USA > Ohio > Hancock County > Findlay > Twentieth Century History of Findlay and Hancock County, Ohio, and Representative Citizens > Part 130
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It has been shown by numerous investigators that the de- struction of erythrocytes during the paroxysms of this disease is not due to any inherent weakness of the cells but to a pecu- "liar action of the serum of these patients and that this serum is capable of dissolving not only the corpuscles of hemoglo- binuric patients, but also those of normal individuals. With the exception of the variation of resistance of hemoglobinuric corpuscles I know of no reason why they may not be regarded as normal corpuscles. That they show a variable and some- times greater than normal resistance may possibly be ex- plained in the following way.
It seems reasonably certain that the individual corpuscles of any person differ in their resistance. This idea is based on the fact that if one sets up a series of tubes containing falling strengths of salt solution (3 cc. in each tube) and introduces one drop (approximately 1/30 cc.) of corpuscles into each tube, it will be observed that hemolysis begins in a dilution of about 0.475% NaCl but is not complete until a dilution of about 0.30% is reached. That is, in the tube containing 0.475% NaCl only a few of the introduced corpuscles are dissolved. That these few are dissolved and the others are not seems to be best explained on the assumption that those corpuscles which were dissolved were less resistant to the action of hypo- - tonic salt solution than the remainder of the corpuscles. That the small amount of serum (or iso-tonic salt solution) intro- duced with the drop of corpuscles plays but little part in alter- ing the tonicity of the mixture is evident from the proportion used, 3 cc. 0.475% NaCI + 1/30 cc. 0.85% NaCl gives 3 1/30 cc. of a 0.479% solution. The slight increase of tonicity of the 0.475% solution due to the addition of the salt carried over with the one drop of corpuscles and to the solution of a part of the corpuscles, might protect the remainder of the cor- puscles, but this explanation cannot serve in the case of a 0.40% salt solution where only a portion of the added cor- puscles undergoes solution. In this case 1/30 cc. 0.85% NaCl added to 3 cc. of 0.40% NaCl brings the concentration of the resulting mixture only up to 0.405%, which is still relatively far below that in which hemolysis first appeared (0.475%). In the above examples the entire drop of corpuscles has been considered as the equivalent of 0.85% salt solution, whereas it probably has something less than this value in raising the tonicity of the mixture.
Assuming that individual corpuscles of a person vary in their resistance to hypotonic salt solution, it seems not unlikely that they differ in their resistance to other destructive agents, and that during an attack of paroxysmal hemoglobinuria those corpuscles possessing the least resistance would be the ones destroyed, leaving the more resistant ones. If this theory is correct, a resistance test taken shortly after an attack of hemoglobinuria would show increased resistance, while a test
taken at a considerable interval after an attack would stay normal relations. The correctness of this theory remains : be proven.
6. The Wassermann Reaction.
In the reported cases of paroxysmal hemoglobinuria, E. dence of syphilis, usually congenital, has been observed often as to give weight to the suggestion frequently made ta the latter perhaps stands in an etiological relationship. ! efforts to find an infectious agent in the blood of these paties: have, so far as I am aware, failed. The idea advanced ts: the disease is due to an auto-immunization resulting from resorption by the patient of his own blood has never be: proven and there is but scant evidence in its support. Oft various suggestions made that of congenital syphilis seem: have most evidence in its favor.
Dr. C. R. Austrian kindly did the Wassermann reactiond: the three cases here reported. All gave positive reaction: Tests were done on both the father and mother of Case I, a: the mother was found also to give a positive reaction. T. father of Case II gave a negative reaction and although t: mother was not tested, the history of four miscarriages in t: mother is suggestive.
Case III gave no history of syphilis, but had, as stated. i positive Wassermann reaction.
7. The effect of the administration of Ehrlich's "605. (a) on the Wassermann reaction; (b) on the clinical cours of the disease.
On November 15, 1911, Case I was given 0.3 gram "606" intravenously. She remained in the hospital until December 8, 1910. During most of this time she was kept in bed and not exposed to a sufficient degree of cold to induce an attack of hemoglobinuria. Nevertheless, on December 3, withor: premonitory symptoms, she voided a dark brown urine which gave a positive guiac test for blood, as is stated in the case history. The Wassermann reaction was still positive.
After the child's discharge from the hospital, she had mª further attack until about March, 1911. The freedom from attacks during the interval, the patient, since the onset of the disease, never having gone so long during cold weather with- out attacks, led the mother to believe that a cure had been effected. Accordingly, of her own initiative and without my knowledge, she frequently sent the child out to play during cold, damp weather, without hat or coat, in order to see if an attack would be induced. Notwithstanding this marked im- provement in the clinical condition, the patient's serum is still able, in vitro, to hemolyse her own and other corpusclas. when subjected to the cold-warm test, although not to the same degree, I think, as before the administration of "606;" and she still has a positive Wassermann reaction.
It seems advisable to repeat the administration of "606" in this case, and I hope to have the opportunity of trying it on the other two cases before the onset of cold weather.
SUMMARY.
The serum of patients suffering from paroxysmal hemo- globinuria contains a complex hemolysin, of amboceptor- complement nature, which is capable of bringing about the
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.vnjum ucmugiuviuuric patents, and of all other indi- iduals, as far as tested.
Patients suffering from paroxysmal hemoglobinuria are not onfined to one group, as determined by the iso-agglutination 'eaction, and their serum may contain normal iso-hemolysin n addition to the hemolysin characteristic of their disease.
The auto-amboceptor may be absorbed from patient's serum, eaving the iso-amboceptor and conversely the iso-amboceptor nay be absorbed, leaving the auto-amboceptor, thus enabling ach to be tested separately on any given set of corpuscles.
Only the amboceptor component of the hemolysin of pa- 'oxysmal hemoglobinuria is peculiar to the disease. The com- lement differs in no way, so far as tested, from that present n normal serum.
The amboceptor peculiar to paroxysmal hemoglobinuria lifers from other known hemolytic amboceptors in that it will inite with the red blood corpuscles only at a low temperature n the presence of complement, and furthermore, in that it is apable of bringing about the solution of the patient's own ells (auto-hemolytic action) and those of other members f the group to which the patient belongs, as well as the cells f members of other groups.
Hemolysis due to the auto-hemolysin of paroxysmal hemo- lobinuria unlike normal iso-hemolysis, may occur entirely ndependently of agglutination.
The red cells of the three cases here reported showed a ariable and usually increased resistance to hypotonic salt so- ition. Never a resistance less than that of normal corpuscles.
Case I received 0.3 gram Ehrlich's " 606" in November, 1910. Prior to that time the patient, never, since the onset of the disease, went more than two or three weeks, except during summer, without an attack of hemoglobinuria, and often had attacks at shorter intervals. Since receiving " 606," the Was- sermann reaction has remained positive, but the patient has, up to the present time, May, 1911, suffered but two attacks, although repeatedly exposed to cold.
REFERENCES.
1. Eason: Pathology of paroxysmal hemoglobinuria. Edin- burgh M. J., 1906, XIX, 43; J. Path. and Bacteriol., 1906-7 XI, 167.
2. Donath and Landsteiner: Ueber paroxysmale Hämoglobin- urie. München. med. Wchnschr., 1904, LI* 1590.
3. Hoover and Stone: Paroxysmal hemoglobinuria. Arch. Int. Med., 1908, III, 392.
4. Donath and Landsteiner: Ueber paroxysmale Hämoglobin- urie. Ztschr. f. klin. Med. Berl., 1906, LVIII, 173.
5. Meyer and Emmerich. Ueber paroxysmale Hämoglobinurie. Deutsches Arch. f. klin. Med., 1909, XCVI, 287.
6. Janský: Hämatologische Studien bei Psychotikern. Sborn. klin., v. Praze, 1906-7, VIII, 85. Ref. Jahresb. f. Neurol. u. Pschiat., 1907.
7. Moss: Studies on `Iso-agglutinins and Iso-hemolysins. Johns Hopkins Hosp. Bull., 1910, XXI, 63.
8. Decastello and Sturli: Ueber die Iso-agglutinine im Serum gesunder und kranker Menschen. München. med. Wchnschr., 1902, XLIX, 26, 1090.
'HE CALCIFICATION OF THE COSTAL CARTILAGES, THE CARDIO- THORACIC INDEX AND OTHER SIGNS OF PUL- MONARY TUBERCULOSIS.
By W. W. BOARDMAN, M. D., Assistant Physician, The Phipps Tuberculosis Dispensary, The Johns Hopkins Hospital,
AND
H. KENNON DUNHAM, M. D., Cincinnati.
The radiographic diagnosis of pulmonary tuberculosis is ed upon more or less characteristic alterations in the idows of the hilum and lung fields, and by some radio- uphers also upon alterations in the shadow of the heart, dia- ragm and thoracic walls. The alterations in the shadows the hilum and lung fields are dependent upon morbid nges present in the lungs and hilum, as a result of the il activity of the tubercle bacilli. The alterations in the dows of the heart, diaphragm and thoracic walls are due changes in these structures, and are generally considered ither secondary changes, or as predisposing factors to the monary disease. In a previous article' we have consider- it length the appearance and diagnostic value of the shad- Jee first paper in this number.
ows of the hilum and lung fields. At this time we wish to consider the nature and diagnostic value of the alterations in the shadows of the heart, diaphragm and thoracic walls.
On reviewing the literature one finds that there are many alterations in the shadows of these structures, to which more or less importance has been attached. The most frequently mentioned are the "small pendulous heart," and the calci- fication of the rib cartilages. Other alterations noted are narrow interspaces, contraction of one side of the thoracic wall, decrease in the angle made by the neck muscles and the clavicle, various abnormalities in the shape of the upper aperture of the chest cavity, alterations in the outline and height of the diaphragm, etc.
For the studies here reported, the radiographs taken in
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connection with the stereo-rontgenographic work done in the Research Laboratory of the Phipps Dispensary of the Johns Hopkins Hospital, were used. In taking these plates the relative position of X-ray tube, patient, and photographic plate was the same in every case. As previously reported, each pa- tient radiographed was subjected to careful clinicalexamination and the conclusions, independently arrived at by these different methods of examination, compared. In this series only those cases are considered in which there was complete agreement in the findings by both clinical and radiographic examination.
Turning now to a consideration of the heart in pulmonary tuberculosis, we wished to determine, if possible, the occur- rence of any characteristic alteration in the heart shadow which might be of diagnostic value. As previously stated, the so-called " small pendulous heart " is most frequently mentioned by radiographers as a sign of value. By some it is considered as merely indicating a marked predisposition to pulmonary tuberculosis; by others, however, it is consid- ered a change secondary to tuberculous infection of the lungs. In studying this question a series of ninety-eight cases was examined, in which the clinicians had given special attention to the condition of the heart. As a basis of comparison of individual cases or of groups of cases, it is evident that the actual area of the cardiac shadow would be valueless, as this must vary with the size, age, sex, etc., of the patient. It was, therefore, necessary to consider the size of the heart shadow in comparison with the size of some other shadow, the orig- inal of which varies in the same way as does the heart with the size, age, sex, etc., of the patient. To this end the greatest transverse diameter of the heart shadow was compared with the greatest transverse diameter of the chest shadow and the resulting ratio, which therefore expresses the size of the heart in relation to the size of the chest, was termed the Cardio -- Thoracic Index.
TABLE I
SHOWING THE INFLUENCE OF SEX UPON THE CARDIO-THORACIC INDEX.
Cardio-Thoracic Index
Sex
No. of Cases
Average
Max.
Min.
Male
.47
0.446
0.52
0.35
Female
33
0.430
0.50
0.37
Table I shows that in the cases examined the average car- dio-thoracic index, independent of age or physical condition, was slightly greater in the males than in the females.
TABLE II
SHOWING THE INFLUENCE OF AGE UPON THE CARDIO-THORACIC INDEX. Cardio-Thoracic Index
Age
No. of Cases
Average
Max.
Min.
5-15 years
11
0.446
0.50
0.41
30-40 years
15
0.443
0.52
0.39
50-60 years
2
0.42
0.45
0.40
Table II shows the cardio-thoracic index, independent c sex or physical condition, to be practically constant in te different age periods, with a slight tendency to decrease z later life.
TABLE III
SHOWING THE INFLUENCE OF PULMONARY TUBERCULOSIS UPON TEI CARDIO-THORACIC INDEX.
Cardio-Thoracic Index
Stage of
Disease
No. of Cases
Average
Max.
Min
Neg.
14
0.452
0.50
0.35
Doubt.
16
0.440
0.48
0.39
I Stage
6
0.435
0.46
0.41
II Stage A
14
0.437
0.50
0.37
II Stage B
13
0.449
0.48
0.40
III Stage
17
0.438
0.52
0.39
Table III is of special importance. As will be seen, tl- cases are divided into Non-Tuberculous, Doubtful and Tube- culous. The Tuberculous are sub-divided into four group depending on the stage of the disease,-first stage, early seort stage, late second stage and third stage. Here the cardi- thoracic index is practically constant in the different groups with, however, a slight tendency for the average to be small in the tuberculous than in the non-tuberculous and doubti. cases. However, one fact must be borne in mind, and this is. that the cardio-thoracic index varies between fairly wide limits in the individual cases, both normal and tuberculos as is shown by the maximum and minimum indices given i: the various tables.
TABLE IV
SHOWING THE INFLUENCE OF CARDIO-VASCULAR DISEASE UPON TEI CARDIO-THORACIC INDEX.
Cardio-Thoracic Index
Disease
No. of Cases
Average
Max.
Min.
Myocarditis
5
0.564
0.59
0.54
Mitral Insufficiency 7
0.502
0.57
0.43
Aneurism
6
0.543
0.58
0.5!
Table IV shows a high cardio-thoracic index in 18 case with definite cardiac lesions. These cases naturally are x .: included in the previous tables.
From our pathological experience we know that a sms. heart is a common finding in individuals dead of chronic was: ing disease, such as tuberculosis, carcinoma, etc. Here ch. small heart is merely an expression of the general wastin: and is not characteristic of any special disease process. This in one of our cases, dead of carcinoma of the oesophagus, t. radiograph taken just before the autopsy showed & cardis- thoracic index of 0.37. However, in our third stage cas- (Table III) which were all ambulatory, the average cardi- thoracic index was 0.438 with the maximum 0.52 and a m."- imum of 0.39. Evidently, then, the small heart is far fnv: constant even in third stage cases. Now as the value of th radiographic examination must depend upon one's ability " discover disease processes at a time when the clinician is . doubtful, or anxious for confirmation of his findings, it is rs- 1
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0-5 years
3
0.456
0.47
0.39
15-30 years
45
0.450
0.50
0.37
40-50 years
4
0.42
0.52
0.40
E the disease.
vic falt plages
From the preceding we may safely conclude that the average ardio-thoracic index is practically constant in the different ze periods, that it is slightly smaller in females than in lales, and that in the tuberculous, although on the average shows a very slight tendency to be somewhat smaller than the non-tuberculous, this average tendency is so slight and aries so widely in individual cases, that it cannot be consid- 'ed a sign of any value in the radiographic diagnosis of pul- .onary tuberculosis.
The pendulous character of the heart shadow, sometimes escribed as significant of pulmonary infection, is dependent r its appearance upon the small size of the heart and must herefore share with the cardio-thoracic index the same lack : value as a diagnostic sign.
Regarding the occurrence and diagnostic value of calcifi- tion of the rib cartilages, two theories have been advanced. he one that calcification, by interfering with the free move- ent of the thoracic walls, renders proper aeration of the oices impossible and therefore acts as a strong predisposing ctor to pulmonary tuberculosis, the other that the calcifi- tion is secondary to the pulmonary disease and depends pon altered metabolic processes. Pathological experience ems to favor the latter view. In tables V-VII, the results : the investigation of 153 cases are tabulated. Cases showing mplete calcification of the first cartilage, with or without lcification of the other cartilages, are designated positive. ases showing partial calcification of the first cartilage, with · without partial calcification of the other cartilages, are signated slight.
TABLE V
LOWING THE INFLUENCE OF SEX UPON THE CALCIFICATION OF THE RIB CARTILAGES.
Calcification
%
%
%
Sex
No. of Cases
+
Slight
-
Male
85
30
22
48
Female
68
17
17
66
Table V shows that calcification was more common in the le cases, independent of age and physical condition.
TABLE VI
OWING THE INFLUENCE OF AGE UPON CALCIFICATION OF THE RIB CARTILAGES.
Calcification
%
% Slight
%
Age
No. of Cases
+
0-5 years
6
0
0
100
5-15 years
20
0
0
100
15-30 years
78
19
17
64
30-40 years
29
33
33
34
40-50 years
9
40
47
13
50-60 years
9
68
32
0
60-70 years
2
50
50
0
TABLE VII
SHOWING THE INFLUENCE OF PULMONARY TUBERCULOSIS UPON CALCIFICATION OF THE RIB CARTILAGES.
Calcification
Stage of
%
%
Disease
No. of Cases
+
% Slight
-
Neg.
37
36
28
36
Doubt.
35
10
27
63
I Stage
9
0
10
90
II Stage A
37
19
22
59
II Stage B
16
22
7
71
III Stage
19
46
5
54
Table VII shows that calcification was present in a large percentage of the non-tuberculous cases. It also shows that calcification was absent in the first stage of the disease and in- creased in frequency with advance in the disease; however, only in the third stage cases did the percentage of positive cases exceed that found in the non-tuberculous cases. It might be mentioned that the patients comprising the third stage group were slightly older than those comprising the non- tuberculous group.
From these tables we may conclude that calcification of the rib cartilages, especially the first, is more common in males than in females, that it increases in frequency with advancing years and finally, that its incidence in pulmonary tuber- culosis is only accidental, or a late secondary change, and that its occurrence is of no diagnostic significance whatever in the individual case.
The size of the aortic shadow was studied in relation to the size of the heart but nothing of importance in regard to the diagnosis of pulmonary tuberculosis was determined.
TABLE VIII
SHOWING THE ABSENCE OF ANY RELATION BETWEEN THE WIDTH OF THE 2ND INTERSPACE AND PULMONARY TUBERCULOSIS.
Width of 2nd Interspace
Stage of
Disease
No. of Cases
Average
Max.
Min.
Neg.
36
3.0 cm.
4.4 cm.
1.5 cm.
Doubt.
35
2.7 cm.
4. cm.
1.8 cm.
I Stage
9
2.9 cm.
3.8 cm.
2.2 cm.
II Stage A .. 37
2.9 cm.
4.5 cm.
2. cm.
II Stage B .. 16
3.3 cm.
4. cm.
2.5 cm.
III Stage ... 20
2.8 cm.
4. cm.
1.8 cm.
1
Another sign to which attention is sometimes called is the presence of narrow interspaces in individuals suffering from pulmonary tuberculosis. The width of the 2nd inter- space in the left midclavicular line was measured and the results recorded in table VIII. From this it is seen that no apparent relation exists between the width of this interspace and the presence or absence of pulmonary infection. Whether we may take the width of the 2nd interspace as a basis for comparison is, however, open to argument.
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TABLE IX
SHOWING THE ABSENCE OF ANY RELATION BETWEEN THE ANGLE OF THE 6TH RIB AND PULMONARY TUBERCULOSIS.
Angle of 6th Rib
Stages of
Disease
No. of Cases
Average
Max.
Min.
Neg.
36
100°
104
85
Doubt.
35
97°
103
99
I Stage
9
101°
105
97
II Stage A
37
99°
104
97
II Stage B
16
100°
103
80
III Stage
22
97º
109
85
No very absolute measurements could be made of the angle of the ribs, but in table IX we have recorded the average angle made by the spine and the sixth rib on the left side. Apparently no relation exists between this angle and pul- monary tuberculosis.
The position in which our cases were radiographed made : impossible to study the shape of the upper aperture and &! terations in the angles of the neck muscles.
No definite conclusions were reached from our study of te height of the diaphragm, since the average height was abx, the same in the tuberculous and non-tuberculous cases a: the variation in individual cases was very great. There a: however, several interesting features about the diaphragz shadow, especially the occurrence of irregularities, which a: worthy of more extended consideration, especially in cia- nection with post mortem examinations.
In conclusion, we believe we are justified in saying ter: these signs small pendulous heart, calcified cartilages, zar- row interspaces, and excessive sloping of the ribs-are t .: only valueless, but are absolutely misleading, if considered t: positive signs in the radiographic diagnosis of pulmonar. tuberculosis.
EXPERIMENTAL STUDIES ON TUBERCULO-PROTEIN HYPERSENSI- TIVENESS AND THEIR POSSIBLE APPLICATIONS.'
By ALLEN K. KRAUSE, M. D., Saranac Lake, N. Y.
It gives me great pleasure to appear before the Laennec So- ciety as an envoy of the laboratory whose founder, Dr. Ed- ward L. Trudeau, has so often acknowledged his indebtedness to the men of the Johns Hopkins Medical School, who by their generous advice and assistance contributed in no small measure to the success of his work at Saranac Lake.
Ever since Koch's discovery of tuberculin it has been uni- versally taught and believed that the tuberculous animal dif- fers fundamentally from the non-tuberculous animal in its response to injections of derivatives of the tubercle bacillus. The tuberculous animal becomes acutely ill several hours after a subcutaneous injection of tuberculin : it suffers from weakness and prostration and a rise of temperature, and at the same time there are evidences, such as increased cough and expectoration in pulmonary disease, or swelling, pain and redness in joint or glandular involvement, that there is an exacerbation of the disease at the focus. Besides this, at the site of injection there is frequently an area of redness, swell- ing and pain. The tuberculous animal is therefore found to react to tuberculin in three different ways, to which the terms general, focal, and local or puncture reactions have been ap- plied. It was also discovered by Babes and Proca that if tubercles were induced in an animal by the intravenous in- jection of dead tubercle bacilli, such animals would likewise react to tuberculin with general, focal, and local signs and symptoms. The general reaction is in both instances consid- ered to be some kind of an intoxication, while the focal and local reactions are forms of inflammation.
Such animals were therefore said to be specifically sensitive 1 Address delivered before the Laennec Society, Johns Hopkins Hospital, April 24, 1911.
to tuberculin; and, as our knowledge of the products of the bacillus extended, it was found that practically every prepa". ation that contained bacillary protein could bring about - actions in animals that harbored tubercles set up by living or dead bacilli. Bacillary emulsion, T. O., T. R., water E- tract, bacillary filtrate, precipitated tuberculin and a bee; of other preparations were all like old tuberculin in that er- tremely small amounts of them rendered the animals il.
At the same time it was noted that healthy, non-tuberculoz: animals could sustain relatively enormous doses of tubercoli and tuberculo-derivatives without harm. Although STR workers, particularly Landmann, by methods of concentratix: succeeded in obtaining from tubercle bacilli products the: would poison the healthy animal in moderate amounts, st. the non-tuberculous always resisted much larger doses of az given preparation than the tuberculous. The healthy anin: was accordingly considered to be insensitive to tuberculin :. its related products. More than this, the claim was genere" made that the animal without specific tubercles could not - any way be made sensitive to tuberculo-protein. Only with: the last year no less an authority than Hamburger has oor .- to this conclusion, and within the past two or three month. Kraus, Loewenstein and Volk have supported his contenti: on experimental evidence, while Wassermann, Pappenbei: and von Pirquet have recently voiced the same assumption.
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