SECTION IV. Diseases of the Blood and Bone Marrow

DISEASES OF THE BLOOD AND BONE MARROW

The production and physiology of the circulating blood seem closely similar in the two classes under consideration, although the anatomy is not the same in birds and mammals, variations also occurring within the latter group. Pathological responses follow comparable lines in that hemolyzing agencies, be they hemosporidia, absorptions from metazoan parasites or bacterial toxins, produce a reaction in erythropoietic centres, and positively chemotactic viruses call forth increases in the colorless elements. We have also observed a decrease of leucocytes in an Orang Utan suffering from influenza, a finding analogous to that in the human attack. There is, however, a much less ready response on the part of birds to any leucocyte-stimulating influence, in this class the mononuclears seeming to bear much of the burden assumed by the myeloid cells of Mammalia or at least appearing on the stage very quickly so that any increase of the latter is overshadowed by them. Perhaps this apparent difference may be further explained by the greater number of colorless blood cells, structures which might be called the principal secondary defences of the body and constantly at the disposal of the organism, normally present in the birds’ blood; they amount to 25,000 per cubic millimetre in birds, while in the mammals very few varieties have half this number. On the accompanying Table (6) will be found a few differential leucocyte counts now known to us.

TABLE 6. Differential Percentages of Leucocytes. The Figures are based upon Counts of Two Hundred Cells upon Two Slides unless Otherwise Specified. Blood Films were taken from Apparently Healthy Animals in the Exhibition Cages. ════════════════╤════════════╤═══════╤═══════╤═══════╤══════════╤══════════════════ Animal │ Polymor- │ Small │ Large │Eosino-│ Special │ Notes │phonuclears.│Lympho-│Mononu-│philes.│ │ │ Per cent. │cytes. │clears.│ Per │ │ │ │ Per │ Per │ cent. │ │ │ │ cent. │ cent. │ │ │ ────────────────┼────────────┼───────┼───────┼───────┼──────────┼────────────────── Potto │ 20.│ 67.│ 7.1│ 5.9│ │ Perodicticus │ │ │ │ │ │ potto │ │ │ │ │ │ Rhesus Macaque │ 30.2│ 61.4│ 5.6│ 2.8│ │ Macacus │ │ │ │ │ │ rhesus. │ │ │ │ │ │ │ (Av. 5 counts) │ │ │ │ Raccoon-like Dog│ 62.2│ 32.│ 2.│ 3.8│ │ Canis │ │ │ │ │ │ procyonoides. │ │ │ │ │ │ Swift Fox Canis│ 65.│ 18.│ 13.│ 1.│ 3 per │ velox. │ │ │ │ │cent. Baso│ Dingo Canis │ 77.│ 15.4│ 3.8│ 3.8│ │ dingo. │ │ │ │ │ │ Timber Wolf │ 76.5│ 15.5│ 3.5│ 4.5│ │ Canis │ │ │ │ │ │ mexicanus. │ │ │ │ │ │ Wild Cat Felis │ 55.8│ 34.│ 7.│ 3.8│ │ ruffus. │ │ │ │ │ │ Gray Ichneumon │ 52.6│ 44.4│ 2.3│ .7│ │ Herpestes │ │ │ │ │ │ mungo. │ │ │ │ │ │ Indian │ 66.│ 20.│ 14.│ 0.│ │ Paradoxure │ │ │ │ │ │ Paradoxurus │ │ │ │ │ │ niger. │ │ │ │ │ │ Large spotted │ 60.│ 31.2│ 1.2│ 7.6│ │ Civet Viverra │ │ │ │ │ │ megaspila. │ │ │ │ │ │ Ocelot Felis │ 79.│ 15.6│ 3.5│ 1.9│ │ pardalis. │ │ │ │ │ │ Texas Skunk │ 44.1│ 46.3│ 4.3│ 5.3│ │a. There are Mephitis │ │ │ │ │ │several grades of mesomelas. │ │ │ │ │ │eosinophilic │ │ │ │ │ │granulations, │ │ │ │ │ │ranging from very │ │ │ │ │ │fine to very │ │ │ │ │ │coarse. They are │ │ │ │ │ │entirely discrete, │ │ │ │ │ │however, and the │ │ │ │ │ │eosinophile cells │ │ │ │ │ │are quite distinct │ │ │ │ │ │from the │ │ │ │ │ │homogeneous │ │ │ │ │ │neutrophiles. Tayra Felis │ 75.6│ 19.2│ 4.1│ 1.1│ │ tayra. │ │ │ │ │ │ White nosed │ 60.│ 20.│ 18.│ 2.│ │b. The Coati Nasua │ │ │ │ │ │protoplasm of the narica. │ │ │ │ │ │leucocytes shows │ │ │ │ │ │practically no │ │ │ │ │ │stain. Mitotic │ │ │ │ │ │figures are │ │ │ │ │ │frequent among the │ │ │ │ │ │polymorphonuclear │ │ │ │ │ │cells. The small │ │ │ │ │ │lymphocytes show │ │ │ │ │ │basophilic │ │ │ │ │ │granules. Crab eating │ 45.│ 42.│ 2.5│ 10.5│ │ Raccoon. │ │ │ │ │ │ Procyon │ │ │ │ │ │ cancrivorous. │ │ │ │ │ │ Ring tailed │ 39.2│ 54.7│ 4.3│ 1.8│ │ Bassaris │ │ │ │ │ │ Bassariscus │ │ │ │ │ │ astutus. │ │ │ │ │ │ Kinkajou Potos │ 47.4│ 42.5│ 6.│ 4.1│ │ caudivolvulus.│ │ │ │ │ │ Common Raccoon │ 46.│ 42.9│ 7.4│ 3.7│ │ Procyon lotor.│ │ │ │ │ │ Texas White │ 67.│ 19.│ 11.│ 3.│ │ footed Mouse │ │ │ │ │ │ Peromyscus │ │ │ │ │ │ leucopus. │ │ │ │ │ │ Kangaroo Rat │ 55.│ 33.│ 6.│ │ 5 per │c. Many Perodipus │ │ │ │ │ cent. x │leucocytes were richardsoni. │ │ │ │ │ cells. │noted, with deeply │ │ │ │ │ │staining nuclei │ │ │ │ │ │filling up most of │ │ │ │ │ │the cells. The │ │ │ │ │ │protoplasm was │ │ │ │ │ │colored a deep │ │ │ │ │ │brown. These were │ │ │ │ │ │called x cells │ │ │ │ │ │pending │ │ │ │ │ │investigation. Polecat Mustela │ 42.4│ 54.6│ 2.1│ .9│ │ putorius. │ │ │ │ │ │ Common Opossum │ 44.│ 39.│ 7.│ 9.│ 1 per │d. Polynuclears Didelphys │ │ │ │ │cent. Mast│quite large, with virginiana. │ │ │ │ │ cells. │deeply staining │ │ │ │ │ │nuclei which are │ │ │ │ │ │in many instances │ │ │ │ │ │entirely separate │ │ │ │ │ │and distinct. Bridled Wallaby │ 58.3│ 38.8│ 2.│ 4.2│ │ Onychogalea │ │ │ │ │ │ frenata. │ │ │ │ │ │ Six banded │ 57.1│ 23.2│ 6.3│ 13.4│ │ Armadillo │ │ │ │ │ │ Dasypus │ │ │ │ │ │ sexcinctus │ │ │ │ │ │ Elephant Elephas│ 15.│ 47.4│ 7.6│ 5.8│ (Bilobed │e. The ordinary indicus. │ │ │ │ │ 23.8) │polymorphonuclears │ │ │ │ │(Basophile│are very few in │ │ │ │ │ .4) │number, and those │ │ │ │ │ │seen have nearly │ │ │ │ │ │all a faint │ │ │ │ │ │acidophilic or │ │ │ │ │ │basophilic │ │ │ │ │ │character. The │ │ │ │ │ │eosinophiles are │ │ │ │ │ │quite distinct and │ │ │ │ │ │their granulations │ │ │ │ │ │are large and │ │ │ │ │ │globular. The │ │ │ │ │ │cells called │ │ │ │ │ │bilobed are │ │ │ │ │ │unusual and can │ │ │ │ │ │probably best be │ │ │ │ │ │accounted for as │ │ │ │ │ │directly dividing │ │ │ │ │ │small lymphocytes. │ │ │ │ │ │The staining │ │ │ │ │ │properties and │ │ │ │ │ │shape of the │ │ │ │ │ │nuclei of the │ │ │ │ │ │bilobed cells are │ │ │ │ │ │most closely │ │ │ │ │ │related to the │ │ │ │ │ │lymphocytes. They │ │ │ │ │ │are not always │ │ │ │ │ │regular, however, │ │ │ │ │ │but may be almost │ │ │ │ │ │as irregular as │ │ │ │ │ │the polynuclears. │ │ │ │ │ │In practically │ │ │ │ │ │every instance, │ │ │ │ │ │however, a │ │ │ │ │ │connecting isthmus │ │ │ │ │ │may be found │ │ │ │ │ │between the │ │ │ │ │ │spherical nuclear │ │ │ │ │ │portions. No │ │ │ │ │ │mitotic figures │ │ │ │ │ │seen. The │ │ │ │ │ │protoplasm is │ │ │ │ │ │homogeneous and │ │ │ │ │ │pale blue or lilac │ │ │ │ │ │in relatively │ │ │ │ │ │large amount. No │ │ │ │ │ │granules were ever │ │ │ │ │ │seen. ────────────────┴────────────┴───────┴───────┴───────┴──────────┴──────────────────

It would seem, from a general observation of simple and infected wounds and from a few blood counts, that the response of leucocytes in the lower animals is greater than in monkeys and man. The ease with which animals endure a wound and the rapid local pus formation about an infection speak for an easy mobilization of their cellular defenders; their connective tissue elements seem equally well brought into play. In so far as birds are concerned perhaps the normally large number of leucocytes and the participation of local tissue cells in response to irritation is a preparatory protective mechanism because of their relatively small amount of bone marrow which may not be able to mobilize new cells rapidly; many of the birds, notably those prepared for long flight, have much of their osseous system given over to air space. The number of red blood cells is also greater in Mammalia, which show a variation from 4,000,000 per cubic millimetre in some small genera to 12,000,000 per cubic millimetre in some ungulates, while birds vary from 2–5,000,000 per cubic millimetre. Despite these fundamental differences in the classes, pathological changes of anemia, leucocytosis and leucemia are comparable; polycythemia in lower animals is unknown to me but may of course occur.

ANEMIA.

As in human pathology this condition may be divided into the group that follows some disease which damages the red blood cells or their source, called secondary, and those cases not preceded by such a condition, called primary. Formerly this latter group, known as progressive pernicious anemia, was copiously represented, but study has discovered that worms, inorganic poisons and infections can produce a picture of grave anemia so that the formerly large group has dwindled. We now conceive a primary anemia to be one without discoverable responsible antecedent pathology, therefore a disease of the bone marrow itself. There is one variety, hemolytic anemia, which seems to be an intoxication of the bone marrow with solution of red cells, but the affected tissue puts up some struggle against the poison. In another primary, the so-called aplastic anemia, no activity at all is shown by the marrow, no young cells appearing in the circulation. Clorosis, or green sickness of young persons, is a primary anemia and presents itself as a moderate cell reduction with a disproportionately low hemoglobin percentage. As a disease entity this does not occur in the lower animals, so far as I am aware, but a very few hemoglobin estimations and a reference to the literature would indicate that well marked hemoglobin anemia does occur.

In so far as the pathology of anemia is concerned we are obliged usually to judge by the appearance of the blood and tissues, the yellowish pallor of the mucous membranes, the condition of the marrow and the amount of pigment; severe rapid cases show hemorrhages and prolonged cases have fatty degeneration of the parenchymatous organs. For a decision of the primary or secondary nature we must judge the accompanying pathology and the condition of the bone marrow.

SECONDARY ANEMIA.

Secondary anemia can be laid in general to insanitary housing or inappropriate diet over a long period, to chronic bacterial infection of low grade, to the action of blood parasites or those of the bowel which either suck blood or elaborate an absorbable toxin, or to single great or repeated small hemorrhages. We shall now consider the cases at the Garden. Perhaps many other animals have had a substandard blood, but these are the cases in which the gross appearance attracted close scrutiny in this direction. London has had much anemia, probably from their reported heavy infestation with parasites, but this factor has with us apparently played a small rôle in the production of anemia.

IN MAMMALIA.

In so far as the Primates are concerned the one outstanding cause of anemia is degenerative disease of the osseous system. In both rickets and osteomalacia there is an irregular hyperplasia of the marrow, which is usually more marked in the latter. In osteomalacia one finds irregular areas of congestion or even hemorrhage besides masses of a gelatinous fatty tissue while scattered about are pink spots where the marrow is better preserved. In rickets, on the other hand, the tissue is more uniformly congested and less sharply separated from the endosteal osseoid material or the irregular epiphyseal spongiosa. The fibroid or osteoid growth of osteomalacia seems to be fairly well differentiated from the marrow tissue although it may send strands into the canal and across the spongy area. Histologically there is not a distinct difference in the appearances nor do they differ from the human analogue. In those cases which develop late in life the red cell centres are very few in number but usually active. In the blood, one finds a few nucleated and stippled cells, but not much change in size and shape of the erythrocytes.

It does not seem that the anemia can be the cause of death, for among our thirty-nine cases of osteomalacia and rickets, the prosectors have thought it of sufficient importance to record in the diagnoses but eleven times. There are usually complications of pneumonitis or enteritis to finish the animal before the poverty of the blood will do so, and our records show only a Black Spider Monkey (Ateles ater), a Silky Marmoset (Leontocebus rosalia) and a macaque (sp.?) with osteomalacia and grave secondary anemia. It would seem, however, that hemoglobin anemia must exist, for, despite one record of 40 per cent., Fleischl, no excess of pigment deposit is noted in the spleen, liver or marrow.

Carnivora have shown a moderate number of diseases of the skeleton but the occurrence of a marrow involvement seems less frank, although the anatomical changes are similar. However, there are three grave secondary anemias recorded in eleven carnivores suffering from osteomalacia and rickets. Another prime cause of low blood value in this order is gastrointestinal inflammation; in seventeen cases of anemia, of secondary nature, five showed gastroenteritis of severe grade or protracted character. Perhaps the most prolific single cause of this blood change is parasitism, six of the seventeen cases showing infestation, five of which are nematodes and two cestodes, one showing both. The details of these are worth recording. Two young Jungle Kittens (Felis chaus) from the same litter died of enteritis with a noticeable anemia; they harbored in their upper small intestine ascarids, and one of them had a few hookworms (sp.?). A Kinkajou (Potos caudivolvulvus) died from a general mild infection, emanating from a pneumonia perhaps, and showed a heavy infestation with tænia (sp.?). An American Wild Cat (Felis ruffus) died from acute catarrhal enteritis and anemia; the parasitological findings included Filaria fasciata, adults in abdominal and gluteal muscles, larvæ in the blood; Dibothriocephalis felis, Ascaris mystax and Uncinaria canina in the small intestines. While the blood was thin and pale and some pigmentation existed, the condition could not be called a picture of grave anemia. A noteworthy finding was the deep pigmentation of almost the entire intestinal wall. Ascaris mystax was found in an under-sized inbred gray wolf, killed because of poor coat; there was a marked anemia and atrophy of the skin. An Ocelot (Felis chibigonazon) gave a picture of anemia due to uncinariasis, but is not so instructive as the following. A Swift Fox (Canis velox) exhibited clearly a case of progressive secondary anemia from uncinaria, and the history is worthy of a brief recital.

Muscles atrophic, greenish black over abdomen. Fat absent. Lung is blotched by darker red markings where parenchyma contains distinct excess of frothy pink watery fluid. No fluid or adhesions in pericardium. Heart is contracted, and muscle is pale yellow and firm. The only abnormality consists of slight yellowing of musculature. The abdomen shows great omentum firmly adherent to fundus of bladder. No fluid or other adhesions in abdomen. The liver is normal in size, smooth in surface and has sharp edges, is friable and bright orange yellow. The section surface is glistening, smooth and dry. Organ is poor in blood content, greasy and breaks easily. Bladder is large, contents fluid green bile; duct patulous. Spleen normal. Kidney is small and smooth, diminished in bulk, normal location, smooth surface, and pale yellowish gray, consistency, soft, flabby. Ureters normal. Mouth and teeth normal. Stomach contains scanty brown fluid. Duodenum— Mucosa bile-stained, contained a solitary nematode worm. In its lower portion it becomes filled with a blackish red fluid, and its mucosa becomes studded by heavily outlined punctate hemorrhages whose positions are best seen through serosa. Jejunum similar in condition to duodenum and contains four small nematode worms. At one point, i.e., where the worm is located at beginning of ileum the blood staining of mucosa is strictly in neighborhood of the worm. Capillaries nowhere congested. Ileum contains slight amount of brownish black material, mucosa normal. Large intestine and rectum normal. Pancreas normal. Lymphatics normal. This is a case of death by anemia as result of bites of hookworms. There were certainly more than four worms present antemortem since no males were found, and this may be explained by a possible diarrhœa which has flushed them out. This idea is borne out by empty condition of gastrointestinal tract. Animal Parasites—Uncinaria canina. The four small nematode worms above mentioned conform in all respects to the given anatomical points of uncinaria. All four specimens are perfectly formed females. The location of the hooks was easily determined and established as being in the most dorsal portion of buccal cavity, and as projecting forward and ventrally in two groups of three each in same manner as described heretofore in similar infestations in foxes. The large nematode worm found in duodenum is, from its possession of three lips and its general form, an ascaris. The mustache, however, which is so commonly seen in ascaris worms from this region is absent. Postmortem blood of heart shows red cells granulated and almost worthless for histological study. Nucleated reds, however, are absent but other points valuable in settling the question of anemia cannot be determined.

Lung.—There are no abnormalities in supporting tissue. Alveolar walls are markedly congested. Bronchi normal and show no trace of larval hookworm infestation. Air sacs contain many red blood cells together with a few heart-failure-cells. Congestion of lung.

Liver.—No excess of fibrous tissue. Finer details of structure cannot be made out owing to advanced autolytic changes. The only possible pathological changes consist of localized areas where liver cells have fused to form notable masses of pink granular material suggesting local necroses. Autolysis.

Intestines.—Four sections are present and all show essentially the same character of changes. Interstitial tissue between muscular tissue and submucosa loosely arranged as though separated by edema.

On luminal side of muscular mucosa is a distinct zone of striking tawny yellow color with hematoxylon-eosin combination. This zone is smooth homogeneous and contains a few spindle and stellate cells with no capillaries and with little or no fibrillation. It abuts upon the fundi of the crypts. Interstitial tissue of mucosa is loose and infiltrated with round and spindle cells in its deeper portions. Here it is also congested but congestion is most marked toward lumen where masses of free blood cells occur in interstitial tissue, within lumina of crypts and within lumen of intestine itself; no parasites or ova are found. Epithelium of crypts has granular cytoplasm; goblet cell formation frequently seen; cilia well preserved. Edema; Subacute catarrhal enteritis Hemorrhage.

Six instances of nephritis, four parenchymatous and two diffuse, are recorded in the total of seventeen cases of secondary anemia in carnivores. Except in the skeletal disease the marrow is very mildly affected, some edema and reddening grossly and moderate hyperplasia minutely, being the only noteworthy changes.

The next order is that of the Ungulata wherein we have found but two cases of frank anemia, an Isabelline Gazelle (Gazella isabella) and an Aoudad (Ovis tragelaphus). The former had several lesions of different etiology and nature so that an impoverishment of the blood is not astonishing: parasitic (?) cyst in lung, chronic infective arthritis, calcareous tuberculosis, congestion and edema of lungs, osteomalacia, and osteofibroma of maxilla. The condition of the aoudad was too indefinite to permit conclusions.

The marsupials are represented by two common Opossums (Didelphys virginiana) and a Rufous Rat Kangaroo (Aepyprymnus rufescens), two of which suffered also from rickets. The condition of the bone marrow was unfortunately not recorded, but in other rachitic marsupials this tissue follows the changes seen in other orders. One opossum had a hypertrophic gastritis with numerous Physaloptera turgida, a worm frequently associated with chronic thickening of the mucosa; there was also an early portal hepatic cirrhosis with enlargement of the spleen.

Among the Rodentia we have had anemias in a Beechy’s Gopher (Citellus grammurus beecheyi) and a Southern (Sciurus niger niger) and Western Fox Squirrel (Sciurus rufiventer). The first had a myeloma also, and will be discussed later. One of the squirrels had osteomalacia, while the other suffered with diarrhœa and showed hydropic degeneration of the kidneys, conditions probably due to acute intoxication.

IN AVES.

The class Aves is represented by the orders Passeres, Psittaci, Columbæ, Herodiones, Gaviæ, Picariæ, Striges, Galli and Accipitres; the first four are well represented, but in the other orders only one or two cases have occurred. The causes of anemia in birds are essentially those discussed for mammals with the provision that greater attention must be paid to parasites, particularly those of the blood. Several slightly varying protozoa inhabit the blood corpuscles of birds, and numerous embryos may circulate after they escape from a parent lying in some organ or tissue. The rôle of blood parasites, intra- or extracorpuscular, in the cause of death or of anemia is, however, somewhat paradoxical. Plimmer seems to credit a heavy infestation with great value in the cause of death. In the human being an infestation of one cell in a hundred is a fair grade of malaria; such a relation is apparently common in birds, and we have repeatedly seen a much heavier seeding while Plimmer reports as many as 70 per cent. of the erythrocytes to be carriers of hemogregarines (he has seen 92 per cent. in reptiles). Can then the effect upon hemic function and vital resistance be great? It has been our practice to interpret the finding of circulating protozoa or of larval metazoa as merely reducing the resistance of the birds so that they succumb more readily to incorrect food, strange environment or infection.

It is perhaps well to show the state of our records in the Passeres by a table.

Passeres—Secondary anemia associated with intestinal or visceral parasites 11

blood parasites 9

intestinal inflammation 6

skeletal diseases and chronic infection (osseous) 3

nephritis 4

miscellaneous and unassociated anemias 8

(entries in this line not included under any other heading)

Total cases 37

In the first group, two of the birds showed cestodes, one a tænia, the other not examined for identification; three showed coiled filaria in the air sacs, two, tropidocerca in the proventricular wall and five had coiled filaria in the serosa of the stomach. The second group was infested five times with Halteridium and five times with embryo filariæ. Anemia was associated with gastrointestinal inflammation alone only once, the remaining five cases having other finding of greater significance. The three birds of the next group concerned one with tuberculosis, one with mycosis and one with a long continued abscess. It seemed worthwhile to separate four cases of anemia in which nephritis was a prominent association, in three indeed being the only other diagnosis. While it is impossible to state that either is dependent upon the other, and they may of course be coincidental, it is nevertheless noteworthy that such an obscure relation occurs here as well as in human pathology. In one of these birds seen recently there was in all probability a distinct hemoglobin anemia suggested by jaundice, pallor of the tissues, absence of pigmentations and the finding of large pale erythrocytes in the heart blood. The last group is a mixed one including some birds in which only anemia was diagnosed, others with prolonged hemorrhages, two tumors, intestinal sand, congestion of the lungs and the like.

The parrots and their relatives are represented by nine specimens, among which two had proventricular spiroptera, two had long standing tuberculosis and two had osteomalacia. The notes of the other three are not sufficient to warrant deductions.

Herodiones showed eight cases of anemia, five herons, one bittern and two storks. Parasites are noted in only three examples, herons, and it is noteworthy that these all had flukes in the proventricle or intestine; one also had ascarids in the proventricle. Two of this order suffered with long standing inflammation following bone injuries. Perhaps the outstanding features of this order are the erythrocytic picture and the condition of the spleen. The red blood cells seem very fragile or soft, for one often encounters in their fresh or stained preparation vacuoles or rifts in the protoplasm surrounding the nucleus. At first we thought these were hemosporidia, but repeated attempts at their coloration and the absence of pigment granules seem to warrant an assumption that they are artefacts. In five of the seven instances there is very definite evidence of present or past activity of the spleen. We have not always considered it sufficiently prominent to call it a splenitis, but follicular activity is commonly discoverable, and two cases of definite fibrosis are recorded. The sun bittern (Eurypyga helias) showed a chronic interstitial nephritis in the atrophic stage. No other of the wading birds showed secondary anemia. There are seven cases among the pigeons (Columbæ) where anemic tissues attracted our attention. Three were associated with osteomalacia, in one of which the marrow picture was that of an aplastic form being everywhere pale and flabby without cells under the microscope; it is further interesting in this case that there was a distinct but ineffectual attempt at bony regeneration by the periosteum. In another case, this time brought to death by an enteritis and cloudy swelling of the viscera, the marrow was hyperplastic and red, there being activity in the basic staining areas of the head and in the shafts. (Notes of the third case scanty.) None of the seven cases seems to have been associated with animal parasitism; one had tuberculosis. The other cases are obscure and not definitely connected with other pathology.

Ten more cases of anemia were scattered among seven orders. There is nothing striking or even individual about them worthy of special mention.

SUMMARY OF SECONDARY ANEMIA.

A review of our records shows that among 5365 animal autopsies we have recorded anemia of probable secondary character in 122 instances, 53 (2.8 per cent.) mammals and 69 (1.9 per cent.) birds. The orders represented, with the percentage for the order, are Primates, 25 or 5 per cent.; Carnivora, 18 or 3.7 per cent.; Ungulata, 3 or .8 per cent.; Marsupialia, 4 or 2.2 per cent.; Rodentia, 3 or 1.5 per cent.; Passeres, 37 or 2.7 per cent.; Psittaci, 9 or 1.3 per cent.; Herodiones, 8 or 8. per cent.; Columbæ, 7 or 4.7 per cent.; Picariæ, 2 or 2.3 per cent.; Striges, Galli, Gaviæ and Accipitres, each one case. A consideration of their associated pathology reveals the fact that four changes are prominently associated with secondary anemia, to wit: gastrointestinal inflammation, 26 times (15 mammals and 11 birds); parasitism, 29 times (7 mammals and 22 birds); osteomalacia, 24 times (18 mammals and 6 birds), and nephritis, 18 times (12 mammals and 6 birds); a few of these cases overlap, but this is rather the exception than the rule, and this does not militate against the importance of the connection with anemia. It will be noted that practically all the important orders of animals are represented, including species from all over the globe. There is, however, no especial relation of anemia to the kind of diet or digestive tract. Conclusions as to the meaning of these figures of incidence are hardly justifiable. In so far as the blood picture is concerned we can only record the qualitative appearance and the effect upon tissues. It cannot be stated that to external observation a secondary anemia presents any distinguishing features that a specimen in poor condition may not exhibit. The monkeys formerly dying of tuberculosis had not infrequently pale buccal mucosa and skin around the eyes, but upon examination of their viscera, blood or marrow the quality of their blood could not be called greatly substandard. Slide smears of secondary anemia in many specimens would occasionally show stippling or a moderate number of nucleated cells with anisocytosis and poikilocytosis. This is much more frankly exhibited in the Aves, wherein displaced karyolytic or pyknotic nuclei are very common. Mention has been made of the rifts in the protoplasm, seen in Herodiones, and this has been observed in other orders. Perhaps the most striking change is the increase of young erythrocytes and of thrombocytes in the winged creatures. The nucleus of the former reminds one of that of the human plasma cell.

The condition of the bone marrow corresponds with fair accuracy to that which one is accustomed to see in the human being. Certainly this holds good for the mammals, while among the birds, the few observations upon which we feel like relying indicate a nodular erythropoiesis of rather striking character. In the areas of reddening as seen grossly there will be found under the microscope an orderly arrangement of large red cells with loose chromatic nuclei about a very much larger cell of the same type, apparently the primary erythroblast. Outside of this group, red cells such as appear in the circulating fluid, are rather irregularly distributed in a marginal zone. I have seen small areas like this in apparently normal marrow, but the central grouping was not so large as in the anemic cases; it thus appears that we probably have the anatomy of erythropoiesis.

The deposition of pigment in the birds is in much coarser granules than among the mammals, in the former case large masses sometimes obscuring several liver cells or apparently blocking a lymphatic sinus; the Kupffer cells do not seem to be heavily laden.

The extramedullary formation of blood cells has been a matter of considerable interest and study in the human being, and as far as it concerns the circulating mononuclears, the general opinion seems to be that such a histogenesis exists. A decision in the negative is perhaps reached by the majority in the case of erythropoiesis, and as far as my observations go, this holds for all mammals. It seems worth while, however, to record an occasional finding in some birds, especially anemic ones, which may be of importance in their erythropoiesis. The adult red cell is a clearly formed ellipse with a distinct, deeply stained, sharply outlined nucleus of a shape corresponding to that of the whole cell. Young red cells have a more nearly circular outline but almost truly circular nucleus, the short diameter being at least proportionately greater than is the corresponding short diameter of the whole cell; this is also the nucleus whose internal structure resembles that of the human plasma cell. Groups of such cells have been seen in the interstices of the liver, sometimes as many as twelve, in a rather orderly formation. An excess seems at times visible in the spleen but not in orderly arrangement. Observations are under way toward determining the relation of this finding to the amount of marrow, the condition of the blood and the habits of the bird.

Primary Anemia.

As already specified primary anemia is apparently causeless, aside from the assumption that it is a disease of the marrow itself. Since there are only four cases, representing three orders and they cannot be grouped as could the secondary variety, the individual instances will be discussed separately.

Ring tailed Bassaris (Bassariscus astutus). Adult died after two weeks’ stay in the Garden with a history of general failure of condition. The diagnosis at autopsy was primary anemia, fatty degeneration of the liver, hemorrhages in intestines and spleen, hyperplastic bone marrow. The external appearance is of general good condition, fair skin, mucous membranes pale. Lungs collapsed, and gray-red. There are several small hemorrhages scattered irregularly throughout respiratory tissue. Lymph Nodes—small, soft mottled gray- red. Pericardium had slight excess clear fluid, and no adhesions. Heart normal in size, and of pale brown color. The liver of normal size, smooth surface and sharp edges, of a pale brown color, soft and friable. Has indistinct markings like yellow brown mottlings on section surface. gall-bladder contains some viscid brown bile. Spleen, normal or slightly less in size, consistency firm, capsule pale pearl gray, apparently not thickened. There are numerous small hemorrhagic spots on section surface. Interlying pulp is homogeneous deep red. Follicles not visible. Kidney, normal in size and shape. Trabeculæ faint. Capsule smooth, strips easily, smooth surface, and brown. Consistency soft. Medulla prominently striated, cortex homogeneous salmon pink. Stomach contains a little glistening mucus. Mucosa pale, flat yellowish, slightly opaque. There is a recent clot lying in some mucus just above pyloric valve. There is, however, no open vessel nearby. From pylorus to anus lumen contains some rather fresh smeared out or slightly clotted blood and mixed in with mucus. Mucosa is flat translucent, submucosa slightly injected in a mosaic fashion, otherwise gut wall is negative. No recognizable food present. Follicles not visible. Mesentery glands small, soft, pale yellow. Bones seem entirely normal. Marrow of long bones is firm, bloody. Marrow of ribs also deep red. Blood in intestinal tract is probably a recent slow oozing from intestinal walls, and was probably the last straw. Cause of this anemia could not be determined. Blood preparation not made because it was too long after death. Liver shows moderate fatty infiltration of marginal areas. Pigment is scarce, only a few granules being present in the Kupffer cells, not more than is often seen without marked anemia. There is a slight increase in interstitial nuclei but not in fibres. No obstruction or increase of bile ducts.

Kidney.—Very mild swelling of tubular epithelium but no exudative processes. Glomeruli show a few vacuoles but capsular space is negative to pigment. Bone marrow (Femur) fairly cellular in construction, but fat well mixed. Cellular areas well arranged, active, most of cells are small members of the larger mononuclear variety. Small lymphocytes abundantly represented. Most of the larger cells are non-granular, with centrally placed nucleus. Megakaryocytes fairly numerous, nuclei seem closely jammed into centre. No recognizable certain nucleated red blood cells, moderately number stippled cells, few adult red cells. Eosinophiles and basophiles quite few. Pigment small quantity.

This is a case of primary anemia of moderate severity and short duration, and probably of hemolytic character if one may judge by the bone marrow, although excessive pigmentation of the liver and kidneys was not found. Unfortunately the spleen was not minutely studied, nor was the central nervous system investigated. Atrophy of the intestinal tract did not exist.

Two cases occurred among the monkeys, but one example will answer, since the two were essentially the same.

The case to be cited was that of a Japanese Macaque (Macacus fuscatus). ♀ Young, weight three pounds two ounces, exhibited in the Garden about four months, and apparently in good shape until two weeks before death when it rapidly became emaciated.

DIAGNOSIS.—Aplastic anemia, chronic atrophic gastritis. Atrophy of heart muscle, fibrosis of liver, slight local cloudy swelling of liver. Perilobular diffuse nephritis (subcapsular type). Congestion of spleen. Fibrillar fibrosis of spleen. Hemosiderin pigmentation of spleen. Local amyloid infiltration of spleen. Calcareous infiltration in medulla of adrenal.

Coat only fair, body emaciated. Pale muscles, fat scanty. Respiratory tract normal throughout save for slight emphysema. The Pericardium showed no fluid or adhesions. Epicardium glistening and slightly thickened. Heart pale in color. Abdomen shows no fluid or adhesions. Liver slightly decreased in bulk, smooth surface and sharp edges, hard, and rusty brown. Gall-bladder distended, contained green fluid. Spleen firm and normal in size. Capsule smooth, shape normal. Section surface, dark reddish brown, trabeculæ distinctly visible. Kidney, normal in shape, capsule smooth, strips easily, smooth surface, glistening, pinkish gray, consistency hard. Section surface, poor demarkation between cortex and medulla. R. Adrenal, thick orange yellow cortex, solid small brown medulla. Mouth and teeth normal. Stomach distended, contains gas and small quantity yellowish mucus. Mucosa everywhere normal. Postmortem blood examined, stained by Romanowsky, but red cells were disintegrated possibly by laking so examination is not satisfactory. Histological Sections: Heart shows normal epicardium quite free of fat. Myocardium peculiar in that fibres immediately under epicardium show marked broadening in a very narrow rather sharply indicated zone where nuclei are extremely large although not especially chromatic. Transverse markings here easily, although faintly recognized, have very indefinite borders, their longitudinal fibrillæ being ranged in form of a coarse reticulum. This comes about from frequent and extensive lateral anastomoses with fellow fibres giving appearance of a syncytium. In deeper parts, fibres are of more normal size but nuclei are still large and fibres, now cut in transverse section do not appear to anastomose so freely; there appears to be a slight excess of fibrous tissue in their deeper parts. Arteries quite normal. Atrophy with regeneration.

Liver.—Capsule and interstitial parts on whole normal. Perilobular fibrous tissues largely missing, but where remaining show an overgrowth occurring in peculiar zonal arrangement and of old adult almost hyaline type. Its fibres are often arranged strikingly in whorls. Bile ducts, arteries and veins quite normal. Parenchymal cells of normal size, finely granular, prominent normal nuclei and contain small quantities of finely granular, golden brown pigment not really as abundant as commonly seen in severe anemias. Blood capillaries narrow, contain small quantities R.B.C., and Kupffer’s cells very frequently contain fine granules like those of parenchymal cells but of a greener tint. In a few isolated areas parenchymal cells distinctly more swollen than others and many show disintegration of nucleus. Hemosiderin pigmentation. Perilobular fibrosis. Slight local cloudy swelling.

Kidney.—Capsule smooth, interstitial fibrous tissue of organ proper highly fibrosed in peripheral parts, but slightly in deeper. No lymphocytic infiltrations anywhere or sclerosis of vessels. Tubular epithelium highly atrophic in subcapsular regions where tubules are narrow. In deeper parts epithelium is at times so swollen as to occlude lumina, where they are coarsely granular and occasionally show some karyolysis, a pink hyaline or finely granular material. Tufts never show fibrosis, normal size. Bowman’s capsule heavily thickened. Chronic diffuse nephritis (subcapsular type).

Spleen.—Slightly hyalinized capsule, normal thickness. General reticulum of pulp slightly fibrosed and poor in lymphocytes. Sinuses broad, crowded with red blood cells, but only small numbers of lymphocytes. Coarse granular blood pigment abundant, showing greenish cast on focusing. Malpighian follicles normal size, slightly fibrosed, and in several instances show a deposit of smooth pink material between cells. Congestion. Fibrillar fibrosis. Hemosiderin pigmentation. Local amyloid infiltration.

Adrenal.—Organ appears normal in all respects save for presence of a few small irregular areas of calcification in medulla. These occur apart from any recognizable necrotic or fibrous areas. In one place one appears to lie within lumen of blood vessel. No fibroses or special congestions anywhere in organ, and cells show normal details and normal numbers of vacuoles. Calcareous infiltration of medulla.

Stomach.—Muscular tunic normal. Submucosa thin, has densely arranged bundles of smooth, pink character. Mucosa distinctly thinned, shows comparatively few regions holding acid cells, consisting for most part of peptic type of gland. These are short and of broader calibre towards lumen than deeper, suggesting a hyperplasia of luminal portions; stroma richly infiltrated with lymphocytes, not fibrosed or congested. Epithelium of crypts has rarefied appearance, shows no special degenerative changes. Chronic atrophic gastritis.

Bone marrow appears as widely separated large, fat globules with intervening granular edematous material and no hematopoietic elements. Blood capillaries numerous and highly congested.

Although the notes fail to discuss the gross appearance of the bone marrow, the amount of alteration in its microscopy and the relatively small output of pigment in the liver, seem to substantiate the determination of aplastic anemia; it is unfortunate that the blood smears could not be used in the decision. At all events the condition of the intestinal tract, of the heart, liver, spleen, and adrenal, justify us in classing the case as one of primary anemia. The next and last instance is of the same type, although I am inclined now to differ from the diagnoses made at the autopsy table, that of aplastic anemia, and to place it in the hemolytic variety. The rapidity of the fatal attack, the redness of the marrow, the excessive pigmentation, and the prominence of recent degenerative lesions in the organs are much more like the changes of a primary hemolytic intoxication than of an aplastic anemia.

Gray Fox (Canis cinereo). ♂ Weight four pounds, adult, was in the exhibition two years, but in good condition until two weeks before death, when it stopped eating and rapidly fell away.

DIAGNOSIS.—(Aplastic) Primary anemia. Zenker’s Hyaline of heart and skeletal muscles. Mucoid degeneration of bone marrow. Congestion of bone marrow. Atrophy of hemopoietic elements in bone marrow.

Hemosiderin pigmentation of liver. Atrophy of liver. Congestion of liver. Congestion and fatty infiltration of kidney. Patulous lumina in adrenal and absence of pars glomerulosa.

External appearance of coat good. Decomposition advanced in intestines. Skin and subcutaneous tissue faintly yellow. Poorly developed, dark muscles and fat. Respiratory tract normal throughout. Pericardium glistening, transparent, and pale, with no adhesions. Heart a little too pale, consistency slightly soft. Normal or slightly increased size of liver, with smooth surface and sharp edges, consistency friable, and of a brownish red with rusty coloring. Spleen normal. Kidney normal in size, shape, location, and consistency. Capsule strips easily, and of a faintly yellow, under general red, coloring. Adrenal normal. Mouth and teeth normal. Stomach, serosa and wall normal. Mucosa shiny, autolytic, muddy red. Ileum, agminated follicles swollen. Feces from colon examined microscopically. Pancreas normal. Bone marrow tibia and femur gelatinous and red, not slightest trace of yellow. Blood films from heart’s blood show poikilocytosis and anisocytosis; only one nucleated red.

Microscopic Notes.—Heart has torn but normal pericardium. No abnormalities of interstitial tissue or vessels. Fibres of normal width but show transverse markings irregularly since cytoplasm becomes hyaline and swollen in many places along its course. Nuclei prominent, slightly pyknotic. Zenker’s Hyaline.

Bone marrow consists of a matrix of granular or fibrillar mucoid tissue within the delicate reticulum of which highly developed capillaries are placed, together with stellate spindle and sealring cells. In a few places only are myelocytes recognizable and then in decreased numbers. Plasma cells sometimes found containing much blood pigment.

Liver.—Capsule normal; perilobular fibrous tissue only slightly overgrown, moderately infiltrated with lymphocytes and heavily with blood pigment. Arteries, ducts, veins, normal. Parenchymal cell a little smaller than normal with nuclei of normal type, and crowded with fine granules of blood pigment. Latter lie in usual pericanalicular position. Blood capillaries narrow, moderately congested and Kupffer’s cells also contain abundant pigment granules.

Thyroid.—Interstitial framework shows no fibrosis or cellular infiltrates. Blood vessels normal. Acini fairly uniform in size, none ever attaining large proportions, but some being distinctly below normal. They are uniformly filled with a very pale pink hyaline material which in some way gradually increases in color intensity toward one side, attaining in a few examples usual intensity of colloid. Lining epithelium is low cuboidal, shows no special hyperplastic features or atrophy.

Kidney.—Capsule normal. Interstitial tissue normal. Blood vessels slightly congested. Tubular epithelium granular, disintegrated and frequently contains numerous fat globules and obscured nuclei. Lumina of about normal size containing variable quantities of pink granular detritus. Glomerular tufts normal in size and appearance. Subcapsular space and Bowman’s capsule normal.

Adrenal.—Capsule and pericapsular tissue normal. Parenchymal cells throughout poor or practically free of vacuoles, such appearing in only limited portion of pars vesicularis. Interstitial framework and vessels normal. Structure of columns in pars vesicularis is peculiar in that they extend quite to capsule with no intervening pars glomerulosa, and again in that most peripheral parts are expanded at times showing a lumen, while deeper parts show broad cells extending fully across the column. Pars reticularis contains no pigment and medullary cells quite normal. Skeletal muscles show comparatively few fibres with transverse markings. Most are swollen, hyaline, lumpy, and have pyknotic nuclei. Interstitial parts show no inflammatory change.

Tissues treated by Prussian blue test for iron. Kidney, adrenal, heart found to contain none. Spleen, liver contain abundance. That in spleen responds to test showing that it is all iron containing. Two kinds of pigment found in liver. In periphery of lobule as much contains iron as that which does not, while in deeper parts iron predominates. Many times both kinds are recognized in one cell. On the whole it is the finest granules which contain more iron (are bluer) while iron free pigment occurs in bile canaliculæ. That in Kupffer’s cells stains strongly blue.

SUMMARY OF PRIMARY ANEMIAS.

A review of these instances of grave anemia brings one to the conclusion that there is a strong similarity to the disease in man. Perhaps we have constructed a picture that is too narrow for the animal kingdom in general, but surely these few instances deserve to be distinguished from the secondary cases already presented if for no other reason than that no associated etiological condition was exposed. It was hoped in studying the anemias of lower animals, and this hope extends over all the subject of this book, to be able to throw some light upon causation. The thought of incorrect diet came at once, but we are confronted with the paucity of cases among our records. Moreover, secondary anemia from digestive and dietetic troubles is clear, but how we can use this argument for an essential change in hematopoiesis and natural hematolysis, is far from evident. It will be noticed that I have studiously avoided grouping any case with parasites among the primary cases, nor will there be found any evidence of generalized infectious disease. Most of the reported instances of pernicious anemia in the lower animals have been associated with one or other of these factors, although certain authors (Kitt, Hutyra and Marek) maintain that a causeless variety probably exists.

LEUCEMIA.

This condition is fairly well recognized by veterinarians as occurring among domesticated animals, but in the records of this Garden it has occurred rarely, indeed only once in a mammal and but five times in birds. It is interesting that, in the wealth of material at the disposal of Plimmer and his associates, only one case, a polecat with lymphatic leucemia, is noted, and but very few avian instances. Herewith is submitted the protocol of our single mammalian case; perhaps we have missed others of a mild grade dying during the early stages because their resistance to infection was reduced. Unfortunately, perhaps because of the postmortem changes, but more likely because it appeared at first as if we had to do with a case of generalized tuberculosis, the bone marrow in this case was not examined. Nevertheless the infiltrative character of the lesions, the absence of distinct tumors and the numerous mononuclears in the blood as seen in sections seem to justify a diagnosis of leucemia, in all probability of the lymphatic type. There follows this case one with similar gross and microscopic picture which has no visible increase of leucocytes, but a very distinct myeloid picture in many places.

Common Opossum (Didelphys virginianus). ♂ Adult. No evidence of illness. Found dead. Lymphatic leucemia (involving all viscera and lymph nodes). Diffuse nephritis. Both lungs have become entirely involved in a firm, gray-yellow mass not adherent to any serous surface. Practically no normal lung tissue is left. This seems like tuberculosis but no tubercle bacilli could be found in a good smear. Estimation of the normal cubic capacity of an opossum lung was made to be about five cubic inches. In this case not over one-half cubic inch remained respirable. Bronchial lymphatic glands were enlarged, firm, yellow gray, with no recognizable lymphatic tissue. Heart muscle was firm and flaccid, pale and striated. Liver very large, firm and tough, with smooth surface and sharp edges. Color pale brown. Section surface glistening, dry, smooth, opaque. Common bile duct patulous. Spleen, slightly increased, firm, tough consistency, capsule smooth. Section surface, smooth, firm, brown-red, pale pulp, prominent follicles, and trabeculæ faintly visible. Right kidney, slightly decreased, normal in shape. Capsule smooth, strips with difficulty, tears surface. Surface, granular, color brown, consistency firm. Thickness of cortex, narrow irregular, markings irregular and obscure. Small mass of fibrous material in cortex about 3 × 3 mm. like those in lungs. There are also numerous pale yellow gray areas in cortex and outer medulla, round and streaky, distorting the striated architecture. Right adrenal converted to a yellow gray mass like lungs. The mesenteric and retroperitoneal lymph nodes are firm, gray-yellow. This includes those under diaphragm and around cœliac axis.

The histology of the organs may be described together. The infiltrate described is a densely packed mass of large cells with large, well staining nuclei and a very narrow rim of protoplasm. It is not limited by any definite wall or septa. It has no interstitial tissue. There is no blood supply in the densest masses but the walls of the blood vessels remain intact wherever the mass surrounds them. In the lungs it has involved all structures indiscriminately, and has destroyed practically all of the respiratory surface. It seems to follow by preference the peribronchial space. A few glands may be seen in the centre of this mass, but they are rapidly undergoing degeneration. In the liver the infiltrate is chiefly beneath the capsule extending inward but a very short distance. There are no large masses as in other organs but small infiltrates are seen at the portal areas. The spleen shows a diffuse excess of pulp cells and many of the cells above described, the difference being only in the size of the nucleus which is smaller in the pulp cells. There are very small round cells relatively. Follicles are absent, connective tissue not altered. Note states follicles prominent; this is due to nodal hyperplasia of the large mononuclears above described. The parenchyma in the kidney is anemic, the epithelium is slightly pigmented but this is probably not abnormal. Between the tubules especially of the outer layer of the medulla and medullary ray but also in the cortex and around the glomeruli are diffuse, irregular, infiltrating masses of the cells as described above. In some places in the kidney hyaline casts are being formed probably due to the degeneration of the epithelium by pressure. There are a few distentions of the tubules. The capsular space is free. In the neighborhood of the collections the capsules are a trifle thicker than normal. Lymph nodes, similar to spleen in that most of the bodies are thoroughly overrun with the large mononuclears. The sinuses, both marginal and internal, are practically obliterated by these cells. In the blood vessels of the lungs and liver there are many large mononuclears, perhaps not as large a number as might be seen in leucemia, but decidedly in excess of normal.

Common Marmoset (Callithrix jacchus). ♂ Adult. Had cage paralysis for two months before death and declined gradually from that time.

DIAGNOSIS.—Bronchopneumonia. Myeloid hyperplasia of bone marrow. Myeloma in pancreas. Fatty degeneration of liver. Constipation. Nematodes in cecum. Animal is thin, skin bare in spots. Both lungs are pale pink with large areas of deep red consolidation. Heart is dilated, increased in size with firm, red-brown muscle. Liver is firm, red-brown, with smooth surface and sharp edges. Section surface is glistening, smooth and moist. Lobular outlines are clear by reason of pale lines. The gall-bladder is normal in size and contains fluid pale green bile; duct patulous. Spleen is normal in size, smooth capsule, soft, purple pulp, follicles small and faint, trabeculæ fairly prominent. Kidneys normal in size and shape. Capsule smooth. Section surface smooth and brown and firm. The glistening section surface has a narrow cortex, swells slightly, with prominent striæ. Intestines throughout are pale on serosa. Wall thin. Mucosa flat, pale pink. Contents creamy mucus in the upper intestine. Large intestine contains large masses of very firm feces. Cecum is distended with feces and a great quantity of nematode worms. They are not attached to mucosa nor does mucosa seem altered because of their presence. Skeleton and muscles.—Long bones of extremities break easily, but with snap. Skull can be dented with fingers. Bone marrow of femur bright red.

MICROSCOPICAL NOTES.—Liver shows moderate degree of fatty degeneration with capillary congestion. Kidneys negative. Some postmortem change in last two organs. Spleen, marked congestion. Hyperplasia of large lymph cell type, particularly in follicular centres. Blood destruction moderate. Bone marrow seen in condition of marked activity of myeloid type. Aside from enormous crowding of strands there does not seem to be any atypical cell. Intestines show practically no change. Same condition holds in pancreas. In several places in pancreatic ducts cross sections of nematodes may be found. In among lobules of pancreas is a well encapsulated cellular mass without particular architecture. It consists of cells of large lymphocyte or endothelioid series. There are numerous cells of size and staining characters of small lymphocytes. There are no megalocytes but there are some indistinguishable from myelocytes. This may be an intrapancreatic lymph node. One small lymph node found in section; it shows a picture quite like the marrow except for megalocytes. Blood vessels do not show an excess of leucocytes in free or coagulated blood.

Perhaps this latter case belongs to the aleucemic leucemias or pseudoleucemias. These two conditions are recognized by the difference in circulating leucocytes, a piece of information not at our disposal. The whole subject of hemato-lymphatic affection must remain unsettled in so far as a diagnostic name is concerned, for in very few cases has the blood of our animals at autopsy been in a state permitting reliable observations upon stained smears, because of coagulation, lysis or decomposition. After considering a few more of the diseases of the blood and marrow, the lymphatic apparatus will be considered. But there is a borderland to which a word might be devoted at this time, that group to which various names—Hodgkin’s disease, pseudoleucemia, general adenopathy, adenie, aleucemic leucemia—have been applied and which has been accepted as occurring in the domesticated animals. Since I have been occupied for several years in a study of this clinicopathological complex in the human being, such cases have been searched for most diligently, but without success. The New York Zoological Park records a case of Hodgkin’s disease, without specifications, in 1901, and at the London Garden a pseudoleucemia was found. The paucity of leucemia and of the aleucemic adenopathies in lower animals and their relative frequency in man excite speculation as to their interdependence; but more of this under the lymphatics.

AVIAN LEUCEMIA.

The class Aves is rather better represented in the group of leucemias, but here the well known infectious disease may confuse the picture. The birds affected were Psittaci 3 (1 parrot, 1 parrakeet, and 1 amazon), Herodiones (stork) 1, and Galli (Gambel’s quail), 1. There was no close association of these cases either in time or housing. One of the parrots and the stork had a picture suggesting that given by Warthin for avian leucemia while the remainder presented greater evidence of a generalized infection, such as Moore described, associated with the finding of the B. sanguinarium; this organism was isolated once, but no secondary cases succeeded upon the death of this bird. It seems hardly profitable to quote protocols of this relatively unimportant condition, especially since it is fairly well known.

The separation of the two groups just specified might be discussed, however, for it is by no means certain that they are or are not different. When a pathological picture of leucemia gives a decided impression of an acute infection there are very prominent involvements of the viscera but no lymph nodal masses. On the other hand, in the cases with nodular masses corresponding to the scanty lymph tissue of birds, there is much less infiltrative involvement of viscera and less parenchymatous degeneration. This suggests that they are different processes, but an analogous contrast may be found in the pathologic anatomy of acute and chronic leucemia in man, and I am inclined to view them as stages of the same disease. In one of our infectious cases noted above the lesion was certainly myelogenic for the infiltrate in the organs and the cells in blood smears showed an enormous number of eosinophilic and basophilic polynuclears greatly in excess of normal. The study of two of our cases confirms the picture as given for lymphatic and myeloic leucosis by Ellermann, but material corresponding to his lymphoidocytes or erythroleucotic group has not come to our attention. Cells with deeply staining basophilic protoplasm and a lymphoid nucleus are certainly to be found with reasonable ease in the avian marrow normally and, more than this, can be detected by careful search in nearly all cellular infiltrates of organs not leucemic in nature. Perhaps, as Ellermann states, they are collateral stages in normal erythrogenesis.

THE BONE MARROW.

Since the foregoing conditions so vitally concern the bone marrow, it is but natural to give to this structure a separate consideration. From what is known of the origin, physiology, anatomy and regeneration of the marrow from the work of Ponfick, of Neusser, Bunting, Selling, Werigo and many others, it seems highly probable that the principal conclusions reached in the study of human medicine and experimental pathology, apply to the whole group of animals here under discussion. The peculiar arrangement already mentioned as encountered in the marrow of birds differs little if any from the erythropoietic centres seen in man after experimental anemia, although it may be somewhat more orderly. Myeloblasts or megakaryocytes are not numerously present in any order, but seem more prominent in the mammals than in birds. In so far as the mononuclear groups are concerned, one can state with reasonable certainty that they differ little throughout the animal kingdom. They occur in islands, strands, or infiltrate—like groups, are mixed granular and non-granular in character and, with exception of the frankly oxyphilic cells, are distinctly basic in tinctorial affinity. In a case probably myeloma, soon to be discussed, there is not a single acidophilic or multinucleated cell to be found in two sections. As might be expected from the greater eosinophilic content of the circulating blood in the Aves, greater numbers of such cells are to be found in the marrow and they are, understandingly enough, sometimes found in distinct nodes and groups containing mono- and polynuclear varieties. Concerning the platelets, no sufficient data are at our disposal to warrant a general statement. In the avian marrow they can be made out quite clearly, as in the blood, and have a greater diameter and a sharper, more chromatic nucleus than in the higher mammalian blood. Mast cells are quite common in lower mammals and birds, in whose blood they maintain an appreciable percentage, while in the marrow they stand out clearly. It is noteworthy, in the light of Graham’s statement that the hemic basophile is but a degeneration form of the eosinophile, that in the bird’s marrow, large mono- and polynuclear cells with both kinds of granules easily may be found by Romanowsky stain. An increase of eosinophiles, seen in avian as well as in human parasitism, is not necessarily accompanied by basophilia.

Hyperplasia and atrophy of marrow in the lower mammals follow much the same conditions as in higher groups. During acute general infections, as by the paracolon bacillus in carnivores, it is common to find a distinct increase in the mononuclear centres, while in suppurative lesions a polynucleosis results. The bird, however, responds less readily with leucocytes, judged by cross sections of blood vessels and the activity of the marrow. The latter may show a myeloid picture, but mononuclears without granules, with deeply staining nucleus and protoplasm, are usually more numerous; two cases recently studied, one of tuberculosis and one of pneumonia with general congestion, had similar bone marrow— pale homogeneous red with distinct mononucleosis, more outspoken, however, in the former case. Pigment is not common in the avian marrow.

The relation of the marrow to general conditions has been mentioned in the foregoing pages, but perhaps the following diagnoses will illustrate other connections seen among our records:

Bactrian Camel (Camelus bactrianus).—Hydatid disease of lung and liver. Hemorrhagic enteritis. Atrophic bone marrow. Calcified areas in thyroid.

American Gray Wolf (Canis mexicanus).—Cretinoid. Hemorrhagic external pachymeningitis with craniotabes. Secondary hyperplasia of thyroid with colloid. Chronic lymphatic hyperplasia. Chronic interstitial nephritis. Chronic enteritis. Osteogenesis imperfecta. Hemorrhagic bone marrow. Concentric hypertrophy and dilatation of heart.

MYELOMA.

Perhaps no pathological condition has given rise to more varied opinions than the tumor-like hyperplasias of the bone marrow, growths resembling bone sarcoma with and without giant cells—myeloma, chloroma, pseudoleucemia ossium and many others. In brief only two cases occur in our series which could be admitted to this category. There have been osteomata, but they were so clearly local tumors that they cannot be included in myeloid neoplasms that are assumed to be systemic in nature. Here is not the place to engage in a discussion of the correct classification and nomenclature since there are included only the aleucemic newgrowths usually assumed to originate from blood-making cells. The first case seems to be a myeloma because of the involvement of many bones and the infiltrates in the liver. Judging by the cross section of blood vessels there is no leucemia, but of course this is not final, although somewhat supported by the normal size of the spleen and lymph nodes; lymphatic structures need not be enlarged in myeloid leucemia although they usually are.

Beechy’s Gopher (Citellus grammurus beecheyi). Adult ♂ . Gradual loss of power in limbs beginning about two weeks ago. No other symptoms.

DIAGNOSIS.—Multiple myeloma. Anemia. Acute parenchymatous nephritis. Chronic ulcerative gastritis.

External Appearance.—General condition fair, hair in good condition. Fully developed animal. Muscles contained no fat.

Respiratory Tract.—Thymus, large soft gray homogeneous. Both lungs are distended, pale, homogeneous, yellow pink, boggy, do not crepitate, but contain no edema. Lymph nodes, small soft anthracotic. Pericardium contained no fluid.

Abdomen.—No adhesions. Size of liver normal or slightly small, firm and pale brown-red. Architecture irregular showing areas of perfect homogeneity and others where lobules are clear outlined by paler interstices. Gall-bladder distended, contains brown fluid. Common bile duct, patulous. Spleen, normal or slightly small, consistency soft, capsule smooth, location normal; section surface, homogeneous pale pulp, faint trabeculæ. Kidney normal in size and shape, capsule smooth, strips easily, smooth brown surface; section surface glistening, opaque; consistency firm; thickness of cortex normal and of medulla normal; homogeneous cortex, glomeruli not visible.

Adrenal.—Narrow, brown, opaque cortex; pale brown, opaque medulla. Bladder, small quantity of cloudy urine showing albumin, bile and many granular casts, few hyaline casts. Teeth carious broken; mouth pale. Stomach distended; serosa and wall pale, contained gas; mucosa pale, flat, translucent except in pyloric segment where it is slightly thickened, irregular, opaque and there are several saucer shaped depressions covered with black, shiny material; these seem like sluggish ulcers. Intestinal tract throughout seems normal save for its pallor. Few natural fecal masses in lower gut.

Skeleton and Muscles.—All bones are irregular in thickness, very brittle and show in their length irregular swellings made up of periosteal growth and probably increase in marrow. The latter is pale yellow with punctate hemorrhages. Skeleton seems too soft to give support, but there is little deformity.

Microscopy.—Bone section shows a myelomatous growth of costal marrow, new myelocytes predominating. The cells are packed in disorderly fashion through the marrow. They are chiefly lightly granular but a few distinct promyelocytes are found. The hyperplasia is invading cartilaginous bone with absorption. In some places cartilage is of fetal type. Perichondrium is active but there is no round cell infiltration. Ossification is imperfect at costochondral junctions. Kidney shows granular and vacuolar degeneration of epithelium with flattening of tubular lining. Nuclei are for most part normal. Epithelium of tufts and Bowman’s capsule is likewise granular and vacuolated. Distal and discharging tubules seem to be most affected. No well defined casts are found.

Liver.—The fine markings mentioned in the notes correspond to areas of infiltration of large pale mononuclears without granules. There is no fibroblastic or polynuclear increase around them. Very small necroses seen in hepatic lobules. Very slight increase of connective tissue is noted.

This seems to be a tumor of true myelocytic origin; none of the cells was of the plasma type as usually depicted. The second case stands in the files as a myeloma, yet the full description and slides have been mislaid. It is cited briefly for record.

Samoli Ostrich (Struthio molybdophanes). Adult ♂ . Would not eat for three weeks.

Diagnosis.—Tuberculosis of lung, liver, spleen, kidney, mesenteric and cervical lymph glands. Myeloma of periosteum of pelvis.

Skeleton and Muscles.—Large tumor mass lying on inside of pelvis measuring about ten inches by twelve inches with a thickness of about four inches. It is sharply defined and separated from adjacent muscle by a capsule. Inner border is directly below the peritoneum, and outer border lies directly on bony pelvis. Traced to its origin it seems to come from pelvis yet tumor peels off bone easily, leaving a rough surface. The tumor is soft and succulent, of a red gray color and contains some fat and much irregularly placed masses of bony tissue.