Therapeutics

Front matter

iiiiiM; I iiiM I 111 miriii I mi i liUiiiiiiiuiiiiiiiiiiii ! u I !

T

17 PHYS -Î^INQ

Preface

In pursuance with the announced purpose of this system to provide a compact and thoroughly modern digest of ophthalmic practice, Dr. Darier has endeavored to set forth concisely the established up-to-date methods of ophthalmic therapeutics and the results of the latest investigations in this connection. To secure the desired homogeneity in the series there has been exercised free editorial control of the manuscript. The comprehensive index includes complete cross-references to the various drugs and therapeutic methods discussed as well as to the relative diseased conditions.

In the present issue there has been added a chapter on

the new and important subject of Chemotherapy, including

an extensive discussion of Salvarsan.

Walter L. Pyle. 193 1 Chestnut Street, Philadelphia.

Table Of Contents

FIRST PART.

GENERAL THERAPEUTICS.

Chapter I. Pagb

Clinical diagnosis; Anatomico-pathologic, microscopic, and bactériologie diagnosis; Experimental diagnosis; Serum-diagnosis; Therapeutic diagnosis; The method of Arning and Klein for demonstrating the spirochagta of Schaudinn; Living spirochasta; Experimental diagnosis; Sero-diagnosis; Injections of tuberculin; Von Pirquet's cuti-reaction; Lautier's modification of cuti-reaction; Epidermal method of cutaneous diagnosis; Ophthalmo-reaction; Technic of ophthalmo-reaction; Sero-diagnosis of syphilis; Therapeutic diagnosis; Mercurial treatment; Sodivim salicylate; Guaiacol.

CHAPTER n.

Constitutional Treatment 14

Importance of constitutional treatment in ocular affections; Arteriosclerosis; lodids; Nitrites; Milk diet; Anemia; Leukocythemia; Diabetes; Albuminuria; Syphilitic affections; Lymphatism and scrofula; Preparations of iodin; Mercurials; Mercurial inunctions in traumatic infections of eye; Sympathetic ophthalmitis; Silver antiseptics.

Chapter III

Inunctions; Hypodermic medication; Stomatitis; Symptoms of intoxication; Soluble salts of mercury for injection; Oil of biniodid; Intravenous injections; Technic of intravenous injections; Phlebitis; Enesol or salicylarsenate of mercury; Arsenical preparations; Atoxyl; Arsacetin;

vii

Vlll CONTENTS.

PAGE

Potassium iodid; Pilocarpin injections; Sodium salicylate injections; Quinin; Colloidal silver, collargol; Antitoxic serums and tuberculin; Antitetanic serum; Antiplague serum; Iron, arsenic and iodin; Hetol; Rachidian and epidural injections; Bier-Tuffler's method; Lumbar puncture; Intrarachidian injection of colloidal mercury; Method of Cathelin.

Chapter IV

Rationale; General efïects; Sympathetic ophthalmitis; Infective ulceration of cornea; Action upon choroid; Myopic choroiditis; Retrobulbar neuritis; Diseases of ciliary body and iris; Contraindications; Action of subconjunctival injections; Technic of subconjunctival injection; Indications for subconjunctival injections; Corneal leukomata; Interstitial keratitis; Hypopyon keratitis; Sympathetic ophthalmitis; Chorioretinitis; Episcleritis or iritis; Salicylates; Opacities of crystalline lens; Infiltrations of sclera; lodate of Sodium; Glaucoma; Injections of sterilized air; Guaiacol; Serums.

Chapter V

Phagocytosis; Opsonic index; Antitoxic serum; Paraspecific serotherapy; Pyocyanase; Activity of serum estimated by antitoxic units; Anaphylaxis; "Serum-sickness;" Antipneumococcic serum; Serpiginous ulcer of cornea; Technic; Results; Antitetanic serum; Deutschmann's serum; Antistreptococcus serum; Simultaneous employment of several sera; Vaccins; Hypopyon keratitis; Infected penetrating wounds of the cornea, ciliary region, or sclera; Infective complications of operation for cataract; Oral administration of sera; Prophylactic employment of serum; Tuberculins; Opsonic theory; Opsonic index; Method of employing Tuberculin T. R. ; Subconjunctival injection of tuberculin; Important clinical observation; Guaiacol; Oral administration; Instillation into conjunctival sac; Oxydases, metallic ferments, and colloidal metals; Staphylase; Colloidal metals; Warmed horse's serum; Hemophilia; Hemorrhagic afïections of the eye; Bacteriolytic agents; Pyocyanase; Bile; Antiformin and thalianin; Hemolytic serum;

CONTENTS. IX

PAGE

General remarks upon serotherapy; Roemer's jequiritol serum; Ehrlich's side-chain theory; Organotherapy; Adrenalin; Thyroid-treatment; " Antithyroidin " ; Pituitary body; Parenchymatous keratitis; Retinal hemorrhages; Rheumatism; Lamb's liver; Extract of uveal tract; Extract of ciliary body; Extract of retina; " Optocine"; Vitreous body of rabbits; Pulverized crystalline lenses; Spermin and testicular extract; Bone-marrow and spleen-pulp; Raw meat.

CHAPTER VI. Diaphoretics, Revulsives, Purgatives, Heat, and Cold

Etc 82

Vapor baths and dry heat baths ; Warm packs ; Pilocarpin sweats; Revulsives; Derivatives; Leeches; Wet cupping; Purgatives; Laxatives; Calomel; Diuretics; Milk diet; Antipyretics; Narcotics; Antispasmodics; Stimulants; Physical agents; Heat and cold; Cataplasms; Linseed-meal poultice; Mercurial poultice; Vapor douches; Moist heat; Steam; Thermophore; Dry heat ; Thermoaerophore ; Iced compresses; Cold moist dressings; Priestnitz dressing; Alcohol dressing; lodin; Mercurial plasters; Carbolic plaster; Stasis hyperemia; Bier's method.

Chapter X. Page

Medicamentous corneal massage; Vibratory massage; Pressure-massage of Domec.

CHAPTER XL

Powders; Ointments; Oily collyria; Aqueous collyria; Ocular anesthetics; Cocain; Subconjunctival injections; Mydriatic action; Subcutaneous injections; Cocain-poisoning; Eucain B.; Tropacocain; Holocain; Stovain; Alypin; Novocain; Lusemin; Ocular analgesics; Orthoform; Anesthesin; Acoin; Sodium salicylate; Aspirin; Quinin; Antipyrin; Pyrenol; Pyramidon; Phenacetin; Dionin; Peronin; Codein; Heroin; Morphin; Adonidin.

CHAPTER XIL

Dionin; Adrenalin; Cocarenalin; "Homorenon;" Anterenol.

CHAPTER XIIL

Mydriatics and Cycloplegïcs, Miotics 173

Atropin; Scopolamin; Homatropin; Duboisin; Hydrobromate of methyl-atropin ; Cocain; Ephedrin; Mydrin; Eumydrin; Euphthalmin; Miotics.

CHAPTER XIV.

Drugs Modifying Conjunctival Secretions. The Silver

Compounds 179

Antiseptics; Carbolic acid; Mercuric chlorid; Mercury cyanid; Caustics; Silver nitrate; Protargol; Protargolage ; Zingage; Argyrol; Ophthalmoblennorrhea; Silver salts; Savonnage; Sophol; Argonin; Sulphophenate of silver; Itrol; Actol; Collargol; Lavements; Electrargol.

CONTENTS. XI

SECOND PART.

SPECIAL THERAPEUTICS.

CHAPTER XV.

PAGB

Diseases of the Orbit 197

Orbital periostitis; Osteoperiostitis; Abscess; Tenonitis; Sinuses; Enophthalmos ; Dislocation; Pulsating exophthalmos; Exophthalmic goiter; Strabismus; Paralysis; Ptosis; Trigeminal neuralgia; Blepharospasm.

CHAPTER XVI.

Diseases of the Lacrimal Apparatus 203

Glands; Dacryoadenitis ; Mikulicz's disease; Congenital imperforation; Excessive lacrimation; Probe; Dacryocystitis; Electrolysis; Sac; Mucocele; Prelacrimal tumor; Complications.

CHAPTER XVII.

Diseases of the Eyelids 211

Solar erythema; Eczema; Prurigo; Acne rosacea; Erysipelas; Zona ophthalmica; Xanthelasma; Wounds; Tetanus; Styes; Boils; Chalazion; Edema; Emphysema; Malignant pustule; Hard chancre; Epithelioma; Tuberculous ulceration; Blepharitis.

CHAPTER XVIII.

Diseases of the Conjukxtiva 219

Irritation; Congestion; True conjunctivitis; Pneumococci; Staphylococci; Phlyctenular conjunctivitis; Savonnage; Ophthalmoblennorrhea; Ophthalmia neonatorum; Protargolage; Iritis; Arthritis; Gonococcal infection; Argyrol immersion; Buller's shield; Metastatic gonorrheal conjunctivitis; Beef-serum; Lenicet; Acetate of aluminium; Prophylaxis of ophthalmia neonatorum; Alcoholic con-

Xll CONTENTS.

PAGE

junctivitis; Diphtheritic conjunctivitis; Spring catarrh; Tuberculosis of conjunctiva; Parinaud's infective conjunctivitis; Granulous conjunctivitis, Trachoma; Follicular conjunctivitis; Salts of silver; Copper sulphate; Surgical treatment of trachoma; Galvanocautery ; Thermocautery; Resection; Expression; Grattage; Granulous infiltrations; Forceps; Triple-bladed knife; Jequiritol; Xerosis; Xerophthalmia; Pemphigus; Pinguecula; Pterygium; Hyaline degeneration; Amyloid degeneration.

CHAPTER XIX.

Wounds and infections; Infective organisms; Keratitis dendritica; Keratitis stellata; Galvanocautery; Corneal infection; Infective ulceration of cornea; Serotherapy; Infective traumatism of eyeball; Wounds of ciliary region; Burns; Keratitis; Lymphatic; Phlyctenular; Pustular; Eczematous; Fascicular; Strumous; Pannus crassus; Marginal ulcer; Infective ulcer; Superficial arborescent keratitis; Herpes febrilis; Zona ophthalmica; Vesicular keratitis; Pemphigus; Macular keratitis; Keratitis punctata; Filamentary keratitis; Acne rosacea; Aspergillary keratomycosis; Marginal ulcerations; Lepromata; Rodent ulcer; Neuroparalytic keratitis; Keratomalacia; Xerosis of cornea; Deep keratitis; Parenchymatous, keratitis; Interstitial keratitis; Striated keratitis; Rheumatic parenchymatous keratitis; Traumatic mesokeratitis; "Hutchinson's triad"; Corneal opacities; Corneal leukomata; Opaque staphyloma; Diseases of the sclera; Episcleritis; Posterior sclerochoroiditis ; Scleritis; Sclerosing keratitis; Episcleral nodosities.

CHAPTER XX.

Diseases of the Iris and Ciliary Body, Iritis, Iridocyclitis, Iridochoroiditis 295

Pathologic evolution; Treatment; Syphilitic iritis; Rheumatic iritis; Gonorrheic iritis; Tuberculous iritis; Guaiacol; Local indications; Intravenous injection; Iodic medication; Sympathetic ophthalmia; Treatment; Enucleation; Panophthalmitis; Surgical treatment of iritis; "Seclusion pupillae"; Iridectomy.

CONTENTS. Xlll

CHAPTER XXI.

PAGB

Congenital aphakia; Coloboma; Lenticonus; Ectopia; Hyaloid artery; Congenital cataract; Zonular cataract; Pyramidal cataract; Removal of lens; Discission; Extraction; Wounds; Traumatic myopia; Astigmatism; Rupture of zonule of Zinn; Subluxation; "Tremulous iris"; Luxation; Traumatic cataract; Senile cataract; Spontaneous resorption; Medicinal treatment; Surgical treatment; Technic of cataract operation; Preliminary iridectomy; Precautions; Corneal incision; Minimum of instruments; After-treatment; Accidents during operation; Loss of vitreous; Dislocation of lens; Hemorrhage; Prolapse of iris; Glaucomatous complications; Infective complications; Secondary cataract; Crystalline lens removed in high myopia; Paracentesis; Extraction.

CHAPTER XXII.

Treatment of Glaucom.v 346

Pathogeny; Iridectomy; Necessity of operation; Prodromal glaucoma; Irritative glaucoma; Posterior sclerotomy; Chronic glaucoma; Sympathectomy; Cyclodialysis; Miotics; Hydrophthalmus; "Paradoxical glaucoma"; " Sympathetic glaucoma"; Results of iridectomy; High-frequency currents.

CHAPTER XXIII.

Diseases of Vitreous Body, Choroid, and Retina. . . . ^63 Mouches volantes; Hemorrhages; Fundus oculi; Chronic hyalitis; Synchysis; Cysticercus; Vitreous infections; Diseases of macula; Subconjunctival injections; Pigmentary choroiditis; Dionin; Suppurative choroiditis; Inadequate blood-supply; Anemia of retina; Uremic amaurosis; Embolism of central artery; Massage; Thrombosis of retinal veins; Hemorrhagic retinitis; Specific chorioretinitis; Relapsing central retinitis; Retinitis proliferans; Atrophic macular retinitis; Albuminuric retinitis; Diabetic retinitis; Leukemic retinitis; Septic metastatic retinitis; Pigmentary retinitis; Retinitis pigmentosa sine pigmento; Retinal phototraumatism; Retinal electrocution; Commotion retinœ; Detachment of retina; Con-

XIV CONTENTS.

PAGB

tusion of eyeball; Myopie detachment; Moderate detachments; Grave detachments; Puncture; Electrolytic puncture.

CHAPTER XXIV.

Retrobulbar neuritis; Pathogeny; Etiologic factors; Therapeutic indications; Conclusions; Specific neuritis; Optic neuritis; Intracranial disease; Surgical intervention; Trephining; Lumbar puncture; Vertebral trepanation; White atrophy; Gray atrophy; Tumor of hypophysis; Oxycephaly.

CHAPTER XXV.

Chemotherapy and Salvarsan 411

Contraindications, Advantages of; Curative action; Specific action; Direct parasiticide action; Manner of administering; Results; Experimental researches of Hata; Absolute cure of syphilis; Syphilitic iritis; Interstitial keratitis; Optic neuritis; Atrophy of optic nerve ; Lesions of the retina and choroid; Paralysis and paresis of the musculature of the eye; Influence of salvarsan upon the nervous system.

Index 433

ERRATA

Page 287 last line, for " Oil of almonds" read " Olive oil."

FIRST PART.

GENERAL THERAPEUTICS.

Chapter I. Methods Of Diagnosis

The methods of precise diagnosis are of especial importance in modem ophthalmic practice. They may be classified as follows:

1. Clinical diagnosis, which is the most important and most commonly employed method. It is attained only by a judicious study of the complaints of the patient and of the physical signs, general and local, either perceived by our senses or revealed by special instruments, such as the plessimeter, stethoscope, sphygmograph, tonometer, thermometer, radiograph, etc.

2. Anatomico -pathologic, microscopic, and bactériologie diagnosis, as upon the examination of the secretions from the chemical and bactériologie point of view, the microscopic examination of pieces of tissue obtained by excision or scraping, etc., the recognition of gonococci, bacilli tuberculosis, spirochseta pallida, etc.

3. Experimental diagnosis by transplanting to susceptible animals the malady observed; as, for instance, tubercle to the rabbit or guinea-pig, syphilis to the monkey, etc.

4. Serum diagnosis, or all tests which seek to provoke a biologic reaction by means of vaccins, immunized animal serum, or attenuated cultures of microbes; as, for instance, the reaction to tuberculosis by hypodermic injections, the inoculation of skin wounds, the cuti-reaction of von Pirquet, the ophthalmo-reaction of Wolff-Eissner- Calmette (the conjunctiva), the sero-diagnosis of Wassermann and Neisser, etc.

5. Therapeutic diagnosis, which is as old as clinical diagnosis, naturam mortorum cnrationes osiendant.

For full descriptions of the modern precise methods of clinical diagnosis, the reader is referred to one of the many excellent text-books on this subject.

It is, however, in this connection, deemed advisable to discuss several important recent additions to our diagnostic armamentarium.

The method of Arning and Klein for demonstrating the spirochaeta of Schaudinn is as follows :

In order to meet with success in the search for the spirochœta, one must examine patients who have undergone no treatment by mercury or iodids. The suspicious part is carefully cleansed with a bit of wool soaked with ether or petrol. It is then scraped or rubbed with the angle of a piece of glass until there is collected on the edges of the cover-glass, blood or blood mixed with serum. The presence of blood is absolutely necessary.

By thrusting to a depth of 5 mm. a narrow blade, spirochastes have sometimes been found in cured hard chancres, although the superficial layers had not shown the organisms.

The serum mixed with blood obtained in the manner described is spread on a cover-glass first carefully freed from grease by alcohol and ether. The preparation is fixed by passing it thrice above a flame, and is then stained by the rapid method of Rona-Preis. A mixture is made of distilled water, 10 c.c, and Giemsa's liquid, 10 to 15 drops. Four or five times this solution is poured over the cover-slip, and each time the slip is slightly warmed. In order to avoid applying too much heat to the specimens, the authors recommend that a grease-mark be made half a centimeter from one of the ends of the cover-slip. If too much heat be then applied, the line of grease melts. The spirochastes are to be sought for by an oil-immersion lens.

In searching for the living spirochaeta the authors place a drop of physiologic salt solution upon a cover-slip, very clean and freed carefully from grease. A drop

EXPERIMENTAL DIAGNOSIS. 5

of blood-serum, obtained as previously explained, is lifted with the platinum loop and mixed with the drop of saline solution. The preparation is covered with a glass slip, care being taken that no air-bubbles are imprisoned, and lutted down by means of paraffin. Aniing and Kleii have been able to convince themselves that in such preparations, kept in the dark at room temperature, the spirochaetes may remain alive for as long as four weeks, an observation confirmed by Hoffmann. Preparations of living spirochastes are especially interesting to examine with the new special illuminating apparatus now made in Germany. The latter, indeed, may with advantage replace the ultra-microscope.

When the authors search for spirochaetes in sections they adopt Levanditi's method.

The results obtained have been as follows:

Chancres examined, 140; positive results, 136. Secondary affections examined, 247; positive results, 235. Among the patients who were examined, in thirty-two the certain clinical diagnosis was impossible, and it was only the discovery of the spirochaeta that allowed the existence of syphilis to be affirmed. In eighteen doubtful cases, the absence of the spirochaeta suggested a diagnosis of soft chancre, although in two of these cases the subsequent appearance of secondary symptoms showed the existence of true syphilis.

These brilliant results show the great value of a simple and rapid method of searching for Schaudinn's spirochasta.

Experimental diagnosis may be considered permissible in certain superficial lesions of the eye. After inoculating the cornea and the anterior chamber of the rabbit to reproduce the lesions which will enlighten us as to the origin of the affection, it is sometimes possible to find the initial organisms in the inoculated organs, as, for example, spirochaetes or tubercle bacilli.

In cases of iritis of doubtful etiology, it has been advised that there should be withdrawn with an aseptic syringe a few drops of aqueous humor, for the purpose of injecting it into the anterior chamber of the guinea-pig or the rabbit. By such a method one may discover the tuberculous origin of iritis (Gourfein).

We have, however, as will be discussed later, methods quite as practical as the foregoing, but much less dangerous for diagnosing tuberculosis. It is hardly justifiable to induce a patient to allow the anterior chamber to be opened simply for purposes of diagnosis. On the other hand, whenever one believes that an injection of air into the anterior chamber is likely to have a favorable therapeutic effect, the opportunity should be seized to utilize the aqueous humor for the establishment of an experimental diagnosis. The withdrawn fluid may be injected into the anterior chamber of an animal, and may also be examined microscopically by means of a smear preparation.

Sero -diagnosis is so recent and so interesting a conquest that it merits adequate discussion in works upon opthalmic therapeutics.

If we may look upon the local and general reaction set up by injections of tuberculin as a certain proof of the existence of tuberculosis, it is important to indicate the main principles of this valuable element of diagnosis.

If we inject about o.ooi grm. of Koch's tuberculin into the subcutaneous tissues of a person affected with tuberculous iritis, keratitis, or, indeed, any other malady of which tuberculosis is suspected of being the cause, we observe a febrile reaction more or less marked, which betrays itself by a rise in temperature of one or sometimes of two degrees centigrade, while at the same time the local lesion or its surroundings become markedly hyperemic, and more or less lively pain is experienced by the patient. Dependent on the degree of the affection and, especially, on the individual resistance, it is sometimes necessary to give a second or third injection of tuberculin before the desired reaction is provoked.

CUTI-REACTIONS. 7

There is an even more practical means of proving the existence of tuberculosis, especially in those cases in which the clinical signs point to that diagnosis; namely, commencing treatment with very feeble doses of tuberculin T. R. or of Koch's new emulsion. There are injected every other day progressive and stronger doses, and at the end of several days the reaction wall be produced, which may be local or general, but is less violent and less dangerous than with the foregoing method.

Von Pirquet's cuti-reaction may also be advantageously employed. It is merely necessary in this test to scarify the skin, and then to rub the selected locality with a solution of tuberculin. Soon the region of the tiny incisions becomes red and slightly swollen, as one may observe in false \'accination (faitsses vaccines).

Lautier's modification of cuti-reaction is simpler and less disagreeable for the patient. The technic is very simple. A bit of wool is saturated with three drops of a I per cent, solution of tuberculin and applied to the outer surface of the arm. In order to facilitate diffusion of the liquid and to ensure prolonged contact with the epidermis, the wool is covered with a small square of gutta-percha tissue, and kept in place with wool and several turns of a bandage. The dressing is not disturbed for forty-eight hours. At the end of this time the dressing is removed, when in tuberculous adults, as w^ell as in children, there is seen an hour after having taken off the dressing that a small erythematous and papular area has developed in the place where the tuberculin was in contact with the skin. This region has a slight coppery hue, trenching upon sound skin. The boundaries of the area are clearly thrown into relief by the neighboring parts. The reaction obtained by these means may be strong, medium, or feeble, and in the last case one sees merely a slight redness, slightly wrinkled and in relief with the surrounding parts. Mahe- Desportes (Thèse de Bordeaux, 1908) concludes: i. That healthy subjects never present cuti-reaction by this pro-

METHODS OF DIAGNOSIS.

cedure. 2. That tuberculous subjects generally react, and that this cuti-reaction is parallel to the ophthalmo-reaction-— that is to say, that an individual who reacts strongly to the one test will also do so to the other, and vice versa. 3. That in all cases in which cuti-reaction fails, ophthalmo-reaction will also fail.

The epidermal method of cutaneous diagnosis is effected by injecting a drop of a solution of tuberculin into the dermis, immediately beneath the epidermis. If the subject be tuberculous, a lively reaction will manifest itself on the following day.

The ophthalmo-reaction was discovered simultaneously by Wolff-Eissner, in Berlin, and by Calmette, in Lille. The method is valuable in general diagnosis, but in ophthalmic practice it should not be used, for if a slight tuberculous lesion of the cornea or iris is present it may set up serious complications gravely endangering the sight of the affected eye. Moreover, in the absence of all tuberculosis, the ophthalmo-reaction may provoke a conjunctivitis difficult to cure, especially when a follicular state of the mucous membrane already exists; and still more so when the individual is affected with trachoma, even of slight degree.

An attempt has been made to avoid these complications by using weak solutions of tuberculin. The dose recommended by Calmette was i per cent., and it has been proposed to use in children a strength of 1/2 per cent. But until more numerous experiments have been made, the ophthalmologist will be well advised to abstain from employing the ophthalmo-reaction. At the same time, the cuti-reaction, as well as the hypodermic injection of tuberculin, is capable of rendering great service in ophthalmic practice.

In concluding as to the value and proper place of the tuberculin tests, we can do no better than quote Wolff- Eissner, who wisely says: "The discovery of the local reactions to tuberculin and their diagnostic employment has

THE TECHNIC OF THE OPHTHALMO-REACTION. 9

opened up a new era in medicine. These reactions constitute an important method, but they are of no significance if they are not seconded by chnical observation. To limit oneself to the ophthalmo-reaction or to the cuti-reaction and to ignore clinical investigations would be at once a fault and a danger; the physician should be on his guard against exaggerated and too enthusiastic an appreciation."

The technic of the ophthalmo-reaction, according to Calmette, is as follows: Before placing a drop of a i per cent, solution of tuberculin in the inner corner of the eye, the following precautions are necessary:

1. To determine that no lesion, however slight, exists in the eye or the eyelids, in order to avoid a reaction which exceeds the desired end, and may even compromise more or less an organ which is already the seat of a preexisting microbic infection.

2. To avoid absolutely all blinking at the moment when the tuberculin is instilled, otherwise the liquid may be rejected before it has had time to produce its effect, and erroneous if not actually false conclusions may result. Accordingly, care should be taken to throw back the patient's head and also to keep the eyelids separated for several moments after the application.

3. To advise the patient not to rub the eyelids after the drop has been placed in the eye, since that may falsify the results. In case of necessity, an occlusive bandage may be applied.

4. According to the precepts of Calmette, to avoid all abnormal inflammation (blepharitis, conjunctivitis) by using only tuberculin ])recipitated by alcohol and perfectly aseptic. Never under any circumstances to employ glycerized tuberculin, on account of its causticity.

By conforming scrupulously to the foregoing rules, which are clear, precise, and easy to follow, one may depend upon the relial)ility of this test.

The sero -diagnosis of syphilis depends upon the search lO METHODS OF DIAGNOSIS.

for antibodies and syphilitic antigens by the biologic method of Bordet and Gengou. These authors have found that whenever one places a serum rich in bacterial antibodies — as, for example, antityphoid, anticholera, or antiplague serum — in contact with the microbe that has produced the antibodies, two phenomena take place: first, the antibody fixes upon the body of the microbe, in a way that is strictly specific; and, secondly, as a consequence of this fixation, the same antibody absorbs the hemolytic complement.

These data will show how the most various antibodies may be looked for in the body fluids and tissues, and will serve equally well to show how microbes or their products may be discovered in infected organs or culturemedia. It is especially in the diagnosis of syphilis that the method has been employed. As the result of researches made in common with Neisser and Bruck, Wassermann has shown that the reaction of the deviation of the complement allows one to identify the antisyphilitic antibodies and antigens derived from the treponema pallidtim in the humors and tissues of men and of monkeys aft'ected with syphilis. If one desires to make certain whether a given subject has or has not been infected with syphilis, the serum is warmed to 58° C. for a quarter of an hour (destruction of the complement), and then mixed in variable quantity with the same volume of extract of a syphilitic liver. Then a minimal quantity of guinea-pig serum, rich in the hemolytic complement, is placed in the tubes, and the mixture is kept at a temperature of 38° C. for two hours. As soon as this period has passed, one places in the tubes the hemolytic amboceptor of the rabbit and the red blood-corpuscles of the sheep. Should the serum under examination really contain syphilitic antibodies, there will be no dissociation of the red corpuscles, which will retain their hemoglobin. If, on the other hand, hemolysis occurs as in the test-tubes, it may be concluded that antibodies are absent from the serum.

THE SERO-DIAGNOSIS OF SYPHILIS. II

The apparent complexity of this method vanishes when it has been tried several times. From its faithful employment a certain number of facts have been gathered with regard to the presence of antibodies and antigens in syphilitic subjects.

Neither Wassermann nor his collaborators, nor the observers who have controlled their experiments, have succeeded in finding the antigens or antibodies of syphilis in healthy individuals, save in a few very exceptional cases. On the contrary, in the great majority of cases of human syphilis and experimental syphilis, syphilitic antigens and antibodies have been discovered, sometimes in the blood, and at other times in the tissues. Wassermann and Neisser, in 163 cases of florid syphilis, obtained positive reactions in 75.5 per cent., and in latent syphilis in 58 per cent. The researches of Wassermann have been confirmed by Citron, Mayer, and Fleishmann.

The close relationship between syphilis and general paralysis and tabes are too well recognized to render it necessary to enumerate the arguments that have led practitioners to class the latter among the so-called parasyphilitic processes. This relationship has been rendered even more intimate by the discovery of syphilitic antibodies in the cerebrospinal fluid of those affected with tabes and general paralysis. Wassermann and Plaut, who have sought for these antibodies by Bordet and Gengou's method, found that a positive reaction could be obtained in 88 per cent, of the cases of syphilitic general paralysis.

From a clinical point of view, it would be difficult to exaggerate the importance of the sero-diagnosis of syphilis. Wassermann's method will often allow us to resolve problems with which clinical work alone would be inadequate to deal. Very frequently does clinical enquiry, despite the perseverance of the observer, furnish only indecisive information with regard to the specific antecedents in cases in which certitude would be so useful in determining the proper treatment. Again, it would often be of service to decide whether treatment has ended the infection, so that the patient may safely marry. Lastly, it often is desirable to know whether we may safely confide a baby to a wet-nurse who denies all history of syphilis. In spite of our incomplete acquaintance with the value of Wassermann's sero-reaction, this reaction may be very helpful in answering these and cognate questions.

A. Leber {Berlin Ophthalmological Society, March 19, 1908), in the course of a communication on Wassermann's sero-diagnosis in affections of the eye, reached the following results: In sixteen cases of avowed syphilis of the eye, a positive result was obtained in 93 . 7 per cent. In ninety-five doubtful cases, the result was positive in 42.1 per cent. The result was positive in 84 per cent, of thirty-one cases of interstitial keratitis; in 38 per cent, of forty-eight cases of iritis; in 26 per cent, of twenty-three cases of choroidoretinitis ; and, lastly, in 59 per cent, of twenty affections of the cerebrospinal axis.

Thanks to the kindness of Dr. Levaditi, the writer has had occasion to apply the Wassermann sero-diagnosis at the Pasteur Institute in several cases in which the diagnosis of an ocular affection was impossible by clinical methods. The data thereby obtained have been of the greatest service in the conduct of treatment, and have certainly contributed to the rapid cure of the case.

Therapeutic diagnosis often allows one to make what may be called a retrospective diagnosis. For example, should a doubtful affection yield very quickly to mercurial treatment the conclusion might follow that syphilis was the cause. This is not always true, for sometimes a parenchymatous keratitis is cured by mercurial treatment, and, later, the tuberculous origin of the disease becomes manifest. The same remark applies to sodium salicylate, which quickly relieves acute rheumatic affections, but may also be valuable in many other affections, among them sympathetic ophthalmitis.

Thanks to subconjunctival injections, which permit

THERAPEUTIC DMGNOSIS. 1 3

US to apply the remedy loco dolenii, we may often obtain valuable diagnostic indications. In a case of episcleritis, we may hesitate between a diagnosis of rheumatism, syphilis, or tuberculosis. The rapid cure after one or two injections of salicylates, mercury, or guaiacol often furnishes us with the key to the etiology of the disease. Syphilis, it is true, may be recognized by Wassermann's method. When the reaction is negative, a deep subconjunctival injection of i c.c. of a 2 per cent, solution of guaiacol is made. The reaction is relatively slight, and the pain lasts barely five minutes (guaiacol is analgesic). After three or four days, when the redness and chemosis due to the injection have disappeared, if the affection is tuberculous, the surgeon will be pleased to find a considerable improvement, whether the case be one of episcleritis, iritis, parenchymatous keratitis, or even an affection of the deeper membranes of the eye.

The specific action of guaiacol upon tuberculosis of the eye is so marked that its subconjunctival injection may give great relief in cases in which the hypodermic injection of tuberculin has been followed by a violent ocular reaction, as shown by redness, pain, and sometimes even by a very evident rise in tension. The pain, under these circumstances, disappears some hours after the injection.

In two cases of double optic neuritis from cerebral tumor in which inunctions of guaiacol brought about the disappearance of the headache, vomiting, and neuritis, the inference was that the encephalic lesions were of tuberculous origin (Darier, Arnold).

CHAPTER IL CONSTITUTIONAL TREATMENT.

The Importance of Constitutional Treatment in Ocular Affections. — If it is necessary to make an etiologic diagnosis, it is because nowadays we are no longer contented with purely symptomatic treatment. It is of the greatest importance to treat the local affection at the same time as the underlying constitutional cause. The constitutional cause may proceed from a chronic infection or intoxication of the entire organism, which has little by little set up a general disturbance of the nutrition and of the vitality of the tissues. These disturbances may be transmitted by heredity, with different modifications, but with a type always peculiar to themselves. By its trophic reflexes the nervous system plays an important part in all these troubles of nutrition.

To Bouchard's thinking, that which is called " arthritism" is nothing more than a disease of debility of nutrition. To others, it represents a kind of rheumatismal heredity (an atavistic infection still imperfectly understood), which predisposes to gout and to a number of diseases bound to it by the alternations and frequent coincidences among the members of the same family.

In the many affections that are called arthritic, experience has shown us that alkalies are useful; that sodium salicylate and lithia are indicated, and, in particular, that a special hygiene suits such patients — as, for example, local and general massage, vapor baths, exercise in the fresh air, etc.