LIBRARY 
 
 OK Till- 
 
 University of California. 
 
 GIFT OF 
 
 Class 
 
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 QUININE IN CHOLERA 
 
 BY 
 
 ERSKINE B. FULLBRTON, A. M., M. D., 
 
 Professor of Materia Medica and Therapeutics, Starling Medical 
 College, Columbus, Ohio. 
 
 COLUMBUS, OHIO: 
 
 Press of Nitschke Brothers, 
 
 1893. 
 

The Points of the Argument. 
 
 The strong points in the following papers are, in the 
 writer's opinion, as follows: 
 
 The test accidently made in 1873 in the case that I pre- 
 scribed for but did not see; the more extensive test-ex- 
 periment made by Dr. Schlomann in San Antonio, Texas, in 
 1866; the fresh vegetable and sauerkraut test in the Ten- 
 nessee Penitentiary in 1873. 
 
 The constant reference by the different authorities to 
 the analogies between, or identity of, cholera and malarial 
 disorders. Why this reiteration unless the success of the 
 remedy in cholera strongly suggested or supported the 
 theory of the other disease? 
 
 The pointing out the fallacy of using the remedy hypo- 
 dermically, and the after ability to show about when and 
 where the departure was made, from the earlier method of 
 administration by the mouth, to the unphilosophical intra- 
 venous and hypodermic methods. 
 
 The general trend of the treatment in the worst cases to 
 a mortality of about 20 per cent, only, which led me to assert 
 that the method of administration in the Stille list with its 
 63 per cent, of mortality must have been the hypodermic, 
 and to ask, as well, for a revised translation of the Putelli 
 article with its at-first-asserted death rate of over 46 per cent. 
 
 The facts and figures brought to prove, that the disease 
 treated in the penitentiary at Xashville, Tenn., in 1873, 
 could have been nothing other or less, than malignant Asiatic 
 Cholera, kept in check by the constant administration^ of 
 quinine in sufficient doses. f .*4\Ni^*J* 
 
 219784 
 
 c*yiS.'^ 
 
The figures showing the im])ossible doses of other 
 remedies necessary to e([ual in inliil)itory effect forty grains 
 of (|ninine, and thereby })roving this remedy to be the most 
 promising, in wiiat wiser men, simihirly circumstanced, have 
 tiMiued ''the state of tlie argument." 
 
 The iact tliat tlie proofs come, empiric end foremost, 
 making the method of reasoning inductive and not synthetic 
 and seductive merely. 
 
 The further fact that it is no new and untried i-emedy, 
 with hypothetical potentialities, to which attention is here 
 directed, but one which, by reason of its control over one 
 low foi-ni of organism, has rendered habitable the great 
 interior valley of The Light Continent, and will be as neces- 
 sary as gun])owder, in the conquest and civilization of *'The 
 Dark." 
 
 The articles are, with corrections, chiefly verbal, as they 
 appeared in the i^ew York Medical Record. 
 
 E. B. F. 
 
 Columbus, O., May 17, 1898. 
 
[ From the Medical Record, October 1, 1892. ] 
 
 QUININE IN CHOLERA, 
 
 By ERSKINE B. FULLERTON, A. M., m. D., 
 
 Professor of Materia Medica and Therapeutics, Starling nedical College, 
 
 Columbus, Ohio. 
 
 In the volume entitled "• The Cholera Epidemic of 1873 in the 
 United States," under- the head of " Notes on Treatment,-' quinine is 
 referred to as having been given in small doses, at uncertain intervals, 
 by two writers, and by one in conjunction with atropine, amounts not 
 stated. 
 
 In Dr. Edward O. Shakespeare's " Report on Cholera in Europe 
 and India " no reference is made to quinine in the chapter in which 
 treatment is considered, but it was used in the cities of Teruel, Toledo, 
 and Tembleque in Spain during 1884. The dose is not mentioned in 
 any case, nor the method, except in one only,. where it was the hypo- 
 dermic, with a strong inference that it was so used in the two other 
 cities. The journals at the time gave the dose as fifteen grains, 
 administered hypodermatically. When we recall two well-known facts 
 
 — first, that the Koch germ is found inside the intestine and not in the 
 blood, and secondly, that the direction of quinine is toward the kid- 
 neys, but little, under ordinary circumstances, escaping with the faeces 
 
 — a reason for failure when administered hypodermaticallj^ is apparent. 
 In 188-1 Koch places quinine next to mercuric chloride in develop- 
 ment-inhibiting (not disinfectant) power, the former acting in strength 
 of 1 to 5,000, the latter in that of 1 to 100.000. In other words, one- 
 half grain of the mercurial is the required equivalent for growth-inhi- 
 bition of ten grains of quinine. When it is recollected that the lethal 
 
6 
 
 dose of the one is about two grains, and that of the other about two 
 ounces, the disparity for practical effects is apparent. If five grains of 
 quinine can inhibit the development of the spirillum in three pints of 
 rice-water discharge in situ, what ill effect can be apprehended from 
 four or six times that amount ? All this, however, is " reasoning after 
 the event " with the writer. 
 
 In the epidemic of 1873 the use of quinine was early begun in 
 cases coming under my care in this city. In over thirty cases of 
 choleraic diarrhoea there was only one that proved refractory to the 
 quinine treatment, developing into what under the old nomenclature 
 would be called a mild case of cholera. Of the severer or typical form 
 of the disease I had five cases, in all ol' which quinine was given in 
 doses of seven and one-half grains in solution in the usual way, by 
 means of a sufficient quantity of aromatic sulphuric acid; and this 
 dose was repeated at intervals of an hour and a half or two hours until 
 the symptoms were under control, then in smaller doses at longer 
 intervals. Ice was allowed from the first in guarded quantities, and, 
 so soon as the tendency to vomit was sufficiently controlled, ice-water. 
 In some cases a small amount of morphine was given, in others 
 not. In all cases there was decided improvement after the first dose, 
 and a steady abatement of the symptoms as the treatment progressed. 
 The patient in whom the disease was, jjerhaps, farthest advanced when 
 treatment was commenced vomited but three times and purged but 
 twice after the first dose was given. In this case, with the typical 
 pulse, thirst, cramps in extremities, sunken countenance, and loss of 
 voice, the vomiting was incessant, and the constant discharge from 
 the bowels had penetrated the mattress and stood in a pool on the 
 floor beneath. In one case in which I was consulted by the physician 
 in attendance, quinine was exhibited to the extent of fourteen grains 
 in pill form. The patient's symptoms, typical as described, were con- 
 trolled for forty-eight hours, he returning to his place of business on 
 the second day. At the end of the above mentioned period the 
 symptoms returned and he died in the course of a few hours, no 
 quinine having been administered during the relapse. 
 
 AVhile aware of the danger in forming conclusions too radical on 
 the success of treatment in so limited a number of cases, and also 
 bearing in mind that epidemic diseases differ in tractability and 
 severity during different seasons of tlieir prevalence, and at differing 
 periods of the same epidemic, yet I have been unable to rid my mind 
 of the impression, strongly made nineteen years ago, that the quinine 
 
treatment had much to do with the results above recorded. That the 
 disease prevalent in Columbus, O., in 1873 was of no mild type is 
 shown by the report of Dr. Halderman, where, out of one hundred and 
 thirty-eight cases recorded, there were ninety deaths, a mortality of 
 more than sixty-five per cent. 
 
 Permit me strongly to urge upon the physicians now treating the 
 disease in quarantine or hospital that they try the remedy. I would 
 suggest that one drachm be dissolved in three ounces of water by 
 means of a sufficient quantity of dilute or aromatic sulphuric acid, and 
 that of this solution a tablespoonful be administered and at once 
 repeated if vomiting occurs, and afterward at intervals of an hour and 
 a half, until thirty grains have been taken, and thereafter pro re nata. 
 If judged best, a small amount of morphine may be added, or a few 
 drops of chlorodyne — their necessity I doubt. There are a few provisos: 
 
 1. The ten grain doses should be in solution, so that in case of 
 vomiting some may be retained. 
 
 2. That the patient be not already moribund from toxaemia, or in 
 pulseless collapse. 
 
 While the discoveries of the last few years render the theory of 
 Dr. Cunningham, that cholera is " malaria perniciosa," untenable, there 
 is nothing as yet by which we may infer that the treatment may not 
 be essentiallv the same. 
 
 [ From the Medical Record, December 10, 1892. ] 
 SECOND PAPER. 
 
 A former communication,^ giving my own experience during the 
 cholera epidemic of 1873, contained a comparison between quinine 
 and mercuric chloride, as to amounts necessary to inhabit the growth 
 of the cholera spirillum. Since then, in a ten minute discussion of the 
 '' Treatment of Cholera," before the Medical Section of the Mississippi 
 Valley Medical Association, the following more complete list with 
 comparative amounts was given. The list of inhibitor}^ amounts is 
 from that of Professor Koch, made public in 1884, with the exception 
 of tannic acid, from Cantani, and salol, from Lowenthal, the estimate 
 for the latter being based upon his lowest amount for sterilizing or (as 
 
 ' Medical Record, October 1, 1892. 
 
it did not always sterilize) inhibiting the growth of the germ. One 
 grain of quinine, which inhibits in strength of 1 to 5,000, is used as the 
 standard of comparison, and results are given in round numbers, as 
 inhibitory amounts doubtless were. 
 
 Inhibitory List with Deductions. 
 
 Alcohol, 10 to 100 Quinine, 1 grain = 1 fluid ounce. 
 
 Alum, 1 to 100 " 1 " =50 grains. 
 
 Camphor, 1 to 300 *' 1 " = 16s grains. 
 
 Ac. carbolic, 1 to 400 " 1 " = 12i grains. 
 
 Oil peppermint, 1 to 2,000 " 1 " =2hM. 
 
 Sulph. copper, 1 to 2,500 " 1 " = 2 grains. 
 
 Salol, 1 to 100 " 1 " =50 grains. 
 
 Tannin, 1 to 200 " 1 " = 25 grains. 
 
 Cor. sublimate, 1 to 100,000 " 1 " = ^ grain. 
 
 Forty grains of quinine is not a very formidable amount to be 
 given in the course of a day, or, for that matter, in a few hours, if 
 occasion required, but the relative quantities of these other drugs 
 seem very large ; 2^ quarts of whisky, brandy, gin, or rum ; 666| 
 grains of camphor, 500 grains of carbolic acid, 100 minims of oil of 
 peppermint, 80 grains of blue vitriol, 2,000 grains of salol, 1,000 grains 
 of tannin, 2 grains of mercuric chloride, 
 
 Calomel having little if any effect upon the germ, and opium being 
 necessary to control peristalsis in the guinea-pig, before he can be 
 made to take the disease, the logic of the situation seems to point 
 plainly to quinine as the least harmful, and therefore the most efficient 
 remedy, even in choleraic diarrhoea, or in moderately severe attacks of 
 cholera, where the treatment may be carried through several days. 
 How would it be in " foudroyant," " fulminant," or " explosive " cases, 
 where if anything is to be done it must be done quickly, and enough of 
 the remedy given in the cours'^ of two or three hours to arrest multi- 
 plication of the germ throughout the whole intestinal tract? In full 
 view of the modern theory that such cases may be the result of toxic 
 absorption rather than the presence of the spirilla in overwhelming 
 numbers 'in the intestines, it seems but reasonable tliat l)y inhibiting 
 the growth of the germ one may at least limit tlie furtlier production 
 of the toxines. Whatever other treatment may be used, in foudroy- 
 ant arsenicism we would hardly be justified in withholding the proper 
 antidotes for arsenical poisoning. Even in septicaemia quinine as yet 
 holds the field against all comers. 
 
 The latest estimate from Hamburg (September 8. 1892), places 
 
9 
 
 the death-rate at loiiy lour i)er cent., and the probability is that when 
 the full count is in, the loss will closely approximate the old one of 
 about fiCty per cent. So far as heard from, the good results to above 
 date seems attributable to hypodermoclysis. The word comes from 
 Paris that Beta naphthol (hydro-naphthol) has failed. ^ Salol has failed, 
 and the reason of its failure is apparent when we know that Lowen- 
 thaFs 20 grammes (300 grains) daily, which according to his theory 
 should set free in the duodenum the large amount of 120 grains of car- 
 bolic acid, only equals, after all, so far as inhibitory effect is obtained, 
 6 grains, or, estimating the carbolic' acid alone, less than 10 grains of 
 quinine, the 45 grains of Gonzales, of Salvador, about 1 grain, and the 
 120 grains daily of Nicholson, of Patna, India, less than 3 grains of 
 quinine. Tannin entroclysis has failed in spite ot Dr. Shakespeare's 
 expressed opinion that " with such an instrument not only the whole 
 length of the colon can be filled with the desired fluid, but also not 
 infrequently a quantity can be made to pass the ileo-ctecal valve into 
 the small intestine." That is to say, a small amount of the remedy be 
 placed just where it is most needed. Quinine failed by the hypoder- 
 mic method of administration in 1873 and 1884. The germ being 
 inside the intestine, and not in the circulation, and the affinity of the 
 remedy for the kidneys, and not for the bowel, this method of using it 
 would seem as irrational as the administration of sulphites or sulphur 
 by the mouth in the treatment of sycosis, chloasma, or scabies. That 
 by this method of using quinine the damaged kidneys might be 
 impeded in their function, and if there be aught in the old uraemic 
 theory of blood-poisoning in cholera, this undesired event, insured by 
 the further retention of urea and uric acid to the extent of about forty 
 per cent, where complete suppression of urine has not occurred, is 
 easv to understand. 
 
 To reach the seat ol" the disease the remedy must be given by the 
 mouth, and the only noteworthy objection to this use of quinine is the 
 old idea that quinine, under certain conditions, is very irritating to the 
 stomach. In the disturbed stomach of remittant fever we do not 
 always regard this symptom, and it was my own experience in 1873 
 that this remedy seemed a very good anti-emetic in cholera. In the 
 whole history of that epidemic (Woodworth, McClellan, et al.) there 
 is, if I mistake not, but once inention of its having been vomited, and 
 
 'If the above rumor were not correct we should know it by this time, as it 
 was certainly most extensively tried in Paris last vear. 
 
10 
 
 in that case it was given in conjunction with capsicum, not repeated, 
 the patient put upon other treatment and dying thereafter. 
 
 Has (piinino by tlio month given good results in cholera!' I think 
 it has. 
 
 Botkin, in 1871, in the Wiene?' Med. Presse, reports a loss of but 
 IT.'T iier cent, under the use of quinine. Tie gave 5-grain doses three 
 or four (sic) times daily, and when vomited resorted to hypodermic 
 injections of 8 grains frequently during the day. If the latter dose, 
 dissolved as it was, had been given by the mouth, and in case of 
 vomiting thereafter had been repeated until about 30 grains had been 
 retained, and continued in snuiller doses so long as symptoms seemed to 
 require it, there might have been a better result even than the above 
 very favorable showing. 
 
 Owing to a persistent denial on the part of the authorities at New 
 Orleans that cholera had been imported there in 1873, the profession 
 in the Mississippi Valley (to which this invasion was limited) was left 
 to make its own diagnosis as to the nature of the disease then prevail- 
 ing. As late as September of that year, or seven months after the 
 epidemic broke out in that city, the New Orleans Medical and Surgi- 
 cal Journal discredited the importation of the disease, and the editor 
 admits having considered it at first catarrhal in character. Of the 
 eighty cases first reported, forty-six went on record as cholera morbus, 
 " cholera Asiatica appearing infrequently." The idea of a cholera 
 Mississippiensis was very prevalent during the early history of the 
 epidemic in the lower valley, and throughout its entire history many 
 physicians held to the belief of its malarial origin. This is especially 
 noticeable in Tennessee and Kentucky. Quinine is frequently men- 
 tioned in treatment, but too often it is the last remedy of the list, and 
 in but few cases, comparatively, is the size of the dose, the method 
 employed, or the frequency of its administration noted. Good results 
 occasionally obtain after 5 grain doses by the mouth, and several 
 recoveries after rectal injections of the drug in varying quantities. 
 One writer states that the disease was very fatal unless the patient 
 was seen early and large doses of quinine given, and two instances are 
 recorded where the patient recovered alter the large amounts of half 
 an ounce in the one case and two-thirds ounce in the other, had been 
 taken. On such data, however, it is impossible to arrive at any satis- 
 factory conclusion other than that, generally, the results seem 
 favorable. 
 
 There is one exception to this rule, and the treatment and its 
 
11 
 
 results are so very remarkable as to be nearly unique in the history of 
 medicine, and on ^-o large a scale as almost to force conviction. As 
 recorded in the volume entitled " The cholera Epidemic of 1873 in the 
 United States," the facts are as follows : 
 
 About May 1, 1873, the authorities in control of the Tennessee 
 penitentiary at Nashville, Tenn., received notice that a malignant dis- 
 ease had broken out among two camps of convicts at work along the 
 line of the Memphis & Paducah Railroad. As to how fatal it was 
 there are several conflicting statements. Fortunately we have, on 
 page 137 of the above-mentioned volume, the report of the chief 
 engineer of the road, Mr. J. L. Meigs, which gives the whole number 
 sick of the disease from May 1st to 13th as forty, and the number of 
 deaths twenty-four, a fatality of sixty per cent. On the 12th of that 
 month convicts to the number of seventy-five were sent back to the 
 penitentiary at Nashville, purging and vomiting. On arrival about 
 one-half only of this number could be accommodated at the hospital, 
 the remainder being shut up in cells, usually two in a cell having a 
 capacity of two hundred and fifty cubic feet of air, ventilation being 
 through a grating, fourteen inches square, in the cell door, with the 
 bucket that received the choleraic discharges inside the cell. 
 
 The diagnosis " scorbuto-malaria " was made by the physician of 
 the penitentiary, and the sick put upon a diet of fresh vegetables and 
 saurkraut, with " tincture of iron and quinine freely given^ chlorate of 
 potash being used as an adjuvant." The day after the arrival one 
 man died, this man on reaching the penitentiary " being in so much 
 better condition than the others " that he was not admitted to the 
 hospital, but sent to his cell. A letter recently received from Dr. 
 George P. Henry, the physician, states that this patient had no medi- 
 cal treatment whatever. " The remainder recovered rapidly, and in a 
 few weeks most of them were at work.'- In the above-mentioned 
 letter Dr. Henry further states that to these seventy-four cases " I gave 
 quinine by the mouth altogether." " freely and at short intervals at 
 first," and that '' the cases were usually under control in an hour or 
 two after the administration of perhaps 20 or 30 grains of quinine," 
 " that finding its potency for good I kept it up," using it later on "both 
 by the mouth and hypodermically." Dr. W. M. AV right, at that time 
 Superintendent of the penitentiary, in a letter recently received, 
 states : " I think that 20 grains of quinine were given in about four 
 hours." 
 
 From May 12th to June 8th there was an average of fifty-seven 
 
12 
 
 oases daily under treat iiicnt in ho^pilnl and in iclU. Al this last date 
 there was an "explosion'' of the disease in the city of Nashville 
 (brought there by these same convicts), and '"the (act was recognized 
 that cholera was epidemic within the penitentiary walls." TJio dietary 
 was changed in conformity to the corrected diairnosis. and during that 
 day and the night following there were three deaths of prisoners from 
 the disease. 
 
 On June 9, 1873, Dr. Thomas Menees, a prominent practitioner 
 and teacher of medicine in the city of Nashville, was called in counsel. 
 and the treatment thereafter was as follows: Calomel and opium in 
 small doses frequently repeated, "quinine freely given either by the 
 mouth or hypodermically." In a meeting of the physicians of Nash- 
 ville, held December 16, 1874 (1873 0, Dr. Henry further states, 
 "after June 8th we treated the patfents with quinine, calomel, and 
 opium." "I called it malaria." Dr. Menees. at the same meeting, 
 said, "we also used quinine freely,"' and he ])lnces the whole numl)er 
 treated at between four and five hundred. *" prisoners and attaches." 
 In the letter from Dr. Henry above referred to, he places the numiier 
 severe enough to be called cholera at three hundred and fifty, the rest 
 choleraic diarrhoea. Dr. Menees states that '* from the 9th day of 
 June to the 12th day of July there were twelve deaths. There 
 were some that had chronic diseases, and when they were attacked 
 they would die.'' It will be seen l)y the abov(> that there were 
 fifteen deaths after the idea that the disease was malaria was given 
 up and the proper diagnosis of cholera made, but only one death 
 prior to this. There are three of these cases in which it is very 
 doubtful that they had any quinine, or if so. whether it was given 
 in sufficient doses in the light of modern discoveries to inhil)it 
 the growth of the germ. Dr. Henry writes he cannot reineml)er 
 whether the three dying on June S had quinine or not. It will be 
 recalled that on that date the diagnosis of cholera was made. Count 
 ing these, however, and allowing nothing for those al'-eady enfeebled 
 by "chronic diseases,'' and taking the lowest figure (350) as the num- 
 ber of cholera patients, and the result is a death rate of less than \^ 
 per cent, finder similar circumstrrnrefi, onh/ thai the hnspital arrnm- 
 modations were sufficient for alU the dietary arranged ^'iih reference 1o 
 cholera and not to scxirvy, and only a few of the diarrh<pa cases given 
 quinine in tonic doses^ the death-rate in the Ohio penitentiary in this 
 city was over seventy-five per cent. 
 
 That the disease was Asiatic cholera, which obtained access to the 
 
13 
 
 Mississippi \';illey tlir<)iii:li llic lickolty states rights' quarantine at 
 New Orleans, is no longer a debatable question. The death-rate of 
 lifty-two per cent, for the epidemic would alone show this. That it 
 was of no mild type in the Tennessee penitentiary is attested by the 
 tact that there was sixty per cent, ol' loss before the sick were ordered 
 in. and lurthermore, that there were one thousand deaths in the city 
 of Nashville during the epidemic — a mortality of about one in thirty 
 of the population of the city at that time. That other remedies than 
 quinine were used is true. Tincture of iron, chlorate of potash, " calo- 
 mel, and opium in small doses," camphor, *' calomel inserted dry under 
 the skin," blisters, and quinine hypodermically ; but all these had 
 been tried elsewhere and found wanting. Reasoning by exclusion the 
 treatment other than quinine is certainly insufficient to account for the 
 results. 
 
 To control so fatal a malady the amounts of quinine above indi- 
 cated seem small, but are quite enough in view of modern develop- 
 ments to eifect the wonderful results if continued for several days in 
 sufficient doses to maintain the effect once gained. In my own cases 
 fifteen grains given in the course of two hours always checked the 
 symptoms, and three to hve grains given at about two hours' 
 intervals thereafter were usually sufficient to keep the symptoms 
 under control. For how long a period this treatment was per- 
 sisted in I cannot now recall, doubtless in most of the cases for 
 several days, as there were but two instances ' in my own practice 
 in which the disease tended to return. In another case in which 
 I was consulted the patient got fourteen grains during a forenoon, 
 with the result of checking the disease for a period of forty-eight 
 hours. At the end of that time the symptoms returned, the 
 patient dying in a few hours without quinine. According to the 
 Marseilles experimenters the germ was rarely found in the discharges 
 after lour days, and never after ten days' time. The growth of the 
 germ in the last-named case was certainly not inhibited for a sufficient 
 length of time, and in my own cases I suspect that it was a resultant 
 non-specific enteritis that I had to deal with. 
 
 Plfteen grains of quinine are sufficient to inhibit growth of germ 
 in about five quarts of fluid, in case test tube experiments hold good 
 
 ' In the iuticle in Medical Record for October 1st, but one recurrent case is 
 mentioned. Since then, having liad access to a partial report of cases made 
 soon after tlie epidemic in Cincinnati Clinic, November, 1873, the other case i^ 
 recalled to memory. 
 
 L 
 
14 
 
 on so large a scale. With the rapid pcsristalsis of cholera, and the very 
 small quantity of the remedy that would be lost through absorption, 
 the currents being into and through the bowel, it is quite reasonable 
 to suppose that even in the intestinal tube these experiments would 
 hold good, and the quinine, instead of being absorbed, as it usually is, 
 by the stomach, pass onward into the intestine where it is needed. As 
 to coincident treatment I shall not venture to make suggestions. The 
 symptoms calling for hypodermoclysis, for small hypodermic injec- 
 tions of morphine, for small doses of calomel, for doses large or small 
 of bismuth or other astringents, or alternatives in the treatment of the 
 ensuing enteritis, are sufficiently obvious. 
 
 The statement is made above that the results in the Tennessee 
 penitentiary are nearly unique. T.hey would have been quite so 
 had it not been for the Naples treatment by camphor. According to 
 Dr. Rubini there was no death among 592 patients treated with an 
 alcoholic solution of camphor in such manner that the patient received 
 in mild cases about thirteen grains, and in severe sixty-six grains of 
 the drug in the course of one hour. The latter is a convulsant dose 
 equivalent to four grains of quinine. Tested afterward in the White- 
 chapel Workhouse, England, there were nine deaths out of tifteen 
 cases of the disease. A homeopathic physician who would give such 
 large doses could not be depended upon for accuracy of statement as 
 to results. 
 
 [ From the Medical Record, April 29, 1893. ] 
 
 The Remote History of Quinine in Cholera, with Summary. 
 
 THIRD PAPER. 
 
 (In the very commencement of this paper I wish to return thanks 
 to Major J. S. Billings, Surgeon, U.S.A., and Librarian, S.(J.O., AVash- 
 ington, D.C., for calling my attention to these earlier authorities and 
 putting the same at my service. In my second paper 1 had carried 
 the meagre later history of quinine in cholera back through tlie 
 journals at my command to Botkin only, in 1871, and the hypodermic 
 use generally. My thanks are also due to Major A. A. De Loffre, 
 Surgeon, U.S.A., for rendering into the vernacular a number of French 
 autliorities ; to Dr. A. M. Bleile, Professor ol" IMiysiology, Ohio State 
 
15 
 
 Universitj'. for translations of the invaluable German and Dutch writers; 
 to Dr. Henry Liddell. Washington, D.C., lor translations of Spanish, 
 Italian, Portuguese, and Russian authorities.) 
 
 In an article entitled " A New Specific Method of Cure in Epi- 
 demic Cholera, or, more properly, Cholera-Fever, by the Antifebrile 
 Principle of Cinchona Bark,'' Hanover, 1831, occurs the first mention 
 that I have found of the use of this agent in cholera. The writer cites 
 two physicians in India, who, in 1762, recommended " on the least 
 remission in the cholera-fever to give bark." The anonymous author 
 of the pamphlet suggests "' that opium be regarded only as an adjuvant, 
 the cure to be expected from quinine." His argument is theoretical 
 entirely, based upon the supposed malarial character of the disease 
 and his own experience in isolated cases of what appear to be bilious 
 diarrhoea and cholera morbus, the author never having seen a case of 
 Asiatic cholera. 
 
 Mr. C. Negri, London Lancet. February 1, 1832, commenting on 
 an earlier case of Mr. S. R. Ensor's, says : " I am strongly inclined to 
 believe that had Mr. Ensor substituted bark for opium and brandy, his 
 success might have been more fortunate, and I am the more inclined 
 to this belief because it has been but a short time ago since I had an 
 opportunity of seeing two very similar instances w^hich presented more 
 severe symptoms and were perfectly cured by the free administration 
 of bark alone." Then follow two cases that appear to be tertian or 
 quartan malarial diarrhoeas, successfulh^ treated by bark. It must not 
 be forgotten, in this connection, that cholera was prevailing in England 
 at the time, and that true choleraic diarrhoea often assumes an inter- 
 mittent form. 
 
 Mr. S. R. Ensor, London Lancet^ March 3, 1832, after referring to 
 the same fatal case, adds : '' Within the last month I have seen three 
 similar cases of a milder character, and have found the preparations of 
 cinchona highly advantageous when a determination to the skin had 
 previously been established. But wdien the surface of the body has 
 become cold, corrugated, and dry, the bark has invariably proved 
 emetic." 
 
 Dr. Bluif, Aix la Chapelle {Journal Chir. und Augenheilkunde, 
 April, 1833), precedes his cases by a long discussion to show the rela- 
 tion of intermittent fever to cholera. He gives a report of seventeen 
 cases treated by himself with quinine ; two grains every fifteen minutes 
 at first, and every half-hour after symptoms were under control for a 
 
varying period in oases tliat recovered, resulliiii: in thirteen recoveries 
 and four deaths. 
 
 He further remarks, "of these thirteen, six were the most virulent 
 cases of cholera that could well be imagined. Of the four that died, 
 one had had choleraic diarrhcea for four days before taking any medi- 
 cine, and was in statio mortifi when 1 was called. Another received 
 the medicine regularly, but after every tablespoonful ol' the (juinine 
 mixture received a glass of brandy (lour an hour) to take away tiie 
 bitter taste," etc. (The first record of the ilJ effects of alcoholics in 
 this review.) " The other two cases were amid the worst possible sur- 
 roundings, and only one who died was a robust young person.'' He 
 further recites : '' Dr. Stephen, of this city, also treated eight cholera 
 cases successfully, giving (after an emetic) a tablespoonful every half- 
 hour of a solution of eight to twelve grains sulphate of quinine ; twelve 
 to sixteen grains alum in four ounces mint water. After several 
 hours (at most six) reaction set in and patients recovered." Twenty- 
 five cases, all told, with four deaths — mortality, sixteen per cent. 
 There occurred altogether in Aix la Chapelle 427 cases ; 205 recovered 
 and 222 died. Evidently malignant cholera Asiatica, with a mortality 
 of 51.9 per cent. 
 
 Dr. Kosser, Posen, same journal and date, after remarking on the 
 analogy between cholera and pernicious intermittent fever, its eftects 
 upon the solar plexus of nerves, and recommending litigation of the 
 four extremities ("which will retain sixteen to twenty ounces of blood'"), 
 goes on to say, " As all medicines which have been hitherto used in 
 cholera have done no good, I thouglit of the use of large doses of sul- 
 phate of quinine. . . . I used six grains of ([uinine with a half-grain of 
 extract hyoscyamus every two hours in the first case." '' After seeing 
 the good eflects in the first patient, who was sick to the highest degree, 
 . . . I became bolder, and gave it in the most dangerous cases 
 every fifteen minutes, nay, every ten minutes, in tlie same doses. 
 . . . With this treatment of eleven cholera cases, all affected in 
 the high^ degree, I cured ten. The eleventh, who had improved 
 after the use of this remedy, but whom I had to leave for eight hours, 
 I found on my return in complete paralysis, and died in forty-seven^ 
 hours after beginning of disease. ... In addition to these sick 
 soldiers I treated five civilians in the same way, all recovering. Later, 
 cholera invaded the Eighteenth Regiment. I s-aw the sick. . . . 
 They were treated according to tlie experience laid down in literature. 
 Thev all di^d, however. . . . After a few days 1 was called to the 
 
17 
 
 civilians' iiospital. I foiiiid a patient in the liighest desiree of paralysis ; 
 he was forty years old. For fourteen hours he had had continuous 
 vomiting, and forty diarrlupa discharges. I gave him sulphate of 
 quinine. On my return, after one hour, the vomiting had ceased, and 
 he felt somewhat easier. He now received the second powder, and 
 three hours later the third. Symptoms all improved, but diarrhoea 
 not entirely controlled. ♦ I left three powders, to be given at two hours' 
 interval. On my visit in the morning 1 found the bed empty. I was 
 somewhat startled, but soon the patient came out of the kitchen 
 smoking a pipe. Convalescence went on uninterruptedly. This case 
 was followed by four other soldiers. They had immediately the most 
 violent symptoms — hoarseness, vomiting, diarrhcKa, ice-cold and blue 
 extremities, intense cramps in the stomach and calves, the pulse not 
 to be felt. These patients received every half-hour six grains quinine 
 with one-half grain extract hyoscyamus ; ligates extremities, etc. 
 Vomiting and cramps ceased after second or third powder. Later I 
 gave these powders in some severe cases every ten minutes, and some- 
 times gave two at once — powders given with coffee or wine. In a few 
 cases violent symptoms returned in twelve to twenty-four hours 
 (intermitting from incomplete inhibition ?), and after second to tilth 
 day all symptoms of cholera had disappeared. During the next four- 
 teen days I treated seven more men from the Eighteenth Regiment. 
 They all recovered except one man.'' To another case of Ibudroyaiit 
 cholera in a soldier on guard duty, he gave an emetic followed by 
 quinine in heavy doses, with recovery. Thirty cases with two deaths 
 — a mortality of 6.6 per cent. only. The reckless use of hyoscyamus 
 here would seem to disprove Hamlefs suspicions in regard to his 
 father's ''untimely taking-off " by reason of the '' accursed hebbene " 
 stuffed into his ear by his worthy uncle. In neither case could it have 
 been absorbed. 
 
 Dr. Antonio Putelli, Venice, Annali Universali 2fedicina^ Milan, 
 1836, " On the Use of Sulphate of Quinine \\\ High Doses in the Cure 
 of Cholera Morbus Asiatica administered in the Algid Stage.'' This 
 author considers that cholera morbus Asiatica allects the nervous 
 system of the '' vita organica." He cites no particular case or cases. 
 While he boasts that "■ he has seen his patients in a short time cured 
 and quickly brought to convalescence," he '"is compelled to admit 
 that in the case of tholera fulminante the therapeutic described has 
 but little effect." Jn the algid stage of cholera, accompanied by vomit- 
 ing, and also up to six or eight hours after the disease has developed, 
 
I prescribe forty or fifty grains of sulphate ol" ({uinine, mixed witli two 
 or three grains of opium, and the whole made into five or six pills 
 (eight grains each), to be taken every hour, diminishing the dose 
 according to the condition, sex. individual, constitution, etc. If the 
 first pill be rejected I give another, and a third, fourth, etc., if neces- 
 sary, until retained. I have never seen more than three pills rejected, 
 and the disease is soon tranquilized and the alvine dejections thickened." 
 He gave the remedy to children in a mixture containing alcohol, and 
 also used clysters of a decoction of calisaya. " On the second day I 
 gave fifteen or twenty grains of the sulphate. . . . Such was the 
 therapy adopted by me in many cases, amounting in four years to 
 sixty persons of both sexes, of whom thirty-two were cured." A 
 report very vague and unsatisfactory, but given for what it is worth. 
 That Dr. Putelli should felicitate himself so highly upon the recovery 
 of about fifty-three per cent, only of his cases would seem to indicate 
 that the epidemic in Venice was exceptionally malignant. That he 
 would have had better results if the quinine had been given in powder 
 or in solution I do not for a moment doubt. It has not been my 
 custom to prescribe quinine in pill form for persons suffering from 
 serous diarrhoeas since a patient in the early years of my practice 
 commended very highly the efficacy of some quinine dragees that I 
 had given her, because the next passage from the bowels after taking 
 one she always heard the pill shoot into the vessel. On inspection I 
 found her report correct. An eight-grain pill, jnade up with one of 
 the old excipients, acacia or tragacanth, would, with the rapid peris- 
 talsis of cholera, ricochet down the intestinal canal, tearing through a 
 spirillum bower here and there, and after doing some mechanical 
 violence to that delicate exotic, be found in the stools soon after, if 
 search were made. 
 
 Dr. Thomas Close, Portcbester, in The Scalpel, New York. July 
 25, 1849, reports one case of cholera getting well promptly on one dose 
 of twelve grains by month, with a like amount, together with a teas- 
 poonful of laudanum, given by rectal injection two hours thereafter. 
 Many cases of dysentery and some of the severest attacks of diarrhoea 
 (prevailing at the same time) yielded at once to twelve-grain doses of 
 quinine. 
 
 The same number of T/ie Scalpel quotes from two lectures given 
 by Dr. C. W. Bell, on cholera and intermittent fever. Manchester, 
 England. After- discussing his very elaborate theory of the disease, 
 he savs : *' If I have overrated the ellect of the medicine recommended 
 
19 
 
 (sulphates of quinine and iroii) I have not been induced to do so by 
 theory alone, but after I had used it in many thousand eases. . . . 
 While the epidemic prevailed in Teheran, my court-yard was daily 
 crowded with hundreds of poor wretches praying for the love of God 
 for a supply of the bitter water. It was served out to them in pint- 
 and-a-half mixtures, containing twelve grains quinine, nine of sulphate 
 of iron, and thirty drops of dilute sulphuric acid, with directions to 
 take a coffee-cupful at a dose. ... In some of the most remark- 
 ably rapid cures the whole was swallowed at a draught." Only short 
 extracts from lectures are given. The title of the article in the index 
 of The Scalpel reads, " Dr. Bell's Lectures on Cholera, Five Thousand 
 Cases Cured by Quinine in India." This smacks somewhat of Marco 
 Polo, but like the famous traveler he had doubtless seen something of 
 that which he wrote about. 
 
 Dr. B. F. Sargent : Philadelphia Medical Examiner^ September, 
 1854, in " Notes of a Few Cases of Cholera Treated in the Summer 
 of 1849, showing the Comparative Curative Powers of Sulphate of 
 Quinine in Large Doses," mentions that the " late Dr. Wilson " 
 attended these cases in conjunction with himself. 
 
 This article deals only with " treatment we pursued in the collapse 
 of cholera. . . . We say nothing of the simple diarrhoea which 
 recovered under ordinary treatment. He refers to article in London 
 Medical Gazette^ 1847-48, in which Dr. C. W. Bell's treatment is men- 
 tioned, as giving the clue to the use of quinine in these cases. Follow- 
 ing this come cases treated by calomel, opium, acet, lead, quinine in 
 small doses, chloroform, etc. He mentions the use of large doses of 
 the remedy in pernicious intermittent fever. Then follows a narrative 
 of cases treated by quinine, typical^ tinmistakahle Asiatic cholera of 
 gravest form. The dose given at commencement of treatment varies 
 from ten to twenty grains in the course of an hour or two, either in one 
 or two doses, usually with laudanum and brandy, and followed by 
 smaller doses of quinine for a varying period thereafter. " To recap- 
 itulate, we have cited in all thirty-seven cases of cholera in the stage 
 of collapse. Of these, seven were treated with calomel and opium, 
 sugar of lead, etc., and of this number only one recovered. Four cases 
 treated by Dr. Ayers's plan (calomel, 1 gr.; laudanum, 1 gtt.; every 
 live minutes), all died; four by chloroform, camphor, or oil of turpen- 
 tine, all died; three by quinine and sulphate of iron in small doses, all 
 died; seventeen by quinine in large doses, with thirteen recoveries 
 and four deaths ; two by bleeding, both recovering. In these cases the 
 
j)r<»mj)t cessation of vomiting and diarrhoea and llie pioin]*! rcaitiou 
 are especially noticeable. Of the lour fatal cases treated l)y (iiiinino 
 in lar<:e dozes, one, a nurse, had been sick a week with i)rein()nitory 
 diarrhd'a — she partially reacted; another, having vomited two lilteen. 
 grain doses of quinine, was treated with rectal injections of (£uinine 
 thereafter: the third case was drunk for three days previous to the 
 attack, when treatment commenced was thoroughly collapsed and 
 nearly pulseless — two twenty-grain doses of quinine given ; fourth case 
 not narrated. Fatality, 23.5 per cent." 
 
 Dr. W. Strange,' after stating his theory of the disease to be 
 essentially that of Dr. Bell, having treated by other means thirty-one 
 cases with nine deaths — a fatality of twenty-nine per cent ; had nine- 
 teen cases that he afterward treated with quinine, with four deaths — 
 fatality twenty-one per cent. 
 
 Gave only two-grain doses of quinine, with twenty drops of tinct. 
 ferri chlor., every two or three hours ; recoveries slow, the doses of 
 quinine being too small. He notes immediate etl'ect of quinine in 
 checking the vomiting. Two cases that died under the treatment were 
 intemperate. He notes that '' the choleraic diarrhoea was curable by 
 one or two doses of the quinine and iron, while they obstinately 
 resisted treatment by stimulants, opium or calomel." 
 
 Here comes trouble ! In the leading article. Medical Times and 
 Gazette^ London, October 8, 1853, occurs this : '' But of all remedies 
 used during previous epidemics, with the exception, perhaps, of opium 
 as a palliative, . . . quinine, probably, is most deserving of a 
 further trial. Modern experience in India is leading to increasing con- 
 tidence in its powers. Toward the close of the epidemic it was used in 
 London. Mr. Spencer Wells injected a solution into the veins in four 
 cases. Dr. E. A Parkes did so in tico others ; all died.''" 
 
 As they most properly should, that method of administration being 
 as useless in cholera as the hypodermic. In the same journal are 
 reports of cases treated by Drs. Wells and Tarkes. 
 
 Dr. .J. Sappington,- on •' Quinine in Cholera,"" with much st'lcctive 
 polytherapy. gave (iiiininc in one grain doses for consecutive fever, 
 only — none in the cholera stage — with asserted good results. Had he 
 given it earlier and in larger doses, there might have been no consecu- 
 tive fever. 
 
 ' Letter to Dr. C. W. Bell, Provincial Medical and Surgical Journal, London, 
 1849. 
 
 ■■' Eclectic Medical Journal, Cincinnati, 1849. 
 
21 
 
 Dr. Thomas W. Gordon, Georgetown, O., in Ohio Medical and 
 Surgical Journal^ 1853, gives a report of eighteen cases occurring in 
 Georgetown and vicinity in the summer of 1852. Undoubtedly cholera^ 
 niof<t of the cases described being typical and severe in form. Twelve 
 cases treated by himself and brother, by quinine and morphine, in the 
 doses of the former of from two to ten grains, at intervals of ten 
 minutes to six hours {pro re nata). recovered; of the six cases treated 
 by others and otherwise, five died. He notes the absence of consecu- 
 tive fever, but speaks of one of the fatal cases becoming intermittent 
 before death. Elsewhere^ he states, '• I do not expect that quinine 
 will cure every case, but believe it just as certain to cure cholera when 
 properly administered as it is of curing regular intermittent fever/' 
 Quinine given in powders. 
 
 C. Vianna, Gaz. Med. de Lisbon., February, 1856, describes a case 
 of what appears to be malignant cholera supervening upon an inter- 
 mitting febrile attack, and with a consecutive fever of similar character, 
 recovering on quinine, eight grains in two hours, followed for several 
 days by varying quantities of the same drug at varying intervals. 
 Treatment at the cholera hospital, with sulphuric acid lemonade for 
 vehicle. I insert this case more as a protest against the custom of 
 asserting cases cured by quinine to be necessarily ague, than for any 
 other reason. 
 
 Don Clemento Ascarza, in M Siglo Medico, Madrid, 1856 : 
 " Happy Results Obtained with Sulphate of Quinine Given in Large 
 Doses in the Algid Stage of Cholera." He notices an apparent inter- 
 mission in symptoms otherwise those of a grave form of cholera 
 Asiatica. That he was on the lookout for such remissions, and that 
 we must eliminate this "• personal equation," as is done in astronomical 
 calculations, is evidenced by his citing Torti. He gave forty-eight 
 grains quinine in four doses, in pill form, at hourly intervals; improve- 
 ment, but final outcome of first case not stated. Five other cases that 
 had received " extreme unction " recovered under the treatment. 
 That there were one hundred and forty-seven cases in the city and only 
 five that passed into the algid stage would indicate either a mild epi- 
 demic of cholera or one equally mild of gastro-enteric malaria. 
 
 Dr. Vial, in a letter to the editor of V Union Medicale., September, 
 1860, states that he used the medicine with happy results. Dose and 
 method not given. 
 
 1 Transactions of Ohio State Medical Society, June, 1856. 
 
22 
 
 Here come sweetness and light, however, and they come from the 
 Dutch country, that Campbell has recently shown to be the source in 
 our own land of much of what we have been accustomed to think- 
 ing our Anglo-Saxon institutions, among which may be mentioned the 
 equality of man ; the separation of Church and State : tiie town meet- 
 ing; the free school, and the relation of separate states to a national 
 government. The writer's name is Dr. J. L. Pompe van Meerdervoort, 
 " On the Treatment of Cholera Asiatica by Quinine Sulphate in Japan, 
 Ntderl. Tljdschr. Geneesk.^ Amst., 3865. He says : 
 
 '' During my residence in Japan, from September, 1857, to Novem- 
 ber, 1862, 1 passed through three ditlerent fearful epidemics of cholera. 
 In these three epidemics I personally treated 2,467 patients, all with- 
 out a doubt affected with cholera; of this number 1,746 recovered and 
 721 died. This result is very favorable, about seventy per cent, saved, 
 and about thirty per cent, dying, especially when one considers that in 
 many cases I was not called at the beginning, or soon after, and that I 
 was the only physician in a city of 60,000 inhabitants (Nagasaki), 
 which, so to speak, would prevent a proper control of the epidemic. 
 This favorable result I ascribe to the treatment with the sulphate of 
 quinine.'" The epidemic was brought to Nagasaki by the American 
 ships Powhattan and Mississippi from China. It came in the time of 
 the fruit harvest, and the Japanese, according to the doctor, " eat no 
 ripe fruits and sleep half naked on their verandas."" His first and 
 second reasons for using quinine were the prevalence before the epi- 
 demic of malarial troubles. "• 3d. Several of my colleagues in Nether- 
 lands, India had previously used quinine in cholera with great advan- 
 tage. 4th. All other recommended medical treatments had been of 
 no avail."' After recommending its use as early as possible, he goes 
 on to say : '' If vomiting is severe and continuous the remedy will not 
 be tolerated any more, and one had better then resort to hypodermic 
 injections, which were then, as yet, unknown to me."" Very for- 
 tunately so, as had this method been resorted to, the favorable results 
 in so large a number of cases, and under the circumstances above indi- 
 cated, would not have been obtained. He recommends in the com- 
 mencement three to six grains of quinine dissolved in sul]>huric ether, 
 alcohol, and peppermint oil. '' Should symptoms become worse, how- 
 ever, and vomiting, cramps, and abdominal pains come on with the 
 well known cholera excreta, then one should give, every half-hour, 
 four to six grains of quinine, with warm bath." He uses champagne 
 and ice for vomiting, and says, '■ I verv seldom use narcotics, especially 
 
23 
 
 in large does. . . . Often, nay, almost always, did I see distinct 
 collapse come on in those sick to whom the Chinese doctors gave large 
 doses of narcotics. . . . Bleeding, which was used in the beginning 
 of the epidemic of 1858 by the Japanese physicians, usually caused 
 death. As soon as the crisis has appeared one should continue for 
 some time the use of the quinine, as otherwise there is danger of 
 exacerbations, during which the sick may yet die. Later, the dose 
 may be decreased. . . . There need be no fear of quinine intoxi- 
 cation. ... I saw this intoxication but three times, and warm 
 baths, cold affusions to head, port wine and beef-tea soon obviated 
 these symptoms." The writer shows his theory-bias by the remark : 
 " The use of quinine in cholera or similar malarial epidemics is to be 
 recommended, especially in the tropics. . . . I do not wish to say 
 that I consider it as a certainty that pernicious fever and cholera are 
 identical.'" 
 
 " The cholera mixture I prescribed in Nagasaki has the following 
 formula : 
 
 T?, Sulphate of quinine 1 drachm 
 
 Dilute muriatic acid 1 drachm. 
 
 Alcoholic sulphuric ether IJ diachm. 
 
 Eleo-sacch. menth. \np 2 drachms. 
 
 Pure water 8 ounces. 
 
 In mild cases one tablespoonful every half-hour ; on improvement, 
 every hour ; in severe cases one tablespoonful every quarter hour ; on 
 improvement every half-hour, and then in decreasing doses. After a 
 short use of the above mixture there is usually improvement, at least 
 if it is used in time. . . . The number — 2,467 — here given, pertains 
 only to those cases treated by me personally — all severe and well 
 developed cases of cholera — not cholerine. Of these one-sixteenth were 
 treated in hospital, fifteen-sixteenths outside in the city. The Japanese 
 physicians who followed my treatment obtained just as favorable 
 results." 
 
 The hypothesis is often used as a method of arriving at accurate 
 results in the exact sciences Let us suppose that instead of one 
 physician to 60,000 people, there had been the usual ratio obtaining in 
 the United States, of one to five hundred population ; that instead of a 
 vegetable and fruit-eating population (the Buddhist priests in Japan 
 have only in the last few years begun to frequent the butcher stalls) 
 there had been a better fed people of a stronger vitality to deal with ; 
 that instead of seeing these cases only in the severest stage of cholera, 
 
24 
 
 llu'v liiul hec'ii seen iluriiiir the cnrlier slnjiC's of choleraic diarrlKra. ov 
 so-called cholerine, what an enormous reduction in tlie niortalily 
 niiirht have been secured by this treatment can best be.judiied by the 
 results in the 'i'ennessee Penitentiary in 1878, of which Jiiore anon. 
 The more exact mortality of Dr. \'an Meerdervoort's cases was 20.22 
 l>er cent. W. (). Shakespeare says, " In Ja]»an in 1854, there occurred 
 154,373 cases, with 101,(>9r) deaths, a mortality of (Ul.S. slK)win^- the 
 ordinary severity of the disease in Japan."* 
 
 Di-. A. Schloniann' says: '' In the cholera epidemic of the Mis- 
 sissippi Valley and the Gulf States, summer and fall of 18Hf), several 
 American physicians obtained surprisingly good results from the 
 sulphate of quinine. Such a coincidence might seem strange, but is 
 explained, however, by the fact that everywhere in these States the 
 appearence of cholera came during the time for intermittent fevers. 
 This would tend to experimentation with quinine salts, which are the 
 staple drugs of the Southern pharmacist. . . . Our cholera loas the 
 real cholera of the Ganges Delta axd )\ot a doubtful hybrid form of 
 intermittent. . . . The tbllowing observations were made during 
 the epidemic in San Antonio de Bexar, a town in Western Texas, 
 having a population of l(),0<t() souls. . . . The outbreak of the 
 epidemic was preceded b}' the usual endemic and intermittent fever, 
 which, however, was not of a malignant type, and was declining before 
 the cholera came. . " . . In these cases (non-febrile choleraic 
 diarrlueas) I carried over the (|uinine treatment with the same unvary- 
 ing good results. The constancy of success and the continued 
 immunity of my clientele in the midst of the prevailing great mortality, 
 caused me to wonder whether this result was due to the medicine or 
 to other accidental and unknown conditions. To find this out, I con- 
 cluded to change the quinine treatment for opium, and aromatic and 
 astringent remedies. . . . During the tirst half of the new day 
 everything passed oil' pleasantly, and the diarrhfea seemed to be 
 checked in all cases. During the night, however, after the effect of 
 the opium (quinine had passed o(f, diarrha-a returned in every case, 
 and worse than before. The discharges became so threatening that I 
 speedily returncMl to the use of quinine. After this day 1 continued 
 the quinine treatment with the same previous good results, so that at 
 the end of the epidemic 1 had come to the conviction that quinine 
 
 ' Treatment of Asiatic Ctiolera by Quinine, Ber. klin. Woclienschr., Sept- 
 ember 4, 1871. 
 
25 
 
 would be, at some future day, of the same importance in the treatment 
 of cholera as it is in the treatment of intermittent fever." (This writer 
 had formed the theoretical opinion that quinine would do only harm 
 in the "" asphyctic '' stage, and so did not give it in his worst collapsed 
 cases.) '' I wish to remark that all cases that came into treatment in 
 the asphyctic state and all lighter ambulant cases of diarrhoea have 
 been excluded. Under the quinine treatment 220 cholera and choler- 
 ine '^ patients recovered and three died. Mortality, 1.3 per cent." 
 Then lollows a history of these three fatal cases. 
 
 '' 1st. Vomited the medicine, becoming an hour therealter 
 ' cyanotic ' and died. 
 
 "■ 2d. Intestinal diphtheritic form with complete anuria ; thirty 
 grains quinine did not arrest disease. He died on fifth day. 
 
 '' 3d. A child, three or four years old, that got only five grains of 
 quinine died." 
 
 Commenting on these three fatal cases, he goes on to say : "' In 
 regard to these thre^ cases, which might be used as testifying against 
 the value of the medication, the first needs no further comment. In 
 the second the medicine was absolutely without effect. The tenesmus 
 present makes it probable that the disease was located in the large 
 intestine, and I regret, with my present views, that I did not give a 
 quinine clyster. The method of treatment was always the same, with 
 small modifications. I always carried gramme doses of quinine, and a 
 morphine solution for the purpose of hypodermic injection. The quinine 
 was always given without delay, either in half or whole dose, and 
 repeated after the next evacuation, or also after two or three hours if 
 there was not a slight intoxication. Generally opium was added to 
 this. In vomiting or nausea often a subcutaneous injection of mor- 
 phine was given." Bases his objection to use of drug in the asphyctic 
 state on the fact that he had seen "■ disastrous results " from using it 
 in the " fever period of remittent or in typhoid fever." a doctrine 
 hardly of universal acceptance even at that time, and certainly not 
 now. He quotes other authorities, and mentions hypodermic use of 
 the drug. 
 
 The French authorities are of but little moment. In 1865 M. 
 Pidoux recommended it in tonic doses — a '"weak mixture," contain- 
 ing one-third grain of quinine to the dose ; a strong mixture containing 
 
 ' German nomenclature — choleraic diarrhoea, cholerine, cholera ; French- 
 cholerine and cholera only. 
 
about one-half grain to the dose. P'ollowing his treatment. Dr. O. Des 
 Broulais used it in what appears almost certainly to have been an 
 epidemic, malarial in character, but attended b.y intestinal disorders, 
 in the Valley of the Loire Inferieure, witii asserted good effects. Men- 
 tion is made that these small doses seemed to have had a beneficial 
 effect upon the vomiting. 
 
 In Z' Abeille Medicate^ 1865, Drs. Bourgogne and B. de la Gran- 
 diere dispute over a case of cholera (as asserted by the former but 
 denied by the latter) that was cured by tannate of quinine after 
 reaction had taken place. 
 
 L, V. J. Gruzot, Process Imperial Medical Society of the Caucasus, 
 1871, states that '' in the summer of 1866, in Abchasia Huduat, the 
 author had charge of the cholera division of the regiment." He gives 
 no figures, but says the death rate was small under the quinine treat- 
 ment. Further on he gives two mild cases of cholera (cholerine?), 
 occurring in 1871, successfully treated by hypodermic injections of 
 quinine. He also criticises Professor Botkin, of St. Petersburg, for 
 using four to five grains of quinine by the mouth as " entirely inade- 
 quate and too risky ; " recommends the hypodermic use instead, and 
 finally adds, "the very small percentage of death-rate (17.3 per cent.) 
 in the treatment of cholera with quinine in Professor Botkin's clinic 
 and my own personal preference for the hypodermic injection method, 
 lead me to make the present communication." It may be recollected 
 by some that in recording Professor Botkin's results I said in my last 
 article in the Medical Record that had Professor Botkin given the 
 larger doses, eight grains in solution, by the mouth, and when vomited, 
 promptly repeated the dose instead of resorting to the hypodermic 
 method, " he would have had still better results than the above very 
 favorable showing." 
 
 " For truth is this to me and that to thee." 
 
 My two records meet here and contain all that is known or accessi- 
 ble to me pertaining to the use of quinine in cholera. When my atten- 
 tion was called, in the Columbus Academy of Medicine, to Stille's 
 summary of results on board the Belleisle, ' in which, with varying 
 results under other treatment, out of the number (nineteen) treated 
 by quinine, twelve died, I stated that "I had no doubt that the hypo- 
 dermic method was used." Later, in writing to the friend, in Wash- 
 ington, D. C, who kindly looked up the reference for me, I modified 
 
 * Medical Times and Gazette, 1866, vol. ii., p. 590. 
 
27 
 
 this judgment by adding, "or only the worst collapsed cases were so 
 treated." How nearly my judgment, based on my researches at that 
 time, came to being correct will be best shown by the following 
 extract from the article entitled " Treatment of Cholera on Board the 
 Belleisle." 
 
 1. " Quinine treatment consisted in the hypodermic injection of 
 twenty grains of quinine in solution. ****** 
 As this plan of treatment was new, the worst cases were selected, all 
 but two being in a pronounced stage of collapse on, or soon after, 
 admission." It was the hypodermic method, used in the worst 
 cases, too. 
 
 On the British flag the sun never sets, and the British drum beats 
 round the world. Wherever that flag floats and drum beats are British 
 surgeons to whom come these great London journals. The cases of 
 Messrs. Spencer Wells and E. A. Parkes, experimented upon in 1853 
 and dying after intravenous injections of quinine, must have had their 
 effect, as these cases were noted everywhere. In the sixties it will be 
 recollected that the great rage for hypodermic medication was on, and 
 here comes another failure by this " new method of treatment," and 
 this reportj too, went its rounds, undoing much of the work that had 
 been done by these earlier writers whom I have here recorded. 
 Strange enough, the lack of success by this method did not excite 
 a return in any great degree to the earlier method of administration. 
 It is my belief that the hypodermic method was more commonly 
 resorted to in the epidemic in the Mississippi Valley in 1873 than the 
 other by the mouth. That it was so in the city of Nashville, Tenn., I 
 am convinced, and for the following reasons : 
 
 1. The method is not mentioned as having been used in the peni- 
 tentiary until the very able counsel came in from the city. 
 
 2. Another practitioner of equally high reputation, ^ writing me, 
 says, " I also gave quinine freely, using an ethereal solution hypo- 
 dermically." 
 
 Furthermore, the number of deaths in the city — 1,000 — show 
 either that there were about two thousand cases in the city, giving the 
 usual fifty per cent, rate of mortality (the rate for this epidemic of 
 
 1 I know that these Southern gentlemen will view this statement in its right 
 bearing, analysis, not criticism. It is my belief that there are no better physi- 
 cians anywhere than in Nashville, and if I am correct in my above surmise, in 
 using this method they were following the lead of the advanced thinkers in the 
 profession the world over. 
 
28 
 
 1873 in the Mississippi Valley being fifty-two per cent.) under other 
 treatment, or else the death-rate in the penitentiary carried into the 
 city would give the astonishing result of over 33,000 cases of all grades 
 of the disease, some 5,000 more cases than there were people then 
 resident in the beautiful capital of the brave old State of Tennessee. 
 In this estimate I have taken the highest number of cases mentioned : 
 " There were about five hundred prisoners and attaches at the peni- 
 tentiary, and almost every man, woman, and child there were afflicted 
 with the epidemic.'- The number of deaths of those having medicinal 
 treatment being fifteen, gives the rate of three per cent. 
 
 That the penitentiary cases ^ treated by quinine were malignant 
 cholera is evidenced by the fact that it was malignant cholera, with a 
 death-rate ot sixty per cent., before the seventy-five convicts were 
 brought in from their camps along the railroad ; that it was malignant 
 cholera in the one of the seventy-five prisoners who received no 
 quinine ; that it was malignant cholera in the negro (McClellan, quoted 
 by Wendt), discharged from the penitentiary and dying in the city a 
 few days afterward ; that it was malignant cholera on the day when 
 the physician of the prison corrected his diagnosis, changed the dietary 
 of the sick, and presumably modified his treatment, as three died on 
 that day ; that it was more malignant cholera after other treatment 
 was in part even introduced, twelve cases dying thereafter ; that it was 
 most malignant cholera that was introduced into the city of Nashville 
 by these same convicts. 
 
 As to the cause of the results obtained, it was not the dietary, for 
 that was arranged for scorbuto-maleria and not for cholera ; it was not 
 the hygienic surroundings, for two prisoners, for the most part, were 
 in one cell with 250 cubic feet of air-space, and the slop bucket to 
 receive the discharges within the cell ; it was not the other treatment, 
 for this had given a mortality of about fifty per cent, in previous, as it 
 has in subsequent, epidemics; it was not faith-cure, for in Western 
 penitentiaries they do not "■ batter the gates of heaven with storms of 
 prayer." 
 
 It must have been the quinine first given, "by the mouth 
 wholly,'' by Dr. Henry, and continued thereafter, with rare good sense 
 and judgment, by the consultant, Dr. Menees, who doubtless saw the 
 
 ^ For details of epidemic in Tennessee Penitentiary, see Cholera Epidemic of 
 1873 in the United States, or my own article. Medical Record, December 10, 
 1892. 
 
29 
 
 good results inuring from its use and continued it, ''''freely hy the 
 mouthy as loell as hypodi'Txiically. 
 
 Summary. — After writing the above, I waited for a few days before 
 completing this paper in order to hear from my translator in Washing- 
 ton, D. C, to whom I had written to please verify his translation in 
 the Putelli article above quoted, as from the large amounts of quinine 
 taken there should be a better result than the forty-six per cent, death- 
 rate, even with the pill form of administration of the remedy. The 
 following extracts from his reply speak for themselves : " I regret to 
 find on reference to Putelli that there is an inaccuracy in the transla- 
 tion of the passage relating to the results obtained by the administra- 
 tion of quinine in cholera. The true translation is, ' Such was the 
 cure by me adopted in many cases in persons aged from four years to 
 sixty, and of diverse sex, of whom two thirds were cured.' Mortality 
 thirty-three per cent." 
 
 When upon the results of treatment alone I can say of Stille''s list 
 the remedy must have been given hypodermically and not hy the mouthy 
 and for the like reason in PutellVs case suggest where the translator 
 has erred^ it would seem that we had the Asiatic scourge l)etween the 
 hammer and the anvil^ and a step had heen taken hy therapeutics 
 toivard a place among the exact sciences. The report of Putelli and 
 my remarks upon the same I shall permit to stand as they are above. 
 The pill form used will still serve to explain why the recoveries fell so 
 low as sixty-seven per cent. 
 
 1. In my first paper ^ are given the results of treatment of 
 cholera by quinine, in 1873, among my own clientele. The cases were 
 few, but the end attained such as to satisfy my own mind that the 
 remedy had a remarkable elfect over the disease. In my second 
 paper ^the inhibitory list of Koch, with additions of Lowenthal's salol 
 and Cantani's tannin are discussed, with amounts of these remedies 
 furnishing the inhibitory equivalents of forty grains of quinine. It is 
 my belief that this comparison has shown that quinine is the only one 
 of these that can be given ad lihitum ad inhibitum. In both of these 
 papers I pointed out the error into which the profession had fallen in 
 giving the remedy hypodermically instead of by the mouth, the germ 
 being inside the intestine, and the emunctory through which the drug 
 escapes being the kidneys. 
 
 1 Medical Record, October 1, 1892. 
 
 2 Ibid., December 10, 1892. 
 
30 
 
 2. As to special sj'^mptoms all authorities agree that quinine in 
 almost all cases very shortly stops vomiting, this being remarked 
 even by the French authorities who gave it in very minute doses. In 
 the report of McClellan et al., it is only once mentioned that the 
 remedy was vomited. 
 
 3. That in the few cases where the quinine was persistently vom- 
 ited the patient always died. 
 
 4. That the diarrhoea was usually checked within a few hours, 
 rarely lasting on for a few days when the dose was large. 
 
 5 That where the dose was sufficient reaction promptly followed 
 the cessation of these symptoms, that there was no consecutive fever, 
 and that convalescence was rapid as compared with that resulting 
 from other remedies. 
 
 6. Furthermore it appears from this record that doses at the rate 
 of about ten grains per hour for a sufficient time, seemed usually to give 
 as good results as larger doses, and much better, generally speaking, 
 than smaller amounts. 
 
 7. That these results did not depend upon the sulphuric acid, the 
 hydrochloric acid, or the various salts of iron with which the quinine 
 was sometimes combined, as quite as brilliant effects came from the 
 quinine powders alone, given by many. 
 
 8. That the hypodermic syringe should be used only (if at all) for 
 the small morphine injections that may be needed to control certain 
 symptoms — pain, spasm, etc. — as in all cases mentioned where bad 
 results were obtained this method or the intravenous was used. If bad 
 results ever came from administration by the mouth, there is no record 
 of the same. 
 
 9. That the pill form should be eschewed. 
 
 10. That the above results strongly confirm the belief that Koch's 
 germ is the true cause of cholera; that it is confined to the intestinal 
 tract, and that quinine, inhibiting in strength of one to five thousand, 
 is the "• quinine of cholera " that Semmola wished for but could not 
 
 find. 
 
 11. It is the uniform testimony that although the remedy seems 
 
 sometimes to have been given in very, probably needlessly, large 
 doses, yet no very unpleasant effects resulted. 
 
 12. That the objections that the disease was not cholera but 
 malaria successfully treated by quinine;' that it was only a mild form 
 
 ' The germ test cannot be made retroactive. What method of diagnosis was 
 pursued in the cases from which Koch first obtained his comma bacilli ? 
 
31 
 
 of the disease which would get well under ordinary treatment, are alike 
 set aside by the above chronicle. 
 
 13. That the curative effects of quinine in cholera are only less 
 certain and sure than in malaria because of the greater rapidity with 
 which the former poison acts. The oontrol of the remedy being as 
 evident in the one disease as in the other. 
 
 14. That in fulminant cases the thing to do is to fulminate the 
 quinine more rapidly — lightning strikes up as well as down. 
 
 15'. That in cases of obstinate vomiting entero-clysters of quinine, 
 forty to sixty grains in two or three quarts of warm water, should be 
 made trial of. There would be an inhibitory margin for four times 
 the amount of fluid mentioned, and some of this might be got beyond 
 the ileo-colic valve. 
 
 16. That after thorough quinine inhibition in collapsed cases 
 hypodermoclyses may be made use of with a better hope that the 
 saline solutions will not only temporarily galvanize the patient into 
 life in order that he may again collapse when the intestinal discharges 
 once more set in. 
 
 17. That there is a limit in therapeutics ; " we cannot make a 
 withered palsy cease to shake," and resurrections from the dead are 
 few, far between, and none too well authenticated. Quinine will not 
 cure heart-clot. 
 
 The following tables seem to show about what the rate of mortality 
 has been heretofore (the quinine having been given by the mouth) : 
 
 In Japan Collapsed and Collapsing Cholera. 
 
 Number npatha Percentage 
 
 of cases, ^leams. of mortality. 
 
 Dr. Van Meerdervoort 2,467 721 29.22 
 
 In Europe and America, Collapsed and Collapsing Cholera. 
 
 ■CT^-j^™,--, Number t\„„h,= Percentaere 
 Epidemic, of eases. °«^'^^- of mortality. 
 
 Dr. Bluif 1831-36 17 4 23.5 
 
 Dr. Rosser 1831-36 30 2 6.6 
 
 Dr. Close 1849 1 0.0 
 
 Dr. Sergeant 1849 17 4 23.5 
 
 Dr. Strange 1849 19 4 21.0 
 
 Dr. Gordon 1852 12 0.0 
 
 Dr. Fullerton 1873 5 0.0 
 
 101 14 About 14.0 
 
nths. 
 
 Percentage 
 of mortality. 
 
 14 
 
 14.0 
 
 
 
 0.0 
 
 3 
 
 1.3 
 
 15 
 
 4.2 
 
 32 
 
 Sick-abed Cholkr.\, Collapsed, Collapsing and Quinine-inhibited Cholera 
 (choleraic diarrhoea, ","ambulant cases," Dr. Schl<tmann ; " that came at sick 
 call," Dr. Henry exchtded.) 
 
 Number 
 of cases. 
 
 Cases in last table 101 
 
 Dr. Stephen I Aix-la-Chapelle), 1831 8 
 
 Dr. Schlomann, 1866 220 
 
 Dr. Henry, 1873 360 
 
 679 32 4.8 
 
 This is all I have to present. Were it a gun warranted to kill two 
 hundred thousand men in one campaign, wounding as many more. 1 
 would have no doubt as to its prompt recognition in Europe. Were an 
 enemy's fleet to " sail yonder round by the hill," or an armed universe 
 set foot upon our shores, how quickly would we spring to arms ! how 
 soon be heard the old war refrain, " We are coming, Father Abraham," 
 four or five millions more ! That sound as " of a trumpet on before " 
 would penetrate the " dull, cold ear of death," and from Maine to 
 Texas all but rouse the sleeping heroes in the " bivouacs of the dead." 
 
 Of course thus far this defence against the pestilence has been but 
 sharp-shooting, or at the most squad or platoon firing here and there, 
 for sixty years. But wherever this resistance has been made, effective 
 work has been done. Let us suppose that instead of this desultory 
 method, when again the foe is among us, we attack in force all along 
 the line, an army of life savers, seventy thousand strong, from the 
 Lakes to the Gulf, Union and Confederate. If, after one charge of 
 this sort we do not gain a victory over this death, and plant the Ameri- 
 can flag on the last of the major universal epidemics, there would 
 seem to be no use reasoning in the therapeutics of cholera either before 
 or after the event. 
 
 But heroics are for war, not for pestilence ; for slaying, not for 
 saving alive ; for gunpowder, not for quinine. 
 
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