Venereal diseases; their complications and sequelæ

Front matter

ifel

Class.

Book

Preface

A FORMER work of identical title, from the pen of the senior author of this volume, appeared in January, 1880, twenty years ago, as one of " Wood's Library." It had two objects in view, both of which have been accomplished.

The first object was to combat the then raging furor for anterior urethrotomy which possessed the younger members of the profession. This is now happily over, and a certain amount of good has followed the excess. Strictures of the pendulous urethra are understood and managed better to-day than twenty years ago.

The second and most important object was to disseminate the author's teachings upon the treatment of syphilis. This tonic treatment, by the prolonged mild use of mercury in such a way as to do the patient no harm while his malady was being mastered, is to-day so widely spread and so well understood, and has been accepted so largely, if judgment be rendered according to the evidence at command, that there is no reason to make any radical change, in so far as syphilis is concerned, in the presentation of this subject.

But that book has long since ceased to be a safe guide in its urethral teachings on account of the strides made in bacteriology and therapeutics during the last decade.

The younger blood of the junior author and his point of view, together with a general growing experience, have revolutionized many of the ideas advanced in the former treatise, and the time has seemed ripe to us to join hands in authorship for the purpose of placing the result of our combined experience before the profession in a practical way.

This volume is the result.

In it is reproduced the senior author's original teaching concerning chancroid and syphilis, the latter practically in the whole piece making little change further than to cut out references and cases to reduce the volume of the text, but the chapter on chancroid has been reconstructed.

A valuable chapter on nervous syphilis has been contributed by Dr. Pearce Bailey, consulting neurologist at St. Luke's Hospital, and to him the authors render public acknowledgment. Dr. Chetwood, the junior author, has so entirely remodelled and rewritten that portion of the book

VI PREFACE.

relating to the urethra that it has seemed proper to place this section first and to issue the volume as a new book rather than under the name of a second edition of the old book.

The authors' warm thanks are extended to Dr. F. M. Jeffries, director of the laboratory of the New York Polyclinic College and Hospital, for excellent work in collecting references and assisting in preparing the section on the Bacteriology of Urethritis. To Dr. A. F. Btichler we are indebted for clinical material, and to Dr. D. A. Sinclair for various good offices. E. L. Ketes.

C. H. Chetwood.

PART II. Chancroid and Syphilis, chapter i

Chancroid : Definition, Etiology, and Clinical History, 167

CHAPTER II.

Chancroid {Continued) : Diagnosis, Prognosis, and Treatment, .... 177

Vill CONTENTS.

CHAPTEB m.

PAGE

CHAPTER IV.

Syphilis : Definition — Origin— Course— General Pathology, . , . . 198

CHAPTER V.

The Transmission of Syphilis : Methods of Contagion— Prognosis, c . . 203

CHAPTER VI.

The Chancre — Primary Lesion of Syphilis, c .211

CHAPTER Vn.

Constitutional Syphilis — Stages of the Disease, ....... 220

CHAPTER VIIL The General Treatment of Syphilis, ......,,, 224

Syphilis of the Eye and Ear, 330

CHAPTER XVIL Inherited Syphilis, . . .336

Introduction

A STEICT application of the title of this treatise should include only -^^^ those diseases acquired during sexual intercourse and starting in the sexual organs. But these maladies may by direct contagion make their initial appearance elsewhere, and through their complications and sequelae invade the adjacent organs or involve remote parts of the body.

Of the three principal divisions of venereal disease — syphilis, chancroid, and gonorrhoea — the first two commonly appear upon the external genitals, while the last is essentially a disease of the urethra, and is, on account of its microbic origin, otherwise known as specific urethritis.

Each of these maladies is distinct from the other etiologically, pathologically, and clinically. All of them are virulent and contagious, and while they never arise de novoy yet in the case of chancroid and gonorrhoea there exist spurious examples which bear so close a resemblance to the real malady that the difference is only bacterial, and the selection of treatment must depend upon a knowledge of this fact. These spurious cases are of idiopathic origin and may be non-venereal in their nature, but as they are frequently acquired during the sexual act and so closely resemble their prototypes as often to be mistaken for them, their consideration becomes a necessity in a work upon venereal diseases. The same remark applies also to the complications and sequelae of the venereal diseases. These latter are not confined to the genital regions, but include, through contiguity, the neighboring organs and, by reinoculation and metastases, remote parts of the body.

Finally, syphilis is not a disease of any organ or of any region, but of every tissue in the body and of the blood as well. Hence the title venereal refers only to the source from which these several maladies and their complications are derived and to the customary location of the primary lesions occasioning them ; but as the name is sanctioned by time and custom it must be retained, although entirely too narrow to indicate the scope of a treatise which a proper consideration of the group of maladies involved necessarily calls for.

PART I.

ACUTE AND CHRONIC URETHRITIS.

COMPLICATIONS AND SEQXJELjE.

VENEREAL DISEASES.

Chapter I. Specific And- Non-specific Ueetheitis— Gonorkhcea

Definition and Etiology.

The term urethritis, without qualification, signifies inflammation of any portion of the urethral canal. Such inflammation is designated, according to its cause, specific or non-specific ; according to its locality anterior or posterior ; and, according to its duration, acute or chronic.

Specific urethritis, commonly spoken of as gonorrhcea, is, in the male, an intense urethral inflammation, characterized by a period of incubation, and by a profuse discharge of pus which possesses virulent qualities, due to the presence of a diplococcus — the gonococcus of Neisser.

This definition at once places gonorrhoea in the rank of virulent diseases. It has a period of incubation, runs a course of varied length, possesses its virulence to the very end, and is in the highest degree contagious.

Non-specific urethritis, as its name implies, differs from gonorrhoea in that it is not referable to a single cause. It is etiologically complex. Its causes arise from without and from within the urethra. Generally speaking, it comprises those cases of urethral inflammation not directly traceable to the gonococcus. It may resemble gonorrhoea so closely in all its symptoms that, clinically, a diagnosis between them often cannot by any possibility be made. This, however, is simply due to the fact that the symptoms of inflammation of the urethra, when they run high, are alike, whether their cause be specific or non-specific. Theoretically, a distinction must be recognized between non-specific urethritis and gonorrhoea, although practically such a difference oftentimes cannot be demonstrated except by resort to the microscope. Clinically the symptoms of non-specific inflammation of the urethra have to be treated symptomatic ally in accordance with the grade of their intensity ; whereas gonorrhoea is treated with special regard for its specific cause.

The intensely contagious quality of gonorrhoeal pus has been too long and too well known to require more than a mention. It has been demonstrated b}" direct experiment from urethra to urethra long before the discovery of the gonococcus. It was demonstrated witli equal certainty by oculists, by inoculation of the conjunctiva for clinical purposes. In the course of nature it is demonstrated upon the victim who has exposed himself to it in sexual intercourse ; and the eyes of a patient with gonorrhoea may also attest the powerful contagiousness of this disease.

No one can possibly dispute the fact that, if pus taken from a case of true gonorrhoea be placed upon the orifice of the urethra of the male, or the vagina of the female, an inflammatory disturbance of considerable intensity will be lighted up. But it was not until the discovery of the gonococcus by Neisser and its cultivation and reinoculation upon the human urethra by Bumm that the true etiological factor of this disease was disclosed.

On the other hand, it is known that pus of the most varied character, not gonorrhoeal, but containing various forms of bacteria may be placed upon the meatus of the male urethra, or poured along its course, without inflaming the canal. In cases of intense balanitis beneath a very tight prepuce, the cavity of the foreskin is constantly filled with dense creamy pus ; yet in such a case, if the foreskin be slit up, it is often found that the glans penis is excoriated in patches, and the meatus of the urethra raw perhaps, but no urethritis exists. Pus from pyelitis may be voided as thick as cream through the urethra, but it does not occasion inflammation of the canal.

In the female, pus from the kidney or bladder, passing through the urethra, or pus in vast quantities coming from the uterus, may exert little more than a mild amount of mechanical irritation upon the parts over which it passes.

Finally, the male often cohabits with a female whose vagina contains more or less pus from the uterus, and remains well ; while in many cases a mau with a more or less purulent discharge may lie with a woman, and she will remain sound. Not so in either case, however, if there be present the microbic poison of gonorrhoea. A gleet after gonorrhoea which is nearly well may give a gonorrhoea to a woman if the gonococcus be still present, as will a mild lurking inflammation in the vagina readily poison the male when its secretion harbors the presence of this specific organism.

A large percentage of men in cities have a small amount of gleet from one cause or another; yet gonorrhoea in the females (their wives), with whom they cohabit, is not common — it is, indeed, exceptional. In France a gleet is considered a natural thing with a soldier, so much so that it is called the " military drop " ; but the women with whom they live are not necessarily affected with an analogous disorder. Indeed, there are certain forms of urethral discharge, which, the gonococcus having been carefully excluded, may call for the married state for their cure, and which get well during regular sexual hygiene, without involving the wife in any disorder.

As to the power of pus in the vagina to give gonorrhoea to the male. Doubtless the male often gets his urethritis from contact with such irritating discharges, but he does not necessarily become irritated by them at all. Indeed, he usually escapes, unless his own urethra has been damaged by previous gonorrhoea, and he happens to be himself either debilitated, overtired, or full of liquor, or suffering coincidently from very acid urine, or unless he overstimulates himself sexually. All of these causes are capable alone of producing urethritis when the mucous membrane is in a morbid or congested condition, but are more apt to be predisposing in their nature, and the means of inducing acute inflammation, through the activity of the various micro-organisms which commonly infest the urethra and vagina, and which, although not necessarily pathogenic, may become so under certain conditions.

When a patient, however, offers himself, in sexual exposure, to the diplococcus of true gonorrhoea, he is almost certain to become poisoned without the co-operation of any of the adjuvants mentioned above. A simple exposure is enough.

The theoretical distinction, therefore, between gonorrhoea and urethritis is clear; the clinical distinction is often equally so. Yet, without do^ibt, an intense urethritis is one and the same in its symptoms, whether its cause be the gonorrhoeal virus or any other microbic agent internal or external.

From what has been written, it may be inferred that the causes of urethral inflammation are quite varied. The cause of true virulent gonorrhoea is single, namely, contact of the affected person with gonorrhoea! pus from another person. Urethritis, however, may be produced in a variety of ways almost infinite, and it cannot be distinguished in its symptoms, when intense, from a gonorrhoea. This fact cannot be too often repeated. That surgeon is bold indeed, who, in the face of a certain urethral discharge of given intensity, without the use of the microscope will pronounce upon its origin with any confidence, and some writers on account of the close resemblance in every particular of other micro-organisms to the gonococcus by microscopic examination, deem it necessary to resort to further bacteriological technique with the purpose of obtaining a pure culture in a suitable medium, before the question of its presence in a given discharge can be satisfactorily passed upon (see Bacteriology of Urethritis). No one can be accused of impure relations because he has a profuse urethral discharge. It cannot even be said that such a person has had sexual intercourse at all ; for it is possible for a man, virgin of all venery, to have an intense urethral inflammation, and much injustice may be done by accusing him, on the one hand, or, on the other, of accusing his partner — if he has had one — of having given him a disease.

The moral is, that the physician is not a judge. His function, if he has any of the judicial sort, is to shield the innocent. He should accuse no one, but confine himself to his own proper duties.

If the urethra be healthy, it does not easily become inflamed, excepting by contact with gonorrhoeal pus. Yet a healthy urethra does sometimes suppurate after mechanical violence, such as the rough introduction of instruments through it; after chemical violence — the injection of irritating substances for experiment, or under the idea of employing a prophylactic against supposed infection. Under these circumstances the micro-organisms which are latent in the urethra exert a more or less virulent action against it as a result of the traumatism induced. A healthy urethra may also become inflamed by the combined influence of venereal excitement — especially if intense or prolonged — and contact of an irritating discharge, leucorrhoeal pus, menstrual blood, etc. Here the virulent factor is derived from without.

An unhealthy urethra is always ripe and ready for inflammation. In strumous, strongly lymphatic, gouty, and rheumatic subjects, the urethra seems prone to take on inflammation easily, especially if the person be cachectic, overworked, or reduced in general health from any cause. In such cases all the mucous membranes are apt to be in an irritable condition, and to take on subacute inflammation from trivial causes.

When the urethra is actually diseased, on account of the previous existence in it of acute inflammation — when it contains a thickened, hypersemic patch, constitutiug a slight stricture — then it is in a prime condition to be irritated into suppuration — often a suppuration of formidable proportions — by the action of those micro-organisms which, in the healthy urethra, fail to produce any apparent irritation. This is especially true when the urethra, besides being the seat of a chronic patch of congestion left behind by an old gonorrhoea, is, at the same time, diathetically unhealthy, owing to the broken health, the bad hygienic surroundings, the cachectic condition, the nervous prostration, or the scrofulous or gouty constitution of the patient.

When the mucous membrane of the urethra is unhealthy, the introduction of a sound will sometimes produce quite a sharp attack of urethritis. The passage of very acid urine through the canal may bring about the same result, whether the uric-acid crystals be due to indigestion, an attack of gout, or over-stimulation by alcohol (particularly beer or champagne). Mere excess of sexual excitement will sometimes produce a flow of pus, and prolonged sexual intercourse may do the same, particularly if there be any purulent discharge in the vagina. In early married life the male is not unlikely to get a little urethritis from his wife; but after his approaches become less amorous, he has no further trouble.

In connection with many morbid states of the prostate (cancerous, tuberculous, inflammatory) and of the urethra (herpetic, chancrous — tuberculous, syphilitic) a more or less purulent flow from the urethra may be encountered, and a purulent discharge attendant upon organic stricture is of every-day occurrence.

Bacteriology of Urethritis.

The various micro-organisms which normally inhabit the anterior urethra have been isolated and studied by different observers, notably Lustgarten and Mannaberg, Stein Schneider, Pettit, and Wassermann. The writings of these and other authorities furnish us with a knowledge of the bacterial flora of the normal urethra. An enumeration of the different forms would occupy unnecessary space. It is sufficient to state that these comprise bacilli of varying lengths and contour ; cocci variously grouped; diplococci, round, oval, and hemispherical; streptococci, small and large ; staphylococci, round and oval and of different sizes. Therefore when the gonococcus is implanted upon the urethra it is not inoculated upon a sterile territory, but one where already thrive myriads of different micro-organisms. How these latter modify the action of the gonococcus is hardly known, or what part they play in limiting its career in the urethra. That their presence is harmless in the quiescent state is beyond dispute, but that they assume under certain conditions very virulent properties seems to be proven in those forms of urethritis which come under the title of non-specific inflammation.

It is now generally accepted that the gonococcus is the microbic agent of true gonorrhoea. It is also known that there exists a close analogy between some of the other diplococci and the specific organism of true gonorrhoea (the gonococcus of Neisser). In fact it is maintained by some that the so-called pseudo-gonococcus and the gonococcus of Neisser are indistinguishable in some instances, in which the former partakes of the characteristics of the latter without variation. Improvement in bacteriological technique, however, and the discovery of a reliable culture medium for the gonococcus make its differentiation a practical certainty, as it has been possible to reinoculate upon the human subject from a pure culture and demonstrate conclusively the specific action of the gonorrhoea! organism. When the evidence furnished by means of the microscope and cover-glass preparations is negative, resort may be had to cultivation on a proper medium when absolute certainty of diagnosis is required. The advantage of cultivation is mainly in those cases in which a few shreds or filaments are present in the urine and nothing more, and in the case of patients who suffer from a very mild catarrhal gleet and who contemplate matrimony. In either of this class of cases a positive diagnosis may be desired, but the gonococci, if present at all, are so scarce that the microscope may fail to find them until their number is greatly augmented by propagation upon a suitable medium. But when there are present in a given discharge suspicious organisms, which .^an be seen with the microscope to resemble the gonococcus, differentiation can be satisfactorily made without cultivation, by means of the Gram method of staining (Plates III.-VII.).

In cases of non-specific urethritis and pseudo-gonorrhoeal inflammation examination of the discharge reveals the presence of different kinds of bacteria, such forms as cocci and bacilli, which are known to be present in normal vaginal aud urethral secretions. That these organisms enter somewhat into the causative agency of non-specific inflammation there is no doubt, but in this particular they differ materially from the gonococcus, that their separation in pure culture and reinoculation do not result in the production of a similar inflammation, and therefore they may be said to be only one of the factors which enter into the causation of non-specific urethritis.

Bockhart, ' in examining cases of catarrhal urethritis, found present in large numbers specimens of bacteria which inhabit the normal vaginal secretion. Bacilli were found only in small numbers. As the process of inflammation advanced, the number of organisms diminished so that finally one form only remained — a micrococcus. He found a coccus like the staphylococcus grouped as diplococci. These were smaller than the gonococci, the segments being hardly as large as the erysipelas cocci. No concavity in the segment was observed. They were isolated or jn clusters of great colonies. They were found within epithelial cells as well as within the protoplasm of the pus cells.

Krause and Hirschberg, in examining several hundred ocular secretions, frequently found micro-organisms closely resembling the gonococcus Neisser, which were hard to differentiate from the latter.

Elkhund found a similar form of diplococcus in the secretions of acute and chronic suppurative processes of the lungs and intestines and in ulcerous stomatitis.

Bumm with Bockhart discovered organisms closely resembling the gonococcus in the genital tract of women. The former observer in extensive investigations has made a study of the various organisms which closely resemble the gonococcus in the minutest detail. Some of these are pathogenic and others not. He enumerates several of the spurious forms and gives their bacteriological characteristics. The principal ones are: 1. A lemon-yellow diplococcus, non-pathogenic, found in the dust of the air, also in purulent secretions of the urethra and conjunctiva. 2. A milk-white diplococcus, non-pathogenic, found in the preputial smegma and in various secretions of the body and in ulcerous processes of the vagina and mouth. 3. A yellowish-white diplococcus, pathogenic, found in the lochial discharges, in the catarrhal urine of women after childbirth, also in mammary abscesses. 4. A gray -white diplococcus, non-pathogenic,

1 Monatschrift fiir Derm., 1886, p. 134.

KEYES AND CHETWOOD.

PLATE I.

1. Colony on nutrient agar of large dlplococcus from normal urethra. Magnified.

2. Microscopical examination of same organism. 1,000 diameters.

3. Pure culture on acid gelatin of Turro's diplococcus urethrJB. 1,000 diameters.

4. Colony on nutrient agar plate of diplococcus found in catarrhal colpitis. Magnified.

5. Microscopical examination of same organism. 1,000 diameters.

CULTURES OF DIPLOCOCCI SOMETIMES MISTAKEN FOR THE GONOCOCCUS. (Heiman.)

found in vaginal secretions. 5. A red diplococcus found in the dust of tlie air, non-pathogenic. Most of the above organisms are found to be readily cultivated at ordinary temperatures.

It seems possible to cultivate them on gelatin and other ordinary media without difficulty, differentiating them from the gonococcus, which is difficult to cultivate and requires a special medium (Plates I. and II.).

Neisser^ declares that urethritis can be caused by other bacteria than the gonococcus. He mentions a case in which no gonococci were found, but a large number of intra- and intercellular " bacilli diplococci " (" Stabchen diplococci ") were present.

The Gonococcus. — The gonococcus was discovered by Neisser in 1879 in gonorrhoeal pus, and was first cultivated by Bumm in 1895. These organisms consist morphologically of micrococci, usually joined in pairs (diplococci) or in groups of four. The separate elements are flattened or hemispherical with the flattened surfaces approximated, and in the stained preparation presenting an unstained interspace. The approximated faces sometimes present a slight concavity. Their average size is 1.25 [j. in the long diameter. Their multiplication occurs by fission, alternately in two planes, as a result of which groups of four are frequently observed. The diplococci are more frequent. Single spherical individual cells are rarely seen. The microscopical appearances are not entirely characteristic of the gonococcus, as various other diplococci cannot be distinguished morphologically from the gonococcus. It readily stains with the basic aniline colors, especially with methyl violet, gentian violet, and fuchsin. It is negative to Gram's stain — that is to say, it is decolorized by the iodine solution used in this method. It has been stated that this characteristic does not serve to differentiate it, as other diplococci have been found in gonorrhoeal pus which react in the same way (Bumm); but it is held on equally good authority that the characteristic action of the Gram method upon the gonococcus is the best and most reliable means of establishing its identity, and that when confounded with other diplococci the error is due to faulty technique. In our judgment there is no better means than the Gram test for recognizing the gonococcus, but the greatest pains must be taken in every detail to make this test conclusive.

Another distinguishing characteristic but of lesser diagnostic value is the fact that the diplococcus gonorrhoeae is found within the protoplasm of the pus cells. It is found also within the epithelial cells. Pus cells are observed entirely filled with these organisms. Bumm describes what he considers the one exception in a diplococcus found within pus cells from a case of puerperal cystitis. These cocci retained their color after being treated by the Gram method of staining.

1 Deutsche med. Wochenschrift, 1893.

To fix the identification, then, of the gonococcus there should be diplococci of the right form, size, and arrangement. They must be negative to Gram staining, and should be observed within the protoplasm of the pus cells. The method of establishing the identity of the gonococcus by more elaborate bacteriological technique — namely, its cultivation upon a proper medium, also demands recourse to the Gram staining as a final means of identification.

The gonococcus does not grow upon the ordinary cultivating media. It thrives best at the body temperature. The extreme degrees of temperature in which it grows are between 25° and 39° C.

Various special media have been used successfully in the cultivation of this organism. Hammer^ describes a mixture of albuminous urine containing 1 to 1.5 per cent albumin with glycerin agar. The two constituents are separately sterilized and then mixed. Upon this medium the author obtained rich growths of the organism.

Bumm first succeeded in cultivating the gonococcus upon human blood serum prepared from the placenta of a recently delivered woman. The other media used successfully have been prepared by mixing two parts of glycerin agar with one part of fluids rich in albumin, such as ascitic fluid, fluid from hydrothorax, hydrocele, or ovarian cysts. A more simple plan is the use of the ordinary nutrient agar, the surface of which has been richly spread with human blood. The blood may be obtained directly from a small cut.'^

The gonococcus is a facultative anaerobe. Cultures upon the surface of blood serum are thin and scarcely visible. The surface is smooth, moist, and shining, yellow by reflected light; the edges of colonies are finely serrated. The growth spreads but slightly and does not continue more than two or three days, as the cocci lose their vitality. It is a strict parasite. (Sternberg.)

Unless dried out, the gonococci may retain their vitality upon serum agar at the body temperature for four weeks. If dried they lose their vitality within a few hours. ^

The gonococcus has never been found outside of the body as a harmless saprophyte. According to Heiman* the gonococcus remaining in the urethra after a gonorrhoea may lie dormant there and remain innocuous for years, and yet at any time excite an acute gonorrhoea in another person ; but this same author believes^ that the statements of Strauss, Pescioni, and Eraud, that the gonococcus occurs as a denizen of the normal urethra, are not satisfactorily proven by their published experiments.

1 Deutsche med. Woch., 1895, p. 60.

2 Abel: Deutsche med. Woch., 1893, p. 265. Fischer: Berliner klin. Woch., 1895, p. 1156.

* Medical Record, December 19, 1896. ^lUd.

KEYES AND CHETWOOD.

PLATE II.

lir

1. Colony on chest-serum agar of gonococci from male urethra. Magnified.

2. Microscopical examination of a pure culture. 1,000 diameters.

3. Gonorrhoeal pus sown on chest-serum agar, showing a pure gonoooccus culture.

CULTURES OF THE GONOCOCCUS. (Heiman.)

The various localities in which the gonococcus has been found comprise the urethra and prostate of man, the urethra, Bartholin's glands, and the cervix uteri of women. It has been found as the cause of vaginitis and urethritis of young girls. It has been discovered in endometritis, urethritis, salpingitis, oophoritis, peritonitis, proctitis ; probably also in epididymitis and cystitis J also in blennorrhoea neonatorum, conjunctivitis, rhinitis, otitis, and arthritis. It is still uncertain whether it occurs as the cause of pleuritis and malignant endocarditis.

Flattened epithelial cells seem to serve as a better protection against infection than do columnar epithelia.

This parasite has been observed to have penetrated the epithelium, and to have reached the connective tissue beneath.

Immunity does not follow infection.

Attempts to inoculate the lower animals are not successful and do not produce the true gonococcus of Neisser, but may yield a spurious organism, somewhat resembling it morphologically, but which can be differentiated from it by means of the Gram test properly conducted.

In order to demonstrate the presence of the gonococcus in cover-glass preparations we believe that the method of Gram should be relied upon entirely, and therefore a clear understanding of the various steps included in this staining method and differential test is absolutely necessary to success.

In a valuable communication of his work in the library of the Paris Necker Hospital Dr. M. Weinrich, of Berlin, ^ lays great stress upon what he considers the most fruitful source of error in the conduct of this test, namely, the use of water for washing purposes in any of the steps. He believes that by so doing complete decoloration of the gonococcus, when washed in alcohol, is interfered with.

What is known as Gram's solution consists of the following combination : Iodine 1 part, iodide of potassium 2 parts, water 300 parts. This preparation is used in bacteriological technique for demonstrating the presence of various bacteria. The specimen is previously stained for one or two minutes by a solution of gentian or methyl violet, when it is treated by the Gram solution for the same length of time. This solution in the presence of the aniline dye forms an insoluble deposit which is confined to the bacteria, and which in the case of most bacteria is not dissolved out when treated with absolute alcohol until the specimen appears colorless to the naked eye. In treating the gonococcus of Neisser, however, in the same manner as above, it was discovered that the Gram stain is dissolved out of these organisms by the alcohol, while it remains fixed in any other organisms which may be present in the same field. Thus it may be seen that we have here a most valuable differential test for the