Twentieth Century History of Findlay and Hancock County, Ohio, and Representative Citizens, Part 108

Author: Jacob Anthony Kimmell
Publication date: 1910
Publisher:
Number of Pages: 1189

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and occasionally a few red corpuscles. Microscopically, there was no excessive amount of fat; no amoeba were found on careful examination.

The blood pressure was rather low-95 to 120 mm. Hg.

The leucocytes were normal in number, even sub-normal, 4500, on the day before death.

An Ewald test meal showed 100 cc. of thin watery fluid which separated into two layers, the upper consisting of a turbid, dirty yellow liquid and the lower of finely-divided food elements. It was acid; total acidity, 18; free hydrochloric acid, absent; lactic acid, absent; test for occult blood, negative. Microscopically, fat droplets were present in considerable numbers; starch granules. epithelial cells and vegetable fibres.

The Wassermann reaction was negative.

The urine apparently rather reduced in quantity, showed a specific gravity of 1.011, a heavy ring of albumen, and numerous hyaline, finely and coarsely granular casts.

On the 18th of March, the writer noted that both apices showed a slight tubular modification of the respiratory murmur, and fine crackling rales were detected, especially above the left clavicle,

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148

JOHNS HOPKINS HOSPITAL BULLETIN.

[No. 24

as well as a peculiar superficial crackle, which sounded almost pleural in character over the whole left chest. There was little modification on percussion of the bases behind. Numerous fine râles were to be heard at the apices and occasional crackles throughout both backs. Abdomen, large and full. Flanks bulged. The umbilicus protruded. Diastasis of recti. Respiratory move- ments free. Edge of liver sharp, firm and smooth, but not quite so sharp in the right flank as elsewhere. Upper limit of liver flatness, 6th space in mammillary line. Lower border, 10 cm. below the costal margin in the mammillary line, 9 cm. below xyphoid; notch, well felt. No fluctuation detected.

March 21. The patient had been growing progressively weaker and for three days, the posterior parts of both lungs had been filled with fine, moist râles although there had been no dulness. The heart has been markedly irregular at times. There appeared to be no fluid in the abdominal cavity.

The patient became gradually weaker, the anæmia, more marked.

Blood count:

R. B. C. Hb.

3,000,000

50%

Numerous fine râles appeared throughout the chest. At 8.30 p. m., she died.

In summary, then, the history is that of a colored woman of 49, who, a little over a year before her death, came to the hospital suffering from remittent and intermittent fever and vague abdominal manifestations-tenderness, resistance. Six months later, she returned with a history of diarrhea of four or five weeks' duration : weakness and general debility. There was irregular fever with morning remissions or intermissions. The liver, which was somewhat prolapsed, was much enlarged and firm and there was a well-marked anemia of a secondary type. There was, at times, occult blood in the stools which showed considerable mucus. No excess of fat or fatty acids.

The diagnosis of tuberculous peritonitis, made on her pre- vious entry, seemed reasonable when one considered the race of the patient, the fever, and the general abdominal symptoms, the diarrhea suggesting a tuberculous enteritis, but the hepatic enlargement seemed difficult to account for on the basis of tuberculosis, although the possibility of a fatty cir- rhotie liver was considered.

Considering the age of the patient, the degree of anamia, the progressive enlargement of the liver, its firmness and slight irregularity, one could not but think of the possibility of a neoplasm of uncertain origin. The well known occur- ience of fever in association with hepatic neoplasms would not have been against this diagnosis, although no suggestion as to the primary seat of such a growth could be found beyond the possible significance of blood and mucus in the stools.

Another possibility which suggested itself was that the case might be one of amcbic abscess of the liver. The slight fever, the diarrhea, the jaundice present at one time, although amorbæ had not been found in the stools, and the progressive hepatic enlargement formed a clinical picture not unlike that which is occasionally seen in such cases.

The necropsy was performed on March 22 by Dr. Winternitz (No. 3188).

( Abstract.) Anatomical diagnosis: Tuberculosis of the mesen- terie and retroperitoneal lymph glands with involvement of the

receptaculum chyli; chronic adhesive peritonitis; chyliform at- cites; tuberculosis of the spine with abscess formation; general- ized tuberculosis; extensive tuberculosis of the liver with carity formation; tuberculosis of the spleen and liver; tuberculous broncho-pneumonia, caseous and gelatinous; fatty degeneration of the liver; chronic fibrous pleurisy; chronic diffuse nephritis; arteriosclerosis; chronic fibrous myocarditis; thrombosis of ovarian vein.

The peritoneal cavity contained a considerable amount of chyli- form fluid which was extremely milky in appearance. The omen- tum was definitely plastered to the parietal peritoneum but was not evenly adherent, so that encapsulated areas appeared in which the above-described fluid was found. The intestinal peritoneum was not adherent either to the omentum or to the parietal peritoneum of the anterior surface, so that when the omentum was severed from its attachment, the abdominal contents were easily exposed and the intestines were found to lie almost entirely in the lower half of the abdominal cavity. A large mass was found in the upper portion of the abdominal cavity filling the entire epi- gastrium and the upper half of the umbilical region as well as the hypogastric region on the right side. This mass which proved to be the liver, was covered over its entire surface by adhesions which were formed by fibrous œdematous union le- tween the peritoneal surface of the organ and the parietal peri- toneum. The liver was closely bound to the diaphragm above on both right and left sides. The stomach was bound down by dense adhesions. The mesenteric lymph glands were extremely large and yellowish-grey. On section. they were rather firm and mottled, the greater part of their structure being composed of a rather friable yellowish substance which had a faint green tinge. while throughout one could see other areas which were slightly more translucent and depressed.

There was nothing remarkable in the heart.

The lungs showed a disseminated tuberculosis with larger areas of broncho-pneumonia here and there.

The spleen measured 10 x 61/2 x 41/2 cm. The capsule was everywhere adherent to the diaphragm and surrounding viscera. On section, the Malpighian corpuscles were indistinct, and smaller opaque yellow tubercles were to be made out.

The stomach, duodenum and pancreas showed nothing of im- portance.

The liver was considerably enlarged, measuring 30 x 28 x 10 cm. It was flabby, and the surface was covered with nodules varying from 0.5 to 1 cm. in diameter, which were yellowish-grey. On section, the liver was everywhere studded with these nodules. some of which were firm and yellow and caseous; many were. however, cavities showing greenish bile deposits in their centres. Many of these caseous masses were surrounded by thin. traus- lucent, reddish-gray capsules. The remainder of the liver was pale. Lobulation was indistinct. The tissue about the hepatic vein was reddened and the peri-portal veins were everywhere very visible. Small tubercles were also scattered throughout the liver tissue, many surrounded by transparent gelatinous zones.

Kidneys: The right measured 11 x 61% x 31/2 cm. The capsule stripped off with slight difficulty, leaving a rather smooth, pal- surface. On section, the kidney was everywhere studded with yellow nodules which, in some spots. were as large as 1 cm. in diameter. Most of these were small, measuring 2 mm. The cortex of the kidney was swollen, averaging 7 mm. The striations for the most part were regular and the parenchyma was ex- tremely pale, showing here and there yellow irregular areas more opaque than the surrounding. The glomeruli were prominent and transparent, pale pink in appearance. The left kidney re- sembled the right in every respect.

The thoracic duct, which was dissected out carefully was found! to be in communication with a mass of glands which lay in the region of the receptaculum chyli.

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-av prunus iying over the spine on the right side from the eighth dorsal to the first and second lumbar, were soft and a puri- form fluid escaped from them. There was tuberculous caries of all the vertebra from the sixth thoracic to the first lumbar. There was no essential curvature of the spine.

Examination of the ascitic fluid showed that, after standing for several hours. it had become more milky in appearance. Specific gravity 1.018. Microscopically, there were large numbers of de- generated peritoneal epithelial cells. In addition, a few small round cells and some fat globules were seen. No tubercle bacilli were found.

The liver, microscopically, showed many large areas of case- ation, some involving bile ducts the remains of which could be seen in the necrotic ulcerated centre. The remaining liver tissue showed an extensive fatty degeneration. Around some of the larger tubercles, there was a zone of tuberculous granulation tissue which was rather fibrous showing here and there well- formed tubercles. This doubtless represented the translucent grayish zone which was observed about the large tubercles in gross. There was no definite cirrhosis throughout the remaining portion of the liver, but one found here and there small patches of cellular tissue which were possibly healing tubercles. In these one found no areas of degeneration but a mass of rather well- preserved spindle cells and round cells. Among these numerous blood vessels might be seen. Some of these were evidently the tips of well-formed tubercles. Others of the larger tubercles showed a dense mass of fibrous tissue surrounding a caseous centre. The fibrous tissue, however, was not well preserved and had apparently undergone hyaline degeneration. Tubercles, how- ever, in these areas, were definitely circumscribed and were apparently old processes that are walled off. In other areas, masses of miliary and conglomerate tubercles were to be seen which seemed to proliferate irrespectively of any general position. These did not involve the bile ducts and were not in close rela- tion to any particular portion of the vascular system.

The kidneys showed here and there dense bands of fibrous tissue extending in from the capsule. Here the renal tissue had under- gone definite atrophy, the tubules being very much smaller than in the surrounding tissue. Glomeruli might be found in this mass as dense hyaline staining masses. In fact, the glomeruli seemed to show most marked changes. One found in many places, where he uriniferous tubules were apparently not markedly degen- rated, that the glomeruli were large, filling up, as a rule, the entire capsule. In some places, there was a slight exudate between the glomerular capsule and the tuft, but this was not ften found. There were not very many intermediate stages be- ween glomeruli which appeared normal and those in which there vas a dense fibrosis. Where these were to be seen, the thickening eemed to start in the glomerular capsule which proliferated at he expense of the glomerular tuft. The uriniferous tubules iroughout stained diffusely red. Their lumina were dilated nd contained serous-like material and many casts. Many of the pithelial cells of the tubules showed large vacuoles which filled le entire cells, and smaller vacuoles might be seen near the sement membrane, but not as large as those which have been escribed. In some places the entire tubules showed this icuolar degeneration.

To summarize then, we have before us the history of a lored woman, 49 years of age, with a record of rather in- finite abdominal pain of a year's duration and almost con- nous remittent or intermittent fever of a moderate degree, th sweating at night and progressive emaciation. Examina-

10 01 die trivian sifonea little beyond the appearance towaru the end, of rather diffuse fine rales throughout the lungs. During the last eight months of the patient's life there was a steady enlargement of the liver which finally extended to a point 10 cm. below the costal margin in the right mammillary line. It was somewhat tender and very firm, and, on one occasion, slight irregularities of surface were noted. The border which was distinct, seemed a little blunter in the right mammillary line. There was considerable anemia of a secondary type, but without leucocytosis, a persistent albumin- uria and cylindruria without polyuria but with a rather low specific gravity, and, in the end, diarrhea with mucus and occult blood in the stools.

The progressively enlarging liver, the age of the patient, the anemia, the fever which after all, is common in hepatic neoplasms, all led us to lean toward this as a possible diag- nosis, despite the fact that beyond the diarrhoea with occult blood in the stools no suggestion as to the seat of a primary lesion was to be made out.

The indefinite abdominal pain, tenderness and fever, to- gether with the diarrhea occurring in a colored woman were strongly suggestive of peritoneal tuberculosis, despite the ab- sence of definite pulmonary signs, but the progressively and apparently great enlargement of the liver did not appear to us to depend upon tuberculosis alone. It was thought that a rolled-up omentum might be adherent to the liver, thus in- creasing its apparent size, but the sharp border of the liver was against this.

A steadily enlarging liver, with persistent, slight fever, even in the absence of leucocytosis, is by no means unusual in amcbic abscess which occurred to us as a possibility.

Syphilis was ruled out by the absence of a Wassermann re- action and by the fact that anti-luetic treatment had been without result.

The case was, indeed, presented to the class with the main possibilities as to diagnosis set forth in the order named : hepatic neoplasm ; amœbic abscess of the liver ; peritoneal and intestinal tuberculosis with a rolled-up omentum adherent to the liver in such a manner as to exaggerate its apparent size.

The anatomical appearances, well illustrated in the plate, are rather remarkable in their extent. A disseminated caseating tuberculosis of this degree in the liver of an adult is most unusual. But the feature of the case which is of special importance is that such disseminated cascous tuberculosis of the liver should have given rise to a tumor sufficient to con- stitute the central figure in the clinical picture.

It is also important to note that for a week at least during the course of this case there was jaundice-a rare manifesta- tion in hepatic tuberculosis.

In conclusion then, it may be emphasized that disseminated caseating tuberculosis of the liver in an adult may be asso- ciated clinically on the one hand with appreciable jaundice and on the other with hepatic enlargement sufficient to form the most striking feature of the clinical picture.

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150

JOHNS HOPKINS HOSPITAL BULLETIN.

[No. 28

A PEPTID-SPLITTING FERMENT IN THE SALIVA.

By LOUIS M. WARFIELD, A. B., M. D.

(From the Laboratory of the Milwaukee County Hospital.)

While experimenting with the glycyltryptophan test de- seribed by Neubauer and Fischer, some very inconstant results were found which led to the trial of saliva in the hope that an explanation might be found.

The presence of a peptid-splitting enzyme in cancer tissue from the stomach had already been shown by Emerson. Ile demonstrated its presence by taking macerated cancer tissue, dividing it into two portions, one of which was heated to 80° C. In the unheated portion the digestion of albuminous sub- stances was carried beyond the albumose stage.

In 1909 Neubauer and Fischer utilized this property of can- cerous tissue to perfect a test which they thought was of value in the diagnosis of cancer of the stomach. They called at- tention to four sources of error :

1. Presence of tryptophan in the stomach contents.

2. Presence of peptid-splitting bacteria.

3. Presence of trypsin (pancreatic juice).

4. Presence of blood.

They also affirmed that an HCI content of over 0.36 per cent vitiated the test. They concluded that "1. In the contents of a carcinomatous stomach there is present a ferment which with pepsin splits glycyltryptophan. 2. This ferment is de- stroved by an acidity of 0.36 per cent HCI. 3. The presence of this ferment can be used for purposes of diagnosis."

The test is said to depend upon the presence in the carcino- matous tissue in the stomach of a peptid-splitting enzyme which carries protein digestion of peptids to the amino-acid stage. Neubauer and Fischer used the di-peptid glycyltrypto- phan, a combination of glycocoll and tryptophan. The trypto- phan when split off can be readily recognized by a specific color reaction with bromine vapor or bromine water.

Normally pepsin digestion in the stomach is not carried beyond the stage of albumoses and peptones. When the chyme is acted on by the trypsin of the pancreatic secretion, there is further hydrolysis of the peptones into the amino-acids. In the complete digestion of coagulable proteins the stages are: proteins, meta-proteins (commonly called albumoses), proteoses (albumoses). peptones, polypeptids, amino-acids. We are concerned only with the polypeptids. These sub- stances were discovered by Emil Fischer. He succeeded in linking together the amino-acids, the generic formula of which is R-CHI-NII .- COOHI, with one another. This combina- tion takes place between the carboxyl group of one amino- acid and the amido group of the other with the loss of one molecule of water. The most complex polypeptid yet produced is one containing 15 glycocoll and 3 leucine residues. The name polypeptid is applied to all the group of combined amino-acids. These large molecule peptids are much like the albumoses and peptones in that they do not crystallize, are

precipitated by ammonium and zinc sulphate, and give the. biuret test.

Tryptophan is indol-a-amino-propionic acid, which in com- bination with glycocoll forms the di-peptid glycyltryptophan. When this is acted upon by a ferment which is able to spli: the peptid, it is decomposed into the two amino-acids.

H. Fischer showed that in the normal stomach pepsin split- albumin into peptid chains which react alkaline to litmus. These combine every one with one molecule of HCI, and theti react acid to litmus. Normal peptic digestion ceases at this stage. He also found that in stomachs in which there was cancer this chain is broken probably by a ferment. The fre HCI vanishes but the total acidity may rise. This is due ta the power of the amino-acids to bind the free HCI.

Lyle and Kober studied 21 cases with the glycyltryptophan test .* They conclude that " Results with the test have been satisfactory. A repeated negative reaction is very valuable. When the test is positive the complication of a regurgitation. of trypsin must be thoroughly investigated. No deductist: ought to be drawn from less than three tests."

Weinstein worked with the test and suggested some modi- fications. He disagrees with Neubauer and Fischer that when tryptophan is in the fresh contents the specimen should Ix rejected. He believes that the presence of tryptophan in the recent contents shows the presence of the peptid-splitting enzyme and the glycyltryptophan test is then superfluous. With this I agree. He also thinks that the danger from: peptid-splitting bacteria is exaggerated as well as the danger from occult blood. It is difficult to test for bile in the gastri contents. He agrees that a specimen containing macroscopir bile should be discarded. The danger is, of course, that there may be duodenal contents containing trypsin. This is to be guarded against. He prefers bromine water to bromine vapor.

* The test is performed as follows: Ten cubic centimeters of the filtered gastric contents free from bile, removed from forty. five minutes to an hour after an Ewald test breakfast, are placed in a vial with 2 cc. of glycyltryptophan in solution over which is a layer of toluol. This is placed in the thermostat for several hours. Two to 3 cc. are then taken out with a pipette, trans- ferred to a test-tube, acidified with a few drops of 3 per cent acetic acid, and fumes of bromine or a small drop of bromine water added. Care must be taken to pour only a small amount of bromine fumes or to add only a small drop of bromine water. The presence of tryptophan is shown by a rose or reddish violet color. The further addition of bromine vapor or water will. in excess, produce a yellow color. Unless the bromine is added carefully, a little at a time, one might miss a very slight pink reaction. It is also well to allow the tube to stand several minutes. as a very faint reaction often becomes more pronounced on standing.

I have procured the substance from Arthur H. Thomas Com- pany. Philadelphia, Pa. It is expensive, six dollars for one dozen tests. One can now obtain it in bottles containing material enough for twenty-five or fifty tests.

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meat of bread, butter, beef and sweetened tea which he re- moves after 3 to 4 hours and tests directly for tryptophan. If tryptophan is negative he places the filtered contents in the thermostat and tests again after 24 hours. From his work (150 tests) on 63 cases suffering from cancer of the stomach, and other diseases of the stomach, he concludes that the tryptophan test is a valuable sign in the diagnosis of cancer of the stomach. It is a sign in itself. The negative reaction is of more value than the positive. The results are inconstant, he admits. Whether or not it is an early sign of cancer he does not know.

Kuttner and Pulvemacher used silk peptone in their work. It is very much cheaper than glycyltryptophan, and compara- tive results showed that the tests paralleled each other ac- curately. The reaction with the silk peptone depends upon the splitting of the substance by the hypothetical cancer fer- ment into amino-acids, chiefly tyrosin. This is recognized microscopically. Their process is tedious and doubtless will never be used to any great extent in the clinical laboratory. It is academically of interest. They made 163 tests on 92 persons with and without stomach disease. Seven gave defi- nite results, 19 gave variable findings. Vomitus was examined in five cases. Their results were so variable they conclude that the presence of the reaction has no meaning for the diagnosis of cancer of the stomach. For example, in 14 cases clinically cancer of the stomach, the contents reacted five times posi- tively and nine times negatively. In 25 examinations of material removed from the fasting stomach 13 were positive and 12 negative. They call particular attention to the re- gurgitation of pancreas secretion and the confusion of this with the peptid-splitting enzyme. They think that the test may be of use in the demonstration of the functioning power of the pancreas, particularly after the ingestion of oil.

PERSONAL OBSERVATIONS.

The first case in which I tried the test with stomach con- ents and glycyltryptophan reacted positively on two occasions. There was no free HCI in the stomach contents, no evidences f bile. The clinical diagnosis was acute endocarditis. At utopsy the stomach, œesophagus and intestines were abso- itely free from tumor. It was thought that in both the tests ne influence of pancreatic secretion could be excluded, so my iliva was placed with the glycyltryptophan in the hope that me light might be thrown on the positive tests in a normal omach. It was a great surprise to find that the saliva split te glycyltryptophan; the test was absolutely positive. No ich action of the saliva could be found in literature. Only ro enzymes have been described in saliva, ptyalin and maltase. ext my assistant's (C. M. J.) saliva was tested. It reacted gatively. With three separate lots of the test material, pro- red at different times, my saliva reacted positively. The action to litmus is definitely alkaline. Moreover, it was and that by dividing a specimen of my saliva, which had en well centrifugalized, into two parts, after heating one rt to 100° C. and not heating the other, the heated portion

did not spilt the glycyitryptophan, while the unheated portion gave a positive reaction. A control with distilled water per- formed at the same time was negative. How was the negative test with C. M. J.'s saliva to be accounted for? It was found that her saliva was acid to litmus.

It was thought that saliva from one who smokes might account for the positive test. This was shown to be false by the fact that the saliva of my assistant (R. T. G.) who never uses tobacco, gave also a definite positive result. The salivas of the six internes were then tested. Three are smokers, three never use tobacco. All reacted positively and all salivas were alkaline to litmus. Next the salivas of six nurses were tested. These were alkaline and these reacted positively.

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Twentieth Century History of Findlay and Hancock County, Ohio, and Representative Citizens, Part 108

Author: Jacob Anthony Kimmell Publication date: 1910 Publisher: Number of Pages: 1189

Author: Jacob Anthony Kimmell
Publication date: 1910
Publisher:
Number of Pages: 1189