Chapter VII: Part II: , Showing Predominance of Malarial Element . . . . 617 (6)

The importance of this distinction is obvious when the occurrence of tumors, called cancers, is observed in parts which contain no epithelium. Aside from the vagueness of the term cancer, as applied clinically, tumors are sometimes met with, even in parts where epithelium normally does not exist, whose structure resembles more or less closely that of cancer as usually recognized. Such tumors are to be regarded as of an endothelial rather than epithelial character, and as such their histogenesis falls under the general laws of the development of tissues.

Waldeyer[85] has suggested that the primitive basis for the development of the genito-urinary tract contains cells which are equivalent in their possibilities of ultimate development to the epithelium of the limiting germinal layers--a suggestion which is of importance in permitting the {118} epithelial tumors of the ovary to be brought under the general embryological laws of development.

[Footnote 85: _Eierstock und Ei_, 1870.]

As the growth of embryonal tissues is so defined that descendants are like their ancestors in all respects, so the development of tissues in the adult is regarded as defined with equal precision. Eberth and Wadsworth[86] have shown that the regeneration of corneal epithelium takes place from pre-existing epithelium. E. Neumann and others claim in like manner the development of muscular tissue from antecedent muscular cells.

[Footnote 86: _Virchow's Archiv_, 1870, li. 361.]

The relation of cancer to epithelial tumors is regarded as similar to that borne by sarcoma to tumors composed of connective tissues. The growth of the epithelial elements into the neighboring parts is through paths determined by pre-existing or new-formed connective tissue. The active element of the cancer lies more especially in its epithelioid cells, and its growth takes place in an atypical rather than a typical manner. Of the various epithelial tumors, there are those like the cutaneous horn or corn, the adenoma or cystoma, whose epithelial growth takes place in accordance with normal methods of production. The epithelioid constituent of the cancer, on the contrary, grows often with great luxuriance and with but little tendency to carry out the normal mutual relations of the epithelium and connective tissue of the part from which it proceeds. The epithelioid masses or sprouts are composed of cells whose relation to each other resembles that of normal epithelium in the absence of an intercellular substance, while the shapes of the cells correspond more or less closely with that of the epithelium in the region from which the tumor arises. The epithelioid cells of cutaneous cancers resemble those of the surface, the rete, or the glands of the skin. Cancers of the stomach or uterus contain epithelioid cells whose shape simulates the varieties in the stomach and uterus. Such resemblances are carried out in the degenerations which the cells of cancer undergo. The horn-like, keratoid, transformation of epidermoid cells in cutaneous cancers, the mucous degeneration of the epithelioid cells of cancers of mucous membranes, are sufficiently familiar. Notwithstanding these resemblances, which are also present in secondary tumors at remote parts of the body, the epithelioid growth advances without limit and without reproducing the normal type. Cancer is therefore defined as an atypical, epithelial new formation.

Sarcoma, on the other hand, whose clinical features correspond so closely with those of cancer, simulates, as shown by Virchow, the connective tissues. It is composed of cells and intercellular substance, both of which may be as varied as are those of the connective tissues. The shape of the cells is as diverse and their contents as various, while their possibilities of degeneration are alike. The cells of the sarcoma are not simply cemented together, as are epithelial cells, but they are separated from each other by an intercellular substance, which corresponds in its appearance and chemical properties with that of mucous, fibrous, cartilaginous, or osseous tissue. The structure of the sarcoma differs from that of these tissues in presenting a predominance of cells over intercellular substance, while the reverse is the characteristic of most varieties of connective tissue. In this predominant cell-formation lies its absence of type, {119} whereas the atypical character of the cancerous growth is manifested rather by the irregular grouping of the cellular masses than by an abundance of cells.

As the original cancer is considered as possible only in parts where epithelium is a normal constituent, so the primitive sarcoma is possible only in parts where connective tissue is present. The apparent great frequency of sarcoma in recent times is thus obviously explained. With an agreement as to its histological characteristics, its possible place of origin is any of the connective tissues of the body, and their presence is universal. In the manner of its growth, its recurrence, and generalization it is subject to the same laws which determine similar events in the history of cancer. Its degenerations are often the same, and its symptoms are due to the action of like causes.

The importance of distinguishing between these atypical tumors is real, in that it is only through the association of causes, symptoms, and results with defined and constant characteristics that a practical knowledge of tumors is to arise. The time-honored distinction between malignant or semi-malignant and benignant growths is always to be sought for, and can only be fully possessed when the natural history of the new formations is known. With an exact appreciation of the structure of a tumor it becomes possible to study its special pathology. From a knowledge of the latter are to be derived those features of importance in determining the relation of morbid growths to other deviations from normal and physiological processes. An immediately practical benefit arises from the Thiersch-Waldeyer modification of Virchow's theory of the origin of tumors, in that it permits with greater ease a more accurate clinical diagnosis. Lücke[87] has been prominent in calling attention to the suggestions thus presented.

[Footnote 87: _Volkmann's Sammlung klinischer Vorträge_, 1876, xcvii.]

The diagnostic value of the theory above-mentioned is rather negative than positive. With rare exceptions, a tumor cannot be epithelial in character if its origin is from an organ or a part in which epithelium is absent. The possible exceptions admit theoretical explanations which present considerable degrees of probability, and are also based upon the existing views of the development of tissues.

A tumor whose origin from the connective tissues is determined partakes of the characteristics of its matrix, and is a connective-tissue tumor. Its development from fibrous tissue is more likely to result in a fibroma; from fat tissue, a lipoma, or a myxoma; from cartilage or bone, a chondroma or osteoma.

Tumors developing at certain periods of life in certain parts of the body are more likely to belong to one than another of the histogenetic groups. Tumors of the connective-tissue series are stated by Lücke as more prevalent before the age of thirty-five years, while those of the epithelial group are more likely to occur after this age, and cancer of the lip is of special frequency in old age. The fibro-myoma is of most frequent occurrence in the uterus, and rarely attains a large size till the approach of the climacteric.

The rapidity of growth of tumors is also associated with their genesis. It has previously been stated that the more rapidly growing tumors are those whose cells are most abundant and in the closest and most {120} intimate relation to blood-vessels. The type of such tumors is the sarcoma with its scanty intercellular substance, while the other (histoid) tumors in the same series, as the fibroma, lipoma, chondroma, etc., are of relatively slow growth. Tumors of the epithelial series are of slow growth, from the constantly increasing distance of the new-formed cells from the vascular connective tissue which provides their nourishment. When, however, the growth of the epithelium advances into the connective tissue, pushing out in all directions and coming in contact with new series of vessels, the opportunities for nutrition are favorable. In like manner, when the new formation concerns the connective-tissue stroma, as well as the epithelial sprouts, vascularization proceeds with the development of the tumor, and favorable conditions for rapid growth are presented. Large epithelial tumors may thus arise within organs, but, as the surfaces are reached, the sources of nourishment become farther removed and the degeneration of the epithelium favors its detachment and the formation of ulcers. Hence the tumors whose advance is associated with ulceration belong rather to the epithelial than the connective-tissue group.

The tendency of the cancerous tumors to become generalized through the lymphatics, and that of sarcomatous growths through the blood-vessels, is admitted as an important feature in the differential diagnosis. Although there are numerous exceptions, the rule is available. Its explanation is based upon the assumed inability of the larger epithelial cells of the cancer to pass through the lymph-glands; being detained, they serve as new centres of growth. The smaller cells of the sarcoma, on the contrary, are permitted a passage through the gland. The numerous and thin walled blood-vessels present in the rapidly growing sarcoma permit an extension of the latter into their interior, and thus a ready opportunity is offered for the formation of emboli.

Another important modification in the classification of tumors has resulted from the recent discoveries regarding the nature and effects of infective agencies. Virchow grouped together under the term granulomata certain growths composed of granulation-tissue occurring in syphilis, lupus, leprosy, and glanders. Their relation to inflammatory processes was very intimate, yet they were recognizable as tumors from their possession of many of the characteristics generally admitted as belonging to such morbid growths. Although at times their presence might be regarded as evidence of an inflammatory disturbance, their frequent appearance independently of general symptoms of the latter was apparent. These tumors, furthermore, were so frequently accompanied by inflammatory products as to suggest a like cause for both. Virchow stated that the recognition of the etiology of these tumors was indispensable to their separate consideration, and laid stress upon the presence of a specific virus, contagious and infectious, in the case of syphilis. His views concerning the etiology of leprosy, though more guarded, yet carried the suggestion of the importance of exact investigation concerning the assumed contagious character of this disease. The contagiousness of glanders was not only admitted, but the similarity of its manner of origin and propagation to the invasion of syphilis was also stated. Not only were the resemblances between glanders and syphilis recognized, but lupus, leprosy, tubercle, and scrofula were also admitted as presenting a similar relation.

{121} The importance of recognizing the etiology of these tumors rather than their anatomy as a basis of classification was strongly urged by Klebs,[88] who proposed the term infective tumors for the group of granulomata, including syphilis, lupus, leprosy, and glanders; and for tubercle, scrofula and the pearly distemper of animals, which Virchow had classified as lymphomata. This group has been still further extended by the addition of the lymphomata occurring in typhoid fever, scarlet fever, and diphtheria. Ponfick[89] has recently added the disease actinomycosis to the series, and Cohnheim suggests that certain of the lympho-sarcomata may be similarly classified.

[Footnote 88: _Prager Vierteljahrschrift_, 1875, cxxvi. 116.]

[Footnote 89: _Die Actinomykose des Menschen_, 1882.]

The growths thus included have a common element of structure--the granulation-tissue, with its possible disappearance through absorption or its transformation into an abscess or dense fibrous tissue. Such features are those common to the granulation-tissue resulting from ordinary inflammation. Their essential characteristic, however, lies in the etiology of this granulation-tissue, and for many members of the group the cause has been discovered to be microscopic organisms. The constant presence of these is determined in sufficient numbers, in such distribution, and in such relation, as to explain the nature and occurrence of the tumors.

The evidence recorded is not equally full and exact for all members of this group. Neisser[90] has discovered the bacillus of leprosy, and the discovery by Koch[91] of the bacillus of tuberculosis, scrofula, and pearly distemper has already been referred to. Schütz and Löffler[92] have lately announced their isolation of the micro-organism causing glanders, and Bollinger[93] discovered the fungus whose presence is necessary for the existence of actinomycosis.

[Footnote 90: _Virchow's Archiv_, 1881, lxxxiv. 514.]

[Footnote 91: See page 99.]

[Footnote 92: _Deutsche medicinische Wochenschrift_, 1882, lii. 707.]

[Footnote 93: _Centralblatt für die med. Wissenschaften_, 1877, xxvii.]

In the above affections the organisms are to be regarded as the characteristic active agent in producing the phenomena of the disease in which they occur. The presence of micro-organisms in syphilis, typhoid fever, scarlet fever, and diphtheria is admitted, yet their absolute identification and constant presence as a cause of the various manifestations of the respective diseases still remains to be proved.

The classification of tumors herewith presented is essentially that of Virchow, with such extensions and modifications as have arisen in consequence of the investigations and discoveries during the twenty years which have elapsed since the delivery of his memorable series of lectures. Cysts are mentioned, as well as growths, from the importance of the former in practical medicine. The frequent simultaneous occurrence of cysts and growths in the same tumor should be mentioned, and the cystic feature is usually indicated as a qualification.

CYSTS.

Cavities, either new formed or pre-existing, with various contents. The latter are blood, liquid other than blood, and gland-secretion or retained secretion. The wall varies in structure in accordance with the method of origin of the cavity.

{122} _Hæmatoma._

A collection of extravasated blood, usually within the tissues. Examples, hæmatoma of the pericranium (periosteum), of the external ear, muscle, dura mater, ovary, broad ligament, vulva, anus, uterus (from retained placenta), hæmatocele, dissecting aneurism.

_Hygroma._

A collection of transuded or exuded fluid in pre-existing or new-formed spaces. Examples, hydrocele, hydromeningocele, hydromyelocele, hydrencephalocele, ganglion, inflamed bursa.

_Retention-Cyst._

An accumulation of retained secretion in follicles or canals from obstruction to its escape. Examples, atheroma and comedo of the skin, mucous cysts of the gastro-intestinal mucous membrane, ovula Nabothi, and cystic polypus of the uterus; retention-cyst of the antrum, vermiform appendage, gall-bladder, and bile-ducts; dropsical dilatation of the ovarian follicles, Fallopian tube, uterus (hydrometra), parovarium (cyst of the broad ligament); hydronephrosis and multilocular cystic kidney, spermatocele, ranula, galactocele.

* * * * *

The growths are classified according to the tissues of which they are chiefly composed and from which they originate, and according to their etiology. There are consequently the connective-tissue group; that of tissues of higher function, as muscle, nerve, and vessels; and the epithelial group, in which the new formation of epithelium is the essential feature. The teratoid group comprises a more complex massing of tissues, representing a combination of those derived from all the germinal layers of the embryo. The infective group includes those tumors whose structure is closely allied to that of the products of inflammation, but whose origin is the direct result of the introduction from without of a microphyte.

CONNECTIVE-TISSUE GROUP.

Each member mainly composed of a more or less typical growth of a connective tissue:

Myxoma,
Lipoma,
Glioma,
Chondroma,
Fibroma (including papilloma and melanoma),
Osteoma.

To these are added tumors composed of an atypical growth of a connective tissue, chiefly manifested by a predominance of cells:

Endothelioma,
Sarcoma.

The sarcoma includes as many varieties as there are tissues in this group, hence,

Myxosarcoma,
Liposarcoma,
Gliosarcoma,
Chondrosarcoma,
Fibrosarcoma, melanosarcoma,
Osteosarcoma.

{123} GROUP OF TISSUES OF HIGHER FUNCTION.

Myoma, of striped (rhabdomyoma) and smooth (leiomyoma) muscular
tissue,
Neuroma, of nerve tissue,
Angioma, of blood-vessels,
Lymphangioma, of lymphatics,
Lymphoma (?), of lymph-gland tissue.

EPITHELIAL GROUP.

Epidermis:

Callus,
Corn,
Keratosis,
Horn,
Onychoma.

Epithelium of mucous membranes or glands:

Struma (?),
Adenoma,
Cystoma.

In the above varieties the growth of epithelium is more or less typical, a simple hyperplasia, either alone or combined with the new formation of fibrous tissue. Only the last three members of the series are tumors in the limited sense.

CANCER.

Cancer remains as an epithelial tumor, representing the atypical growth of cells resembling epidermis or the epithelium of glands and mucous membranes, extending into parts where epithelium is not found as a normal constituent. A new formation of connective tissue is usually associated with that of the epithelial cells.

Numerous varieties of cancer are described, according to the physical and structural peculiarities of the tumor. The scirrhus and encephaloid of the earlier writers are now transformed into fibrous and medullary cancer. This change in name is due to the stress laid upon the predominance of the fibrous stroma as the usual cause for the hard, dense, scirrhous cancer, while an abundance of epithelioid cells in relatively large alveoli is present in the encephaloid, marrow-like, medullary variety.

When the growth takes place from the skin or mucous membranes, the surface frequently presents numerous and usually arborescent papillæ or villi. The papillary cancers of the skin and the villous cancers of mucous membranes are thus distinguished.

Cancerous growths of the skin and transitional membranes, often called epithelioma or cancroid, usually contain epithelioid cells resembling epidermis, and are therefore designated as epidermoid or pavement-celled cancer. The alveolar contents of certain cutaneous cancers are cells resembling those of the deeper layers of the rete mucosum, while those of other cancers of the skin resemble rather the epithelium of sweat-glands. Growths of the former character extend laterally, ulcerate early, and are known as superficial cutaneous cancer. They form one of the varieties of the so-called rodent ulcer. Cutaneous cancers, simulating in their structure a reproduction of the epithelium of sweat-glands, represent a variety of glandular cancer. The latter term is applied to cancerous growths which arise in glandular organs, with suggested resemblances of their cells to the gland-cells of the respective organ. {124} Cylindrical-celled cancer is frequently met with in those parts of which a cylindrical epithelium is a normal constituent.

The degenerations of the epithelioid cells and stroma suggest qualifying terms. The mucous and colloid cancers are those whose alveolar contents or stroma have undergone a mucous or colloid degeneration. The keratoid cancer is one which presents the horn-like transformation of its epidermoid cells. The melanotic cancer contains abundant pigment, melanin, within its cells.

These differences in the structure and appearance of the tumor are frequently associated with certain modifications of growth and clinical properties. The epidermoid cancers are less likely to recur after early removal; the medullary cancers are of rapid growth and prone to ulceration; while the fibrous or scirrhous forms are of extreme slowness of growth. In general, however, the pathological importance of cancerous tumors is essentially the same wherever the seat and whatever the peculiarities of structure.

TERATOID GROUP.

Includes those tumors, usually of congenital origin and apparent at birth, composed of connective tissue, epithelium, nerves, muscle, and vessels. These tissues are often so grouped together as to suggest systems of the body and parts of an individual. Cysts are often present which simulate cavities found in the body, whether of normal or pathological origin.

In this group are the dermoid cysts with their various contents, epidermis, sebum, hair, teeth, and bone. The solid teratomata, with all varieties of connective tissue, as fibrous tissue, fat tissue, cartilage, bone, neuroglia, in addition to nerves, muscle, and vessels. Squamous, cylindrical, and ciliated epithelium may be present and line cavities, at times tubular, whose walls are formed of skin or mucous membrane. Other tumors of this group are commonly included under monstrosities, and comprise the varieties of duplication of parts of the body, of which the extreme instances are such double monstrosities as the Siamese Twins, Ritta and Christina, the Spanish Cavalier, and the like.

INFECTIVE GROUP.

The chief characteristic is the cause, micro-organisms, which, introduced into the body, produce, through their dissemination and development, multiple growths of tissue like those resulting from persistent inflammation. As their structure corresponds with the productive results of inflammation, and their cause is analogous to the infective causes of inflammation, these morbid growths are closely allied to inflammatory disturbances. Their classification among tumors is desirable, as they represent circumscribed growths whose appearance, persistence, and effects closely resemble those characteristics of the morbid growths, in the limited sense, in which the new formation of tissue occupies a wider range:

_Granuloma_ of tuberculosis, scrofula, leprosy, glanders,
actinomycosis, syphilis, lupus.
_Lymphoma_ of diphtheria, scarlet fever, typhoid fever.

{125}

GENERAL ETIOLOGY, MEDICAL DIAGNOSIS, AND PROGNOSIS.

BY HENRY HARTSHORNE, M.D.

ETIOLOGY.

Recognizing pathology as simply morbid physiology--that is, the study of the body and its functions in states of disorder from morbid conditions--how these morbid conditions are produced is the complex question to be answered by Etiology.

Nor is this question (or series of questions) by any means only of speculative or theoretical importance. It is, indeed, eminently practical. What a difference, for example, there must be in the diagnosis, prognosis, and treatment of an attack of inflammation of the eye, in accordance with its causation by ordinary conditional influences (taking cold), by a particle of steel imbedded in the cornea, or by syphilis! How great the difference between the wound made by the teeth of an animal, in one case with, and in another without, the presence of rabies in its system! Take the instance of what we call fever: at a certain stage it is almost the same in half a dozen diseases. By the causation, when known, of this common congeries of symptoms we judge of the essential nature of the malady, and so of its proper treatment.

It is a maxim in philosophy that every event or effect must have at least two causes. In medical etiology we often find many causes conspiring to produce one effect. These may be, and commonly have been, grouped together under two heads; as, 1, predisposing, and 2, exciting, causes. But under each of these may come a number of agencies contributing toward the production or modification of disease. Thus, of predisposing causes we may enumerate inherited constitution, habits of life, previous attacks of disease, atmosphere, and other immediate surroundings. Exciting causes--say, of an attack of apoplexy--may be, in the same case, mental shock, a stooping posture, an over-heated room, etc. One disease is very often the next preceding cause of another. So we speak of the great class of sequelæ of acute or subacute disorders; as, ophthalmia after measles, deafness following scarlet fever, or blindness small-pox, abscesses following typhoid fever, paralysis diphtheria, etc. But this kind of causation is extremely common also in chronic affections. What a train of organic troubles, of kidneys, heart, arteries, brain, and other parts, attend the affection to which we give the name of Bright's disease! How complex the sequence often of valvular disease of the heart, itself in many instances the effect of rheumatic fever, with {126} endocarditis as a local manifestation of that disorder! Hardly any discovery in pathology (or pathogeny, the generation of diseases) of the last half century has been more remarkable and fruitful than that of thrombosis and embolism, with their serious and not rarely fatal consequences, through obstruction of the blood-supply to different organs.

Previous diseases constitute an often overlooked class of factors in predisposing to new attacks, and also in determining their course and results. Of some affections one attack prepares the way for another, as is the case with intermittent fever, convulsions, delirium tremens, and insanity. Just the reverse is true of yellow fever and of all the exanthemata, as scarlet fever, measles, small-pox; likewise of the analogous disorders, mumps and whooping cough. The moot question in this regard concerning syphilis may be left for discussion elsewhere.

Our classification of the causes of disease may be set forth in simple form, thus:

1. Pre-natal causation--viz. hereditary transmission of a proclivity to certain disorders, and also the influence of circumstances acting on either parent at the time of conception or on the mother during gestation.

2. Conditional causation--_i.e._ that belonging to variations of temperature, humidity, etc., affecting individuals.

3. Functional causation--that which is connected with excessive, deficient, or abnormal exercise of any of the functions of the economy.

4. Ingestive causation--_e.g._ bad diet, intemperance, poisoning.

5. Enthetic causation--viz. that of all contagious, endemic, and epidemic diseases. Closely allied to this is epithelic morbid influence--namely, that of the parasites producing certain affections of the skin, as itch, favus, etc.

6. Mechanical causation. The effects of this belong chiefly, though not exclusively, to the domain of surgery.

Pre-natal causation is of immense consequence, and its study takes in the whole scope of the influences of species, race, family, and individual parentage. Darwin's observations and speculations, and those of other evolutionists, have not ignored the field of human life in considering the struggle for existence and the survival of the fittest. If we are obliged to admit that such a struggle and survival do exist for men as well as for animals and for plants, it is nevertheless obvious that either man's reason and will introduce exceptions to the ordinary laws of development and selection in nature, or else a very peculiar standard of fitness must be recognized in the survivals of humanity. Many feeble, inert, deformed, and diseased forms survive and perpetuate offspring through a long series of generations, while strong and admirable ones perish, often even destroying each other.

Leaving this theme, upon which biological science has not yet pronounced its last word, we may inquire, What diseases are reasonably ascribed to hereditary transmission? First, it must be remarked that seldom is a disease actually received directly from a parent. Putting aside a few asserted instances of variola and allied or analogous affections in utero, congenital constitutional syphilis and (more rarely) scrofulosis seem to afford almost the only examples of this. Nearly always it is a predisposition merely that is inherited. This, however, may be very strongly marked. Its seat is evidently in that (as yet) occult law or {127} process of individual organic development to whose manifestation we give the name of the constitution. In some families all the men grow bald before forty; in others, scarcely so at eighty. Some may expect deafness in middle life, others blindness in old age, and others, again, have a probability of death from disease of the heart at about fifty or apoplexy at about sixty years of age. Such considerations enter into every examination for life insurance, and they are no less important in our prognostications of the results of diseases in practice.

Speaking more definitely, gout is undoubtedly often hereditary. That is, a healthy childhood may be followed by liability to gout in adult or middle age, even in the absence of direct provocatives to that disorder, but much more frequently when they are present. Gout affords an example of the general fact that inherited proclivity to special diseases shows itself at nearly the same time of life in each generation--scrofula in childhood, phthisis in adolescence or early maturity, gout from thirty to forty, apoplexy after sixty, etc. But exceptions to such rules are not at all rare. Gout also exemplifies another important fact--viz. the occasional modification of the transmitted morbid tendency or "diathesis." Parents who have regular gout--_i.e._ painful attacks of acute inflammation of the smaller joints, followed by deposits of urates, carbonates, etc.--not unfrequently have children who are subject to neuralgia or dyspepsia or modified rheumatic attacks (not sufficiently recognized in practical treatises), to which the name "gouty rheumatism" is most applicable. Again, in one generation there may be a marked tendency to insanity; in the next, to paralysis; in a third, to tubercular meningitis during infancy.[1] Or some of these successions may occur in a reverse order.

[Footnote 1: For example, in one family known to me the grandmother had paralysis, the mother died insane, and her three children all died of tubercular meningitis.]

Constitutional syphilis is undoubtedly often conveyed by inheritance from either parent. Sometimes the impression of this diathesis is so intense as to devitalize the foetus in utero, causing still-birth. Or the manifestations of the disease occur early in infancy, with symptoms like those of the secondary or tertiary affection in the original subject of it. Not often, indeed, is the exhibition, in some manner, of inherited constitutional syphilis delayed beyond the time of childhood.

Scrofulosis is well known to follow in the same family through successive generations, in a manner apparently demonstrative of hereditary derivation. It is true that here we have a problem not without complication. Certain circumstances, as poverty of living, dampness of locality, want of fresh air in houses, etc., promote scrofula in children. Now, are we sure that it is from its parents that each child, exposed to these morbific surroundings, has obtained its disposition to strumous disorders? or may it not be that every time the diathesis is thus originated de novo? It is to be answered that decisive evidence in favor of inheritance is present in a number of cases where the affection occurs so early in infancy as to be almost or quite congenital in its beginnings; and in other instances where removal of the parents into improved localities, and with better living altogether, has not prevented the manifestation of the same tendency in their offspring for two or three generations. The inquiry does not differ very greatly in its nature from that concerning cases of enthetic diseases--_e.g._ cholera, yellow fever, typhoid fever; as to which the {128} succession of cases may be such as to allow hypothetical explanation, either by transmission from one individual to another or by the subjection of all to a common local infection or epidemic influence. But in both sorts of cases crucial instances may, with care, be found which determine at least the general etiological law for each malady.

Pulmonary phthisis has been always considered to be, in a marked degree, a hereditary disease, until, latterly, the hypothesis of a tubercular virus has threatened to displace old views about it. If, however, we accept the classification of cases of pulmonary consumption approved by several leading pathologists, in which a position is provided for non-tubercular phthisis, we may at least place hereditary vulnerability, or proclivity to consumption, in this category, while awaiting the final decision of science upon the real nature and origin of tubercle. My own conviction continues to be positive, that tubercular phthisis is often transmitted by inheritance, in the same sense as other diseases are generally so--namely, by the bestowal upon offspring of a constitution especially liable to the occurrence of the disorder at the time of life when it is generally most apt to appear. The investigations of Villemin, Cohnheim, Schüller, Koch, Baumgarten, and others have given (1882) much prominence to the idea of the possibility of the transplantation of tubercle from one human or animal body to another. Koch's elaborate experiments especially are asserted to have shown the existence of a bacillus tuberculosis, a true, minute vegetative organism, which can be cultivated outside of the body, in a suitable material, at a temperature like that of living blood, and which, when inoculated, produces tubercular disease. The discussion of this subject will occur on a later page as a part of the general topic of the causation of enthetic diseases.

Rickets occupies a much less prominent place in the experience of American practitioners than in that of some countries abroad, and it is therefore less easy here to obtain materials for the study of its etiology. Among those who have had large opportunities for its observation, opinion is divided very much in the manner above referred to. Thus, Wiltshire and Herring assert it to be certainly hereditary; Jenner denies this altogether, while Aitken adopts the ground that predisposing causes are derived from the parents or the nurse, which are so capable of influencing the health of the child as to lead in course of time to the establishment of the disease.

Goitre is manifestly a family disorder to a large extent in certain regions, most familiarly in Alpine valleys in Switzerland. But this local feature takes us back to the same kind of question: Is it the transmission of a specially modified constitution from parents, or the direct action of morbid local influences on the children themselves, that produces bronchocele and its frequent attendant, cretinism? Undoubtedly, goitre often occurs in children of healthy parents brought from another locality into one where the disease is common; and, per contra, goitrous subjects not infrequently recover from the affection when removed for a length of time from the place where it was developed in them. We are, apparently, at least safe in taking here a position like that of Aitken concerning rickets: viz. that predisposing causes are derived from parentage, whereby, more easily than in those of different descent, certain influences will develop goitre or cretinism, or both together.

{129} As to leprosy, there seems no more room for doubt that it is often--nay, generally--hereditary. The obscurity attending its history, however (more than one cutaneous affection having been from time to time classed under the same name), will justify our referring the reader for the particular discussion of its etiology to another part of this work. (See DISEASES OF THE CUTANEOUS SYSTEM.)

Hæmophilia is clearly hereditary in certain families. Immermann asserts it to be even a race-liability in the Jews. "Bleeders" upon occasion of very small wounds of the skin, gums, etc. have been known in several successive generations, including (Börner; Kehrer) women at the time of parturition, who then are apt to have dangerous hemorrhages.

Cancer presents as unmistakable examples of inheritance as any other disease. Paget asserts this to be traceable in one case out of three; Sibley, in one of nine; and Bryant, one of ten cases. De Morgan and others have shown the same thing to be true of non-malignant morbid growths. But, as Paget has remarked, when other local disease or deformity is inherited, it usually involves in the offspring the same tissue, often the same part of the body, as in the parent, but the transmitted cancerous tendency may show itself anywhere: "Cancer of the breast in the parent is marked as cancer of the lip in the offspring. The cancer of the cheek in the parent becomes cancer of the bone in the child. There is in these cases absolutely no relation at all of place or texture."

Cataract is believed by good authorities to be promoted by hereditary tendency. It is of the nature of a degeneration. Possibly, in a greatly-prolonged decay of all the organs with age, all eyes tend to become cataractous from structural alteration of the crystalline lens. Under observation a quite different rate of degenerative change takes place among the organs of the body in different individuals and families. Thus, the lens becomes opaque in some at an age when the hearing continues good and the muscles retain considerable vigor, while in members of other families the eyes remain in a sound condition at a time when other organs and powers have failed. Congenital cataract appears to be altogether independent of any proclivity transmitted from parents in the nature of an inheritance.

Affections of the nervous system very often show hereditary descent. Neuralgia prevails strongly in certain families. Particularly, that form of cephalalgia called sick headache is apt to appear, in the periodical form, through several generations. Apoplexy and paralysis are prone to occur at nearly the same time of life under the transmission of like constitutions by parentage. Still more often this has been observed of epilepsy and hysteria, and, most of all the neuroses, in insanity. Monomania and melancholia have been in a great number of instances traced to generative succession--sometimes, especially suicidal monomania, through four or five generations. Predisposition to intemperance, methomania, is also a terrible inheritance in some families. Although the production of this malady requires the provocative of indulgence in the use of alcohol for its development, yet the facility with which this result occurs under the same circumstances in different families is too marked to leave room for doubt of its hereditary nature.

Less certainly, but with much probability, we may assign parental endowment as one of the factors in the causation of organic disease of {130} the heart, arteries, liver, and kidneys, as well as of angina pectoris, asthma, croup, dyspepsia, and hemorrhoids.

Is a special proclivity to any of the group of enthetic febrile diseases ever inherited? Dr. George B. Wood believed this to be the case with enteric or typhoid fever. Few others have shared this opinion, but it is not impossible that it has a basis of truth.

Reference has been made already to the difference between periodical malarial fevers (intermittent, etc.) and yellow fever, in that an attack of the latter does, and one of the former does not, protect the individual, usually, from liability to the disease on exposure to its cause. Does this protection extend to offspring of parents who have been "acclimatized" to yellow fever? Facts on this point are not easy to obtain. While, however, there appears to be no proof that a single generation can ever suffice to outgrow (so to speak) liability to this disease, it is well known that creoles in Louisiana and the West Indies are less susceptible to it than recent white residents, and that the negroes are much less so, as a race, than the whites. Furthermore, negroes whose ancestors have long been domesticated in our Southern States appear to re-acquire susceptibility to yellow fever in a degree more nearly like that of white people than is observed in natives of Western Africa imported within one or two generations.

As to autumnal malarial fevers (remittent, intermittent), the black race exhibits a sort of race-acclimatization, giving negroes, both in Africa and in America, a much less degree of liability than is common to all races of European descent.

How far any similar modification may occur in the course of generations in regard to susceptibility to small-pox and allied diseases remains at present a matter of speculation. Some authors insist that there must be at least a kind of natural selection, according to which a great epidemic of variola, destroying the lives of many of those most predisposed to suffer from it, will leave the remaining population less likely to be attacked by it. The endeavor has even been made to explain away in this manner much of the diminution of mortality from small-pox commonly credited to vaccination. But the statistics of the ravages of variola in different countries before and after the introduction of vaccination show that, while we cannot deny that some alternation (of generations respectively more and less susceptible) may occur, no such law can compare in influence with that of vaccination in the protection of individuals subjected to it. Indeed, the argument may be inverted; thus: if in the days before Jenner small-pox itself weeded out the persons most liable to it, or in some way prepared a partial family- or race-protection, such a protection ought to be gradually conferred upon a whole population through universal and persistent vaccination carried on for several generations.

Is it possible for one hereditary constitution or diathesis to become, in transmission, not only modified, but transmuted, into another? Some of the older pathologists imagined this to be the case with syphilis, to whose past influence upon parents and ancestors they traced the origin of scrofula. But no sufficient ground for such a pathogeny can be ascertained. All that appears to be left after scrutiny of the facts is, that syphilis is a depressing and perverting agency, and so may join with {131} other depressing causes in preparing the way for the engendering of scrofulosis.

A few points still remain to be briefly mentioned in connection with the hereditary conveyance of proclivity to disease. One or several members of a family will often pass through life without any manifestation of such transmission, while others, their brothers or sisters, give marked evidence of it. Sometimes a whole generation may be passed over, and yet the predisposition may be abundantly shown in that next following. This is closely similar to atavism, as it is called in zoology and general biology, according to which traits occurring under admixture or variation of animal or vegetable stocks may be absent in the immediate offspring of a couple, but reappear in their next succeeding descendants, or even a still later reversion may take place. Such instances are not rare, and they need to be considered in the proper study of the influence of parentage, intermarriage, etc. upon health and disease.

A practical question of much importance (belonging, however, rather to sanitary than to medical science) is, how far confirmation or modification of hereditary proclivities may occur through the effect of the conditions of marriage upon offspring. Consanguineous marriages have been, time out of mind, held to be very objectionable. The question has been much discussed whether the ground of sanitary objection is properly against such marriages as per se injurious to offspring, or whether the bad effect consists merely in reduplicating and intensifying family constitutional taints. It would not be in place here to go into this controversy. My own conclusion is, that a natural law of sexual polarity or affinity exists, according to which, in all the higher organisms, reproduction is most normal and gives the best results when a considerable genetic difference (within the limits of species) exists between parents. While, however, this is probable, but difficult to demonstrate, it appears to be certain that when a father and mother both possess morbid constitutional predispositions (say, to phthisis, insanity, or gout), their children will be at least twice as likely to suffer from the same as if only one parent were so endowed. Whether or not, then, the marriage of two perfectly healthy first-cousins may be expected (as several statisticians aver to have been shown) to be attended by defects of health in their progeny, the union of such relations when their common progenitors were in marked degree consumptive, or scrofulous, or liable to insanity, epilepsy, etc., has attached to it so unfavorable a prognosis for offspring as to be rightly forbidden. Moreover, so few families possess an absolutely faultless health-record that the chances of increasing existing morbid traits by intermarriages are quite sufficient to justify the commonly held objection against them.

We must allude very briefly to the influence of conditions affecting conception and gestation upon the health of offspring. Intemperance in parents has, in many instances, been known to promote convulsions, infantile or epileptic, and other cerebral or nervous disorders in children, besides a general feebleness of constitution. Even intoxication at the time of procreation has been asserted to mark a similar difference between one child and another of the same parents.

All are familiar with the (no doubt often quite imaginary) accounts of the effect on infants in utero of powerful sensory or mental impressions upon the mother during gestation. Abortion has, unquestionably, been {132} often produced by violent nervous shocks. Without deciding the question whether "monsters" are ever developed in correspondence with particular experiences of the mother, we may hold it to be clear that all depressing and disturbing agencies may interfere with the process of nutrition of the foetus, and thus develop mental anomalies, and that constitutional impairments may thus be greatly promoted.

All inherited predispositions, it is important to remember, are aggravated, and each proclivity changed to actuality, by those influences which in individuals tend to like effects upon health. Such become exciting causes of various diseases. If these be constantly avoided, and all the surroundings and the mode of life of the individual be maintained in a manner most favorable to health, the hereditary tendency may remain inert through a long lifetime. Every physician must have seen this in scores of instances. The application of the principle through special precepts belongs to personal hygiene. But no physician can rightly ignore the study of this subject, or omit the utilization of his acquaintance with it by preventive advice to members of the families under his professional care.

Our last remark in connection with pre-natal causation must be upon the effects of circumstances and modes of living on masses of men, especially in large cities and populous countries. Something has been said already of race-acclimatization by which there may be acquired a lessened susceptibility to certain endemic fevers.[2] Almost a reverse action is exhibited in the gradual lowering of vital energy under what has been called the "great-town system." While those having all the comforts of life and avoiding excesses may manifest but little of this deterioration, it is very observable in that mass of men, women, and children who become the subjects of medical charities. Closeness and uncleanliness of living, with more or less exposure to dampness and extremes either of heat or cold, with intemperance and syphilis, are the main causes of this general constitutional impairment. So important is it that it should never be forgotten, not only in our estimate of the causation of diseases, but in our anticipation of their results, and also in our adaptation of measures of treatment, medical and surgical, to different classes of patients. All that it is allowable here to suggest in this regard may be summed up (although very imperfectly) in the word hospitalism.

[Footnote 2: It is important (but not before remarked in this article) that cholera does not appear to allow of any such diminution of liability to it among the natives of the country in which it is endemic.]

Conditional causation has been, to a certain extent, included under what has been above said, as it is the action, in part at least, of surrounding conditions, that establishes a family- or race-proclivity and inheritance. But we must say something more about the direct action of conditions upon individuals.

Man, although organized with great delicacy of structure, is capable, by the use of his intelligence, of adapting himself to a wider variety of external conditions than any other animal. He is the only truly cosmopolitan being on the earth. From the remote Arctic regions to the hottest tropical climates there are tribes whose ancestors have dwelt for centuries in the same localities. Not that no unfavorable influence attends these extremes. The Esquimaux are stunted, the Southern Hindoo and {133} Central African are enfeebled and degenerate, partly from climate. But with man's numerous protective devices, great cold and great heat only exceptionally affect individual health. Freezing to death follows unusual exposures; the loss of an extremity by sphacelus from congelation is more often met with; heat-stroke also is tolerably frequent; and the influence of heat in producing cholera infantum in some large cities is very important; but much the most common kind of conditional morbid causation is produced either by sudden changes of temperature or by diversity of exposure of different parts of the body. These are the two usual modes of "taking cold." When dampness accompanies a relatively low temperature, such an effect is much more apt to follow than in a cold dry atmosphere.

Actual cold-stroke, the analogue of heat-stroke, may sometimes happen. I once saw such a case in a previously healthy boy twelve years of age, who, after standing for an hour in his night-shirt on a cold winter night, became almost immediately ill, fell into a comatose state, and died in about thirty-six hours.

A simple rationale may be discerned for the phenomena of catching cold. When, for example, a draught of air blows for a time upon the back of a person at rest (especially one who has just before used active exertion), the local refrigerant impression induces constriction of the superficial blood-vessels. Hence follow two effects: one, the repulsion of blood in undue amount toward interior organs; the other, diminution, perhaps arrest, of excretion from the skin of the exposed portion of the body, and consequent retention of some effete material, promoting esotoxæmia.[3] If, then, there be in the body any weak organ--that is, one whose circulation is partially impeded or whose nutritive and functional activity is low--it suffers first and most from the impulsion of blood from the surface. Congestion, irritation, and inflammation may follow, and we have an attack of pneumonia, pleurisy, bronchitis, or some phlegmasia.

[Footnote 3: That is, blood-poisoning, originating within the body itself; exotoxæmia being that which is enthetic--_i.e._ resulting from a poison derived from without.]

Excessive heat with dryness, as under the blasts of the Simoon or the Harmattan of Arabia or Northern Africa (apart from insolation, sunstroke, or heat-stroke), may sometimes parch the body even to a fatal degree. Much more common is the combination of high temperature with humidity. This has a relaxing effect, promoting indolence of temperament and predisposing to disorders of a catarrhal nature, especially of the digestive organs, such as were called fluxes by the older writers.

Cold climates are well known to present the greatest number of cases of acute and chronic affections of organs of the respiratory system; warm and hot climates, those of the stomach, liver, spleen, and bowels. But we must recollect what various complications belong to climate. Two important factors, especially, must be kept in view in comparing the causation of diseases in colder and warmer countries--namely, the difference in the articles of food partaken of in each, and the external sources of enthetic disorders; _e.g._ endemic and epidemic fevers, etc.

With humidity must be considered variations in atmospheric pressure. Physicists have long known that while watery vapor, by itself, is heavier than air which is perfectly dry, moist air is lighter than air containing {134} little or no moisture. Hence the barometer falls as the quantity of atmospheric moisture approaches saturation. Other causes, however, also affect barometric pressure. With the same degree of humidity, cold air is denser and heavier than warm air, and by its contraction lowering the "column" of atmosphere--the temperature of which is reduced--a flow toward the upper part of the column increases the actual mass of air pressing upon a particular place. Elevation of a locality above the general level of the earth reduces atmospheric pressure, sensibly as well as measurably. So "the difficult air of the iced mountain-top" has become proverbial.

These variations are familiar, though all their effects upon human health have been by no means, as yet, fully studied. Most difficult to determine and analyze are the influences of changes of pressure, chiefly hygrometric, upon the course of diseases and upon the result of severe surgical operations. Among the few important series of observations bearing on this topic have been those of Dr. S. Weir Mitchell on neuralgia,[4] and Dr. Addinell Hewson on the prognosis of major operations,[5] in connection with the state of the weather. The former ascertained a marked relation between the approach of a wave of low barometric pressure and attacks of irregularly periodic neuralgia; the latter proved, by the statistics of the Pennsylvania Hospital for a number of years, that the most favorable time for amputations or other capital operations is when the barometer is high, or at least on the ascent.

[Footnote 4: _American Journal of Medical Sciences_, April, 1877, p. 305.]

[Footnote 5: _Pennsylvania Hospital Reports_, 1868.]

Electrical atmospheric states and vicissitudes have, quite probably, a practical consequence beyond what is usually ascribed to them in connection with health and disease. But their effects are so difficult to disentangle from those of other meteorological causes that we must be content at present without attempting their exact specification. The same observation may be made with reference to ozone.

Elevation of site has importance, not only in regard to climatic hygiene, but also to its therapeutic use, particularly in the treatment of phthisis, goitre, and some affections of the nervous system. But in our brief and general survey of Etiology this topic must be left without discussion, since no disorder appears to be traceable to elevation alone, beyond the temporary prostration on exertion, with hemorrhages from the nose, lungs, etc., often produced in those who climb to great mountain-heights or ascend rapidly in balloons. It has been shown by ample experience that considerable populations may live in ordinary health through long periods at altitudes more than 10,000 feet above the level of the ocean.

Depression below the surface of the earth has never become a part of human experience beyond the limit of a few hundred feet. Miners living underground in a few places in Europe have been found to exhibit comparatively feeble health, but the privation of sunlight, the confined atmosphere, and the dampness of such unnatural abodes will suffice to account for these effects.

Under functional causation of disease we may include all excessive, deficient, or abnormal exercise of any of the organs of the body. To simple excess may be ascribed the scrivener's or bank-officer's paralysis of the muscles of the hand used in continuous writing; brain {135} exhaustion from mental labor or anxiety, unrelieved by sufficient sleep; and sexual impotence, temporary or lasting (or sometimes even general paralysis), from inordinate sexual or sensual indulgence.

Deficiency of functional exercise is observed to produce disability, as when the muscles of a limb, for instance, are for a long time restrained from use. Surgeons meet with this inconvenience (unless assiduously guarded against) when a fractured limb is kept long at rest in a fixed position. Atrophy of the mammæ in single women of retired lives is common; atrophy of the testicles in unmarried men much less so. These changes, however, are physiological, not pathological; upon alteration of conditions--_e.g._ marriage--the atrophy will disappear altogether.