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Phyiioiui to the Montreal Qaneral Hospital ; Aniitant Profearar of Madieine and Oltnioal Medi- eine, MoQill Univenity. Of the two capses reported below both were regarded daring life as pernicious anaemia. The second, however, was clearly shown by the post-mortem examination not to be of this nature. As they both presented a severe form of anaemia, poikilocytosis and absence of free acid in the stomach, they are recorded inasmuch as the asso- ciation of these conditions is still involved in considerable obscurity. Case I. — Pernicious anamiia, ahaence of hydrochloric acid in gas- tric juice — Marked improvement after thymol — Failure of arsenic and bone marrow. Case. — H. J,, male, aet. 52, of temperate habits, was sent to the Montreal General Hospital by Dr. Hutchison on November 17, 1894, complaining of indigestion, vomiting and weakness. He states that he has had small-pox and gonorrhoea. He has not been strong for ten years and has suft'ered from vomiting, lasting a day or two at a time, two or three times yearly. He has been mu^ih worried of late by family trouble. Present illness — Began in August, 1894, with weakness and loss of flesh. For several months he suffered from nausea and occasionally ^'omiting induced by slight exertion. At no time was there any abdoir ' pp^n or haematemesis. Increasing weakness obliged him to take ti A about the end of October and the vomiting continued up t •. the time of admission to hospital. He has lost about twenty-five pounds in weight. Family history — Father is healthy, set. 82 ; mother, a sister and brother died of con'^amption and a brother is stated to have died of anaemia. Present condition — He is moderately nourished, the panniculus adiposus is small. The muscles are soft but of fair size and the weight is 124 pounds. The skin is moist and perspiring. The face and back of hands are of a decided lemon colour, and the coiyunctivae show a slight yellow hue. The mucous membranes are pale and there is a considerable degree of anaemia present. The tongue is moder- ately coated and flabby. The abdomen is normal, presenting no tenderness or tumour, and the liver and spleen are not enlarged. The ^% 'i heart is of normal size ; a soft systolic murmur is heard with maxi- mum intensity at the pulmonary cartila^, transmitted to the aortic and down the sternum ,as far as the fourth costal cartilage. The liiAgs al*e normal. The urine is acid, S.O. 1020 ; no albumen, sugar, urobilito or bile colouring matters are present. November 18. — Blood examination shows slight irregularity in the shape of the corpuscles (poikilocytosis) and a few small corpuscles (micro-cytes) are present. On Nov» 25th red cells, 1,928,770 to cm.; heemoglobin 45 per cent. (Fleischl). Stained specimens show some irregularity in shape and size of the corpuscles and a few microcytes. Batio of red to white 3 to 508. The gastric contents withdrawn after a test meal show an entire absence of hydrochloric acid (Congored, Boas and Qunzberg's tests) ; lactic acid absent The red corpuscles have become more irregular in shape. Careful measurements show that many of them ai-e larger than normal, measuring 9 to 10 m., instead of 7 to 8 m.; a few microcytes 3.6 m. The white cells ai-e relatively but not absolutely increased. Nucleated red cells have not been found in repeated examinations. The urine has varied considerably, S.G. 1015-1020, being on some occasions dark in colour and at others light. Urobilin (Huppert's test) has been frequently but not always present, and the spectrum of pathological urobilin has also been occasionally seen. On January 23, the spleen was felt below the costal border, and has since continued enlarged. On March l7 a severe attack of facial erysipelas set in, the temperatures ranging from 103° to 105°, and terminating by crisis on the sixth day. Witti the exception of this attack of erysipelas referred to, there was no fever during the six months that the patient was under ob- servation. Retinal heemorrhages were almost absen^. The weight fluctuated from 119 to 124 lbs. Vomiting occurred a few times in the fortnight following admission and then ceased. The stools were examined for intestinal parasites with a negative result. The blood began to improve in the fii*st half of March, and, as will be seen by referring to the table appended, by the end of April almost I'eached the normal. Corresponding with the improvement of the blood conditions, the patient's strength and energy returned and he was able to leave the hospital on May 16. The shape of the blood corpuscles has always continued irregular, and hydrochloric acid has been persistently absent from the gastric juice. Treatment — Arsenic has been faithfully used for several months, also bone marrow, iron and latterly thymol have also been given a 8 trial. Arsenic has been used throughout internally in the shap^ qt Fowler's solution in doses of from m ii to m x ti.d. t'he stomach would not tolerate a lar^j^e dose, and on several occasions it had to be discontinued. Arsenious acid in pill form was better borne, and hypodermics of Fowler's solution in water were also tried but proved painful and were discontinued on the forn^ation of a small abscess. A glycerine extract of bone marrow was used from January 8 to February 8, during which time the corpuscles decreased from 1,792,- 000 to 1,320,00, although there was a slight increase in the haemoglobin 35 per cent, to 45 per cent.. Blaud's pills in doses of 10 to 15 grs, t.i.d. were used from February 8th to March 4th, the red corpuscles rising in this period from 1,320,000 to 1,770,000, but with a decrease of heemoglobin. On March 3rd thymol was commenced. A reference to the table below will show the relation o^ the blood count to the principal drugs used. Nov. 25. . Jan. 7... 26... Feb. 6. . . 12... March 4 14 April 5. . 12.. June 26.. BLOOD Counts. Red B.C. 1,028,000 Hglobin 1,792,000 FleiHchl 1,820,000 1,320,000 1,340,000 1,770,000 2,440,000 2,860,000 3,140,000 4,810,000 2,107,000 46% si to 25% to 35% to 70^ to86£ Treatment. Nov.!24tb. Arsenic in v to x, and also alternating witb ^ gr. wsepi- ous acid t.Ld. taken during almost whole period of hospital residence. Jan. 8 to Feb. 8. Bone marrow: March 3 to June 16. Thymol gr. i to gr. U t.i d. March 17 to 22. Ery.sipela8. On comparing the blood counts with the treatment it will be noted that no improvement appeared with arsenic. All the blood counts made after March 4th showed a steady improvement, an improvement which was coincident with the use of thymol and arsenic, and which had not been effected by the use of arsenic alone. The experience of this cfise is certainly suggestive of the beneficial action of thymol. The attack of erysipelas complicated the case at this stage, and sug- gests the possibility of its exerting a modifying influence over the disease. It will, however, lie noted that the improvement began befm^e the attack of erysipelas, and co-incidentally with the use of thymol. A blood count made June 25th showed a great decrease in the num- ber of corpuscles and haemoglobin, a relapse so frequently seen in pernicious anaemia. Case II. — Severe arnvmia — Arterial sclerosis — Dilated heart — Absence of hydrochloric a^id in Gastric fluid — Autopsy. B. O'C, aBt. 61, labourer, admitted to the Montreal General Hospi- 4 tal on January S5th, 1895, complaining of weakness and shortness of breath. Personal history — He has had measles, whooping cough and scarlet fever, but no venereal diseane. Present illness began in the spring of 1894 with frequency of mic- turition, and in November, there were severe paroxysms of pain in iie right groin. In October, 1894, began to be much troubled with shortness of breath, especially on going up steps, and about this time he noticed his face to be of a slight yellow colour. He has noticed for some time back small red spots on the hands, lasting from a week to ten days, evidently subcutaneous hsemorrhages. He has had palpitation, dizzi- ness, and has lost about 30 lbs. in weight. He has never had head- ache, nose bleeding or diarrhcea. He has vomited on three occasions and suffered a few times from heartburn. • Family history — Father died from fever and ague ; mother died at 57 from an illness attended by cough and expectoration. Present condition — He is rather thin, the muscles are soft and the panniculus adiposus is small ; weight 125 pounds. The face and back of hands are of a marked yellow hue and there is marked pallor of the conjunctivae and gums. Two small sul^utaneous heomorrhi^es on the back of the right hand. The arteries show a moderate degree of thickening ; pulse 84, slight irregularity in rhythm and tension not increased ; the apex impulse is strong and in the nipple line, the cardiac sounds are normal. The lungs and abdominal viscera present no abnormality on physical ex- amination. Urine pale, S.Q. 1015, no albumen or sugar. Urobilin negative with the spectroscope. Jan. 26.— Blood count, red cells 3,320,000 ; haemoglobin 25 to 30 per cent. (Fleischl). Irregularity in size and shape of the corpuscles is well marked. Hydrochloric acid absent from gastric contents in a test meal by same tests as used in first case. Subsequent blood ex- aminations were made as follows : Feb'y. 12. Red cells, 2,250,000 ; hsemoglobin, 20 to 25 per cent. 28 " 2,660,000 ; " 20 to 25 March 3 " 2,390,000; " 20 to 25 " Numerous examinations were made of stained specimens of blood. These always showed marked irregularity in size and shape of the red blood corpuscles. Most of the cells were under rather than over the size of a rod blood corpuscle, a very common size being 5.4 m.; microcytes were not numerous and the largest cells have not been :>ver 10 m. No nucleated red cells have been seen. J The urine has been for the most part pale in colour, althouf^h occasionally somewhat dark. It has frequently in both pale and dark specinens shown the presence of urobilin with Huppert's test, but not with the spectroscope. The sp. gr. has usually been about 1015. The temperature has been normal throughout. There have l)een no retinal haemorrhages, but occasionally small subcutaneous heemor- rhages have appeared on the hands. A htemic murmur developed at the pulmonary cartilege shortly after admission and the pulse has at times been intermittent. The gastric contents have persistently shown an absence of free acids. The weight has increased to 133 pounds. The treatment, in addition to cardiac tonics, consisted in the administration of arsenic, beginning with m. ii. Fowler s solution t.i.d. and increasing the dose by m. i. daily until m. xvi were given, when it was omitted for two days on account of vomiting, and then recom- menced with a dose m. xv. t.i.d., which has been continued to the present. A glycerin extract of bone marrow in doses of 5ii- to 5iii' t.i.d. was begun on March 1st in addition to the arsenic. The results of treatment have, as in the first case, been unsatisfactory, the blood con- ditions being precisely the same as on admission. i*.S. — ^This patient developed great anasarca of the lower extremi- ties, double hydrothorax and dyspnoea, obviously of cardiac origin^ and died April 7th. Autopsy performed by Dr. Wyatt Johnston showed a moderate quantity of fluid in the pleural cavities. The heart wa^ 'luuch en- larged on both sides and the right distended with blooa. CEdema and slight emphyssema of the lungs. Kidneys — Left slightly enlarged, capsules adherent and a few cysts present. Prostate presented two adenomata projecting into the bladder. The liver was rather small and on section the veins were promi- nent. The spleen was large and firm. The mucosa of the stomach was soft and the organ contained a pint of curdled matter. The red marrow of sternum, ribs and vertebrse was increased. On microscopic examination pigment was found about the central vein. No iron reaction and no pigment in peri- pheral zones. Stomach on microscopic examination showed a loss of the super- ficial part of the mucosa from post-mortem digestion, but the glands in the deeper portion of the mucosa were normal in every respect* 6 presenting neither atrophy, increaHe in connective tissue, nor altera- tion of the epithelium. The lemon tinge of skin present in both cases was extremely sug- gestive of pernicious anaemia. The diagnosis of the first case rests chiefly on the condition of the blood, together with an absence of any of the usual causes for a secondary anaemia. The blood counts invariably showed a relative excess of hsenoglobin, a sign which is usually present in the perni- cious form of anaemia. The marked irregularity in shape and size without increase of the white cells is also very characteristic. The presence of nucleated red cells which has been insisted on by some as essential in the diagnosis of pernicious anaemia are in my experi- ence rather the exception than the rule. In five cases under my observation in which they have been carefully looked for they were present only in one. The splenic enlargement present in this case is rather exceptional, although it is a well recognized feature of the disease. The presence of pathological urobilin is an important diagnostic feature, and urine of high colour and low sp. gr. is also suggestive of the condition. The absence of free hydrochloric acid from the gastric contents at first raised the question of the possibility of carcinoma of the stomach being the cause of anaemia. The absence of pain, of tumour, of haematemesis and of persistent vomiting, together with the relatively embonpoint of the patient were decidedly against this view, and the absence of progressive emaciation during the past three and a half months also bear out the original diagnosis. A leucocytosis, again, which is commonly present in cancer, was here absent. In the second case the diagnosis of pernicious anaemia in a patient with arterial sclerosis and dilated heart, made during life, was not borne out by the results of the autopsy. The deposit of iron in the liver was absent, and only the ordinary senile pigmentation in the center of the lobule was found Hufler, quoted by Ewald, records a number of cases where hydro- chloric acid was absent in cases of valvular disease, and it may be that this was the cause here. Such a degree of anaemia with marked poikilocytosis must, however, be unusual in cardiac disease, and the kidneys were so slightly afleeted that the anaemia of renal disease was hardly possible. Whether any relation between anaemia and absence of hydrochloric acid exists can only be determined by fur- ther observation. The case under consideration is, however, not onti of anaemia associated with atrophy of the gastric tubules. X' The absence of such an important constituent as hydrochloric acid does not seem to have caused any serious ^^astric disturbance in either case. We may perhaps assume that compensation is effected by the pancreas. In tlio first case nausea, occasional vomiting and heart-burn began apparently coincidently with the onset of the symptoms of anaamia, and in the second case such symptoms were entirely absent. It is well known that the weight and general nutrition are usually retained in the subject of pernicious anaemia, and the loss of weight occurring in these cases may be satisfactorily accounted for by the absence of gastric digestion. The association of atrophy of the gastric glands and a grave form of anaemia has been recognized for a number of years. BMrst pointed out by Austin Flint, this observation has been confirmed by Feawick by Osier and Henry and many others, and the fact is now well estab- lished. There has been and still is considerable divergence of opmion about the interpretation of these observations. Many observers re- gard the atrophy as a consequence and result of the anaemia and as having, therefore, but little bearing on the condition. There are others, however, Flint and Fenwick among the number, who do not hesitate to state that the atrophy is primary and the anaemia second- ary, so that the term idiopathic anaemia is not strictly correct in such cases. Osier and Henry, for instance (Am. Jour. Med. Sci., 1886)* relate a case with all the clinical features of pernicious anaemia, in- cluding the blood changes, in which extensive atrophy was found in the gastric tubules at autopsy. The onset of the malady was pre- ceded for years by loss of flesh, indigestion and vomiting, and the authors therefore conclude that the gastric condition was primary- Hunter (British Med. J., 1890-93), records a case in which atrophy of the gastric glands was found nfter death in a case of pernicious anaemia* and he brings ,forward arguments based on pathological investigation and urinary analysis to show that abnormal fermentation in the gastro- intestinal tract may generate certain toxic agents which have a dele- terious action on the blood, and induce a process of blood destruction. As hydrochloric acid is the natural antiseptic agent of the stomach, its absence would naturally favour these abnormal chemical changes. Without dwelling on this point. Hunter has made a valuable addition to our knowledge by pointing out that pathological urobilin is fre- quently present in large quantities in pernicious anaemia. As this substance is derived from blood pigment, its presence in the urine indicates excessive destruction of blood. Hunter regards the presence of this substance as of much diagnostic valu*;*. It may be detected by ippnp<