Twentieth Century History of Findlay and Hancock County, Ohio, and Representative Citizens, Part 121

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

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2. The tearing of an aortic valve producing an aortic in- fficiency causes the heart to perform an extraordinary amount work, part of which is devoted to the maintenance of nearly normal rate of flow on the vessels, while the remainder is pended upon the forcing out of a quantity of blood which ch time regurgitates through the torn valve.

3. This extensive and violent excursion of the ventricle rether with the effect of the regurgitation produces a very at pulse pressure with low diastolic pressure and the low ision of the arterial wall allows a great systolic fling which upies a relatively large part of the height of the pulse curve 1 thus causes the dicrotic notch to occupy a low position ich is another characteristic of the collapsing pulse.

The following protocols will show the character of the re- ts obtained by measurements and may be compared with corresponding curves in so far as they are reproduced. It st be emphasized that the figures have practically no abso- : value. An approximate idea of the output of the aorta rarying pressures is obtained but there are many sources of r. So, too, the results obtained by calculation from the bration of the excursions of the plethysmograph seem to pf very doubtful absolute value. It is possible to change [excursion so greatly by the slightest movement of the pysmograph or by the slightest inaccuracy of the adapta- of the rubber to the auriculo-ventricular sinus that any trary uniform calibration would seem to me as valuable je particular factor which is found by calibrating the tam- Although this is so, when the plethysmograph is once

the valvular lesion is produced are perfectly trustworthy, and although as absolute figures they may mean nothing, they give a perfectly good indication of the changes which ensue upon the tearing of the valve. In considering these figures allowance should have been made also for the fact that under such abnor- mal conditions the size of the two ventricles does not vary equally, so that while in the normal heart an increased flow of blood into the heart might mean an equal enlargement of the ventricles, such an effect might be modified in the heart with torn aortic valve, by the fact that an increased regurgitation would cause a disproportionate enlargement of the left ven- tricle. This would accentuate the modifications of the " resi- dual blood " which are given in the protocols in which no such allowance is made.

Further, it will be seen that the malnutrition of the heart muscle which follows the severer insufficiencies, may be enough to cause the rapid dilatation of the heart and the death of the animal. In such cases the results are quite different from those in which the heart maintains its activities and one of them is given as an illustration (Table IV). Another (Table III) shows a milder degree of the same thing as the curve progresses and shows also the compensation that may take place when the lesion is merely a hole in the valve by the filling of the hole with clot.

The principles outlined in the above discussion are, however, shown to be true in all the curves if allowances be made for the disturbing effects of malnutrition of the heart muscle.

TABLE I .- February 23, 1911. Normal dog. Wt. 10 kg.

Peripheral pressures

70 cm. 18.75

150 cm.

70 cm. 15.

Pleth. swing

24.

27.5

81.

Calibration.

.158+2

079=1

mm.

Estimate

1.48

1.896

2.172

2.449

1.185

Pulse rate.

180

225

240

220

No. of beats to give 10 cc. ..

10.8

5.87

5.5

6.5

10.5

One beat gives

.97

1.708

1.818

1.538

.952

. Residual blood.

0.51

.198

.354

.911

.233

Aortic output per minute ..

174.6

382.5

436.8

809.12

209.4

Heart work per min. (Pleth. x rate) ..

266.4

526.6

521.2

587.7

260.7

The table shows the changes in the work done by a normal heart with changes in outflow and inflow pressure.

TABLE JV .- January 8. Dog, weight 8.7 kg. Inflow and outflow at 62 cm. Extreme injury, death from dilation.

Normal.

Aortic insufficiency.

Pleth. swing

.158 =1 mm. divide by 2 == . 079

Calibration

.948

1.185

Estimate

170

120

Pulse rate

22.7

No. of beats to give 10 cc

.688

.440

One beat gives

.360

.745

Residual blood.

100.

89.4

Aortic output per minute.

Heart's work per min. (pleth. x rate)

161.16

142.2

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TABLE II .- December 23. Outflow 57 cm., inflow 75 cm.

Plethysmographic swing

12.

26.5

Calibration.

1 mm =0.1584 cc.

Estimate .

.9504

2.0988

2.455

2.772

2.534

Pulse rate ..

240.

120

90 7

110

120

No. of beats to give 10 cc ... One beat gives .

.427 523

1.155

1.027

1.268

1.432

1.262

1.284

Aortic output per minute (rate x beat value) Heart work done per minute (pleth. x rate)

102.48 228.

113.16 251.8

128.52 220.9

135.36 249.4

127.30 263.3

248.2

278.7

The table shows the effect of the production of aortic insufficiency just before B.

TABLE III .- January 19, 1911. Dog, weight 10.8 kg. Inflow 80 cm., outflow 60 cm.

Valve cut.

Valve cut again.

Plethysmographic swing.

29.5

Estimate .

1.343

1 mm. =. 158 cc. 1.896

2.291

1.975

1.896

1.975

2.133

2.33

2.686

3.008

9.607

Pulse rate.

190

160 16

175 12.8

175

170

165

170

160

190

No. of beats to give 10 cc.

One beat gives.

.625 1.271

78 1.511

578

.464

.464 1.432

1.25 725

1.219 .914

1.065

1.467

1.565

1.277

Aortic output per minute ..

100 303

133.50 400.9

101.15 345.6

81.2 831.8

81.2 331.8

212.5 335.7

201.18 351.9

208.72 384.4

207.2 456.6

242.4 492.8

495.8

In this experiment the inflow pressure was higher than the outflow and was not changed. Insufficiency was slight in the first curve, the parts which are numbered. In the second curve the heart had gained in vigor and a further tear of the valve was produced between B and D. Apparently for regurgitation was nowhere very great.

TABLE V .- January 11. Dog, weight 11.8 kg. Pressure 60 cm.

Normal.

Aortic insufficiency.

Pleth. swing.

Calibration

1 mm. = . 079

Estimate

1.185

1.975

Pulse rate

130

No. of beats to give 10 cc.

19.8

19.7

One beat gives

0.505

0.507

Residual blood

.680

1.468

Heart's work per min. (pleth. x rate) ....

189.6

256.75

TABLE VI .- March 14, 1911. Weight 6 kg.

Normal.

Aortic Insufficiency.

Periph. pressure

120

150

Pleth. swing.

14.8

27.5

16.24

13.26

29.6

37.7

Estimate

1.1297

1.4256

2.178

1.286

1.05

2.344

2.9858

Pulse rate

150

155

160

180

160

No. of beats to give 10 cc

7.6

5.5

Residual blood

.1297

.1096

-7495

.377

.325

.526

1.1678

Cardiac output per min. (pleth. x rate) .

169.4

220.9

348.4

231.48

$75

477.7

TABLE VII. April 24. Dog, wt. 7.6 kg. Small aperture pierced in valre

Valve cut.

Pressures.

100

120

100

Pleth. swing.

20.1

28.16

Calibration

5 cc. = 35 mm.

Estimate ..

28.7

38.5

40.2

EzSion

Pulse rate.

200

195

190

Number of beats to give 10 cc.

5.8

5.7

One beat gives.

1.42

1.72

1.75

1.54

Residual blood.

1.45

2.13

2.97

Aortic output per minute.

284

335.4

339.5

Heart output per minute (pleth. x rate)

574

750.7

763.8

TABLE VIII. April 24, 1911. Dog, weight 9.4 kg.

Aortic valve cut.

Pressures

100

120

120 20.9 (17.46)

18.2

Pleth. swing.

10.3

13.66

Calibration

35 mm. =

5 cc.

9.6

Estimate.

1.47

1.95

840

Pulse rate

250

8.57

Number of beats per 10 cc.

8.26

7.5

1.316

1.4285

0.909

0.625

1.818

Aortic output per min. 150

203

228

163

100

290.8

Aortic output per minute.

302.50

332.50

849.50

Heart output per minute. (pleth. x rate)

367

487.5

745

plet

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1.430

Residual blood

0.26

0.62

1.37 (1.28)

One beat gives.

1.21

1.33

7.3 (7.8)

One beat gives

=. 01584

All results divided

by 2.

Calibration

1 mm.

.4 .943 76.0 255.1

17.3

21.5

8.2

7.9 1.265

8.2

8.6 1.515

1.219

1.33

Residual blood ..

1.397

1.432

6.65 1.504

7.46

7.4

.943

1.428

1.840

1.351

1.25

15.85 .63

Residual blood

128.34

137.50

69.3

33 ventricle. 2.613 95

Each result is divided by 2 for left

23.4

10.6

Calibration ..

All results divi ded by 2.

Heart output (pleth. x rate)

252.70

89.5

195

6.5

100

2.98 (2.49)

1.61 (1.21)

100

120

150

185

-March 30. Dog weight 9 kg. The curve shows the changes in the position of the dicrotic notch, upon the Hurthle tracing and the of the heart with increasing inflow of blood. The excursion of the heart is also seen to be greater at the higher pressure.

May 7th. Dog weight 7.2 kg. Plethysmographic and other tracings from dog with intact aorta, and after the tearing of the aortic valve. ographic excursion is increased and the increased pulse pressure is characteristically shown in the curve from the Hurthle manometer.

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100cm Valoceut

Vali

$20

CURVE III .- March 30. Dog weight 9 kg. Character- istic change in all curves on tearing of the aortic valve.

CURVE IV .- March frutti

100

Valor Cal 120

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CURVE V .- April 24. Dog weight 9.4 kg. Curves at pressures of 100 and 120 cm. of blood, before and after que

120 cm flows 70

d inflow pressures of 80, 120, 70 and 40 cm., before and after cutting of aortic valve.

CURVE VI .- April 17. Plethysmographic and Hürthle curves in aortic insufficiency in the curve which has become hyperdicrotic. . It was in this curve that auscultation showed the part of the curve occupied by the murmur.

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ampana paula

150.

CURVE VII .- April 6. Dog weight 6.3 kg. Curve shows the accentuation and elevation on the slope, of the dicrotic notch on compression of the aorta.

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CupyE VIII .- February 7. The curve shows the appearance of a collapsing pulse pro- duced by allowing regurgitation from the artificial aorta by tapping it with a "T" tube as described in the text. It is observed that the output is decreased during this regurgita- tion. Other particulars are mentioned in the text.

CURVE IX .- Shows absence of alteration of character of pulse on introducing artificial arrange- ment of circulation. It also shows that the fling of the mercury manometer has no influence upon the Hurthle record.

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A FURTHER NOTE ON THE CLINICAL USE OF SCARLET RED AND ITS COMPONENT AMIDOAZOTOLUOL, IN STIMULATING THE EPITHELIATION OF GRANULATING SURFACES .*

By JOHN STAIGE DAVIS, M. D.,

Instructor in Surgery, The Johns Hopkins University.

INTRODUCTION .- In a paper published in THE JOHNS HOP- KINS HOSPITAL BULLETIN, in June, 1909, I reported the re- sults of my observations during the treatment of 60 cases with scarlet red in various combinations.

Since that time I have been impressed by the great in- terest in the clinical use of this dyestuff as shown by the large number of papers on this subject which have appeared in the foreign journals, and also by a number of personal communi- cations reporting favorable results.

The object of this article is to bring the subject up to date as far as possible, and in addition to make a few observations on the clinical use of amidoazotoluol, which was first tried by Haywardt and is a component of the scarlet red originally used by Fischer.

I was very skeptical when I began to experiment with scar- let red. It was difficult to believe that by the application of a commercial dyestuff such rapid epithelial stimulation could take place in sluggish wounds, some of which had been un- healed for many years.

It has been suggested that possibly the wounds healed with scarlet red were in a period of development in which, after being inactive for a longer or shorter time, the rapid epithelial growth would have taken place just as well under any other method of dressing. This may be true in a few instances, but I hardly believe it could have been the case in the large num- ber of cases reported, where the process of healing had been at a standstill until this dressing was begun.

Carrel, in his very interesting article on "The Treatment of Wounds " (J. Am. M. Ass., 1910, p. 2148), says that when at the end of the period of " granulous retraction " of a large wound the edges of the old epidermis are still at a distance of 20-25 mm., the new epidermis cannot spread on the granulations and the cicatrization of the wound comes to a standstill.

Now, in practically all of the wounds which I have treated with scarlet red and amidoazotoluol, the period of " granulous retraction " had long since ceased, the period of epidermiza- tion had also come to a standstill, and the areas were, for the most part, very large. In spite of these facts, in the large majority of cases there was marked epithelial stimulation from the hitherto sluggish edges following the application of the dyestuff, and subsequent rapid healing.

Scarlet red was used exclusively as a dye until 1900, when Michaelis found that this coloring matter was very suitable

* Read before the Johns Hopkins Hospital Medical Society, April 3,1911.

t All references are arranged alphabetically under " Bibliog- raphy " at end of this article, so that the papers referred to under authors' names are readily to be found.

for staining fat in the cellular tissue for microscopic erami- nation.

EXPERIMENTAL USE .- B. Fischer in 1906, in a paper oz the " Experimental Generation of Atypical Epithelial Pr- liferation," produced by the subcutaneous injection of a satt- rated solution of scarlet red, in olive oil, in a rabbit's ear, first called attention to the remarkable stimulating properties of this dyestuff, and suggested that therapeutic advantage might be taken of it. Since his publication a number of it- vestigators (Ritter, Jores, Geipel, Snow, Stahr, Wyss, Helt- holz, McConnell, Seckel, Hertzler, Schreiber and Wenglez. Werner, Enroth, Stoeber, Grimani, Dixon, Cords, Wesley, Meyer, Borst), following Fischer's lead, have repeated his experiments and extended them. As far as I can ascertain. all, with the exception of Snow, have agreed that a new growth of epithelium is produced.

Several kinds of animals have been used, rabbits, Belgian hares, guinea pigs, white rats, mice, monkeys, dogs, cats, ete. These proliferations have also been produced in man. Wes- ley experimented on himself, and Stoeber upon a man &? years old, whose leg was to be amputated for ununited frac- ture. The results were not as marked as in the rabbit's ear, on account of anatomical conditions, but were definitely posi- tive. Stoeber injected scarlet red, amidoazotoluol and alphs naphthylamin, but did not succeed in producing epithelial proliferation by alpha naphthylamin. It is beyond the scope of this paper to discuss the theories as to the cause and sourtr of these atypical epithelial proliferations.

An interesting point is made by Claribel Cone, who says that in the epidermis of man the fat which is shown by th: scarlet red stain is especially noted in the basal (germinal) layer at the point of contact of the cell body and nucleus; ic other words that the scarlet red attacks the living cell just et the point where physiological cell changes are most active. She suggests that this may cause a chemical or physical stima- lation of the cell, and thus account for the active proliferation. following its clinical use.

CHEMISTRY .- In looking over the literature on the clinical and experimental use of scarlet red I find that there are ser- eral chemically different dyestuffs which are marketed under the name scarlet red. I will consider the chemical formula of four of these.

(1) The dye used in my series in 1909 was the sodium salt of diazo-azo-benzene-disulphonic acid Beta naphthol.

Commercial Names .- Biebrich Scarlet; Ponceau 3 RB. Pouceau B; Fast Pouceau B; New Red L; Imperial Scarlet (Schultz & Julius, 1904, p. 110, No. 163).

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N=N-C.H,-N=N-C1.H.OH (Beta)

Method of Preparation .- Amido-azo-benzene-disulphonic cid and Beta naphthol. It is a red powder, soluble in water nd slightly soluble in alcohol. Insoluble in ether.

(2) Benzene-azo-benzene-azo Beta naphthol.

Commercial Names .- Soudan III; Cerasine Red (Schultz Julius, 1904, p. 106, No. 143).

C.H,-N=N-C.H .- N=N-C1,H.OH (Beta)

Method of Preparation .- Amido-azo-benzene and Beta aphthol. It is a brown powder, soluble in alcohol and fats. nsoluble in water.

(3) Toluene-azotoluene-azo Beta naphthol. This is the arlet red originally used by Fischer and Schmieden.

Commercial Names .- Oil Scarlet; Red B Oil Soluble xtra-concentrated; Pouceau 3 B (Schultz & Julius, 1904, 108, No. 150).

CH, 1 1 CH, C. H. - N=N-C.H, -N=N-C1,H.OH.

Method of Preparation .- Amido-azo-ortho-toluene and Beta iphthol. It is a dark reddish-brown powder which cakes about 175° C. and melts at 184° to 186° C. Insoluble in ater, soluble in alcohol and chloroform, fats, fatty oils, and so warmed vaseline and paraffine.

(4) Sodium salt of xylene-azo Beta naphthol monosul- onic acid.

Commercial Names .- Scarlet G. R; Scarlet R; Brilliant range R; Orange L (Schultz & Julius, 1904, p. 86, No. 54).

(CH3), C.H3 -N=N-C1,H; - So3 Na. 1 OH.

Method of Preparation .- Xylidene and Beta naphthol nosulphonic acid. It is a cinnibar red powder, soluble in ter.

[ have used clinically the first three of these preparations h success, and also xylidene scarlet (Schultz & Julius, 1904, 96, No. 55) which is closely related to the fourth prepara- 1. I find the best and most consistent results with scarlet have followed the use of the dyestuff originally employed Fischer and Schmieden. Hayward says that in the few 's reported where no result was attained this special dye

probably not used. He has also experimented with dan I, Soudan IV and Soudan G, with more or less suc- .

le says that Fischer and Schmieden thought that Alpha hthylamin caused the epithelial stimulation in the most reaching way. Hayward used this substance clinically, found that it caused only marked irritation. This was my experience when I used Beta naphthol ointment of a igth corresponding to that actually entering into the ation of 8 per cent scarlet red, i. e., 2.4 per cent. xperimenting further Hayward employed amidoazotoluol,

stance caused a more marked stimulating effect on the growth of epithelium than did the scarlet red.

CH, 1 CH, C.H. - N=C6H3 -NH2.

Method of Preparation .- Slowly add a saturated solution of sodium nitrate (1 mol.) to a mixture of orthotoluidine (4 mols.) and concentrated hyrochloric acid (2 mols.) and keep at a temperature of 30° to 40°. It is a reddish-brown granu- lar powder. Melting point about 100° C. Nearly insoluble in water, but easily soluble in alcohol and ether.

CLINICAL USE .- A few words concerning the papers which have appeared on the clinical use of these substances may be of interest.

Schmieden was the first to follow Fischer's suggestion that scarlet red be used therapeutically, and in February, 1908, published a paper on his clinical results, which were very favorable. He reported rapid healing of sluggish ulcers of various kinds and in different situations. He used 8 per cent ointment and alternated the dressing every 24 hours with some bland ointment on account of the irritating properties of the scarlet red. He also used with success adhesive plaster impregnated with 10 per cent scarlet red for strapping leg ulcers.

He insisted that the granulations must be perfectly clean and flat, and said that it was useless to apply the ointment to an unclean ulcer. He noted that there was little chance of cicatricial contraction under this healing, and showed by microscopic examination that the newly formed skin was the same as the normal skin.

In May, 1908, Kaehler substantiated Schmieden's work and modified his technic. He found good results could also be obtained when scarlet red was used on unhealthy granulating wounds. He healed a varicose ulcer with scarlet red, and then was able to thoroughly clean up this new skin and operate through it for excision of varicose veins, thus showing the stability and quality of the newly formed epithelium. He completely healed defects of similar size, one with grafts and one with scarlet red, in exactly the same time.

Krajca, in September, 1908, described further good results. He was the first to use scarlet red in conjunction with partial Thiersch grafts, and found that the edges of the grafts were stimulated as well as the wound edges. He mentions a num- ber of interesting cases. Some of the ulcers, although of large size, healed in a very short time under this treatment. He found the cutaneous irritation due to the scarlet red to be the exception rather than the rule.

Enderlen, in September, 1908, published very satisfactory results, as did Cernezzi and Hubner, in February, 1909. Wol- from and Cords in the same month wrote on the successful treatment of ulcers and wounds of the cornea by 5 per cent scarlet red salve. Excellent results were obtained in a case of keratitis neuroparalytica. An old corneal fistula was closed by this means. A more rapid regeneration of the tissues was

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noted and sometimes an excess of tissue formation, but this soon flattened.

Sprecher, in March, 1909, reported good results in the treatment of ulcerated lupus vulgaris, ulcers of prepuce, vulva, labia and cervix, varicose leg ulcers, syphilitic ulcers, ulcers of the breast, etc. He did not observe any local irritation or toxic effect in his series.

Rebaudi, in April, 1909, described the use of scarlet red in gynecological conditions and obtained excellent results in the treatment of erosions, tears, etc.

Pleth and Pleth, in May, 1909, detailed the successful use of scarlet red on ulcers of various kinds. Heermann, in June, 1909, reported the success of his treatment with scarlet red of tympanic membrane perforations. He said the duration of the perforation seemingly had no effect on the rapidity of the healing. Suppuration did not appear during this treatment.

Ducros, in July, 1909, reported favorable results on granu- lating wounds, as did Morawetz, in September of the same year. Hayward wrote in the same month concerning the use of an 8 per cent ointment of amidoazotoluol, which is, as I have mentioned before, a component of the scarlet red used by Fischer. His results on a number of granulating wounds were even more favorable than with the scarlet red, and he felt convinced that this was the stimulating portion of the dyestuff.

It does not seem possible that amidoazotoluol is alone re- sponsible for the epithelial stimulation, as a number of ob- servers, myself included, have noted very favorable results produced by the clinical used of dyestuffs which do not con- tain amidoazotoluol.

Grossmann, in December, 1909, reported favorable results with scarlet red salve, amidoazotoluol ointment and amido- azotoluol gauze, in the treatment of wounds following opera- tions on the nasal passages, and in perforated tympanic mem- branes. Halle, and also Levy, said that they had been successful in similar cases with the scarlet red.

Hartman and Beyer stated at the same meeting that they had used scarlet red in a small number of cases without any particular success. Sonntag and Brühl said they had failed to get rapid results in similar cases.

Auerbach, in 1909, published a number of successful re- sults in the treatment of ulcers occurring in skin and ven- ereal diseases, varicose ulcers, etc. He was unsuccessful in only one case, a multiple leg ulcer which was complicated by extensive varices. The other leg of this patient had been previously amputated for leg ulcer. He used the treatment with success on wounds which were discharging copious puru- lent secretions. He had irritation with 8 per cent scarlet red, so tried 4 per cent, which he found could be used continu- ously. Dauthuile also reported favorable results.

The papers which have appeared in 1910 are as follows: Rammstedt and Jacobsthal mentioned excellent results in the healing of ulcers due to X-ray burns. Dreifuss reported favorable results in the treatment of granulating wounds.

Cords said it was of use in the eye only in clean ulcers of the cornea, especially if there was deep loss of substance.

Pein detailed a number of cases successfully treated with scarlet red, and gave, a very interesting table of the measure ments, taken from 25 leg ulcers, from the beginning of the treatment to the time of healing.

Strauss published his very favorable results in the trad- ment of X-ray burns and other ulcers of various kinds. H: says he does not value the use of scarlet red for the rapidit? of epitheliation alone, which, in some cases, does away mit the necessity of Thiersch grafting, but for the solid epithelium which is of great value, especially in the region of the jointe By this healing contractions and scar tensions can be avoided Stein reported good results in otiatrics. Scharezki was very successful in the treatment of skin defects of various kinds.

Katz reported favorable results with 8 per cent scarlet rei and amidoazotoluol. Simin had excellent results following the use of scarlet red.

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Twentieth Century History of Findlay and Hancock County, Ohio, and Representative Citizens, Part 121

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

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