syphilis, malaria, typhoid, la grippe, etc., that it is impossible to ascribe any specific relation to them.

In Berlin in ten years there were admitted to the three large city hospitals 148,000 patients, of whom 274 were diagnosed as pernicious anemia, that is, about 2 per cent of all of the hospital cases. It is also stated that 22.4 per cent of the above cases showed evidences of syphilis. This indicates, if it mean anything, that a small percentage only of syphilitic patients develop pernicious anemia. It is said that individuals of a weak constitution and poor development are especially liable to the disease, yet the strong and full blooded may develop it. The disease occurs more frequently in women than in men. Of the 274 cases mentioned, 172 were women, and 102 men. It may occur at any age, but it is more common in the fourth decade than at any other time in life. It has long been observed that the disease is frequently associated with some disturbance of the digestive tract. This consists in many instances. of an atrophic condition of the walls of the stomach and of the intestine, with or without enteroposis, which may become much thinned. The glandular elements of the mucous membrane have been found much atrophied. Achylia gastrica exists in many instances. In carcinoma of the stomach and in chronic glandular gastritis the same atrophy of the stomach wall may occur without pernicious anemia. An atrophic condition is also found in other portions of the body, and it is not at all unlikely that the condition of the stomach and the intestinal wall has only a contributory etiologic relation to the disease. Intestinal parasites have been found present in the disease, especially the bothriocephalus latus, and the ankylostoma duodenale. The disease, however, does not develop in all cases in which these parasites are present. That they have some relation to the disease is shown by the fact that some patients, who present characteristic blood findings, get well when the parasite is discharged by the patient. The condition of profound anemia, with deformed red cells, the presence of fetal red cells in the circulating blood, the presence of an abnormal amount of iron in the liver, together with degenerative changes in the muscles and in the marrow of bone, is a reasonable hypothesis for the assumption of the presence of a circulating poison-a hemolytic toxin as the fundamental cause of the disease. The source of the poison has been the subject of many theories.

Schauman and Tallquist have brought forward the theory that in cases of pernicious anemia due to the bothriocephalus latus, the

parasite was the source of a toxin because the worm itself was either sick or dead in the host. In this condition the worm was the source of the toxin which produced the anemia, and explained to these reporters the reason for the nondevelopment of pernicious anemia in most cases of individuals affected with the bothriocephalus latus. They made the following experiment: The extract or bruised links of the bothriocephalus latus was fed to dogs. In one dog, after two weeks, marked anemia occurred, the red cells falling from 7,200,000 to 3,400,000.

The view has been advanced that the toxin is of bacterial origin, but no definite observations have been made which would establish this, with the exception of the research work done by Professor Adami and his pupils. In his studies upon hypertrophic cirrhosis of the liver and on hemochromatosis in pernicious anemia, Adami advances the opinion that many of the sclerotic processes of the body are due to acute or chronic infection through the presence in the tissues of bacteria or bacterial poisons, which may be derived from the intestines. The organism is successful in overcoming the general infection, but the tissue cells become exhausted through the specific infection, with resulting degeneration and connective tissue hyperplasia. He described diplococcoid forms of bacteria in the stomach and intestinal walls, and in the liver cells, which he believed to be altered colon bacilli. The suggestion of Adami is very pertinent, especially if one believes that pernicious anemia is due to a toxin.

More recently Hunter, who had confirmed the observations of Quincke and others as to the hemolytic effect of a possible toxin, suggested the origin of the poison in the intestinal canal from the altered anatomic condition of the stomach and bowel. Still later, Hunter has suggested the idea that the toxin and the condition of the gastro-intestinal canal have their source in a foul condition of the mouth of the patient, who suffers from pernicious anemia, and he notes the condition of carious teeth, gingivitis, etc., in many of his patients. It is not improbable that from the evidence we have, that pernicious anemia is due to some hemolytic toxin, but whether of bacterial or autogenetic origin we cannot at present definitely say.

SYMPTOMS.

The symptoms of pernicious anemia are chiefly those due to a profound anemia manifested by weakness, lessened endurance, with dizziness, dyspnea, palpitation of the heart, etc. The disease is not necessarily steadily progressive, as it is interrupted by waves of im

provement. It may be either very acute or chronic in its course, as cases are known to die within a few weeks and others to live for several years. In probably a large percentage of the cases the body weight is preserved, and in a few others there is a loss of weight, and in some, emaciation. There is a tendency to subcutaneous, submucous, retinal and other hemorrhages. Gastro-intestinal disturbance is very commonly present, and especially diarrhea. The appetite if often poor or capricious. There may be a craving for acids, salts, or some other thing with decisive taste. The disease is associated with nervous phenomena in the great majority of cases; usually, however, subjective in character. There is often paresthesia of the feet, sometimes of the hands. Cerebral disturbance in the form of lessened cerebration may occur, and Minnich has observed fixation of the pupils, while Bemis, Müller and Nonne report cases of slight facial paralysis, or of one sided paresthesia, aphasia, etc.

The spinal cord lesions, which are now recognized as occurring in a small percentage of the cases, may appear as one of the earliest manifestations of the disease, or they may occur late, and may be manifested slightly or not at all up to the time of death. The spinal cord lesions, which will be discussed more fully later, do not always bear a direct ratio to the symptoms. In some instances, with no perceptible spinal cord changes, there may be marked subjective paresthesias, and even slight ataxia and spasticity, while in other cases, with marked cord changes, the symptoms may be subjective only, and not in keeping with the marked changes in the cord. In the severer degrees of spinal cord lesions, when established, the course of the disease is usually rapid to a fatal ending.

Bastianelli divides the cases into two groups. One in which the pernicious anemia is the predominant factor, and the cord lesion developing late, with only slight clinical manifestations, or possibly with only subjective disturbances. The second, in which the nervous phenomena develop first or coincidently with the anemia, the nervous phenomena predominating and overshadowing the symptoms due to the anemia, and the case rapidly developing into oneof paraplegia, with flaccid muscles, loss of sphincter control, bed sores, and death within a few weeks.

This makes a fairly good division for clinical use, but not all cases can be placed within the two divisions.

During the last few years I have had under direct observation forty-one cases of pernicious anemia.

ANALYSIS OF MY GROUP OF FORTY-ONE CASES.

Of these, 23 were males, and 18 females. The preponderance of males over females is unusual. The ages were as follows: There were three in the second decennium, eight in the third, twelve in the fourth, ten in the fifth, seven in the sixth, and one in the seventh. The youngest was 24 years of age, and the oldest 76. In six cases tuberculosis existed in the family within two generations. In three patients carcinoma existed in the family within two generations. Three of the patients had suffered from syphilis. In two a severe attack of grippe was apparently the cause of an illness which finally developed into pernicious anemia. One was overcome by smoke and gas at a fire in a large building. One suffered from exophthalmic goitre; fifteen had suffered from diarrhea as the first manifestation of the disease. Diarrhea had existed for three years as the longest time, and in one, after an acute attack of diarrhea, the disease suddenly developed. Constipation, obstinate in character, occurred in two. Nausea and vomiting were present in the majority of the patients at some time in the course of the early stage of the disease. Loss of appetite, amounting in some to complete anorexia, was present in all, and a capricious appetite existed in a few. In thirteen repeated examinations of the stomach contents were made after test meals, and disclosed the absence of hydrochloric acid in all. There was enteroptosis of a severe degree in three. The association of grippe with pernicious anemia has been noted by Bastianelli and by Putnam as a contributory factor in spinal cord lesions. In all patients two or more complete blood examinations were made which gave the characteristic blood condition of pernicious anemia. Retinal hemorrhages occurred in four; chorio-retinitis existed in one; subcutaneous and submucous hemorrhages, occurred in eight; epistaxis was a not uncommon factor, and in several bleeding of the gums was observed. Of the twenty-three male patients, in only three were the teeth bad, and in four only was the mouth in an unhealthy condition. Of the women, the condition of the mouth and teeth was notably bad. In three cases no note was made of the condition of the teeth and mouth; in fifteen women, either the teeth were decayed or the gums were infected in all. In forty cases paresthesia occurred. It appeared in the feet and hands in most of the cases, with the exception that in one it was confined to the toes of one foot and to the ulnar border of one hand. In four female patients the anemia preceded the nervous phenomena by two years and four months, and in two men the ner

vous phenomena appeared one year and sixth months, respectively, after evidences of pernicious anemia were established. In twentyseven of the cases the nervous phenomena were confined to subjective disturbance only, manifested by tingling, numbness, coldness, heat, formication, etc., of the hands or feet, or of both, and in one instance involving the entire lower extremities. Hyperesthesia occurred in one. Disturbed temperature sense, inability to recognize quickly heat and cold, occurred in two, otherwise objectively the sensation of the feet and hands was normal. These twenty-seven patients complained frequently of a sense of numbness and tingling, and usually this condition remained, even when the patients were on a wave of improvement. In only one did it disappear during a wave of improvement, and it reappeared when a relapse occurred. In eleven patients the subjective nervous disturbance was associated with a spastic, and usually with an ataxic condition, which grew steadily worse, and in three developed into complete flaccid paraplegia, with loss of knee jerk, loss of voluntary bowel and bladder control, and the development of edema and bed sores. One died while in a state of spastic paraplegia. Five are living with spastic ataxia, spasticity, or paraplegia, whose spinal cord showed dorsolateral degeneration. One case died with simple sensory disturbances only without ataxia, spasticity, or paraplegia, whose spinal cord showed dorsolateral sclerosis. One died with all the evidences of . insanity, but a post mortem was not obtainable.

Burr states that a girdle sensation is never present in the spinal cord lesions of pernicious anemia. Girdle sensation was present in all of the cases which developed spasticity in my group. As observed by Putnam, some of the patients complained of a peculiar paresthesia of the mouth. One complained of a sensation as if his mouth contained threads of cotton; another that his mouth had the sensation of dryness, although saliva was present; another of a sense of burning which cold water did not allay. The sexual power of the males was uniformly diminished. Menstruation ceased, as a rule, in all of the younger women. Severe spinal cord lesions. occurred in the female cases, in the relatively young. One was thirty-nine, one forty, two forty-seven, and one thirty-four years of age. In the males severe cord symptoms occurred in one individual of thirty-six, another of forty, in two of fifty-six, in one of twenty-six and in one of sixty-two.

CASE 1.-Female; aged 60; a copyist; the mother of two children; was admitted to Cock County Hospital in my service on