Case 1.-Ague occurring in a person labouring under phthisis, and the combined diseases proving fatal:

Susan Roberts, aged 34, a married woman, residing at Woolwich, was admitted into St. Thomas's Hospital, under my care, on the 15th of September, 1856. She stated that she had been suffering for five months from symptoms of irregular ague, and had gradually got worse notwithstanding that she had had medical advice. The attacks came on generally every forenoon: she had not decided rigors, but felt chilly for about three hours, and then became hot and perspired profusely. She had a malarious aspect; the pulse was quick and feeble; the tongue slightly furred; and the bowels confined. She also complained of cough, and was very thin. She was directed to take two grains of quinine three times daily.

Up to the 20th she had an attack each day, and the last seizure was the most severe; the quinine was increased to three grains, and wine was ordered. On the 4th of October, four grains of quinine were given, and the quantity of wine was increased. On the 8th, the following notes were taken-she has continued to have attacks every other day; they come on at 8 A.M., but are slighter than before, and the last two have not been followed by perspiration. Her face is pallid and thin, her eyes glassy, and her general aspect malarious; the pulse is quick and feeble; she takes her food well; and the bowels are acted upon once or twice in the twenty-four hours. She states that she has always been delicate, and, two years ago, she had inflammation of the chest, with pain in the right side, difficulty of breathing and cough, but no expectoration; she, however, once spat what looked like blood; but her medical attendant told her it did not come from the chest. She took much cod-liver oil at that time. She was then living on the sea-coast of Lincolnshire, but never had ague till she came to live at Woolwich. Her father and mother are living, but she has lost one brother and three sisters of whom a brother and sister died of consumption. Her husband has had three attacks of ague since he resided at Woolwich, and had been each time under treatment by myself. At the present time she has a cough, and much expectoration. There is some deficiency of resonance on percussion at each apex, and falling in, especially on the right side. Bronchial respiration is also there heard, and with a full inspiration there is some subcrepitation. At the left apex the signs are less marked. There is some deficiency of the resonance on percussion, low down on the right side, both before and behind, subcrepitation is there audible. To continue the quinine, and take the cod-liver oil; 3 ij. bis quotidie; 3 glasses of wine. On the 10th, the dose of oil was increased to 3 drachms. She died suddenly, without any obvious cause, and apparently syncopic, when up in the ward, on the 15th.

Post-mortem examination.-The pericardium was healthy; the opposed surfaces of the right pleura were so firmly attached by old adhesions as to render it difficult to remove the lung entire; the left lung was adherent at the upper lobe; both lungs were studded with tubercle, but the right especially. The right upper lobe was excavated into an irregular cavity, and the middle lobe and posterior portion of the lower lobe were solid; the anterior portion was crepitant, and free from tubercle; the upper lobe of the left lung was solid from tuberculous deposit, with intercurrent inflammatory exudation; the lower lobe also contained interspersed miliary tubercles, but was still, to a considerable extent, crepitant; the abdominal organs were healthy, except the liver, which was large and waxy-looking; and the kidneys, which were also large, and had their capsules adherent, but were not apparently otherwise diseased. In this case it may fairly be inferred that the patient was phthisical before she took ague, but the disease had advanced rapidly during the time that she suffered from that disease, and its fatal termination had certainly been accelerated by the complication.

Case 2.-Ague occurring in a person labouring under incipient consumption; the former disease cured, the latter still progressing:

Mary Turner, aged 31, a married woman, residing in Gravel-lane, in the Borough, applied at St. Thomas's Hospital as an out-patient, on the 30th of September, 1858. She stated that she had been ailing for two years, suffering from cough, and that she had spat a little blood occasionally, and had lost much flesh. She had been more seriously ill for two months. She complained of cough and expectoration, and for the last two weeks had had aguish symptoms, consisting of rigors, which commenced at eleven in the forenoon every other day, followed after about an hour and a half by heat, and then by profuse sweating. She also had perspirations, which came on at nights. She had not, for several years, been out at service, and had never previously had ague. She was pale and malarious-looking; the pulse 100, and feeble; the bowels regular. On examining the chest, the resonance, on percussion, was found to be impaired at each apex, more especially on the left side, and bronchial respiration and loud cough resonance were there heard, and there was some rhonchus, with a forced inspiration. She was directed to take the cinchona and acid mixture, with 5 grains of the

disulphate of quina, and half a drachm of the compound tincture of camphor, three times daily, and the hyoscyamus, and Dover's powder pills at night.

On the 17th of October she stated that she had had the shivering every other day, though less severely than before. She had gained strength, and her cough had been less troublesome. On the 21st, she said she had been too ill to attend on the 14th. During the week in which she continued to take the medicine she had only one attack; but during the last week, being without medicine, she had two attacks, but they were less severe than before.

Case 3.-Ague occurring in the early stage of phthisis; the former disease cured, the latter still progressing:

James Tayler, aged 25, a painter, residing at Rochester, was admitted an out-patient of the Victoria Park Hospital on the 6th of August, 1858. He stated that he had been declining in health and subject to cough and expectoration, and occasionally of blood, for the last three years. About two years after the commencement of his illness, and one year before he applied at the hospital, he had an attack of ague, which disease he contracted while working at Cliff in the marshes between the Thames and Medway. The aguish attacks were decided, and recurred every other day for four or five times, and slightly for a longer period, but they were ultimately stopped by medicine. He has not had any symptoms of ague since, but his health had rapidly given way. When he applied at the hopsital he complained of a severe cough, which was attended by copious expectoration, especially in the morning; he was pale and thin. The tongue coated at each side, and the pulse quick. The whole of the left side of the chest expanded very imperfectly, and there was a distinct bruit de pot-felé heard on percussion beneath the left clavicle, with loud cavernous sounds and gurgling in that situation. He was directed to take the cinchona and acid mixture, with cod liver oil three times daily, and a soap and opium pill every night. He was last seen on the 16th of Dec., and the phthisical symptoms were then advancing.

Case 4.-Signs of commencing consumption and aguish symptoms coincident; result not known:

Hannah Jones, aged 52, a married woman, residing in Blackfriars Road, applied as an outpatient at St. Thomas's Hospital on the 6th of November, 1857. She stated that she had been ailing for nine months, suffering from cough and expectoration, and that four months before she had spat blood. She had a very malarious aspect and complained of suffering from chills, commencing about 10 o'clock every forenoon, and followed by heat, but without sweating. On examining the chest the resonance on percussion was found to be deficient at the apex of the left lung, but there were no other marked signs of tuberculous deposit. She was directed to take quinine, and was relieved from the aguish symptoms, and ceased attending on the 27th of November. Her subsequent history is not known.

In addition to the cases which I have now related, and two to be reported hereafter, I have met with three other instances of the coexistence of consumptive symptoms and ague. One of these was that of a lady residing in the Isle of Sheppy, who with slight evidences of consumption had decided ague, which was removed by treatment. Another was the case of a young girl from Rochester, an out-patient at St. Thomas's Hospital, who had advanced consumption and decided ague, and died shortly after she was brought to me. The third was an out-patient at the Victoria Park Hospital, residing in Stepney, a middle-aged man, who presented the usual signs and symptoms of phthisis in the second stage, and had irregular aguish symptoms, which were relieved by treatment. Of the subsequent history of three of these cases in which the pulmonary affection was in an early stage, I have no knowledge; but leaving them out of consideration, the others which I have reported are sufficient to show that phthisical patients may take ague, and that when that complication occurs the symptoms of consumption are greatly aggravated and its fatal result hastened.

It is, however, quite possible, that though consumption may not grant immunity from attacks of ague, yet the occurrence of ague may prevent the subsequent development of consumption. My attention has only recently been directed to this inquiry, and it is not a large number of phthisical patients from aguish districts which come under my notice, but I have at present two patients, who inform me that they have had attacks of ague before their phthisical symptoms occurred, and that they have continued to reside

up to the present time in the districts in which they contracted the disease. The following cases, indeed, may be regarded as "crucial instances," in deciding the question of the antagonism of phthisis and ague, inasmuch as they not only afford examples of the coincidence of the two affections, but show that phthisis may develope itself in persons who have had previous attacks of ague, and who have continued constantly exposed to the malarious influence.

Case 5.-Ague occurring in the phthisical patient, who had previously had several attacks of ague. The former disease cured; the latter still in progress: M. A. Heard, aged 30, a married woman, residing at Aveley, near Purfleet, in Essex, applied as an out-patient at St. Thomas's Hospital on the 23rd of September, 1858. She stated that she had been ill for five months, suffering from cough and expectoration, and had occasionally spat small quantities of blood; her voice had been for some time hoarse, and she had lost much flesh, and was pale and thin. She also suffered from attacks of ague, which came on every other day at 11 a.m., with shivering, after which she became hot and sweated profusely. She said that she had had an attack of ague when ten years old, and while residing in the neighbourhood of Rochford, which continued at intervals for fifteen months, and she had since had two or three other attacks, and she had resided all the time in different parts of Essex bordering on the marshes. On examining her chest the resonance on percussion was found to be impaired, and there was loud cough resonance at each apex. She had been taking quinine and cod-liver oil, and the same remedies were continued; on the 21st of October the aguish attacks had entirely ceased, and she was otherwise improved. Since this time she has been admitted into the Victoria Park Hospital for Diseases of the Chest. She has had some recurrence of the aguish symptoms in the form of chills, coming on at a regular period. There is marked dulness on percussion with bronchial respiration, and undue cough resonance at the right apex, and the resonance on percussion is impaired, and the respiration harsh, and the resonance with the cough increased at the left apex.

Case 6.-Phthisis and ague in a person who had previously had ague. The latter disease relieved, the former progressing:

William Cox, aged 46, a labourer who had resided at Woolwich for the last twelve years, and had had ague six years before, applied as an out-patient at St. Thomas's Hospital in August last, and was admitted into Jacob's Ward, under my care, on the 2nd of September, 1858. He stated that he had spat blood seven or eight years before, but had only been seriously ill for a year, and had been suffering from symptoms of irregular ague for nine weeks. When admitted, he complained of difficulty of breathing, cough, and expectoration; he was emaciated; the pulse was weak, and he had a very malarious aspect. Every other morning he became very chilly, and had violent retching, followed by heat and sweating, but he had no distinct rigors; on examining his chest the resonance on percussion was found to be generally deficient at the upper parts, where also the cough resonance was very loud, and sonorous and mucous rhonchus were heard in all parts of the chest, and were especially marked in those situations. He was directed to take three grains of quinine and 3j of compound tincture of camphor in 3 iss of the cinchona and acid mixture three times daily, and wine and a nourishing diet were allowed. On the 11th a blister was applied between the scapulæ, and an ipecacuan and squill pill was ordered to be given at night. On the 15th he was much better, the aguish symptoms had entirely disappeared, and he looked much less malarious, but he still had a severe cough and copious mucopurulent expectoration. There was some deficiency of the resonance on percussion at each apex, with falling in of the parietes there, and bronchial respiration and loud cough resonance, and these signs were the most marked on the right side. There was also some subcrepitant rhonchus heard low down in each dorsal region, but the respiration was generally free. The cod-liver oil was directed, in doses of two drachms, with the tonic and cough mixture, to be taken twice daily.

On the 22nd he was not improving; he continued to lose flesh, and complained that he had taken fresh cold, and wished to be made an out-patient; this was done, but he has not since returned to the hospital.

The facts which I have now detailed, conclusively show that neither does the existence of consumption prevent the occurrence of ague, nor the occurrence of ague preclude the subsequent development of consumption; but they do not prove that the supposed antagonism may not, in some degree, cxist. For, on the one hand, phthisical patients, subjected to the influence of malaria, may take ague in less proportion than healthy persons similarly exposed; and on the other hand, persons who have had ague may be less

liable to consumption than those who have not had the disease. These objections I have no means of meeting, but when it is considered that, within a period of two years, five cases of the co-existence of the two diseases have fallen under my own notice, at one public institution, where the majority of phthisical patients do not come from malarious districts, the coincidence cannot be regarded as exceptional or rare.* I cannot, therefore, but conclude, that it is not probable any material antagonism exists between phthisis and intermittent fever. The facts do not, however, warrant the denial of the supposition altogether, and there are probably few popular ideas which have not some foundation in truth.

The correct inference would appear to be that the influence, if any, exerted on the prevalence of consumption, by a malarious atmosphere or by ague, is far less important than that of various other causes which affect the development of that disease. The practical conclusion also to be arrived at is, that as phthisical patients may take ague, and as such complication materially aggravates the original disease, we should, in selecting residences for consumptive patients, avoid those situations which are marshy, or in which aguish affections are known to prevail.

ART. III.

By

An Experimental Inquiry on Endocarditis, by the Synthetical Method. BENJAMIN W. RICHARDSON, M.D., L.R.C.P., Physician to the Royal Infirmary for Diseases of the Chest, and Lecturer on Physiology at the Grosvenor Place School of Medicine.

As the eye of the reader falls on the first lines of this paper, I beg him to receive the assurance that the paper is not written to represent any special theory in Pathology; but to record certain experimental results, and to indicate a new way to the discovery of facts as yet hidden in the phenomena of disease. Farther, I would pray that any reasonings which may be offered on the experimental evidence may be considered as apart from the evidence. For the evidence belongs to the present-it is; the argument belongs to the potential-it may be.

The method of studying disease which this paper is intended to illustrate, belongs exclusively to modern science, in so far as medicine is concerned. It has as yet been confined to the labours of a few enquirers, and has received, I believe, no systematic exposition as a general plan, from any one in medicine, except myself. The method consists in inducing, by experimental means, the phenomena of special diseases. The method may be called the "synthetical method" of studying disease.

It is remarkable as an historical fact, that no science, save medicine, has been content to rest on analysis as its only foundation; yet is there no fact more obvious. If the question be asked, Why is not the knowledge of disease positive in its character like other scientific knowledge?-there is a ready answer; that, as compared with other sciences, the science of medicine proper, has always stood on one leg, while the other sciences have walked on two; I mean on analysis and synthesis.

As a philosophical process, I would accord to analysis the greatest importance; it gives finality to fact; but in the first stages of an enquiry into a series of unknown phenomena, I look on synthesis as the co-equal with analysis, in the progress of discovery. Synthesis suggests and produces facts, which at once sug

*During the two years in which these five cases occurred, I treated at St. Thomas's Hospital, among the in and out patients, 236 cases of ague, and at least 262 cases of phthisis. The precise number of cases of the latter disease I cannot give, as some cases of phthisis are entered in the out-patients' book as "affections of the chest." I have also met with several other cases in which there was reason to suspect tendency to phthisis in aguish patients.

gest and produce new modes of analysis, and which, later in the day, support analytical results. Synthesis is essentially inventive as a process, and if it never leads to pure demonstration, it sometimes supplies evidence so closely bordering on the demonstrative, that analysis has little left to perform in the way of completion. All disease is natural synthesis.

I have shown, in another place, to what a grand extent the synthetical process might be applied in the study of various classes of diseases.* I shall not open this abstract question now, for it were out of place such proceeding; but I beg the reader while observing the second and immediate intention of this paper, to receive the paper altogether as a representation of a general scheme of research. The special subject of this paper is, the disease Endocarditis and its artificial production. Let us observe first, the simple facts of an induced endocarditis.

It is the fact then, that endocarditis can be experimentally produced in an inferior animal: the fact I shall endeavour to demonstrate further on.

The mode of producing this condition consists in the introduction into the circulation of an acid.

The only acid capable of producing this effect, so far as present researches teach, is the lactic acid.

The acid is best introduced by the peritoneum into the bodies of the animals subjected to experiment. This mode of introduction has the following advantages:

1. The operation is easy to perform and almost painless.

2. The acid solution, if the animal is deprived of fluids for some hours before and after the operation, is absorbed readily from the peritoneum.

3. The fluid being taken into circulation, with the acid largely diluted, the effects produced are comparatively slow, and are so defined, that the symptoms set up can be watched from day to day.

4. The operation is attended with no immediate danger as an operation, and it can be repeated many times on the same subject.

In my experience, extending now to sixteen experiments, the production of endocarditis has failed in no one instance.

The effect of the acid in producing endocardial inflammation is well marked in carnivorous animals, as dogs and cats, and I have recently tried it on a rabbit with the same result.

As I have already published the details of the first experiments for the production of endocarditis, I need not repeat those details here: it will be better to give the summary of the results of all the experiments.

When an ounce of solution of lactic acid, containing ten per cent. of the acid itself, is introduced into the peritoneal cavity of an animal, I refer more especially to the dog, no symptom is peculiarly manifested for the first six or eight hours, except one, viz., rapid action of the heart. True, the animal, if he has recently been fed, may vomit immediately after the operation, but this may be avoided by suppressing food and drink for a few hours beforehand.

After six hours, symptoms of a general kind occur; the acid having ordinarily disappeared from the peritoneum long before that period; the animal is now feverish, the skin is hot, and there is thirst; he has occasional shiverings, slight in degree, and he seems languid and cross. If the muscles are grasped, there is often evident and angry expression of pain.

The prominent signs of heart affection usually appear about twelve hours after the injection; the breathing is hurried; there is also a short dry cough, and decided uneasiness in the chest; the action of the heart continues to be rapid, and is now irregular and bounding. If the animal is at this point of the experiment freely purged, or if he passes a large quantity of urine, the symptoms all subside, and renewal of the injection is necessary, in order to sustain the effect. The effects continuing, either from the first, or after the repetition of the ope

* On the Investigation of Epidemics by Experiment. Edinburgh Veterinary Review, vol, i, No. II., 1858. Essay on the Coagulation of the Blood. Appendix. London, 1848.