Twentieth Century History of Findlay and Hancock County, Ohio, and Representative Citizens, Part 99

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

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Because of this unsatisfactory characterization of the " eu-" and "pseudo-" globulin by the ammonium sulphate fraction- ing, it seemed of interest to differentiate in some modified way the relative globulin changes. We have accordingly determined as euglobulin that part of the globulins precipi- tated on saturating with sodium chloride.

Freund and Joachim state that saturation with sodium chloride precipitates all the euglobulin, but that this includes only a part of the product obtained at one-third saturation ammonium sulphate. We may consider that we have as sharp a differentiation as possible between the two globulins. The sodium chloride separation, probably, more truly represents the common conception of the euglobulin and pseudoglobulin, though the ammonium sulphate fractioning, heretofore, has usually been employed. With your permission, then, we shall term the globulin soluble in saturated sodium chloride solu- tion, pseudoglobulin; and the globulin insoluble in saturated sodium chloride solution, euglobulin.

The observations of Atkinson and Ledingham were the only determinations of a quantitative relation of the globulins and the antitoxic potency throughout the course of immuni- zation.

The subject is of extreme importance when the significance of the problem as to the chemical nature of the protective sub- stances is considered, because of the constant relation of these substances with the pseudoglobulin, i. e., the globulin soluble in saturated sodium chloride solution. In our work we fol- lowed quantitatively the protein changes in the plasma of

eleven horses. The characteristic globulin increase durita immunization was observed in all the horses. The increase was found in the pseudoglobulin.

We allowed about six weeks to elapse after the immunize :. was started, before taking a sample bleeding for analisi From this time on samples were taken every week during 2. treatment. This first estimation gave us in all the horses e: increase in the pseudoglobulin varying from 45 to 120 p: cent, and a loss of albumin from 25 to 85 per cent. Thos: can be seen that great protein changes had taken place after only six weeks immunization. That we missed the time . early changes we realized after it was too late.

The total proteins showed an increase of from 20 to 45 ; cent. This increase was at its highest after about two mor of treatment and was true in all the horses regardless of re: content. After two and a half to three months treatment the total proteins decreased and fluctuated somewhat throughe: their entire immunization.

The proteins, however, never dropped to the normal amez even though weekly full bleedings were taken; in some (2: extending over a period of many months. This, therefor shows us that the influence of repeated bleedings does Da essentially influence the protein changes induced by immuz- zation. These remarkable regenerative processes are worthy of note.

The highest antitoxic value obtained from these horses was 850 units; at this time the albumin was 75 per cent lower tix: this horse's normal amount, and the pseudoglobulin 90 px cent higher. An exceptionally refractory horse, with its high- est value 125 units, showed a decrease of 55 per cent albumi and an increase of 85 per cent of pseudoglobulin. Thus : can be seen that the decrease of albumin and the increase : pseudoglobulin take place in an immunized horse regards of the antitoxic content. We wish to state, however, that th maximum antitoxic potency does not necessarily mean tax other immune substances are present in greatest amount: :: that they are developed in corresponding degree with the tt: toxin. Immunization aimed to be of specific character rx lead to the production of other antibodies. Collins and others have shown that group and specific bacterial agglutinins (sz be developed by immunizations against yeasts, enzyme prex- rations and nucleins.

These experiments afford actual proof of the development of many widely different anti-substances during immunizati .: A similar stimulation, leading to the formation of numeros antibodies besides the precipitins and specific antitoxins, p. ably occurs on immunization with bacterial toxins. Such &#: stances may represent the increase in the pseudoglobulin w.t: which they are associated.

In the course of immunization, then, there is a marked - crease (even over 100 per cent) in the pseudoglobulin content of the blood plasma. This increase tends to precede the der: opment of maximum antitoxic potency and is quantitatively independent of the latter. With a diminution of the potens, the pseudoglobulin increase is reduced, with a tendency !: this change to precede the antitoxin variation.

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pw vivugin out the fact that

he proteins eliminated in the process of purification were nuch less than we had expected. For, as is well known, in he average normal horse serum the proteins are distributed is follows : albumin 40 per cent ; pseudoglobulin 42 per cent ; uglobulin 18 per cent. Thus it would appear that about 58 per cent of the protein was eliminated in the purifying proc- ss. We now know, however, that in the average immunized torse the proteins of the serum are distributed as follows: lbumin 12 per cent ; pseudoglobulin, containing the antitoxin, '8 per cent; euglobulin 10 per cent.

Thus only 15 to 25 per cent of the protein could be elimi- ated, depending on the fluctuation of albumin and euglobulin ontent of immunized horses.

Early in the spring of 1908, an observation of Stark's came o my notice.

Stark showed that when egg albumen was heated for one our at 56° C. a portion of it was converted into a body, which ppeared to be a globulin because of its precipitation and olution reactions. This fact aroused my curiosity as to what esult would be obtained if antitoxic serum or the antitoxic seudoglobulin solution was heated. With this in view, I arried out a large series of heating experiments with results nat were rather gratifying as a means of further purifying ne antitoxin. This gave at least 50 per cent purer antitoxin man had ever before been obtained. In order to make this lear, we will take the serum of an immunized horse. The roteins of this animal's serum, we will assume, are distributed 3 follows : albumin 12 per cent; pseudoglobulin, containing le antitoxin, 78 per cent; euglobulin 10 per cent. If we heat lis serum from twelve to fifteen hours at a temperature of 7º C. we will have a rearrangement of the precipitation haracterization of the proteins. If we now estimate the bumin, we will find, instead of 12 per cent, only about 9 per nt; the pseudoglobulin, containing the antitoxin, instead of

78 per cent, only about 50 per cent; and the euglobulin, in- stead of 10 per cent, will be increased to about 41 per cent. All of the antitoxin, with the exception of about 7 per cent which is lost by the heat employed, will be found in the re- maining pseudoglobulin.

From a scientific standpoint, this is extremely interesting, in that it opens a new field for further investigation, which may throw more light on the chemical characteristics and the nature of antitoxin.

Formerly, all the evidence was in favor of the pseudoglob- ulin nature of the antitoxins. The antitoxins had every known character of this protein. Mellanby, in 1908, stated that antitoxin is actually a part of the pseudoglobulin. Now, however, we know that we can heat the pseudoglobulin, con- taining the antitoxin, and actually change the precipitation limits of about one-third of it, i. e., from the pseudoglobulin to the euglobulin condition, without loss of antitoxin. From this we can conclude that the pseudoglobulin in an immunized horse is not necessarily antitoxin. The chemical combination of pseudoglobulin and antitoxin, if such is the case, is not a fast and stable one. If a union does exist it must be merely an unstable combination that can be disassociated by heat. As an analogy to this, Calmette's work on cobra venom and its antitoxin might be mentioned. Calmette, you will remember, showed that when neutral mixtures of venom and antitoxin were heated, the antitoxin lost its identity and the venom re- gained its toxicity. He stated that the mixture of venom and antitoxin form an unstable combination and that each of the two substances preserves its individuality in the mixture.

From the knowledge we now have in regard to antitoxin, it is justifiable to conclude that there is a union between the anti- toxin and pseudoglobulin, either a mere adsorption or an un- stable chemical combination, and that the antitoxin can be dis- associated from the pseudoglobulin without losing its identity.

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THE CLINICAL VALUE OF THE DETERMINATION OF THE CATALYTIC ACTIVITY OF THE BLOOD.

By M. C. WINTERNITZ, M. D., Associate in Pathology in the Johns Hopkins University.

(From the Pathological and Medical Clinical Laboratories of the Johns Hopkins Hospital.)

Catalase is an enzyme of universal occurrence characterized its power of decomposing hydrogen peroxide with the eration of water and molecular oxygen. Further than this y little is known concerning its function. Its intimate urrence with peroxidase, however, has led to the assumption t these two ferments are associated in the oxidative phe- nena of the body.

'he following report is based upon a series of experimental clinical investigations in which C. R. Meloy, G. R. Henry, McPhedran, J. P. Pratt, and W. B. Rogers were associated Į the author.

EXPERIMENTAL WORK.

The study of the catalytic activity of both normal and diseased human tissues and of the blood in experimentally produced diseases in animals is confined to a few isolated observations. For this reason we have first interested ourselves in this field and the results of these investigations seem so essential for the proper interpretation of the clinical applica- tion of the test that they will be briefly summarized.

The determination of the catalytic activity of human tissues led to the conclusion that all of the tissues of the body were reduced in their power to split hydrogen peroxide in chronic

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JOHNS HOPKINS HOSPITAL BULLETIN.

[No. 99

nephritis, and that this reduction varied directly with the severity of the condition. The lowest activity was obtained in uræmia. In no other disease, including eclampsia, was this · universal decrease in the activity of the enzyme found (1).

After it had been determined that the catalytic activity of a single rabbit's blood is constant from day to day over long periods of time the influence of the kidney and its function upon the catalase of the blood was studied with the following results: after ligation of the ureters, bilateral nephrectomy or uræmia, resulting from uranium nitrate nephritis there is a fall in the catalytic activity of the blood which becomes more and more evident as death is approached. The tissues of such animals at autopsy show a like reduction (2).

The effect of salts on the catalytic activity of the blood of living rabbits was then investigated for the following reasons, (1) because it is well known that the addition of various salts to a catalase extract in vitro influences the action of the enzyme, and (2) because the decreased activity of the catalase of the blood in nephritis might in some way be related to the salt retention in this disease. The results seem conclusive. Acids, alkalies and salts all reduced the activity when injected intravenously. In these experiments it is important to make observations during the injection and at short intervals after the injection has been discontinued, since there is a rapid com- pensation on the part of the organism with a return to normal of the catalytic activity of the blood. For example, 20 cc. of 5 per cent bicarbonate of soda solution causes a marked fall in the activity of the blood which is rapidly recovered from (1 to 5 minutes after the injection has been discontinued) and then a much more marked fall in the activity followed by a much longer time for compensation occurs after 6 cc. of the same salt. This continues on further injections until compensation is lost and death ensues. It is possible on this basis to construct a hypothetical explanation for the decline of the catalase in nephritis and uræmia (3).

Further studies on the relation of various organs to the catalytic activity of the blood were made with these results. After the extirpation of many organs there is a transient fall in the catalytic activity of the blood. The fall is permanent after extirpation of the thyroid, but is compensated if thyroid be fed (4).

During the above experiments it was found that following an acute peritonitis there may be a sharp rise in the catalytic activity of the blood. This rise usually occurs within 6 hours after the peritonitis is produced, and may continue for several days. The curve of activity is entirely independent of that of the body temperature or white blood count, but corresponds to an increased number of erythrocytes (5 and 6).

From the above experiments several factors influencing the catalytic activity of the blood can be deduced, namely the number of red blood cells, the function of the thyroid and kidney, and the action of salts, acids, and alkalies.

CLINICAL APPLICATION OF THE TEST (7).

Method .-. 025 cc. of blood is removed from the lobe of the ear in a pipette. This is diluted in 10 cc. of water; 5 cc. of

this dilution suffices for a test. It is placed in a 100 g. bottle in which there is also a vial with 5 cc. of neutri! hydrogen peroxide. The large bottle is connected with a gas burette and then uniformly agitated in order to bring fx blood and hydrogen peroxide in contact. The amount oxygen liberated is measured over a given period of time (! seconds). The procedure requires only a few minutes, the error is slight and no precautions beyond ordinary No. temperature and clean apparatus are necessary.

A series of 100 normal individuals of different age and ser were first studied; 80 per cent of these vary within phras logical limits, i. e., 5 cc. of a 1-400 dilution of their blood wil liberate from 13 to 17 cc. of oxygen from 5 cc. of neutralize: 3 per cent hydrogen peroxide in 15 seconds. In the other 20 per cent the amount of oxygen liberated varies within wil- limits, 12-22 cc. These variations are independent of the number of red blood cells and hemoglobin percentage. Tx explanation of this variation is at present not forthcoming It is, however, of the utmost importance to bear it in mind when interpreting the activity of the blood in disease' conditions.

On the other hand the catalytic activity of the blood of ! single normal individual is constant from day to day over lo; periods of time and in this way a base line can be obtained from which the significance of any change in the activity can be readily interpreted.

THE CATALYTIC ACTIVITY OF THE BLOOD IN DISEASE.

Typhoid Fever .- Fifteen cases were followed throughict their illness with the following results. During the early days of their illness there was no change in the catalytic activity of the blood, but towards the third week there was a gradual fall accompanying the anemia. During convalescence tx activity became normal together with the red blood count:

Diseases of the Respiratory Tract including lobar poea- monia, tuberculosis, and empyema (12 cases). There is 1 slight decline in the catalytic activity of the blood during the course of lobar pneumonia. The relation of this decline 1? the crisis and the salt metabolism of this disease has not yet been determined. In other diseases of the respiratory tract there is no noteworthy variation in the power of the blood to split hydrogen peroxide except where the disease is accom- panied by a severe anemia.

Acute Peritonitis .- In 4 out of 5 cases of acute peritonitis examined there was a characteristic rise in the catalytic ac- tivity of the blood. In one a reading had been made before the peritonitis occurred while in the other three the increased activity was confirmed by the decline to normal, following operation. In the one instance where no rise was obtained the reading was only made 20 hours after operation. In tm cases of suspected peritonitis with high fever and leucocytosis the catalytic activity of the blood was normal, and in thes cases the peritoneum was found clean at operation.

Diabetes Mellitus and Catarrhal Jaundice exert no influence upon the catalytic activity of the blood.

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our cases. In diseases

the thyroid gland both hypo- and hyperthyreosis, the cata- tic activity of a single patient's blood is not constant from ay to day. In hyperthyreosis the activity tends to increase hile in hypothyreosis the activity assumes a level lower tan normal. This may be of significance in interpreting the andition of the thyroid gland where the signs and symptoms 'e atypical.

Renal, Cardiac and Cardio-Renal Cases .- Twenty-four cases. Despite the presence of a marked nephritis provided there re no symptoms of renal insufficiency (uræmia) there will e no marked change in the catalytic activity of the blood.

2. Where there is a chronic nephritis accompanied by definite symptoms of renal insufficiency the catalytic activity f the blood will be irregular from day to day and will tend to ssume a level lower than normal.

3. In acute mercurial nephritis there is a fall in the cata- tic activity of the blood.

4. With uræmic coma there is a marked fall in the catalytic ctivity of the blood which is permanent if the coma ends tally but which recovers should the coma disappear.

5. With retention of urine due to obstruction of the lower rinary tract there is a marked decline in the catalytic activity f the blood. This decline may persist for some time but hould the obstruction be removed the catalase will again rise. Cardiac Cases .- Even in severe cardiac disease there is no ignificant change in the catalytic activity of the blood. In ome cases it is high. This may be normal for these individ- als as it will be remembered some normal individuals have a igh activity. In no single case was the activity sufficiently ecreased after many readings had been made to suggest renal isufficiency.

Cardio-renal Cases .- In three cases of cardio-renal disease here the clinical findings suggested a renal insufficiency the talytic activity of the blood was normal. At autopsy only a ronic passive congestion of the kidneys, the result of a compensated heart, was found.

Cerebral Hemorrhage .- In two cases of cerebral hemorrhage catalytic activity of the blood was high. Whether this is increase over normal is not known but it is clear that the ph reading would differentiate apoplectic coma from uræmic na.

THE CATALYTIC ACTIVITY OF THE BLOOD IN PREGNANCY. Neither pregnancy nor labor have any appreciable effect upon the catalytic activity of the blood. Ten cases.

The toxemias of pregnancies accompanied by coma and convulsions can be differentiated into two groups by the deter- mination of the catalytic activity of the blood.

1. Cases where there is no change in the catalytic activity. These will include eclampsia without renal involvement. Seven cases.

2. Cases with decreased catalytic activity ; three cases. These will include :

a. Chronic nephritis where the excessive work thrown on the kidneys by the foetus will bring about renal insufficiency.

b. Eclampsia, etc., with marked renal involvement. The significance of this differentiation in the prognosis for future pregnancies is clear. In the first group future pregnancy may be normal. In the second it will most likely be complicated by a toxemia, the result of renal insufficiency.

MALIGNANT DISEASE AND DISEASES OF THE HEMATOPOIETIC SYSTEM.

The results are still too meagre to be of value.

The interpretation of the clinical results is entirely depend- .

ent upon the experimental work, and in many places will probably be unsatisfactory. The number of cases is likewise too few to allow of anything but broad conclusions. It seems, however, that the work will be of value in the study of the oxidative phenomena of the blood, in further detail than is allowed from the enumeration of the red blood cells and the determination of their hemoglobin content.

REFERENCES.

1. M. C. Winternitz and C. R. Meloy: Jour. of Exp. Med., 1908, Vol. 10.

2. M. C. Winternitz: Jour. of Exp. Med., 1909, Vol. 11.

3. M. C. Winternitz and W. B. Rogers: Jour. of Exp. Med., 1910, Vol. 12.

4. M. C. Winternitz and J. P. Pratt: Jour. of Exp. Med., 1910, Vol. 12.

5. M. C. Winternitz and J. P. Pratt: Jour. of Exp. Med., 1910, Vol. 12.

6. M. C. Winternitz: Not yet published.

7. M. C. Winternitz, G. R. Henry and F. McPhedran: Arch. of Int. Med., not yet published.

8. M. C. Winternitz and F. C. Ainley: Am. J. Obst., 1910, Vol. LXII.

THE JOHNS HOPKINS HOSPITAL BULLETIN.

the Hospital Bulletin contains details of hospital and dispensary practice ; abstracts of papers read and other proceed- of the Medical Society of the Hospital, reports of lectures, and other matters of general interest in connection with work of the Hospital. It is issued monthly. Volume XXII is now in progress. The subscription price is $2.00 year.

foreign postage, 50 cents.) Price of cloth-bound volumes, $2.50 each.

complete index to Vol. I-XVI of the Bulletin has been issued. Price 50 cents, bound in cloth.

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DISTOMA PULMONALE IN WISCONSIN. By HENRY HANSON, M. D.

(From the Pathological Laboratory of the Milwaukee County Hospital.)

The finding of lung flukes (Distoma Pulmonale, or Para- gonimus Westermanii) is of such rare occurrence and great importance that it seems to me the case in question should be reported. Up to the present time there appear to be only three specific cases in which this parasite has been found in domestic animals in this country. One case has been reported for man, an imported case seen in Portland, Oregon. In the March (1908) number of the Denver Medical Times and Utah Medical Journal, E. W. Lazell reported a case of " Cysticercus cellulosa and Distomum pulmonalis in Brain, with Exhibition of Specimens." This paper deals so briefly with the case, and the description of the parasites is so in- complete that one can hardly feel satisfied to class them with the group of parasites known as the Paragonimus Wester- manii, and yet the paragonimus is the only fluke which is known to get into the brain.

Up to the present time the disease has been unknown in the State of Wisconsin. The only two other States previously known to have these parasites are Michigan (Ann Arbor) and Ohio (Columbus and Cincinnati). In Ann Arbor the fluke was found in the lung of a cat and was sent to Dr. H. B. Ward of the University of Nebraska, who identified the para- site and wrote the first report of the presence of this lung fluke in the United States. 'The parasites were later sent to Stiles of the Department of Zoology, Public Health and Marine Hospital Service, U. S., who confirmed Ward's diagnosis and pronounced them identical with the Paragonimus Wester- manii. In the second case the lung fluke was found in a dog in Columbus, Ohio, by Kellicott, who also referred this speci- men to Ward. In the third instance the lung fluke was found in hogs slaughtered at the abattoirs in Cincinnati, Ohio. These cases cited, together with the finding of the dis- ease in a cat and also two of her kittens (kittens born in the village of Wauwatosa, Wisconsin), add further proof of the endemic theory of the infection. This means that we have a new parasite to deal with. The reason this parasite has not been discovered before is most likely due to the fact that it has not been looked for extensively. There is no doubt in my mind that there are cases of this disease in human beings which have been overlooked simply because an infection of this kind has not been known to exist.

This parasite, as is well known to those who have had occa- sion to look up its history, is a particularly unwelcome one. It is especially important that medical men should be on the lookout for possible cases of this infection, parasitic hæmo- ptysis, which are probably called incipient tuberculosis on account of the obscurity of the physical lung findings. The scattered distribution of the cases referred to would also in- dicate that the parasite is quite firmly established and that it is more common than is generally known. The first find- ing of the parasite dates back to 1893, the first report by

Ward to 1894. Other reports have appeared at interrak, i which references will be given at the end of this paper.

The present paper is especially concerned with the finde of lung flukes in two autopsied cats in Wauwatosa, Wisewas

I am indebted to Mr. Edwin Hirsch, of Wauwatosa, W. for the opportunity of making this study, since it is throz his interest in the case that the parasite was discovered. 3. first noticed that one of the cats owned by the family va coughing and in order to determine the cause of the orz he killed and dissected the cat. Later when a second er began to show symptoms it was brought up to the latorca of the Milwaukee County Hospital where the cat was chl". formed and autopsied.

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Twentieth Century History of Findlay and Hancock County, Ohio, and Representative Citizens, Part 99

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

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