatty degeneration of the heart, 612

Mitral disease, influence on causation of hydrothorax, 570 Prognosis, 682, 683 Treatment, 685, 686 Regurgitation, 669 Stenosis, 665 Valve, disease of, influence on causation of brown induration of the lung, 256

Morbid anatomy of acute congestion of the spleen, 955 exudative endocarditis, 640 myocarditis, 604, 605 of Addison's disease, 942 of aortic obstruction, 654 regurgitation, 659 of asthma, 197 of bronchial dilatation, 230 of bronchitis, 175 of brown induration of the lungs, 256 of cancer of the lungs, 460 of the pleura, 582 of cardiac thrombosis, 734 of catarrhal pneumonia, 354 of chronic myocarditis, 607 congestion of the spleen, 957 pharyngitis, 122 of croupous pneumonia, 308 of dilatation of the heart, 633 of fatty cardiac degeneration, 613 of fibroid phthisis, 440 of fibro-serous pleurisy, 484 of gangrene of the lung, 304 of hæmophilia, 936 of hæmoptysis, 286 of hæmothorax, 582 of hemorrhagic infarction of spleen, 961 of Hodgkin's disease, 926 of hydatids of pleura, 585 of hydrothorax, 571 of hypertrophy of the heart, 623 of interstitial endocarditis, 644 of lardaceous spleen, 967 of laryngeal oedema, 115 of leukæmia, 915 of mediastinal tumors, 865 of mitral regurgitation, 670 stenosis, 665 of morbid growths of larynx, 128 of pericarditis, 772 of perichondritis and chondritis of the larynx, 118 of pernicious anæmia, 904 of phthisis, 408 of pneumonokoniosis, 456 of pneumothorax, 576 of pulmonary abscess, 298 congestion and oedema, 261 emboli, 382 hydatids, 467 stenosis, 675 of purulent pleurisy, 540 of rupture of the spleen, 972 of simple lymphangitis, 987 tracheitis, 134 of splenitis, 963 of syphilis of the lung, 450 of the caisson disease, 855 of tricuspid regurgitation, 678 of ulcerative endocarditis, 642 of vesicular emphysema, 242

Morbid growths of the larynx, 127 of nasal passages, 52 of trachea, 139

Morphia, use, in bronchial asthma, 201 in chronic laryngitis, 127 in epiglottic ulceration, 112 in fibro-serous pleurisy, 520 in hæmothorax, 581 in hyper- and paræsthesia of the larynx, 64 in the caisson disease, 858 in ulceration of the trachea, 139 in valvular heart disease, 684, 686

Mortality of acute and chronic bronchitis, 177 of catarrhal pneumonia, 368 of croupous pneumonia, 342 of hæmoptysis, 290 of laryngismus stridulus, 72 of pseudo-membranous laryngitis, 103 of stenosis of the aorta, 827 of valvular heart disease, 680

Murmurs, blowing, in cardiac thrombosis, 727 cardiac, relation to valvular disease, 651 characters, in aneurism of the pulmonary artery, 834 in aortic obstruction, 657 regurgitation, 663 in mitral regurgitation, 668 stenosis, 673 in pulmonary stenosis and regurgitation, 675, 676 in tricuspid disease, 677, 680 and seat, in endocarditis, 648, 649 disappearance of, in acute myocarditis, 606 hæmic, in pernicious anæmia, 902 over splenic region, in splenic congestion, 954 significance, in abdominal aneurism, 822

Mucous membrane, bronchial swelling of, as a cause of asthma, 197

Multilocular areolar pleurisies, 564

Muscular exertion, influence on causation of aortic disease, 656, 660 influence on causation of hypertrophy of the heart, 622 prolonged, influence on causation of functional heart disease, 752

Muscle-substance, condition in dilatation of the heart, 633

Muscles of larynx, 59

MYOCARDITIS, 604 Etiology and morbid anatomy, 604, 605 Diagnosis, 606 Interstitial form, 605 Suppurative form, 605 Symptoms and treatment, 606

MYOCARDITIS, CHRONIC (Fibroid Heart), 607 Diagnosis, 607 Morbid anatomy and etiology, 607, 608 Symptoms and treatment, 608

Myosis, in thoracic aneurism, significance, 805

Myxoma of nasal passages, 53

N.

Narrowing of a vein, 851

Nasal catarrh, acute, 41

NASAL CATARRH, CHRONIC, 42 Atrophic form, 47 Prognosis, 48 Symptoms, 47 Treatment, 48 Arsenic and cod-liver oil in, 49 Galvano-cautery in, 48 Phosphates in, 49 From defective nasal respiration, 43-46 Deflected septum, 44 Hypertrophy of erectile tissue, 44 Osseous obstruction, 44 Treatment, 44-46 Galvano-cautery, 44-46 Iodine, use, 45 From necrosis of nasal bones, 49, 50 Inflammatory form, without hypertrophy, 46 Prognosis, 47 Treatment, 47 Electricity, 47 Silver nitrate, 47

Nasal cavities, anatomy of, 33, 35 diseases, table of, grouped by symptoms, 50 hypertrophies, removal of, in hay asthma, 225 injections in hay asthma, 224 mucous membrane, hypertrophy of, influence on causation of asthma, 193 passages, diseases of, 41 fibroma of, 55 morbid growths of, 52 myxoma of, 53 polypi of, 53 treatment, 54 sarcoma and carcinoma of, 55

Nausea and vomiting in acute congestion of spleen, 954 in Addison's disease, 941 in croupous pneumonia, 330 in pernicious anæmia, 903 in splenitis, 962

Needle-bath, in exophthalmic goitre, 766

Nervous cough, 77 lesions, of Addison's disease, 944 of Hodgkin's disease, 928 of leukæmia, 918 of pernicious anæmia, 905 symptoms of Addison's disease, 941 of Hodgkin's disease, 925 of leukæmia, 911 of pulmonary phthisis, 407

Neuralgia in hyperæsthesia of the larynx, 63

Neuroses of the larynx, 59 of the heart, 747

Night-sweats, of pulmonary phthisis, 405 treatment, 438

Nitro-glycerin, use, in bronchial asthma, 208

Nutrition, bad, influence on causation of catarrhal pneumonia, 354 impaired, of heart-walls, influence on dilatation of the heart, 632

Nux vomica, use, in angina pectoris, 761

O.

Occlusion of the aorta, 824 of the coronary artery, 831 of veins, 851

Occupation, influence on causation of hay asthma, 213 of mediastinal tumors, 871 of pneumonokoniosis, 455, 456 of pulmonary phthisis, 396 of thoracic aneurism, 803 in-door, influence on causation of bronchitis, 165

Oedema, from dilatation of veins, 850 in pernicious anæmia, 901 of glottis, 94, 103 of the lungs, 258 of thoracic walls, in purulent pleurisy, 542, 543

Onset of acute catarrhal laryngitis, 93, 94 of laryngismus stridulus, 70 of leukæmia, 910 of pseudo-membranous laryngitis, 102

Operations, various, in tracheotomy, 48

Operative treatment of pericardial effusions, 794

Opiates, use, in exophthalmic goitre, 766

Opium, use, in acute catarrhal laryngitis, 98 in croupous pneumonia, 348 in hæmoptysis, 291, 292 in pericarditis, 783 in pulmonary phthisis, 436, 437, 439 in valvular heart disease, 684, 685 and morphia, use, in angina pectoris, 760

Organization of heart-clots, 740

Orthopnoea, in mitral stenosis, 667

Osseous obstruction, as a cause of chronic nasal catarrh, 44

Over-training and heart-strain, influence on causation of cardiac dilatation, 631

Oxidation, defective, in fatty degeneration of the heart, 613

Oxygen, inhalations in true croup, 107

Ozæna, 47

P.

Pack, cold, use in croupous pneumonia, 349

Pain, characters, in croupous pneumonia, 322 in lymphangitis, 987 in mediastinal abscess, 862 in pulmonary phthisis, 402 in acute and chronic congestion and enlargement of the spleen, 954, 957 in acute phlebitis, 845 in aneurism of the coeliac axis, 842 in aortic obstruction, 656 regurgitation, 661 in caisson disease, 854 in cancer of the pleura, 584 in cardiac thrombosis, 731 in chronic endarteritis of the coronary artery, 828 in endocarditis, 647 in hydatids of the pleura, 581 in hyperæsthesia of the larynx, 62 in morbid growths of the larynx, 129 in pericarditis, 773, 774 in perichondritis and chondritis of the larynx, 118 in splenitis, 962 in stenosis of the trachea, 142 in ulceration of the trachea, 139 seat and characters, in angina pectoris, 756 in diaphragmatic pleurisy, 563 in fibro-serous pleurisy, 493 in mediastinal tumor, 872 in thoracic aneurism, 804 seat, in abdominal aneurism, 821

Palpation in cardiac malformations, 710 in cardiac thrombosis, 729 in cardiac valvular disease, 657, 662, 668, 673, 675, 677, 679 in croupous pneumonia, 335, 336, 338 in endocarditis, 648 in fibro-serous pleurisy, 503, 504 in pericarditis, 774 in pneumothorax, 579 in thoracic aneurism, 808

Palpitation in cardiac valvular disease, 656, 661, 667, 671, 675, 679 in hypertrophy of the heart, 626 of the heart, 747

Papilloma of larynx, 128, 130

Papillomata of trachea, frequency, 140

Paracentesis in endocardial effusions, 784, 794 in pulmonary hydatids, 470

Paræsthesia of larynx, 63

Paralysis in caisson disease, 854 of adductors and abductors of vocal cords, 81, 84, 86 of arm in thoracic aneurism, 810 of constrictors of larynx, 80 of muscles of larynx, 78 of posterior crico-arytenoids, 86 of tensors of vocal cords, 85, 86 of the whole larynx, 79

Parasites, influence on causation of hay asthma, 216 of the heart, 637

Parenchymatous degeneration of heart-muscle, 610

Paroxysms, frequency of, in angina pectoris, 756 in functional heart disease, 748 of asthma, description and frequency of, 185-187

Patency of septum ventriculorum, 690

Pathology of acute catarrhal laryngitis, 92 phlebitis, 843-845 congestion of spleen, 955 of Addison's disease, 944 of anæsthesia of larynx, 67 of aneurism of the coeliac axis, 842 of angina pectoris, 758 of asthma, 193 of bronchial asthma, 193 of bronchitis, 175 of caisson disease, 855 of cancer of the lungs, 460 of cardiac thrombosis, 734 of catarrhal pneumonia, 354 of chronic endarteritis of the coronary artery, 829 pharyngitis, 122 of collapse of lung, 253 of embolism of the coronary artery, 832 of the superior mesenteric artery, 837 of exophthalmic goitre, 764 of fibroid phthisis, 440 of functional heart disease, 752 of gangrene of lung, 303 of hæmophilia, 936 of hæmoptysis, 286 of hemorrhagic pleurisy, 565 of Hodgkin's disease, 930 of hysterical affections of glottis, 84 of laryngismus stridulus, 71 of mediastinal tumors, 865 of morbid growths of trachea, 140 of perichondritis and chondritis of larynx, 118 of pernicious anæmia, 905 of phlegmasia dolens, 847 of pneumonokoniosis, 456 of pseudo-membranous laryngitis, 100 of pulmonary abscess, 298 congestion and oedema, 261 emboli, 382 phthisis, 408 of simple lymphangitis, 987 tracheitis, 134 of spasm of the glottis in the adult, 75 of stenosis of the aorta, 825 of the trachea, 143 of syphilis of the lung, 448 of vesicular emphysema, 242

Pectoriloquie aphonique in pleurisy, significance, 510, 517

Percussion during paroxysm of asthma, 187 in bronchial dilatation, 228, 229 in cardiac malformation and cyanosis, 710 thrombosis, 728 valvular disease, 657, 663, 668, 673, 675, 677, 680 in catarrhal pneumonia, 359-363 in collapse of lung, 253 in croupous pneumonia, 335, 337, 338 in emphysema, 237 in endocarditis, 648 in fibro-serous pleurisy, 499-503 in hydrothorax, 572 in hypertrophy of the heart, 625, 627 in mediastinal abscess, 862 tumors, 874 in pericarditis, 774 in pneumothorax, 579 in pulmonary congestion and oedema, 260 phthisis, 411, 413, 415-418 in purulent pleurisy, 543, 544 in pyo-pneumothorax, 544 in thoracic aneurism, 812

Perforation in purulent pleurisy, 542-547 of the aorta, 824 of lung, in thoracentesis, 538

Pericardial effusions, displacements of heart, from, 602

PERICARDIAL EFFUSIONS, OPERATIVE TREATMENT OF, 794 Aspiration, method of, 796, 797 Free incisions and drainage, 795 Indications for, 794, 795 Injections into pericardium, 795 Puncture of heart, results of, 798 Results, 798 Site of puncture, 796

PERICARDITIS, 769 Definition, 769 Diagnosis, 779 From cardiac hypertrophy, 780 From cerebral affections, 779 From mediastinal tumors and inflammation, 780 From pleurisy and endocarditis, 779 Etiology, 769 Bright's disease, influence on causation, 771 Cold, influence on causation, 770 Eruptive fevers, influence on causation, 771 Rheumatism, acute, influence on causation, 770 Traumatism, influence on causation, 769, 770 Secondary causes, 770, 771 Frequency, 770, 771 Morbid anatomy, 772, 773 Prognosis, 781 Symptoms, 773 Auscultation, 775 Cerebral symptoms, 774 Friction sounds, characters, 775 Pain, 773 Percussion and palpation, 774 Physical signs of, 774 Pulse and temperature in, 774 Treatment, 783 Blisters, use, 784 Cold, locally, 783 Counter-irritation, 783 Diet in, 783 Digitalis, use, 783 Of effusion, 784 Paracentesis, 784 Potassium, bitartrate and acetate, use, 784 iodide, 784 Quinia, use, 784 Stimulants, 784

Pericarditis, chronic, 784 tubercular, 793

PERICARDIUM, ADHERENT, 785 Adhesions, seat and character, 786 Impulse in, 787 Prognosis, diagnosis, and treatment, 788

Pericardium, cancer of, 792, 793 diseases of, 769

Perichondritis of larynx, 117

Perisplenitis, 965

Peritonitis complicating pulmonary phthisis, 406

Pernicious anæmia, progressive, 898

Phlebitis, 843

Phlebolithes, 853

Phlegmasia alba dolens. See Veins, Diseases of.

Phosphates, use, in atrophic nasal catarrh, 49

Phosphorus, use, in Hodgkin's disease, 931 in leukæmia, 921 in pulmonary phthisis, 435

PHTHISIS, FIBROID, CHRONIC INTERSTITIAL PNEUMONIA, CIRRHOSIS OF LUNG, 440 Course and duration, 441 Diagnosis, 443 Etiology, 440 Symptoms, 441 Cough and expectoration, characters, 441 Cyanosis in, 442 Physical signs, 442 Sputa, characters, 441 Treatment, 444

Phthisis, incipient, diagnosis, 411, 413

PHTHISIS, PULMONARY, 391 Definition, 391 Diagnosis, 410 Auscultation in, 412, 416, 417 Bacilli, significance of presence in sputa, 413 Broncho-vesicular respirations, characters, 412 Dry cough, significance of, 411 Inspection in, 417 Of cavities, 416, 417 Of incipient form, 411 Of intercurrent pneumonia in, 418 Percussion in, 411, 415, 416 Stethoscope, necessity of use in, 412 Vesiculo-tympanitic resonance, characters, 415 Whispered voice, transmission of, 413-417 Etiology, 394 Age, occupation, and sex, 396 Bacillus tuberculosis, relation of, 392, 398 Bronchitis, relation of, to, 394 Communicability of, 396-398 General diseases, influence on causation, 396 Hæmoptysis, influence on causation, 395 Heredity and constitutional predisposition, influence on causation, 395 Season, humidity of soil, etc., influence on causation, 396 History, 392 Morbid anatomy and pathology, 408 Prevention, 444 Prognosis, 419 Symptoms and complications, 400 Anæmia in, 405, 406 Cough, characters, 400 Dysphonia, aphonia, and laryngitis, 403 Genito-urinary disorders, 408 Hæmoptysis, frequency and significance, 401, 402 Heart, and circulatory disorders in, 405 Intercurrent pneumonia, occurrence of, 403, 404 Nervous symptoms, 407 Night-sweats in, 404 Pain in, 402 Peritonitis, occurrence of, 406, 407 Pleurisy and pneumothorax in, 404 Respiration in, 403 Sputa, characters, 401 Temperature in, 404, 405 Vomiting, diarrhoea, and digestive disorders, 406 Synonyms, 391 Treatment, 425 Agaricus, use, in night-sweats, 438 Alcohol, use, 435 Arsenic, use, 436 Belladonna and zinc oxide, use, 438 Climatic, 427-430 Cod-liver oil, use and value, 434 Cold use, 437 Dietetic, 431 Ergotin, use, 437 Injection of cavities, 439 Iodine, use, 435 Iron, use, 436 Marriage of consumptives, question of, 439 Of cough, 436 Of diarrhoea, 438 Of night-sweats, 438 Of pyrexia, 437 Out-of-door life, necessity of, 432 Picrotoxin, use, 438 Quinia, use, 438 Sea-voyages, value, 433 Sanitaria, value, 430 Use of opium, 436, 439

Physical signs during paroxysm of asthma, 187 in emphysema, 236, 237 in fatty degeneration of the heart, 615 in mitral regurgitation, 671 in pulmonary congestion and oedema, 260, 261 regurgitation, 697 in purulent pleurisy, 543 of abdominal aneurism, 822 of acute bronchitis, 169 of acute miliary tuberculosis, 480 of adherent pericardium, 787 of aortic obstruction, 657 of aortic regurgitation, 662 of atrophic lobar emphysema, 248 of cancer of the lungs, 462, 463 of pleura, 584 of capillary bronchitis, 171 of cardiac malformations, 710 of cardiac thrombosis, 728, 741 of cardiac valvular disease, 668 of catarrhal pneumonia, 359-363 of collapse of lung, 252, 253 of croupous pneumonia, 334, 335 in children, 335, 338 of diaphragmatic pleurisy, 563 of dilatation of the heart, 634 of endocarditis, 648 of fibroid phthisis, 442 of fibro-serous pleurisy, 496 of hæmopericardium, 789 of hæmoptysis, 282 of hydrothorax, 572 of hypertrophy of the heart, 625 of mediastinal tumors, 873 of pericarditis, 774 of pneumothorax, 578 of pulmonary abscess complicating croupous pneumonia, 339 of pulmonary hydatids, 468 phthisis, 411 of pulmonary stenosis, 675 of senile pneumonia, 336, 338, 339 of stenosis of the aorta, 826 of syphilis of the lung, 452 of thoracic aneurism, 807 of thrombosis and embolism of the pulmonary artery, 836 of the coronary artery, 832 of tricuspid stenosis, 677

Physiognomy in angina pectoris, 756 in asthma, 186, 190 in croupous pneumonia, 328 in endocarditis, 647 in laryngismus stridulus, 71 in pulmonary embolism, 379-381

Picrotoxin, use, in pulmonary phthisis, 438

Pigment, seat and treatment of, in melanæmia, 896, 897

Pigmentation of Addison's disease, 940 of lungs in pneumonokoniosis, 451, 458

Pilocarpine in laryngeal oedema, 116 use, in pleuritic effusions, 521 in pseudo-membranous laryngitis, 106 in pulmonary oedema, 264

Pimpinella saxafraga, use, in acute catarrhal laryngitis, 99

Plants and grasses, certain, influence on production of hay asthma, 215

Plethora, 886

Pleura, cancer of, 583 diseases of, 483 displacement of heart from, 603 hydatids of, 585 lesions of, in croupous pneumonia, 313

Pleural cavity, morbid growths of, 583 effusions, frequency, in cancer of the lungs, 461 influence on causation of collapse of lung, 251 occurrence in course of mediastinal tumors, 870

Pleurisies, circumscribed, 545 encysted, 545, 546 multilocular areolar, 564

PLEURISY, 483 Complications, 512 Course, 510 Definition, 483 Diagnosis, 514 From abscess of liver, 516 Atelectasis, 517 Hydrothorax, 515 Intercostal neuralgia, pleurodynia, etc., 516 Pneumonia, 514, 515 Tumors and cysts, 516 Of nature of effusion, 517 Duration, 511, 512 Etiology, 491 Age and sex, influence on causation, 492 Atmospheric changes, influence on causation, 491 Of primary form, 491 Of secondary form, 491 Pulmonary affections, acute and chronic, influence on causation, 492 Rheumatism, gout, and nephritic affections, 493 Syphilis, influence on causation, 493 Traumatism, influence on causation, 492 Pathological anatomy, 484 Effused fluid, chemical characters of, 486 distribution of, 487 Exudation, seat, nature, and appearance of, 485, 486 Level of line of flatness assumed by effusion, 488, 489 Prognosis, 518 Sequelæ, 483 Symptoms, 493 Bronchial breathing, significance of, 508 Chills, frequency, 494 Cough, characters of, 495 Cyanosis, 496 Displacement of organs in, 504, 507 Expectoration, characters, 496 Friction sounds, seat and characters, 507, 509 Heart murmur in, 510 Mensuration, necessity of frequent, 497, 498 Pain, seat and characters, 493 Physical signs in, 496 Pneumo-pericardial friction sounds, 509 Pulse, characters, 494 Respiration in, 494 Skodaic resonance, seat and characters, 501 Temperature, 494 Voice sounds in, 510 Whispered voice, significance of, 510, 517 Synonyms, 483 Terminations, 512 Treatment, 519 Alkalies, use, 520 Blisters, use, 520, 521 Counter-irritants, use, 520, 521 Effusion, removal of, 520 Iron, use, 520, 521 Jaborandi and pilocarpine, 520, 521 Laxatives and purgatives, 520, 521 Opium and morphia, use, 520 Potassium iodide, use, 520 Quinia, use, 520 Rest, 519 Strapping of chest in, 520 Thoracentesis, 521 Albuminous expectoration following, 535 Contraindications, 530 Death from, causes, 536, 537 During febrile stage, question of, 525 Indications for, 521 Mode of operating, 530, 534 Secondary pneumonia and tuberculosis following, 536

Pleurisy, complicating pulmonary phthisis, 404 diaphragmatic, 563 double, 562

PLEURISY, HEMORRHAGIC, 564 Diagnosis, 568 Etiology and pathology, 565, 567 Prognosis, 568 Symptoms, 567 Treatment, 568

Pleurisy, interlobular and mediastinal, 564

PLEURISY, PURULENT, 539 Definition, 539 Diagnosis, 543 Exploratory puncture, value, 543 From tubercular cavities and dilated bronchi, 545 Of perforation, 543, 544 Etiology, 539 Age and sex, influence on causation, 540 Eruptive fevers, influence on causation, 540 Puerperal condition, the, influence on causation, 540 Rheumatism, gout, and nephritic diseases, 540 Traumatism, influence on causation, 540 History, 539 Pathological anatomy, 540 Prognosis, 548 Symptoms, 542 Physical signs, 543 Synonyms, 539 Terminations, 547 Treatment, 549 Alteratives, use, 549 By free drainage, 552-556 Injections and washing of cavity, value of, 561, 562 Modes of operating, 550 Pleurotomy, 555 Resection of ribs, 556 Surgical, 549 Thoracentesis, 550-552

Pleurisy, rheumatic, 564, 565 tubercular, 569

Pleuro-bronchial fistulæ, signs of occurrence of, in purulent pleurisy, 543

Pleurotomy, 556, 557

Pneumonia, acute lobar, complicating pulmonary phthisis, 403

PNEUMONIA, CATARRHAL, 353 Complications and sequelæ, 364 Definition, 353 Diagnosis, 365 From acute miliary tuberculosis, 367 From collapse of lung, 366 From croupous pneumonia, 366 Duration, 368 Etiology, 353 Age, influence on causation, 353 Infectious diseases complicated with bronchitis, influence on causation, 354 Mortality, 368 Pathology and morbid anatomy, 354 Bronchi, lesions, 356 Bronchial glands, lesions, 357 Lung-tissue, gross and microscopic appearance of, 356 Relation to collapse of lung, 355 Prognosis, 368 Symptoms, 358 Cardiac failure in, 363 Cough, 360, 361 Death, cause of, 362 Gastro-intestinal, 360 In children, 358 Nervous, 362 Of grave forms, in adults, 360 Physical signs, 358, 360, 362 Pulse and respiration, characters, 360, 361 Sputa, 360, 361 Temperature, 358, 360, 361 Synonyms, 353 Terminations, 368 Treatment, 368 Alteratives, use, 372 Ammonia preparations, use, 370, 371 Apomorphia, use, 371 Chloral hydrate, use, in nervous symptoms, 372 Climate, change of, 372 Counter-irritation, use, 369 Diet in, 369, 370 Emetics, use, 371 Hyoscyamia, hypodermatically, use, 372 Of gastro-intestinal disorders, 370 Of nervous symptoms, 372 Opium, use, 372 Quinia, use, 370, 371 Strychnia, use, 371

Pneumonia, chronic interstitial, 391, 440 complicating pleurisy, 512

PNEUMONIA, CROUPOUS, 307 Definition, 307 Differential diagnosis, 339 From capillary bronchitis, 340 From catarrhal pneumonia, 340 From hypostatic congestion, 340 From meningitis, 342 From pleurisy, 340 From pulmonary apoplexy, 341 congestion and oedema, 339 From typhoid fever, 342 Etiology, 314 Age and sex, influence on causation, 314 Cold, damp, season, etc., influence on causation, 314 Depressing influences, influence on causation, 315 Klebs on specific germ of, 319 Nature of, 315-318 Resemblance to acute general diseases, 317, 318 History, 307 Morbid anatomy, 308 Changes in abdominal viscera, 313 in bronchial glands, 313 in heart and blood, 313 in lung, 308-313 in pleura, 313 Prognosis, 342-345 Cause of death, 345 Mortality, 342, 343 Symptoms, 319 Alimentary tract, state of, 330 Cerebral, 329, 330 Chills, characters, in, 318 Cough, characters, in, 322 Critical phenomena, 331 Dyspnoea, characters, 321, 322 Expectoration, characters, 322 Herpetic eruptions, occurrence, 328, 329 Indicating danger, 331 Objective, 334-339 Of abscess and gangrene, 332 Of bilious and gastric form, 334 Of latent form, 334 Of purulent infiltration, 332 Pain, characters, 322 Physical signs, 334-339 Physiognomy, 328 Pulse, characters, 326, 328 Respiration, characters, 321 Sputum, characters, 322 Subjective, 319-334 Surface of body, state of, 328 Temperature in, 324 Urine, condition, 330 Synonyms, 307 Treatment, 345-352 Alcoholic stimulants, use, 348 Antiseptics, use, 352 Carbonate of ammonium, digitalis, musk, camphor, etc., use, 349 Cardiac depressants, danger, 346 Cold, use, 349 Counter-irritation, questionable utility of, 347 Diet in, 347, 348 Expectorants, use, 347 Of convalescence, 351 Of delirium, 351 Of senile variety, 351 Opium, use, 348 Quinia, use, 350 Reduction of temperature in, 349 Rest in, value, 347 Venesection, harmfulness, 346

Pneumonia, hypostatic, 258

Pneumo-hydropericardium, 791

Pneumo-hydrothorax complicating phthisis, 404

PNEUMONOKONIOSIS, 454 Definition, etiology, and history, 454 Diagnosis and prognosis, 459 Pathology and morbid anatomy, 456-459 Symptoms and treatment, 459

Pneumo-pericardial friction sound, 509

Pneumo-pericardium, 790

PNEUMOTHORAX, 573 Definition, 573 Diagnosis, 580 Etiology, 573 Age and sex, influence on causation, 576 Traumatic causes, 574 History, 573 Pathological anatomy, 576 Air, quantity, 576 Heart, displacement, 577 Opening, shape and seat, 576 Prognosis, 581 Symptoms, 578 Pain, seat and characters, 578 Physical signs, 578-580 Respiration, characters, 578 Treatment, 581, 582 Diet, 582 Opium and morphia, use, 581 Paracentesis, 581 Stimulants, 581

Pollen of plants, influence on causation of asthma, 192 theory of origin of hay asthma, 216

Polypus, nasal, 53, 54

Post-mortem heart-clots, 735

Potain's syphon, use, in purulent pleurisy, 555

Potassium acetate, use, in pericarditis, 784 bicarbonate, use, in cardiac thrombosis, 745, 746 chlorate, use, as an injection in pseudo-membranous laryngitis, 105 in purulent pleurisy, 562 bromide, use, in bronchial asthma, 204 in bronchitis, 179 in chronic inflammation of epiglottis, 110 in hyper- and paræsthesia of larynx, 64 in laryngismus stridulus, 73 in pulmonary hydatids, 470 iodide, use, in acute catarrhal laryngitis, 97, 99 in acute tracheitis, 136 in bronchial asthma, 207 in chronic bronchitis, 182 in chronic phlebitis, 848 in paralysis of the larynx, 91 in pericardial effusions, 784 in pleurisy, 520 in pseudo-membranous laryngitis, 105 in pulmonary hydatids, 470 in thoracic aneurism, 818 in vesicular emphysema, 246, 247 nitrate, use, in bronchial asthma, 203

Predisposing causes of asthma, 190 of bronchitis, 165 of gangrene of the lung, 301 of hay asthma, 212

Pregnancy, influence on causation of hæmoptysis, 278 of pernicious anæmia, 900 of pulmonary phthisis, 396

Pressure symptoms in aneurism of the pulmonary artery, 834 of abdominal aneurism, 821 of goitre, 975 of mediastinal abscess, 862 tumors, 872, 873 of thoracic aneurism, 804-807 upon aorta, for relief of thoracic aneurism, 816

Prevention of angina pectoris, 760 of phthisis, 444-446 of pulmonary embolism, 388

Preventive treatment of functional heart disease, 755

Priapism in leukæmia, 914

Prognosis in lardaceous spleen, 968 in pseudo-membranous laryngitis, 103 in simple tracheitis, 135 in valvular heart disease, 680 of acute catarrhal laryngitis, 96 congestion of the spleen, 955 of adherent pericardium, 788 of anæsthesia of the larynx, 67 of angina pectoris, 760 of asthma, 200 of atelectasis, 255 of atrophic emphysema, 249 of bronchial dilatation, 230 of bronchitis, 177 of cancer of the lung, 465 of the pleura, 584 of cardiac thrombosis, 744 of catarrhal pneumonia, 368 of chronic congestion and enlargement of the spleen, 959 of chronic laryngitis, 124 nasal catarrh from defective respiration, 46 of croupous pneumonia, 342 of dilatation of the heart, 635 of embolic splenic abscess, 964 of embolism of the superior mesenteric artery, 838 of endocarditis, 650 of epiglottic ulceration, 112 of exophthalmic goitre, 765 of fatty degeneration of the heart, 616 of fibro-serous pleurisy, 518 of functional heart disease, 753 of gangrene of the lung, 303 of hæmoptysis, 290 of hæmothorax, 583 of hay asthma, 222 of hemorrhagic pleurisy, 568 of Hodgkin's disease, 930 of hydatids of the pleura, 586 of hydrothorax, 572 of hyper- and paræsthesia of the larynx, 64 of hypertrophy of the heart, 629 of laryngeal oedema, 116 of laryngismus stridulus, 72 of leukæmia, 920 of mediastinal tumors, 876 of morbid growths of larynx, 130 of trachea, 141 of pericarditis, 781 of pernicious anæmia, 906 of phthisis, 419 of pneumonokoniosis, 459 of pneumothorax, 581 of pulmonary abscess, 300 congestion and oedema, 262 embolism, 388 hydatids, 470 of purulent pleurisy, 548 of simple lymphangitis, 990 of stenosis of the aorta, 827 of the trachea, 143 of syphilis of the lungs, 453 of ulceration of the trachea, 139 of vesicular emphysema, 244

Progressive pernicious anæmia, 898

Prophylaxis of acute catarrhal laryngitis, 96 of hæmophilia, 938 of phthisis, 444-446

Prune-juice expectoration, significance in pneumonia, 319, 344

Pseudo-membranous bronchitis, 173 laryngitis, 100

Puerperal state, influence on causation of phlegmasia dolens, 846 of pulmonary embolism, 377 of purulent pleurisy, 540

Pulmonary apoplexy, 293 Definition and history, 293 Diagnosis, etiology, and symptoms, 294 Prognosis and treatment, 295 and hæmoptysis, complicating cardiac thrombosis, 734 artery, closure of, with perfect ventricular septum, in cyanosis, 702 combined stenosis and atresia of, in cyanosis, 706

PULMONARY ARTERY, DISEASES OF, 833 Chronic endarteritis (atheroma; arterio-sclerosis), 833 Dilatation and aneurism, 833 Rupture of pulmonary artery, 835 Stenosis of trunk or main branches, 834 Thrombosis and embolism, 835, 836

Pulmonary artery and right conus arteriosus, defects of, 690 and vessels, anatomy of, relation to hæmoptysis, 269-272 disease, influence on causation of cardiac hypertrophy, 622, 623 influence on tricuspid regurgitation, 678

PULMONARY EMBOLISM, 373 Classification, 373 Death, cause of, 380, 381 Definition, 373 Diagnosis, 387 Etiology, 374 Diseases of thoracic, abdominal, and pelvic viscera, influence on causation, 375 Puerperal state, influence on causation, 377 Source of emboli, 374, 375 Surgical affections as a cause, 377 History, 373 Pathology and morbid anatomy, 382 Effects of emboli, 383 Infarctions, mechanism of production, 384, 385 Specific and septic emboli, effects, 386 Prevention of, 388, 389 Prognosis, 388 Symptoms, 378 Dyspnoea, characters of, 379-381 Of benign form, 382 Of grave form, 380 Of sudden form, 379 Physical signs, 381 Physiognomy in, 379-381 Sputa sanguinolent, in benign form, 382 Treatment, 388 Carbonate of ammonium and bicarbonate of sodium, use as solvents, 389 Counter-irritation and venesection, use, 390 Purgatives, use, 390 Surgical measures, 389

PULMONARY HYDATIDS, 466 Definition, etiology, and synonyms, 466 Diagnosis, 469 History, 466 Morbid anatomy, 467 Prognosis, 470 Symptoms, 468 Treatment, 470 Anthelmintics, use, 470 Of old suppurating cysts, 471 Paracentesis in, 470 Potassium bromide and iodide, 470 Surgical measures, 471

Pulmonary hyperæmia in mitral stenosis, 666, 667 infarction, lesions of, 288 orifice, narrowing or closure of, as a cause of cardiac malformation, 694 phthisis, 391 regurgitation, 676 stenosis, 674 vein, anatomy of, 270

Pulsating empyema, 546

Pulsation in abdominal aneurism, 822 jugular and epigastric, in tricuspid regurgitation, 679 seat of, in aneurism of the cardiac axis, 841

Pulse, characters, in chronic myocarditis, 608, 609 in endocarditis, 647 in fatty degeneration of the heart, 615 in leukæmia, 913 in pericarditis, 774 in thoracic aneurism, 808 in acute miliary tuberculosis, 479

Q.

Quinia, use, in acute congestion of spleen, 956 in acute miliary tuberculosis, 480, 482 in anæsthesia of the larynx, 68 in bronchitis, 79, 181, 182 in catarrhal pneumonia, 370, 371 in chronic congestion and enlargement of the spleen, 959 in croupous pneumonia, 350 in endocarditis, 651 in fever following hæmoptysis, 292 in gangrene of the lungs, 305 in hay asthma, 224 in Hodgkin's disease, 931 in hyper- and paræsthesia of larynx, 65 in laryngismus stridulus, 73 in leukæmia, 921 in pericarditis, 784 in pseudo-membranous laryngitis, 105, 108 in pulmonary phthisis, 438 in purulent pleurisy, 549 in simple lymphangitis, 990, 991 tracheitis, 135 in valvular heart disease, 685 hydrobromate of, hypodermic use, in pulmonary congestion and oedema, 264

R.

Ragweed, influence on causation of asthma, 215, 216

Râle crepitant of croupous pneumonia, 335 redux of croupous pneumonia, 338

Recovery from pulmonary phthisis, 420-423

Recurrence of pulmonary phthisis, 424

Redness of skin, one-sided, in goitre, 975

Reduplication of second sound in mitral stenosis, 668

Reflex causes of laryngismus stridulus, 70 symptoms of nasal polypus, 53

Regiminal treatment of pulmonary phthisis, 432

Regurgitation, aortic, 659 mitral, 669 pulmonary, 676 tricuspid, 677

Relapse in croupous pneumonia, frequency, 326

Remissions, frequency, in acute catarrhal laryngitis, 94

Remittence of pulse in croupous pneumonia, 328

Remittent pneumonia, 334

Resection of ribs in purulent pleurisy, 557-562

Resolution stage of croupous pneumonia lesions, 310

Resonance, subclavicular, in pleurisy, 501-503

Respiration, characters, in catarrhal pneumonia, 359-363 in chronic bronchitis, 171 in collapse of lung, 252 in croupous pneumonia, 321 in fibro-serous pleurisy, 495, 497 in morbid growths of trachea, 140 in pneumothorax, 578 in pseudo-membranous laryngitis, 102 in pulmonary phthisis, 403

Respirator, use, in chronic laryngitis, 126

Respiratory power, defective, relation of, to catarrhal pneumonia, 356 sounds in emphysema, 238 in purulent pleurisy, 543

Rest, absolute, necessity of, in croupous pneumonia, 347 in treatment of thoracic aneurism, 817 necessity, in endocarditis, 651 value, in cardiac hypertrophy, 630 in acute and chronic phlebitis, 846, 848 in dilatation of the heart, 636 and quiet, necessity of, in hæmoptysis, 291 value, in cardiac thrombosis, 745, 746

Retention-cysts of trachea, 141

Reticular lymphangitis, symptoms, 987

Retina, condition of, in leukæmia, 911

Reybard's trocar, use, in pneumothorax, 581

Rheumatic bronchitis, 172 pleurisy, 564, 565

Rheumatism, acute, influence on causation of endocarditis, 645 as a cause of pericarditis, 770 influence on causation of paralysis of vocal cords, 82 of valvular heart disease, 655, 661, 666, 671 and gout, influence on causation of pleurisy, 493 of purulent pleurisy, 540

Rhinoscope, history of, 21

Rhythm of endocardial murmurs, method of determining, 653

Ribs, resection of, in purulent pleurisy, 557

Rickets, influence on causation of laryngismus stridulus, 70

Right ventricle, physical signs of hypertrophy of, 627

Rigors in croupous pneumonia, 320

Rupture of splenic abscess, 963 of the aorta, 823 of the coronary artery, 833 of the heart, spontaneous, 617 of the pulmonary artery, 835 of the spleen, 971 of thoracic aneurism, 815

S.

Sacculated form of bronchial dilatation, 230

Salicylate of sodium, use, in rheumatic bronchitis, 181

Sanitaria for phthisical patients, 430

Sarcoma of larynx, 128-130 of nasal passages, 55 of thyroid gland, 978 of the heart, 637 of the mediastinum, frequency and history, 865-867

Scarification in laryngeal oedema, 116

Schrötter's tubes, use, in perichondritis and chondritis of larynx, 121 dilators, in laryngeal oedema, 117

Schultze's granule-masses, absence of, in blood of pernicious anæmia, 902 in blood of Hodgkin's disease, 924 increase of, in leukæmia, 912

Season, influence on causation of bronchitis, 168 of croupous pneumonia, 315, 316 of hæmoptysis, 277

Seat of collapse, in atelectasis, 253 of lesions, in croupous pneumonia, 312 of nasal polypus, 53 of oedema of the lungs, 260 of pulmonary emboli, 383 of rupture of the aorta, 823 of tracheal ulcers, 138

Sea-voyages, benefit upon course of pulmonary phthisis, 433 value, for relief of hay asthma, 222

Secondary nature of pericarditis, 770 pleurisies, etiology, 492

Secretion, alterations of, in chronic pharyngitis, 122

Semi-lunar ganglion, lesions, in Addison's disease, 944

Senegæ, use, in bronchitis, 179

Senile pneumonia, treatment, 351

Sensation of larynx-perversion, 61

Sensations, peculiar cardiac, in hypertrophy of the heart, 626

Septum, deflected, as a cause of chronic nasal catarrh, 44 of auricles, defects of, cardiac malformations, 689 and foramen ovale malformations, 689 ventriculorum, patency of, in cardiac malformations, 690 theories regarding patency, 699

Sequelæ of asthma, 189 of cardiac thrombosis, 733 of catarrhal pneumonia, 364 of emphysema, 239 of fibro-serous pleurisy, 512 of hæmothorax, 582

Sex, influence on causation of angina pectoris, 759 of aortic obstruction, 655 of asthma, 190 of cardiac thrombosis, 722 of chronic myocarditis, 607 of chronic pharyngitis, 121 of croupous pneumonia, 314 of exophthalmic goitre, 764 of fatty degeneration of the heart, 613 of fibro-serous pleurisy, 492 of gangrene of lung, 302 of hæmophilia, 933 of hæmoptysis, 276 of hay asthma, 212 of Hodgkin's disease, 922 of laryngeal oedema, 113 of laryngismus stridulus, 70 of leukæmia, 909 of mediastinal tumors, 871 of perichondritis and chondritis of larynx, 118 of pernicious anæmia, 899 of pneumothorax, 576 of pseudo-membranous laryngitis, 101 of thoracic aneurism, 803

Sexual excess, influence on causation of exophthalmic goitre, 765 of functional heart disease, 752 of hypertrophy of the heart, 619 avoidance of, in functional heart disease, 755

Shape of heart in hypertrophy, 624

Shoemakers, frequency of mediastinal tumors in, 871

Shrinkage of lung in pulmonary phthisis, 417

Silver nitrate, spray, use, in acute catarrhal laryngitis, 97, 99 use, in chronic inflammation of epiglottis, 110 in chronic laryngitis, 125, 126 in epiglottic ulceration, 112 in erosion of epiglottis, 111 in inflammatory non-hypertrophic form of chronic nasal catarrh, 47 in laryngeal oedema, 116 in simple tracheitis, 135

Simple lymphangitis, 983

Skin, color, in chlorosis, 895 in pernicious anæmia, 901 discoloration of, in Addison's disease, 940 state of, in croupous pneumonia, 328 tumors of, in Hodgkin's disease, 925

Skodaic resonance on percussion in pleurisy, 501-503

Sodium bicarbonate and borate, use, in chronic laryngitis, 125 sulphate, use, in Addison's disease, 938

Soil, humidity of, influence on causation of phthisis, 396

Souffle in abdominal aneurism, 822

Southey's capillary tubes, use, in hydrothorax, 572

Spasm of diaphragm, distinguished from asthma, 199 of glottis in adults, 74 of larynx in children, 70 theory of origin of asthma, 193, 194

Special senses, modifications of, in Hodgkin's disease, 925 in leukæmia, 911

Specific and septic emboli of the lungs, 386 fevers, influence on causation of acute splenic congestion, 953 germ of croupous pneumonia, 319

Sphygmograph, value, in diagnosis of thoracic aneurism, 809

Splashing sound in pneumothorax, 580

Spleen, changes in, in tricuspid regurgitation, 678, 679

SPLEEN, DISEASES OF, 952 Acute Congestion of, 953 Diagnosis, 955 Etiology, 953 Pathology and morbid anatomy, 955 Prognosis, 955 Symptoms, 954 Treatment, 956 Chronic Congestion and Enlargement of, 956 Diagnosis, 958 Etiology, 956 Malaria, influence of, 956 Pathological anatomy, 957 Prognosis, 959 Symptoms, 957 Treatment, 959 Arsenic, use, 960 Extirpation, results of, 960 Ice, locally, 960 Iodine, use, 960 Iron, use, 960 Local, 960 Quinia, use, 960 Echinococcus of, 968 Diagnosis, 969 Morbid anatomy, 970 Prognosis, 970 Symptoms, 968 Size and characters of the tumor, 969 Treatment, 970 Embolic Abscess of, 963 Diagnosis and prognosis, 964 Etiology, 963 Micro-organism, influence of, 963 Prognosis, symptoms, and treatment, 964 Hemorrhagic Infarction, 960 Etiology, 961 Pathological anatomy, 961 Infarcts, seat and characters, 961, 962 Symptoms, 961 Lardaceous Spleen, 966 Diagnosis, 967 Etiology, 966 Pathological anatomy, 967 Prognosis, symptoms, and treatment, 966, 968 Perisplenitis, 965 Etiology, 965 Pathological anatomy, 965 Rupture, 971 Pathological anatomy, 972 Symptoms and course, 972 Splenitis, 962 Pathological anatomy, 963 Symptoms, 962 Syphilis of, 970 Tubercle of, 972 Tumors of, 973

Spleen, displacement of, in pleurisy, 497, 507 enlargement of, in Hodgkin's disease, 924 in leukæmia, 914 influence of, in production of blood-corpuscles, 889 on blood-formation, 884 lesions, in Addison's disease, 943 in Hodgkin's disease, 927 in leukæmia, 916 in melanæmia, 897

Splenic abscess, diffuse, 962 enlargement in syphilis, 971

Splenitis, 962

Spot, pneumonic, 328

Spray-producers, proper, in chronic laryngitis, 125, 126

Sputa, characters, in catarrhal pneumonia, 359-361 in pneumonokoniosis, 455, 459 in pulmonary phthisis, 401 in fibroid phthisis, 441 sanguinolent, in pulmonary embolism, 382

Sputum of croupous pneumonia, 322

Starvation method of treatment of thoracic aneurism, 816

Steam, inhalations, in chronic pharyngitis, 126

Stenosis, aortic, 654 mitral, 665 of trachea, 142 of the trunk and main branches of the pulmonary artery, 834 pulmonary, 674 tricuspid, 677

Stillé, Moreton, on causation of cyanosis, 713

Stitch in the side in pleurisy, 493

Stimulants in catarrhal pneumonia, 371 use, in abscess of lung, 300 in Addison's disease, 948 in angina pectoris, 760 in cardiac thrombosis, 746 in collapse of the lung, 256 in croupous pneumonia, 348 in functional heart disease, 753 in pulmonary phthisis, 435 in pseudo-membranous laryngitis, 108 in simple lymphangitis, 991 in thrombosis and embolism of the pulmonary artery, 836

Stomach, disease of, influence on causation of pulmonary embolism, 375 displacement of, 507

Stomachic asthma, 193

Strain, influence on causation of thoracic aneurism, 802

Strapping of chest in pleurisy, 520

Stricture of trachea, 142

Strychnia, use, in acute myocarditis, 606 in Addison's disease, 948 in anæsthesia of larynx, 68 in paralysis of larynx, 91 in pseudo-membranous laryngitis, 108 in respiratory failure of catarrhal pneumonia, 371 in valvular heart disease, 685 in vesicular emphysema, 216

Subclavian aneurism, localization of, 813

Subjective symptoms of croupous pneumonia, 319

Succussion sound in pneumothorax, 579

Sudden or fatal form of pulmonary embolism, symptoms, 379

Suffocation, sense of, in laryngeal oedema, 114

Sulphur, use, in pulmonary phthisis, 436

Sulphuretted hydrogen, use, in bronchial asthma, 209

Sulphuric acid, use, in epistaxis, 51

Superior tracheotomy, 148, 153

Suppurating hydatid cysts, treatment, 471

Suppuration, influence on causation of lardaceous spleen, 966 of veins, 844, 845

Suppurative myocarditis, acute, 604

Suprarenal bodies, anomalies, 949 atrophy of, 949 changes in, in Addison's disease, 942 cysts of, 949 degenerations of, 949 inflammation of, 949 tumors of, 949

Surgical affections, influence on causation of pulmonary embolism, 376 measures in pulmonary embolism, 390 treatment of paralysis of vocal cords, 89 of purulent pleurisy, 549

Sympathetic ganglia, lesions, in pernicious anæmia, 905 system, relation of Addison's disease to, 945

Symptoms and course of asthma, 185 of bronchial asthma, 185 and treatment of atheroma of the aorta, 800 of hydropericardium, 789, 790 of pneumo-hydropericardium, 791 of pyopericardium, 790 of abdominal aneurism, 821 of acute catarrhal laryngitis, 93 congestion of the spleen, 954 coryza, 41 miliary tuberculosis, 478 myocarditis, 606 phlebitis, 845 of Addison's disease, 940 of adherent pericardium, 786 of anæsthesia of larynx, 66 of aneurism of the coeliac axis, 841 of the coronary artery, 831 of the inferior mesenteric artery, 839 of the superior mesenteric artery, 836 of angina pectoris, 755-757 of aortic obstruction, 656 regurgitation, 661 of atheroma of aorta, 800 of atrophic form of chronic nasal catarrh, 47 lobar emphysema, 248 of bronchial dilatation, 228 of brown induration of lungs, 257 of the caisson disease, 854 of cancer of the lungs, 461, 462 of cancer of pleura, 584 of cardiac malformations, 709 thrombosis, 726 of catarrhal pneumonia, 358 of chlorosis, 895 of chorea of larynx, 76 of chronic bronchitis, 174 congestion of spleen, 957 endarteritis of the coronary artery, 828 inflammation of epiglottis, 110 laryngitis, 121 myocarditis, 608 nasal catarrh due to necrosis, 49 from osseous and membranous obstruction, 44 of collapse of lung, 252 of croupous pneumonia, 319 of dilatation of the heart, 634 of trachea, 144 of echinococcus of spleen, 968 of embolic abscess of spleen, 964 of embolism of the coronary artery, 832 of the superior mesenteric artery, 837 of endocarditis, 646-649 of epiglottic ulceration, 112 of exophthalmic goitre, 762 of fatty degeneration of the heart, 614 infiltration of the heart, 612 of fibroid phthisis, 441 of fibro-serous pleurisy, 493 of functional heart disease, 747-749 of gangrene of lung, 302 of goitre, 914 of hæmophilia, 934 of hæmoptysis, 281 of hæmothorax, 582 of hay asthma, 218 of hemorrhagic infarction of spleen, 961 pleurisy, 567 of Hodgkin's disease, 923 of hydatids of pleura, 585 of hydrothorax, 571 of hyperæsthesia of larynx, 62 of hypertrophy of the heart, 624 of hysterical affections of glottis, 83 of inflammation of epiglottis, 109 of inflammatory non-hypertrophic form of nasal catarrh, 47 of lardaceous spleen, 966 of laryngeal oedema, 113 of laryngismus stridulus, 70 of leukæmia, 910 of mediastinal abscess, 862 tumors, 822 of mitral regurgitation, 671 stenosis, 667 of morbid growths of larynx, 130 of trachea, 140 of nasal polypus, 53 of occlusion of the coronary artery, 831 of the aorta, 825 of paræsthesia of larynx, 64 of paralysis of abductors of vocal cords, 87, 88 of adductors of vocal cords, 82 of central adductors of vocal cords, 85 of constrictors of larynx, 80 of external tensors of vocal cords, 86 of tensors of vocal cords, 85 of the whole larynx, 79 of pericarditis, 773 of perichondritis and chondritis of the larynx, 118 of pernicious anæmia, 900 of phlegmasia dolens, 847 of pneumonokoniosis, 458 of pneumothorax, 578 of pseudo-membranous laryngitis, 101 of pulmonary abscess, 297 apoplexy, 294 congestion and oedema, 260 embolism, 378 hydatids, 468 phthisis, 400 stenosis, 675 of purulent pleurisy, 542 of rheumatic pleurisy, 565 of rupture of the aorta, 824 of the heart, 617 of the spleen, 972 of sarcoma, carcinoma, and fibroma of nasal passages, 55 of simple lymphangitis, 987 tracheitis, 133 of spasm of the glottis in adults, 74 of splenitis, 962 of stenosis of the aorta, 826 of the pulmonary artery, 835 of trachea, 142 of syphilis of the lung, 451 of termination of pneumonia in abscess, 332 of thoracic aneurism, 803 of thrombosis and embolism of the coronary artery, 832 of the pulmonary artery, 836 of tricuspid regurgitation, 679 stenosis, 677 of ulceration of trachea, 139 of vesicular emphysema, 233, 236

Syncope and suffocation in pulmonary embolism, 379-381 in cardiac thrombosis, 730

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