Chapter XL: Part II: , Showing Predominance of Malarial Element . . . . 617 (39)

In certain cases of yellow fever reaction from the cold stage is feeble and imperfect, or perhaps may not occur at all. This departure from type is very fatal. The patients are stupid, sometimes semi-comatose and incoherent, from the earliest hours of the attack. The face is listless, drunken, or idiotic in expression. The color of the skin is dark olive and almost livid. The print of a hand on the chest is very slowly effaced. Sometimes the surface is covered with a peculiarly unctuous perspiration. The pulse is feeble and compressible; the temperature seldom more than one or two degrees above the normal standard. Albuminous urine is found during the first day. Death, attended by convulsive rigors, generally closes the scene within seventy-two hours from the moment of seizure.

Hot mustard-baths should be resorted to. Blood may be drawn by cups or leeches from the back of the neck or temples, and this may be followed by the application of a blister. Morphia and atropia may be exhibited subcutaneously in small doses, to be repeated as often as proper. Quinia may be administered per rectum or by the hypodermic method. Lastly, pilocarpine may be thrown into the tissues in sufficient doses to procure its vigorous physiological action.

Almost in precise symptomatic contrast with these cases of failure in reaction is another form of attack, in which violent disturbances of nerve-function occurs; such cases often being characterized as congestive in type. The most typical of these attacks are among children or adolescents. If attended by noticeable chill, it is ordinarily slight. Reaction is quick and excessively violent. The face is flushed, the eyes injected, and convulsions with delirium are liable to occur as early symptoms. I have watched with much interest the alternate flushings and pallor of the countenance occurring in these cases, such as are often observed in basilar meningitis.

The treatment in this type of attacks should include chloroform by inhalation in sufficient amount to control convulsions. Chloral hydrate may be administered by enema, or morphia hypodermically. Cathartic doses of calomel often exert a beneficial effect. Leeches or cups, to be followed by cold applications or by blisters, may be applied about the head or neck. But cupping and leeching should only be resorted to in the treatment of grave symptoms, since obstinate hemorrhage is liable to occur from any and every point from which the cuticle has been removed.

Yellow fever is often masked during the paroxysm by some pre-existing disease. Malarial fevers, the febrile states of pulmonary consumption or of the recently-delivered female, may all mask the early clinical {654} phenomena to such a degree that the most experienced and vigilant practitioners are sometimes astonished to find black vomit, suppression of urine, and all those symptoms which mark the last stages of the disease, suddenly developed.

Walking cases should be classed in the same category as masked forms. In these instances the early symptoms are so slight as to be overlooked or neglected by their subjects. They continue to prosecute their usual pursuits until, by sheer exhaustion, they are driven to beds from which they seldom arise.

The hygienic and dietetic management of yellow-fever patients is extremely important, and the strictest attention must be paid to the condition and discipline of the sick chamber. In this disease those occurrences and circumstances which in other affections would be reckoned as unimportant and trivial become matters of serious magnitude.

The physician, by a composed and cheerful demeanor, often decides which end of the balance shall go down. But an intelligent, experienced, and faithful nurse is equally as important as the excellent physician.

The patient should be confined in strictly recumbent positions, and all drinks and foods must be given through tubes or from pap-cups. It frequently occurs that patients are unable to void the bladder in such positions. In these cases the catheter should be used, rather than suffer any violation of the rule which demands a maintenance of unbroken decubitus.

The sick room should be kept freely ventilated, and the patient's bedding should be changed, when requisite, by removing him to one side of the bed while the other is renovated. If the patient's night-shirt becomes soiled and disagreeable, it may be cut so as to remove it, and another, cut in the same manner, may be substituted and stitched together. The room must be kept quiet, and useless visiting entirely forbidden.

Cool and grateful drinks may be given in any stage or state of yellow fever if demanded by patients. The quantity allowed at one time should be small, since over-distension of the stomach almost certainly causes vomiting. Effervescing drinks are nearly always grateful, and are better tolerated than others. Seltzer-water and lemonade, or Seltzer or Apollinaris on shaved ice, are to be recommended. Sometimes patients call for sparkling wines or beers. I never refuse them or any other alcoholic drink asked for in any stage of the disease. Wine surely possesses valuable therapeutic effects in yellow fever.

Alimentation must be severely controlled by the physician, and the tolerance and effects constantly watched. Even to the most experienced physician the kind of food to be selected, and the time and manner of administration, constitute difficult problems. In simple forms of the disease food had better be strictly withheld during the continuance of the paroxysm. Even after the stage of calm has been reached, sufficient time should be allowed to elapse to enable the physician to form some estimate of the degree of damage his patient has suffered and his competency to retain foods and be nourished by them. This question can seldom be answered in a decided manner, except through a cautious trial of some bland and inoffensive food.

{655} On the third or fourth day of sickness a single tablespoonful of iced milk may be given, and the immediate consequences closely watched. If no retching or gastric uneasiness should ensue, it may be repeated at the end of thirty minutes. Some physicians prefer to begin with spoonful doses of equal parts of sweet milk and thin barley-water. In my own experience chicken-water has proved to be the most universally acceptable, as well as the most beneficial, of all the various forms of nutriment to be chosen as a first venture. I have frequently combined this with barley-water when first given. In this cautious and tentative manner even the most experienced physician prefers to proceed, rather than to attempt to prescribe rules of diet in an abstract and arbitrary manner.

If these light articles of diet are well borne, they are to be gradually and watchfully exchanged for beef-essences, the blood of a rare beefsteak, and the more substantial broths. Solid articles of food should not be allowed during the first ten days after an attack, and for still longer periods patients should be admonished against excesses in eating, and especially in respect to indigestible articles. Those lesions of the blood and of the stomach, and those grave disorders of nerve-function which occasion hæmatemesis in yellow fever, are slowly repaired. Instances are reported in which black vomit and death have followed excessive eating and drinking ten or twenty days after dismissal from treatment.

There are, however, certain conditions which are liable to complicate yellow fever which demand a course of dietetic procedure different from that which I have recommended. Thus, children cannot bear privation of food until the paroxysm is over if its duration is long. In like manner, a more supporting course is required in most of those cases in which yellow fever occurs as an intercurrent affection, in all those cases which are termed typhoid or adynamic per se, and, more emphatically still, in every case in which hemorrhages are occurring. A failing pulse should in all instances admonish us to resort to nourishment and stimulants.

It is a fortunate circumstance that in yellow fever the lower bowel is generally in a state favorable for the retention of nutritious enemas. In the most trying and critical hours of desperate cases I have seen patients tided through by the use of skilfully prepared and skilfully administered injections of some suitable meat-essence. When insomnia exists, chloral hydrate or bromide of potassium may be conveniently given in these vehicles.

It is evident that the discussion of the vastly important sanitary questions pertaining to the prevention of yellow fever cannot be appropriately discussed in the present article.

{656}

DIPHTHERIA.

BY A. JACOBI, M.D.

DEFINITION; SYNONYMS; HISTORY.--Diphtheria is a specific, infectious, and contagious disease, characterized principally by epithelial changes in, and the exudation of fibrin on and into mucous membranes, the surface of wounds, and the rete Malpighii, thereby constituting the so-called pseudo-membrane. Under the names ulcus syriacum, ulcus ægyptiacum, garotillo, morbus suffocans, morbus suffocatorius, affectus suffocatorius, pestilentis gutturis affectio, pedancho maligna, angina maligna, angina passio, mal de gorge gangréneux, ulcère gangréneux, angina polyposa, angine couenneuse, cynanche, croup, diphtheritis, and diphtheria, the disease has been known and described at different periods by the writers of different nations. The Hippocratic writings and some remarks in the Talmud allow of some doubt in regard to their explanation. Whether their authors observed or recognized diphtheria cannot be proven. There is less doubt in regard to Archigenes, quoted by Oribasius. Aretæus of Cappadocia is notably the first, if we except Asclepiades only, who is said to have performed laryngotomy. The description of the pharyngeal and laryngeal manifestations furnished by the former, however, can leave no doubt in our minds that he knew diphtheria and recognized it. Galen, in his remarks on the Chironian ulcer, tells us that the pseudo-membrane was gotten rid of by coughing when the respiratory passages were affected by the disease, and by hawking when the disease was in the pharynx. Cælius Aurelianus recognized diphtheria of the pharynx and larynx, as well as the diphtheritic paralysis of the soft palate; it is to him we are indebted for the information that Asclepiades resorted to scarification of the tonsils, and even to laryngotomy. Aëtius in the fifth century distinguished white and grayish patches and gangrenous degeneration, observed paralysis of the soft palate, and advised against energetic local treatment and the forcible removal of the deposits before they were in a condition to fall off spontaneously. The Arabs and Arabists contain no allusions to the subject, but early chronicles tell of an epidemic raging in St. Denis in 580, subsequent to a great inundation. There appear to have been memorable epidemics in Rome in 856 and 1005, in Byzantium in 1004. The former are mentioned by Baronius, the latter by Cedrenus.[1]

[Footnote 1: Haeser, _Lehrb. a. Gesch. du Med. u. d. Epidem. Krankh._, 3d ed., vol. iii., p. 434.]

According to Morejon, Gutierrez wrote his _Tradado del enfermedad del garrotillo_ in the second half of the fifteenth century. A malignant form of angina raged in 1517 in Switzerland, along the Rhine, and in the Netherlands; in 1544 and 1545 in Northern Germany and on the Rhine; {657} in 1557 in France, Germany, and Holland; to the latter refer the reports of Tetrus Fosterus. Antonio Soglia, quoted by Chomel, describes an epidemic in Naples and Sicily (1563), which spread in the following year as far as Constantinople; Joannes Wierus, epidemics in Dantzic, Cologne, and Augsburg (1565); Ballonius (Baillon), in Paris (1576). At the same time this disease was frequent in Denmark. From Spain there are reports on severe epidemics between the years 1583 and 1618; the year 1613 was long known as the year of diphtheria (anno de los garrotillos).

Mercado (1608) speaks of a child that had communicated the disease to his father by biting his finger. Casealez advised gargles containing alum and sulphate of copper. Herrera described diphtheria of the skin and of wounds, and looked upon the pseudo-membrane as the essential characteristic of the disease. Heredia, in 1690, recognized the suffocative and asthenic forms, as well as the paralysis of the soft palate, the pharynx, and the limbs; he also called attention to the occurrence of relapses, which he attributed to the absorption of the morbid products, and endeavored to prevent by cauterization.

Naples had diphtheria 1610-45, in its worse form 1618-20, together with erysipelas, and diphtheritic affection amongst cattle. About those times tracheotomy was often performed by Severino, the same who found pseudo-membrane in the larynx at a post-mortem examination made in 1642. In 1620 the disease was in Portugal, Sicily, and Malta; in 1630 in Spain, according to Fontechu, Villa Real, and Herrera. It was remarked that in some instances no membranes were perceived in the throat, but the cases were liable to terminate fatally with large glandular swellings round the neck and general symptoms of adynamia. Sicily was again invaded in 1632, Rome in 1634, Italy from 1642 to 1650, Spain in 1666. The Italian reports emphasize the marked contagiousness of the disease and its tendency to depress the vital powers, also the weakness of the mental faculties left behind. In Germany the disease was described by Wedel in 1718. The epidemics observed by him were not very instructive, yet they sufficed to teach the importance of isolating the sick.

In the New England States diphtheria appeared in the seventeenth century. Samuel Danforth lost the four youngest of his twelve children by the "malady of bladders in the windpipe" within a fortnight in December, 1659, in Roxbury, Mass. John Josselyn mentions an epidemic in New England, mainly in Maine, which lasted at least until the year 1671. Mr. Douglass reports another, which commenced on the 20th of March, 1735, in Kingston township, about fifty miles east of Boston, and extended all over, and also to Boston, where it was mild at first. But in 1738 it was very severe, and remained so for some time. Indeed, it did not abate for a long time, to judge from a letter of Cadwalader Colden written in 1753 to Dr. Fothergill, and the two letters of Dr. Jacob Ogden, written in 1769 and 1774 to Mr. Hugh Gaine of New York; as also from John Archer's "Inaugural Dissertation on Cynanche Trachealis, commonly called Croup or Hives," published in 1798.[2] In 1809 there was a severe epidemic in Philadelphia;[3] in 1816 in Crete.

[Footnote 2: For extensive quotations from these and other writers on diphtheria at a very interesting period of our medical literature, see A. Jacobi, _A Treatise on Diphtheria_, New York, 1880.]

[Footnote 3: Caldwell, in ed. of Cullen's _First Lines of the Practice of Physic_, Philadelphia, 1816, 1, p. 260.]

{658} The reports of Le Cât concerning epidemics in Rouen in 1736 and 1737 being doubtful, the first great epidemic must be set down, in France, for 1745. It commenced in Paris, and invaded the provinces afterward. Chomel gave an accurate description of the diphtheritic paralysis of the soft palate, and reports a case of strabismus. Epidemics are reported from the Netherlands in 1745, 1746, 1769, 1770, 1778-86; from Spain in 1764-71; from England in 1744-48 (by Starr), from Plymouth, England, in 1751-53 (Thurham) and 1776. Dropsy and glandular swellings were frequent; emetics and pure air were the sheet-anchors of treatment. The Netherlands, France, and the West Indies were invaded from 1770-80 by the disease, which was found often complicated with scarlatina; Portugal in 1786 and 1787; France again in 1787 and 1788; Northern Germany in 1790. At that time, particularly in France, the main reliance was had on the internal administration of cinchona and the insufflation into the throat of alum.

Epidemics have been described since from different localities in different years: in Glasgow, 1812 and 1819; Switzerland, 1823-26; Norway and St. Helena, 1824; New York and Kentucky, 1826 and 1828; French provinces, 1834; Paris, 1841; several parts of Europe and North America, 1845-56; Paris, 1853-55; England, 1854 and 1859, when 95 per cent. of all the cases of nasal diphtheria proved fatal; Netherlands and Sweden, 1855; all Western Europe, 1855-65, up to the present time, and all Europe since; California, 1856 and 1857; Portugal and France, 1856; Eastern Prussia, 1850, 1852, 1856, 1857; and all the countries with a cold or moderate climate to this very day.

During the second half of the eighteenth century but two writers are worthy of especial notice--Home, a Scotchman, 1765, and Samuel Bard, an American, 1771.

Home deserves credit for having distinctly drawn the line between the pseudo-membranous and the gangrenous affections. He also endeavored to prove that croup and angina maligna were two distinct diseases, notwithstanding all that had been said since the time of Aretæus in favor of their identity. The false membrane of croup he looked upon as an aggregation of mucus. He sought for it exclusively in the respiratory tract, and disregarded any connection between it and the false membrane found in the pharynx.

Bard's experience was very extensive; he saw membranous pharyngitis, laryngitis, and pharyngo-laryngitis; he speaks of the membrane as met upon the skin, of paralysis of the muscles of deglutition and of the larynx, and likewise of paralysis of the lower extremities, as sequelæ. He looked upon the morbific process as the same whichever were the mucous membranes attacked, and made a distinction only according to the localization of the disease. The influence which he might have exercised in shaping the professional opinion on the nature of the disease did not make itself felt, partly because of his classical modesty, and partly because of his remoteness from the centres of European learning. Not before 1810 was his book translated into French (by Ruette). While his style is classical in its simplicity, his observation is astonishingly correct, and his conclusions as to the actual identity of all the diphtheritic processes in the most various clinical symptoms unimpeachable this very day. His description of the various forms of pharyngeal diphtheria is painfully {659} good, his observations on cutaneous diphtheria very accurate, his few dissections well recorded, particularly when he speaks of tracheal and tracheo-laryngeal diphtheria, and his historical reviews very judicious indeed. "Upon the whole, I am led to conclude that the morbus strangulatorius of the Italians, the croup of Home, the malignant ulcerous sore throat of Huxham and Fothergill, and the disease I have described and that first described by Douglas of Boston, however they may differ in symptoms, do all bear an essential affinity and relation to each other, or are apt to run into each other, and, in fact, arise from the same leaven. The disease I have described appeared evidently to be of an infectious nature, and, being drawn in by the breath of a healthy child, irritated the glands of the throat and windpipe. The infection did not seem to depend so much on any prevailing disposition of the air as upon effluvia received from the breath of infected persons. This will account why the disorder sometimes went through a whole family, and yet did not affect the next-door neighbors. Here we learn a useful lesson--viz. to remove young children as soon as any one of them is taken with the disease, by which many lives have been saved and may again be preserved."

Jurine, in his prize essay of 1807, denies the gangrenous nature of angina maligna and emphasizes the frequent complication of membranous croup with membranous pharyngitis. It was reserved for Bretonneau to enforce attention to the ideas of Bard by asserting (though he did not mention either his monograph or its French translation of 1810) the identity of angina maligna, or by whatever other title it may be known, with membranous laryngitis, and by inaugurating his theory with a new name for the disease to perpetuate the views expressed therein. First and foremost, he called attention to the continuity of the membrane (according to him, composed of coagulated mucus and fibrin) of the nose, pharynx, and respiratory tract, its identity with certain morbid conditions of the skin, and promulgated the theory that "diphtherite"--the name dates from that time--is a specific disease, an affection sui generis, and differs both from a catarrhal and a scarlatinous inflammation.

The modern history of diphtheria may be dated from June 26, 1821, when Bretonneau read his first essay on that subject before the French Academy of Medicine, and gave to the disease the name it now bears. His second and third (Nov. 25th) papers belong to the same year; his fourth was read in March, 1826; his fifth appeared in the _Archives gén._ of January and September, 1855. It was only in 1826 that the material, previously gathered, was summed up in his celebrated monograph.[4] Before this time, however, the separate essays had received prominence from the reports and commentaries of Guersant, who laid particular stress on the statement that diphtheria was a non-gangrenous affection, identical, and even synchronous, with croup in the majority of epidemics. Since that epoch the literature on the subject has assumed enormous proportions. It is a matter of regret that the limited space allotted to this subject should exclude much historical detail of the etiology, pathology, and therapeutics of diphtheria. If the history of any disease is interesting, and the neglect of its study has ever punished itself, it is diphtheria. {660} Particularly would the treatment have been more successful if the knowledge of former times had been available and more heeded. As long ago as in the seventeenth century depletion in diphtheria was condemned, and in the seventeenth and eighteenth centuries the local treatment with muriatic acid and the internal administration of cinchona, camphor, and roborant diet were held to be the only admissible ones. Bretonneau urged the same principles, and still in our own times, for want of historical knowledge, we had to learn the old lesson over again.[5]

[Footnote 4: P. Bretonneau, _Des Inflammations spéciales du tissu muqueux, et en particulier de la Diphthérite, etc._, Paris, 1826.]

[Footnote 5: See history and bibliography of diphtheria in Chatto; Sanné, _Traité de la Diphthérie_, Paris, 1874; Jacobi, in _Gerhardt's Handb. d. Kinderk._, vol. ii., 1877; Seitz, _Diphtheric und Croup gesch. u. Klin. dargest_, Berlin, 1879; _Index-Catalogue of the Library of the Surgeon-General's Office, U.S.A._, vol. iii., Washington, 1882.]

The following is a brief review of the main points of discussion upon subjects connected with the symptomatology and pathology of diphtheria since Bretonneau's first paper:

Bourquoise and Brunet express their belief (1823) in the contagious character of this disease. Desruelles (1824) sees a diagnostic difference between the sporadic and the epidemic forms in the participation of the brain in the latter. Louis referred a number of cases of croup in adults to pharyngeal diphtheria as their source. Mackenzie considers that croup has its origin in the fauces, and urges the employment of lunar caustic. Billard (1826) denies the specific character of diphtheritic inflammation. Hamilton describes cases that terminated in suppuration, and which he therefore distinguishes from Bretonneau's cases. He describes two modes of termination of the disease--one in croup, the other in a state of debility arising from the effect of the absorbed secretion on the respiratory nerves. Pretty looks upon those cases of croup that have their original seat in the tonsils as contagious. Bland (1827) explains the difference between croup and diphtheria. Deslandes declares them to be identical. Bretonneau publishes a work in which he compares diphtheria with scarlatina anginosa, and recommends the use of alum. Emmangard is the first one of the physiological school who, likening diphtheria to typhoid and claiming its origin in a malarial infection, calls it angina gastro-enterica. Abercrombie is in favor of distinguishing diphtheria from croup, but reports a number of cases of diphtheria of the pharynx that terminated fatally by stenosis of the larynx. Ribes, who encountered the disease in nine members of a single family, asserts that croup rarely occurred without a preceding diphtheria in his experience; he advises an examination of the throats of apparently healthy individuals. Fuchs relates the history of epidemics of angina maligna, and declares croup to be a genuine angina maligna trachealis, which only does not run through all the stages. Broussais opposes the identity of croup and diphtheria (1829), and gives a report of cures by means of antiphlogistic regimen and laryngotomy. Diphtheria and gangrenous angina are synonymous with him. Gendron expresses a belief in the identity of diphtheria and gangrenous angina. Roche considers the membrane rather of hemorrhagic than of inflammatory origin, and consisting of discolored fibrin. About the same time Trousseau is endeavoring to clearly establish the diagnosis between diphtheria and scarlatinous angina. Shortly after (1830), he reports cases of diphtheria which originated in blistering wounds, and of diphtheria of the skin giving rise to throat affections, and {661} diphtheria of the throat followed by skin disease. T. F. Hoffmann cites a severe case, that ultimately recovered, with consecutive paralysis of certain cranial nerves. Cheyne (1833) makes a stand against the "confounding of croup and cynanche maligna under the name of diphtheritis." Bourgeois witnessed an epidemic succeeding mumps.

Fricout and Burley (1836) declare their belief in the contagiousness of the disease. Bouillaud attacks the theory of its specific character on the ground that abstraction of blood produced favorable results. Stokes makes a distinction between primary and secondary croup according to the original seat of the affection (1837). Kessler advocates (1841) the view of its contagious nature, and Rilliet and Barthez adduce evidence of the occurrence of ulceration and gangrene in the course of the disease. Taupin, like Ribes, enjoins a methodical examination of the throat of every patient during the prevalence of an epidemic of diphtheria, whatsoever be the disease from which the child suffers. Boudet (1842) opposes Bretonneau's hypothesis that croup is a descending diphtheria, and holds to the identity of diphtheria and gangrenous angina. In this contest Durand (1843) also takes sides against Bretonneau, and lays particular stress on the point that the diphtheritic patient succumbs rather from the severity of the constitutional symptoms than from suffocation. Rilliet and Barthez, on the other hand, rally to the support of the attacked master, asserting that the usual form of croup and that resulting from a descending diphtheritis are one and the same, while they claim that diphtheritis and gangrenous angina are distinct affections.

Meanwhile, the strife regarding the nature of the disease continued. Guersant and Blache (1844) describe the stomatite couenneuse (noma, stomacace, according to them, the rarest kind of gangrenous angina) as a form of Bretonneau's diphtheritis, and Landsberg raises the question whether a nerve-inflammation, present in a certain case, was to be looked upon as an accidental or an essential feature of the disease, and finally comes to the conclusion, with Schönlein, that it was a neurophlogosis dependent on the disease. Bouisson (1847) reports a case of diphtheritic conjunctivitis resulting in loss of the eye. Robert publishes his observations on diphtheria of the skin and of wounds, which he attributes to an atmospheric contamination in crowded wards of hospitals, and looks upon it, with Delpech and Eisenmann, as a form of hospital gangrene. Virchow, in the same year, distinguished the catarrhal, croupous, and diphtheritic varieties of the disease. Meanwhile, reports of paralysis of the soft palate after diphtheria came from Morisseau, from Trousseau and Lasegue, and lastly (1854-59) from Maingault. The subject of diphtheritic conjunctivitis was studied by A. v. Graefe (1854), who encountered the disease as a complication of diphtheria of the pharynx, nose, and skin, and hence considered it a part of the general disease rather than an independent local affection. Diphtheria, in its effects on the system, had at the same time been investigated by Trousseau, who sums up with the statement that the principal source of danger lies in the invasion of the larynx, and that the large majority of cases of croup began as a diphtheria of the pharynx, but that, even without the occurrence of a laryngeal localization, many cases terminate fatally owing to adynamia.

Outside of France, too, the subject had attracted attention. West, who had never seen the disease occur primarily, describes diphtheria as a {662} complication of measles. Bamberger (1855) divides the inflammations of the mouth and pharynx into the catarrhal and croupous forms, and considers croup and diphtheria to be subdivisions of the latter form, differing only in degree. The paralysis of the muscles of deglutition is discussed by Dehænne (1857) who had contracted the disease, and the paralysis of other muscles by Faure. A case of diphtheria of the tonsils, nipples, and vagina in a woman recently confined, followed by infection of the new-born and the death of both, is reported by Mathieux; and cases of diphtheritic conjunctivitis by Grichard, Warlomont, and Testelin. The same year Isambert published a work in which he divided the diphtheritic affections into three forms--viz. angine couenneuse, scarlatinous angina, and diphtheritic angina. The last-mentioned is further subdivided into a croupous-diphtheritic angina, in which croup of the larynx plays an important part, and into that form in which death results from adynamia; in the latter form there is a marked swelling of the lymphatic glands. Apparently, at this time the epidemic in Paris underwent a considerable change, for the croupous form does not occur by far so frequently as Bretonneau had asserted, and croup of the larynx without a preceding diphtheria of the pharynx was observed more frequently than he would lead us to believe.

The various changes in the symptoms of the epidemics of diphtheria which were observed in different places and countries, and at different times, explain many of the differences of opinions in regard to the nature of the disease. The literature of that subject is in the last twenty-five years simply stupendous, and a few more notes must suffice for the elucidation of the drift of theories and observations. Beale was the first to look for organic beings as the cause of the disease, without finding any. Laycock sees it in the bacilli and spores of oidium albicans; Wilks, however, found the same parasite in other affections. Cammack declares the diphtheritic membrane to be herpetic. Feron also calls Bretonneau's mild form of the disease a herpetic angina with pseudo-membrane; so does Gubler. Bouchut writes against the identity of diphtheria, croup, and gangrene. Condie describes the disease as occurring with scarlatina. Litchfield claims that it is a concealed scarlatina, and Hillier that it has some connection with it. Millard cites one case in the course of which gangrene occurred, and another in which skin, mouth, pharynx, respiratory passages, oesophagus, and vulva were affected at the same time. Harley vainly endeavored to inoculate the disease in animals. Stephens declares the disease to be infectious. Sanderson looks upon it as identical with the angina maligna of the aged. Farr considered the exhalations from sewers an important etiological factor. Sellerier, Kingsford, and Harley (1859) report paralyses as sequelæ. Maugin speaks of a specific eruption; Ward, of an accompanying purpura. Bouchut and Empis remarked the frequent presence of and danger from albuminuria; so did Wade. Maugin calls attention to the fact that, when present in diphtheria, it occurs early, whereas in scarlatina it is seen during the period of desquamation, and is not of frequent occurrence even then. Gull gives an account of cases in which death resulted from asthenia, and speaks of a nerve-lesion which he attributes to the severity of the local inflammation. Hildige describes diphtheritic conjunctivitis as seen in Graefe's practice, and looks upon it as contagious. Magne denies its contagious or {663} infectious character. Mackenzie, while probably having seen false membrane appear on the conjunctiva when in a state of inflammation, yet refuses to recognize diphtheritic conjunctivitis as a distinct disease.

In the same degree that observations of cases and epidemics increased in number, the nature of the disease and its cause commenced to be studied. The assumption that the latter was a chemical poison was soon doubted, and the parasitic nature of diphtheria considered by many as proven.

After Henle had (1840) expressed his belief in the existence of a contagium animatum, and morbid processes had for some time been compared with the phenomena of fermentation, Schwann demonstrated the presence of lower organisms in fermentation and putrefaction. The discovery of the cause of the silk-worm disease by Bassis, of the achorion by Schönlein, of the acarus by Simon, of bacteria in malignant pustule by Pollender, Brauell, and, above all, by Davaine, in relapsing fever by Obermeier, the teachings of Pasteur concerning the conditions under which putrefaction occurs,--all tended to explain the various infectious and contagious diseases by analogy also, and to stimulate the search for a vegetable organism in diphtheria. Buhl was the first to discover schizomycetæ in diphtheritic membrane, but expressed no opinion as to the part they played in the process. Hüter found them in the gray diphtheritic covering of wounds, in the surrounding apparently healthy tissues, and in the blood. Hüter and Tomasi found them in the diphtheritic membranes of the pharynx and larynx, inoculated them on the mucous membranes of animals, and described them as small, round or oval, dark-colored, active little bodies. The latter observers look upon these organisms as a part of the infectious element. Oertel found them in diphtheritic membrane and in inflamed mucous membranes in the lymphatic vessels, lymphatic glands, kidneys, and other organs; he considers them as the contagious element of diphtheria. Nassiloff, too, after inoculations in the cornea resulted in an enormous multiplication of the microscopic organisms and their appearance with pus-cells in the lacteals and in the lymphatics of the palate, and even in the bones and cartilages, asserts that the development of organisms is the primary step in the diphtheritic process. Eberth made successful inoculations in living tissues; the micro-organisms, introduced into the cornea, proliferated actively and caused an inflammation of irritative character in the surrounding tissue. He asserts, with the positiveness of an evangelist, that diphtheria cannot occur without bacteria. Klebs inoculated the micrococci in pigeons and dogs, and found them in the blood of the animals after death. Orth found them in the pleura, lungs, kidneys, and urinary bladder. But what their action is, whether they are directly pernicious, or deprive the body of certain elements (as of oxygen in malignant pustule, according to Bollinger), or injure mechanically by acting on the coats of the blood-vessels (either directly or by means of altering the blood), thus depriving whole territories of their blood-vessels, is a question upon which the principal advocates of the parasitic theory have not yet agreed. Even Oertel acknowledges the impossibility of explaining the manner in which bacteria act (Ziemssen, _Handbuch_, ii., 1, p. 581, 2d ed.). This much is positive, at any rate: that no one has yet proven that the vegetable organisms alone, and not other, free or fixed, parts of the {664} diphtheritic membrane, are the vehicles of the infecting elements (Steudener); and even now the question has not been decided whether the bacteria met with in diphtheria constitute the cause of the disease, or are a part of the process, or co-effects of the poisonous action--whether they are the carriers of the poison or entirely indifferent entities.

The most important observations made by those who deny a direct etiological connection between micro-organisms and septic diseases in general, and diphtheria in particular, are those of Hiller and Billroth. The latter has proven the morphological identity of the various kinds of bacteria, although it cannot be denied that the apparent similarity may mask a yet unknown difference. Hiller calls attention to the fact that large numbers of micrococci have been found in the cadaver where death has not been the result of septic disease, and also that septic infection is not always severest where the bacteria most abound, but where an extensive chemical decomposition or a mass of putrefying tissue is found. This would indicate that the septic process is rather dependent on chemical decomposition than on the presence of bacteria.

Panum, Bergmann, and Schmiedeberg have isolated poisons that contained no bacteria. Rawitsch and many others prove that septic infection is not dependent on the existence of bacteria. Davaine has shown that an infinitely small amount of a chemical poison, free from bacteria, can kill quickly.

The presence of cocco-bacteria (Billroth) in the blood during life has not once been proven, not even in pyæmia or septicæmia. Yet their being swept into the lungs with the atmospheric air is indisputable. It would therefore seem as though living blood had a greater tendency to destroy bacteria than to allow itself to be decomposed by them. Not only, however, would it seem so, but P. Grawitz (_Virch. Arch._, vol. lxx., p. 546) proves that sporules do not grow in the (tissue and) blood, but that they are in part dissolved, in part eliminated through the kidneys, and that this result is accomplished through the combination of the following four factors--viz. the elasticity of the blood, its constant motion, the absence of oxygen in sufficient quantity in the circulating blood, and the presence of living animal cells. All of these factors appear to be of great importance. Thus it is that, where the constant motion of the blood and the animal living cells are not present (as in the anterior chamber of the eye or in the humor vitreous) a rapid proliferation and accumulation of bacteria can take place. They are also known to increase rapidly and emigrate into the liver when deposited in the abdominal cavity.

The destruction of bacteria in the circulating blood, into which they may have penetrated, accounts for some microscopical facts in connection with (actually or apparently morbid) blood. Their remnants are probably the pale and dark particles which are discovered in the blood alongside the red and white blood-corpuscles. They could not be identified as micrococci, while in the tissue they are more recognizable. In autopsies they have been found in the urinary tubules, pressing forward and piercing the walls, not occupying a nidus of inflammation, however, and probably are even here a post-mortem phenomenon. A direct necrosis or inflammation by the inoculation of diphtheritic elements can only be produced in the cornea, as was shown by Recklinghausen, and particularly Eberth. Besides, there is nothing characteristic in the cocco-bacteria of {665} diphtheria, with the exception, perhaps, of their browner color, to justify their being looked upon as a distinct variety, certainly not as another species. It is more likely that a difference of action is not so much to be sought for in a different parasite as in the peculiarity of the corneal tissue. When fluid containing cocco-bacteria was injected into the eye of a rabbit, in twenty-four hours the eye was destroyed. If injected into the eye of a dog or guinea-pig, only a slight inflammation resulted (Billroth and Ehrlich). If these experiments were continued on a larger scale, we might eventually, by analogy, infer, and even prove, that the immunity against certain diseases enjoyed by some animals is owing to peculiarities in the very structure of their own tissues. In a similar manner I shall prove hereafter that even peculiarities and variations in the tissue and epithelium of the human body give rise to different shades and variable clinical symptoms in the diphtheritic processes.

The views of Curtis, Satterthwaite, and Charlton Bastian fully agree with those of the above observers. The latter is rather inclined to look upon bacteria as an effect of the disease than as a cause. Similar views were expressed by Burdon Sanderson.

Nor are the researches of Weissgerber and Terls, Lukomsky, Weigert, Lücke, any more conclusive; and, finally, Fürbringer, in his most recent and careful studies of diphtheritic nephritis, insists upon this, that it is not caused by immigration of fungi into the kidneys, that the very best methods employed for the finding of parasites result in the absence of micrococci from the inflamed organ, and that the renal inflammation following diphtheria is the result of a chemical process.

H. C. Wood and Henry F. Formad, in Supplement 7 of the _National Board of Health Bulletin_ (1880), declare it altogether improbable that bacteria have any direct function in diphtheria--_i.e._ that they enter the system as bacteria and develop as such in the system, and cause the symptoms. It is, however, possible that they may act upon the exudations of the trachea as the yeast-plant acts upon sugar, and cause the production of a septic poison which differs from that of ordinary putrefaction, and bears such relations to the system as to, when absorbed, cause the systemic symptoms of diphtheria. Now, these bacteria may be always in the air, but not in sufficient quantities to cause tracheitis, but enough when lodged in the membrane to set up the peculiar fermentation; whilst during an epidemic they may be sufficiently numerous to incite an inflammation in a previously healthy throat.

The same authors publish a number of other experiments and conclusions in Suppl. 17 (Jan., 1882): "There is no proof as yet that the micrococci are the cause of the disease. Their presence in the exposed dead tissue is no evidence, for the membrane represents but the necrotic mucous lining.... Indeed, when the healthy mucous membrane of the mouth or trachea is destroyed by caustics--for instance, ammonia--the eschar into which it is converted--really a pseudo-membrane--contains the same micrococci as are found in true diphtheria, as Wood and Formad have learned. Moreover, in the scrapings of the healthy tongue the same micrococci can be seen. Of more significance is the detection of the same or similar micrococci in the blood of the living patients during severe attacks. But since these parasites were found only in the more severe cases, and not in all instances of the disease, were seen also {666} in the blood of other septic disorders, and since no cultures have been made with the fresh blood, there is not yet enough evidence for any decision. In the internal organs bacteria are not found with any regularity in diphtheria."[6]

[Footnote 6: H. Gradle, _Bacteria and the Germ Theory of Disease_, Chicago, 1883, p. 186.]

O. Heubner, while studying both the local affection and the general infection of diphtheria, availed himself of the methods of Cohnheim and Litten, who produced diphtheritic deposits by cutting off the circulation of the blood. He ligated the neck of the bladder in rabbits for two hours. On the first day he noticed a hemorrhagic oedema of the mucous membrane, with loosened and tumefied epithelium; on the second a firm and coagulated exudation took the place of the normal tissue; on the third there were genuine diphtheritic spots in the mucous membrane. The newly-formed pseudo-membrane exhibited all the morphological elements of human diphtheria (genuine or scarlatinous) and epidemic dysentery.[7] Thus Heubner's results agree with the definition of diphtheria as the compound of severe inflammation and necrosis. The inoculation of his diphtheritic artefacts he found sterile. Animals, however, which were inoculated with diphtheritic masses taken from the diseased human patient fell sick with tumor of the spleen, hemorrhages, and general sepsis, besides a local diphtheritic affection. Scarlatinal diphtheria used for the same purpose had the same effect. Bacilli were developed, but they were not found in the blood-vessels (differing in that respect from the bacilli of anthrax), in spite of continued examination. Thus, Heubner refuses to accept the bacilli as the diphtheritic poison; they are, in his opinion, the result of the morbid process, and not its cause. Thus, though he believes the diphtheria poison to be organic, he concludes that its nature is not yet explained; contrary to the assertions of many prolific prophets of the bacteria literature, who now and then claim for this year's microscopic revelations the same infallibility which was claimed for last year's opposite views.[8]

[Footnote 7: _Die Experimentelle Diphtherie_, Leipzig, 1883.]

[Footnote 8: L. Letzerich recognized in former years the specific parasites of diphtheria, whooping cough, and typhoid fever as if they were labelled. Then, again (_Arch. f. Experim. Pathol. u. Pharmacol._), he admitted the great difficulty in discriminating the specific schizomycetæ of diphtheria, croupous pneumonia, epidemic influenza, and typhoid fever.]

E. Rindfleisch[9] expresses himself as follows: "The microphytes of diphtheria, septicæmia, and pyæmia have not been isolated and cultivated as yet. But experimenters are convinced that there are a great many species of microphytes underlying genuine putrefaction. In producing septicæmic conditions in animals their efficacy differs. Not every animal is influenced by the same microphyte. Thus it becomes probable that the human organism is endangered by a certain number of the putrefaction microphytes. Some one may have a particular predilection for granulating wounds and mucous membranes, and thereby produce a diphtheritic inflammation. Another may enter the blood from a recent wound and give rise to a septicæmic fever with rapidly fatal termination. The third may invade the body by means of a phlegmonous inflammation, purulent infiltration, thrombosis, embolism, and metastatic abscesses, accompanied with a pyæmic fever of a remittent type."

[Footnote 9: _Die Elemente der Pathologie_, Leipzig, 1883, p. 301.]

After all, it does not appear to me that the bacteria question has come {667} any nearer its solution in the last few years, in spite of the most eager researches and the fact that some of the best medical names in the world of medicine take the parasitic nature of diphtheria for granted. For instance, in the second Congress for Internal Medicine (Wiesbaden, 1883) C. Gerhardt rises in its favor. He makes the statement, or rather admits, that several parasites have been found by different men, that every one considers his the genuine one, that several writers assume that there are several diphtheria parasites, and suggests that, in his opinion, the disease may be produced by different varieties of bacteria. At the same time, he contends that the essence of the disease consists in the erosion (and change) of the epithelium and the emigration of leucocytes. If that be the case, I understand less than ever why diphtheria is, or is to be called, a parasitic disease.

Panum's words seem still to be the soundest expression of all our knowledge on the subject when he says: "It is a matter of rejoicing that physicians have come to the conclusion that certain microscopic organisms, be they considered vegetable or animal, and designated as bacteria, fungi, monads, micrococci, or vibriones, do not exist merely in the minds of theorists as causes of disease, but are in reality enemies that must be combated with all the known efficient weapons in our possession. But, while thus rejoicing, it must be borne in mind that we have but a feeble insight into the relation between these organisms and diseases, and in order to effect that much-desired advance in scientific knowledge--a matter of considerable importance in the practice of medicine--it is necessary not only to grasp at isolated data, but carefully and deliberately to observe and study all the facts before us, and even to devote some attention to those which would tend to prove that there are bacteria and fungi which, under certain circumstances, are perfectly harmless, and that even some of the malignant ones among them do not commit all those outrages with which they are charged, directly and personally."

SYMPTOMS.--In the majority of cases the disease has a prodromal stage, which usually lasts a day or two, and may run a similar course to that of a catarrhal pharyngitis. The patient feels somewhat indisposed, has slight fever, is dejected, complains of painful deglutition, more marked when swallowing fluids than solids or semi-solids, has headache and occasionally vomiting. The occurrence of the latter, however, is very much less frequent than in the outbreak of scarlatina. In very severe cases convulsions have been observed, chills very rarely; elevations of temperature of from 102.5° to 104° F. are frequent; higher ones, from 105° to 107°, rare. At this time it is often difficult or impossible to distinguish a catarrhal angina from a diphtheritic by the subjective symptoms. Slight glandular swellings under the jaw may occur in either. The characteristic objective symptom of the latter disease is the presence of membrane on the reddened mucous membrane of the fauces, which, usually, is markedly injected over all or part of the surface. The arches of the palate and the tonsils, less frequently the posterior wall of the pharynx, are so affected. A distinctly localized redness cannot be but either traumatic or diphtheritic. Larger or smaller deposits are found thereon, lying loose on the surface or deeply imbedded according to the locality. At times the first examination reveals their presence in large numbers; at other times but a single one can be {668} detected, which is soon followed by others, however. Within a certain period of time, as a rule twenty to twenty-four hours, the single deposits coalesce and form a membrane of greater or less extent. Mostly in the same proportion to its increase in size it increases in thickness. On the uvula, soft palate, and the posterior wall of the pharynx the membrane is located superficially, and at times can be easily removed; on the tonsils it has a firmer hold, and is usually amalgamated with their uppermost tissues. On the other hand, there are cases in which no actual membranous formation is observed; in such cases the tissues are more or less swollen, the surrounding portions more or less reddened, and the grayish-white discoloration is the result of an infiltration of the tissues themselves, and cannot be removed.

There are still other cases in which deposits of membrane and tissue infiltration are found at the same time, and where both history and evidence indicate that these two phenomena are the result of one and the same process. When the uvula takes part in the process the swelling is, as a rule, more marked than when the remaining parts of the fauces only are implicated. Its circumference is very considerable, and amounts sometimes to the treble or quadruple of the normal, in consequence of the oedematous condition of the entire tissue.

We have to deal, then, with three different manifestations of the diphtheritic process: first, with a membrane lying on the mucous membrane, and removable without causing much injury to the epithelium or any to the basement membrane; such membranes were given by some the name of croupous deposits; secondly, with a membrane implicating the epithelium and upper layers of the mucous membrane; to this the title of diphtheritic membrane has been given by preference; thirdly, with a whitish or grayish infiltration of the surface and the deeper tissue, which, if abundant, may give rise to a necrotic destruction of the tissue.

The severity of the disease does not always depend on the predominance of one of these three forms, for any of them may accompany a mild or a severe attack. By a severe attack we understand one attended with chills, temperatures as high as 105° and 107° F., and marked nervous symptoms, such as vomiting and convulsions. It is characteristic of such cases that when the membrane is accidentally or forcibly removed it is speedily reproduced; the lymphatic system, in addition, takes an active part in the process. The neighboring glands become swollen; the periglandular tissue does likewise, so that the circumference of the neck becomes enormous, and the space between the lower jaw and the clavicle appears one immense tumefaction. These are the cases in which, as a rule, loss of strength and general debility speedily ensue, and death occurs from exhaustion. The membrane in cases of this description frequently undergoes changes in appearance; under the influence of the atmosphere and of foreign substances, and by admixture of blood, its color becomes yellowish or brownish. The odor of the membrane and surrounding parts becomes sweetish and musty, and occasionally so fetid that it contaminates the atmosphere of the room, and the air in its transit through the nose and over the pharynx becomes by inhalation dangerous to the patient. His throat becomes more swollen, his respiration loud; he keeps his mouth open constantly, has an indifferent expression; the saliva dribbles continually, the color of the skin is sallow and livid, the {669} appetite very poor, and pulse both frequent and small. When the symptoms are of long duration, and a deep infiltration of the affected parts occurs, hemorrhages not infrequently make their appearance. These may be slight although frequent; occasionally, however, larger blood-vessels are encroached upon in the process of destruction, and dangerous, nay even fatal, hemorrhages may be the result. The septic forms which I have here described are more dangerous than the mild ones previously mentioned. Still, even in the latter bad results may ensue from a direct absorption into the blood of putrid substances and by the penetration of fetid gases to the lungs.

Occasionally, where the infiltration has been extensive, we meet with a condition that can only be considered as gangrene. In such cases we see collections of a grayish pulpy mass, which on falling off leaves a considerable loss of tissue, the further course of the disease being either favorable, or dangerous through absorption of septic material, or accompanied by local hemorrhages. When, after a time, health is completely restored, marked cicatrices are left behind. Such loss of tissue is generally seen in the tonsils only, but it may also be encountered in the soft palate. Its cicatrices on the soft palate are always a source of inconvenience, partly in swallowing, partly in speaking. Actual local perforation of the soft palate I have seen but five times in twenty-five years, sloughing without perforation very often.