USA > Ohio > Hancock County > Findlay > Twentieth Century History of Findlay and Hancock County, Ohio, and Representative Citizens > Part 109
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The stomach contents of a patient, J. C. (Hosp. No. 8971), who has carcinoma of the stomach, in which there was no free HCI, but total acidity of 52, reacted negatively both to tryptophan in the fresh contents and with the glycyltrypto- phan on December 31, 1910. Again, on January 13, there was no tryptophan found in the fresh contents. On January 27, with no free HCl and a total acidity of 46, there was a most marked reaction to tryptophan. This was again found on March 3. This patient's saliva did not split glycyltrypto- phan, but the saliva of another carcinoma case (Hosp. No. 9098), in whose contents there was no free HCI, did split the di-peptid. It was found that the saliva of J. C. was acid, while that of S. was alkaline.
Tests made with stomach contents from a variety of dis- eases, and from R. T. G.'s and mine after an Ewald test break- fast, showed that when free HCI was present in amount from 0.05 per cent on, the glycyltryptophan was not split. On the contrary, of eleven cases containing no free HCI in the stom- ach contents all reacted positively but two. Both the nega- tive tests occurred with contents which contained considerable lactic acid. One case (Hosp. No. 8588) was at first thought to be cancer of the stomach, but later was found to be chronic nephritis and arteriosclerosis; the other was J. C., who had acid saliva and total acidity of 52.
One patient, J. S. (Hosp. No. 9140), in whose contents there was no free HCI, gave negative tryptophan and positive glycyltryptophan reactions. Autopsy revealed no stomach tumor of any kind.
Another patient, J. K. (Hosp. No. 8753), with clinical diagnosis of cancer of the stomach, had alkaline stomach contents in which was no tryptophan but which split glycyl- tryptophan, giving a very positive reaction.
A case furnished by a colleague was rather curious. J. P. B., aged 51, was suspected of having a cancer of the stomach. There was constant absence of free HCI and low total acidity. At the Johns Hopkins Hospital two positive glycyltryptophan tests were obtained, and on these, together with his suspicious symptoms, a laparotomy was advised. In Milwaukee about one month later two tests were negative, but the free HCl was still absent. At operation no evidence of cancer was found. A few enlarged glands which were removed showed only irritative hypertrophy. The saliva in this case has not been tested.
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DISCUSSION OF RESULTS.
All who have worked with the test have reported most in- constant and variable results. The test has been found posi- tive in achylia gastrica. This accords with the view here held that it is the swallowed saliva which is responsible for the splitting of the glycyltryptophan. This explains most of the discordant results. An occasional acid saliva would explain an occasional negative test, when it would otherwise be ex- pected to be positive. An examination of the results in- variably shows that when the stomach contents are acid, 0.05 per cent plus, the test is negative; when there is no free HCI it may or may not be positive. A high total acidity, com- bined HCI, as is here shown, accounts for some of the negative results, and the presence of relatively large amounts of lactic acid accounts for some other negative results. Still other negative results in contents showing no free HCl and a low total acidity are accounted for by the acidity of the saliva.
That there is a peptid-splitting enzyme in cancer juice seems to have been shown (Emerson, Neubauer and Fischer). The very fact, however, that cancer of the stomach is so often accompanied by absence of free HCI in the stomach contents is just the condition most favorable for the action of the salivary peptid-splitting enzyme.
From what glands, parotid or sub-maxillary and sub- lingual, this enzyme is secreted is not at present determined. Whether the splitting is caused by bacteria in the saliva has not been shown yet. Weinstein denies the possibility of bac- terial action, and Neubauer and Fischer did not show posi-
tively that bacteria could split polypeptids, except after pro- longed action for days. At just what temperature the enzyme in the saliva is destroyed has not been accurately determined. Heated to 100° C. it is destroyed.
Care was always taken to centrifugalize the saliva, but it did not appear that this precaution was necessary. Further work is now in progress, but enough has been done to warran: the following conclusions :
1. There is a substance in the saliva, probably an enzyme. which has the power to split glycyltryptophan.
2. This property of the saliva is lost when the saliva is acid or when it is heated to 100° C.
3. Stomach contents containing no free HCI may spli: glycyltryptophan.
4. Stomach contents which have a high combined acidity or which contain a relatively large amount of lactic acid fai: to split the di-peptid.
5. In view of these facts the glycyltryptophan test is of no value in the diagnosis of cancer of the stomach.
REFERENCES.
Emerson, C. P .: Deutsches Arch. f. klin. Med., 1902, LXII, 415. Fischer, Emil: Ber. d. deutschen chem. Gesellsch., XXXIV. 2864.
Fischer, H .: Deutsches Arch. f. klin. Med., 1908, XCIII, 99. Neubauer and Fischer: Ibid., 1909, XCVII, 499. Lyle and Kober: N. York M. J., 1910, 1151.
Weinstein, J. W .: J. Am. M. Ass., 1910, LV, 1085.
Kuttner and Pulvemacher: Berl. klin. Wchnschr., 1910, XLVII, 2057.
THE RELATIONSHIP BETWEEN THE NORMAL AND PATHOLOGICAL THYROID GLAND OF FISH.
By J. F. GUDERNATSCH.
(From the Department of Anatomy, Cornell University Medical College, New York City.)
Recent investigations of the thyroid gland of Teleosts have revealed a great many facts that may be of value to the com- parative pathologist. The thyroid gland of these fish attracts at present a good deal of attention in cancer research, since it is often liable to cancerous degeneration, especially in artificially reared trout and salmon.
The normal anatomy of the gland was briefly described in a paper read before the meeting of the American Association of Cancer Research, November 27, 1909. * It was especially em- phasized that one of the most striking features of the thyroid in bony fish is the absence of a connective tissue capsule, such as exists in other vertebrates. Later this fact was again pointed out by Marine and Lenhart. It will readily be seen that the absence of a capsule makes it rather difficult to define the normal extension of the gland. It would perhaps be better not to use the term "thyroid gland " at all in this group of animals, since physiologically isopotent units (fol-
* An extensive analysis of the normal conditions of the Teleost thyroid will be found in Jour. of Morphology, V. 21, Suppl., 1911.
licles) are not so arranged as to form a closed organ, but are distributed over a wide area (Fig. 2 and Plate 1). This distribution varies not only with the species, but also with the
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FIG. 1 .- These diagrammatic drawings show the expansion of the thyroid gland in the three species: Oncorhynchus, Salvelinus and Opsanus. I, aortic bifurcation; II, III and IV, the second. third and fourth branchial arteries.
individual, and is dependent entirely on mechanical influence. mainly pressure from the sides of the surrounding tissue".
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"wove and lymph vessels. The latter force works chiefly in the early development of the gland, when thyroid cells are carried off from the main point of growth to distant regions, where they form new centers of multiplication.
The thyroid gland develops around the stem of the ventral aorta (Fig. 1), in many species the main bulk lying between the branches to the first and second gill arches. This locality is filled with connective tissue and fat, and is enclosed dorsally
organ in its shape, having the tendency to lose its unity and break into numerous small parts. In some species, the trout and others, this tendency manifests itself most strikingly, so that thyroid follicles are found even far out in the gill arches along the gill filaments (Plate 1, D).
The spreading apart of the thyroid follicles over a wide area and the invasion of neighboring tissues are a normal feature and of no pathological significance. By such an in-
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PLATE I .- A and B, sections through the thyroid gland of Sarda. A, in the region of greatest extension anterior to the aortic bifurcation; B, near the second branchial arteries, the region of greatest extension. C and D, sections through the thyroid gland of Salvelinus. C, in the aortic bifurcation; D, near the second branchial arteries.
(Thyroid follicles in all figures shown in solid black. Transverse muscles lined. Longitudinal muscles in polygons. Skeletal parts stippled. Arteries in heavy lines. Veins in light lines. Lymph sinuses in broken lines. A, ventral aorta, AI and AII, branchial arteries.)
by cartilages or bones and ventrally by muscles. Thus the egion available for the thyroid tissue is rather limited, and herefore the follicles tend to fill every space that is offered y the surrounding structures. Not uncommonly follicles are bund far from the center of thyroid development, invading uscles ( Plate 1, C) or creeping into the crevices which exist etween the osseous lamellæ of the bones in this region (Fig. and Plate 1, A).
vasion the surrounding structures are not destroyed. Often the term "invasion " is even incorrect. Thus Marine and Lenhart's statement that the normal follicles invade the bones is not appropriate, since they do not invade true bone or car- tilage tissue, but merely the spaces that are present between the osseous or cartilaginous lamella (Fig. 2 and Plate 1, A). In their paper Fig. 6 demonstrates this fact definitely, al- though it is supposed to show a true invasion. On the other
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hand, Gaylord was able to show specimens in which thyroid tissue, belonging to a diseased gland, had actually invaded or infiltrated true cartilaginous tissue. The latter invasion, of course, is never seen in the anatomy of the normal gland, but is a strictly pathological feature. Whether or not it is due to a cancerous growth of the gland, may still be an open question. Strong evidence seems, however, to point in that direction.
Should the so-called thyroid carcinoma of brook trout be a cancerous growth and not a mere hyperplasia, as Marine and Lenhart believe, then the question of metastasis again demands the pathologist to keep in mind the lack of a capsule. Cer- tainly no detached nodules in or around the gill region can safely be called secondary tumors, since such misplaced struc- tures in all probability are merely parts of the primarily dis- eased gland. However, tumors on the tip of the jaw or around
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FIG. 2 -Section through the thyroid gland of Brevoortia, an- terior to the aortic bifurcation. AI, first branchial arteries.
the anus, as Gaylord has found them, can hardly be explained as due to normally misplaced thyroid particles. Whether they are true secondary growths or simply implantations, further experimental investigations may show.
Histologically the thyroid gland of the Teleosts offers a great many interesting peculiarities. The size of the follicles varies between very wide limits. Aside from the fact that in young embryos it is naturally very small, the size of follicles cannot be taken as a reliable indication of the age of the fish. It seems much more probable that it is a sign of the age of the individual follicle.
The follicular epithelium varies from an almost flat to a very high, columnar type. It is different in each individual and may somewhat depend on the age and the physiological condition of the animal. Yet the type of the epithelium is not always uniform in all the follicles, sometimes very marked
differences are found (Fig. 3). Even in the individual follicle the height of the epithelium may vary, probably due to difer- ent pressure from outside. It was now and then observed, that in oblong follicles the epithelium on the two longer sides would be lower than on the shorter ones.
The colloid material is sometimes present in all the fel- licles, in other glands it may appear in some only, in stif. others it may be entirely lacking. It, again, is no definite sign of the age of the animal, although it may be somewhat dependent on the age of the fish, its sex (egg-carrying females. for instance) and other inherent factors that need further investigation. The colloid certainly is a sign of the physio- logical state of the individual follicle, yet we do not under- stand it well enough to interpret our observations in a deti- nite manner. There can be no doubt that all the follicles of s gland are not in the same state of physiological activity. Otherwise it cannot be explained why (Hürthle's) colloid- forming cells appear in some follicles only, sometimes in a
FIG. 3 .- Section through the thyroid gland of Salvelinus fon- tinalis. Note the different heights of the follicular epithelium. Dia. 1:300.
group of neighboring follicles, so that we can easily distinguish " colloid zones " from non-colloid-forming parts of the gland.
In interpreting their results after iodin treatment of the thyroid gland of the pike Marine and Lenhart lay great stress on the histological appearance of the treated and not treated glands. Yet from the above discussion it seems obvious that the anatomy of the gland as well as its histology, as far as the type of epithelium and the colloid formation are con- cerned, makes it rather difficult for the microscopist to dis- tinguish a normal from a hyperplastic, and the latter in turn from a " reverted " thyroid gland in these fish.
The presence or absence of the colloid material has Da significance whatsoever. If all glands, the follicles of which spread out far from the main bulk even into the gill region. are highly hyperplastic, then, according to Marine and Len-
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MOOIEHEHE TEV It Is present throughout the gland.
The type of the epithelium is also a perfectly unreliable guide in regarding a gland as hyperplastic. When, of course, the epithelium shows marked foldings and protuberances into the lumen, the hyperplastic condition is evident.
Further studies on the carcinoma of the fish thyroid will have to take into account the peculiar anatomy and histology of this organ in the Teleosts. Many conditions which might be regarded as pathological may prove to be normal as soon as our knowledge of all the factors involved is sufficiently broadened.
Gaylord, H. R .: An Epidemic of Carcinoma of the Thyroid Gland Among Fish. J. Am. Med. Ass., LIV, 227, 1910.
Gudernatsch, J. F .: The Structure, Distribution and Variation of the Thyroid Gland in Fish. J. Am. Med. Ass., LIV, 227, 1910. Gudernatsch, J. F .: The Thyroid Gland of the Teleosts. J. of Morphology, XXI, 709, 1911.
Marine, D., and Lenhart, C. H .: On the Occurrence of Goitre (Active Thyroid Hyperplasia) in Fish. Johns Hopkins Hosp. Bull., XXI, 95, 1910.
Marine, D., and Lenhart, C. H .: Observations and Experiments on the so-called Thyroid Carcinoma of Brook Trout (Salvelinus fontinalis) and Its Relation to Ordinary Goitre. J. Exper. Med., XII, 311, 1910.
TUBERCULAR BURSITIS. TWO UNUSUAL CASES. By SYDNEY M. CONE, A. B., M. D., Baltimore.
There is a great deal being written to-day about diseases of the bursa. The literature is full of references to acute and chronic inflammation of these sacs, and here and there may be found a description of a tumor of a bursa; syphilis is de- scribed involving it as is tuberculosis. The study of the anatomy and development, the pathology and clinical con- ditions involved in these diseases leaves little more to be added.
In Codman's report we get not only an exhaustive descrip- tion of the anatomy and development of the subdeltoid bursa, but learn of the changes that may take place in this little known sac. He describes conditions that may be confused with bursal involvement, and the average medical man will be surprised to learn the seriousness of disease of this much overlooked anatomical structure. He will recall many cases of so-called sprain, rheumatism, tuberculosis, neuritis and other conditions about the joints which, in the light of recent investigations by conservative and scientific investigators, are doubtless bursal disease.
Many odd cases in the Johns Hopkins Dispensary called painful shoulders, referred to by Dr. Finney (Johns Hopkins Hosp. Bull., 1894) are doubtless cases of subdeltoid bursitis.
Many cases of inflammation of the prepatellar and olecra- ion bursæ have been recorded, but little thought has been iven to the possibility of similar involvement of many similar acs throughout the body.
Bursal disease is a common cause of painful .conditions bout the heel and sole of the foot-many cases having been escribed in the orthopedic journals. Lund describes three ases of inflammation of the iliopsoas bursa, and Cullen gives ne history and an excellent pathological description of a cyst 1 the pelvis which developed from the iliopsoas bursa which ontinued its connection with the hip joint.
The numerous bursa about the hip joint have been the seat - ! pathological changes as described by Da Costa, Nicaise, rackett, Thurston, Wietung, Zuelzer, Ducroux and others. eale gives a case of suppuration of the bursa over the great pchanter and its immitation of hip disease. Brackett, in
his article on " Gluteal Bursitis," likewise refers to the simu- lation of hip joint tuberculosis.
The greatest amount of literature on this subject takes the subdeltoid bursa as the text. Codman, Baer, Painter, Duplay, Bousquet and Kaumheimer cover this field quite thoroughly.
Acute infections due to various micro-organisms are re- corded. Kaumheimer describes a purulent pneumococcus in- volvement following pneumonia. One of Duplay's cases was due to a streptococcus following erysipelas of the hand. Weg- ner, Heubner and others refer to a mixed infection following syphilis, and Kreuter describes a case of metastatic infection of the subdeltoid bursa from an original osteomyelitis of the femur. The gonococcus and influenza bacillus have likewise played their part in causing acute inflammation of bursæ.
The older writers referred in the main to syphilitic disease as evident in secondary and tertiary lesions. Churchman, writing on this subject, finds twenty-eight such cases in the literature describing them under the name "Luetic Bur- sopathy of Verneuil." Schuchardt who describes tubercular and syphilitic disease of bursa in trying to solve the question of fibrin formation or fibrinoid degeneration of rice bodies in hygromas of tendons and bursa, aids us materially in view- ing clearly tubercular disease of bursæ.
Acrel in 1779 first described the "Ganglion Crepitans Acrelii " containing rice bodies which were doubtless tubercu- lar. Dupuytren and Cruveillier likewise described cysts at bursal points containing rice bodies. Dupuytren called them hydatidiform cysts and thought the bodies parasites. Virchow noted them in hygromas and took them for fibrin, but con- fessed that he afterwards learned they were organized ex- crescences increasing in size by later gradual fibrin deposits. Although there is a close relationship in anatomy and path- ology, between tendon sheaths and bursæ, one must distinguish the cases of tubercular tendo-vaginitis from those of tubercu- lar bursæ for clinical purposes.
There is no doubt that the pathological descriptions of Acrel, Dupuytren and Cruveillier, and the works of Virchow,
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Neumann, Riese and others, on fibrin and fibrinoid bodies in tendon-sheath hygromas, apply to the bodies as found in bursal sacs. It is unfortunate that in describing or referring to their cases of tubercular bursæ Brackett, Thurston, Gillette, Ketch, Gibney and Sayre did not give more complete descriptions of their pathology. In none of these cases was reference made to fibrin or fibrinoid bodies. Brackett gave a short clinical his- tory with seven cases of "gluteal bursitis " which he thought were tubercular. In Thurston's case we note that there was calcareous and cheesy material in the contents; but as he simply drained and did not examine the walls of the sac, there is left much of value to be inferred. And as Painter de- scribed yellow, cheesy, granular contents and villous enlarge- ments in non-tubercular bursæ, and Cullen described bone, calcareous and cartilaginous masses in a simple cystic bursa, and Kreuter gives a simple subdeltoid bursitis containing cholesterin, fat and brownish fluid, we must still be in some doubt as to the true tubercular character of some of the cases (few as they are) described under the head of " tubercular bursæ."
So far as I can find, the cases of Schuchardt, Riese, Nicaise, Poulet and Vaillard are the only ones which present well- described tubercular bursæ containing rice bodies. They alone described bursal hygromas containing rice bodies. Most of the discussion as to the pathological histology and tubercle bacillus contents of the melon seed or rice bodies in hygromas has been based on work done on those found in connection with tendon-sheaths and joints.
"Tuberculosis of Bursæ" has certainly been not infre- quently described, but not as a rule, in connection with rice body contents.
In some of the cases of tubercular bursitis which have been described there has been doubt as to whether the joint or bursa was the primary seat of the disease. In one of our two cases this relationship is a doubtful point. As a rule the question has not been settled. In a few cases-as for example, Thurston's and Brackett's-the rapid healing and disappear- ance of disease after relieving the bursa of its fluid and drain- ing proves the joint uninvolved.
In some cases it has been demonstrated at operation that there was no connection between bursa and joint by which the disease could have extended from one to the other.
In other cases (Sayre, Lund, Cullen, Gibney and Brackett) a definite communication was demonstrated. From symptoms alone one cannot determine whether the joints are involved. The bursa when inflamed frequently leads one to think it a joint disease. Brackett, speaking of ordinary gluteal bursitis, says it resembles hip disease in its early stages. The X-ray is helpful, as, for example, in one of our cases where there was no evidence of bone lesion connected with the joint. The cloudiness about the joint was evidently due to the bursal con- tents covering the joint. At operation no communication was seen and incision into the joint showed no involvement. In our second case both joint and bursa were involved at the time of operation, the bursa being a dense mass of fibrous tissue and caseous tubercular material, while the joint showed villous
masses of fibrous tissue with lymphoid tubercles in them. Which was the primary seat it is difficult to say. The fact that the disease of the bursa from pathological as well as from clinical data appeared older, would make us believe it to be the original focus of the tuberculosis.
Churchman tabulating twenty-eight cases of " Luetic Bur- sopathy of Verneuil," says that in only one case was the neighboring joint involved.
Several interesting pathological questions are brought to mind in studying these cases of tuberculosis of bursæ and the literature deals with each one in more or less detail.
The question which has been most actively studied is about the formation of rice bodies. In dealing with this question it has been assumed, and we think quite justly, that the so- called rice bodies including all fibrin or fibrinoid bodies of whatever shape or size, and wherever found, whether in bursæ, tendon-sheaths or joints, belong to the same class. In his work on the subject, Riese includes studies on rice bodies found in all three locations. He goes quite extensively inte the history of the knowledge of rice bodies, referring to Acrel as the first, in 1778, to describe real rice bodies; he classified them as atheromatous, comparing them with boiled sago or corn grains. Dupuytren, Brodie, Rokitansky, Virchow, Meckel. von Recklinghausen and others held original views about them.
Cruveillier (1816) and Dupuytren (1839) dealt with them as hydatid cysts. Brodie (1821) considered them coagulated lymph. Rokitansky said they formed from abnormal fluid in the cysts. Virchow first recognized their relation to fibrin in 1846 and originally thought them coagulated masses-clots gradually formed. In 1856 he referred to them as coming from changed intercellular substance by the process of degen- eration. Now no one disputes their relation to fibrin. The greater amount of discussion is based on the question-are the fibrin deposits from fluid, or are they changed cellular material, due to a coagulation necrosis, or degeneration of cells? Thi: side of the subject takes up much of Riese's, Nicaise's and Schuchardt's work.
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