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and perfectly sterile, and without added anti
Brown septic of any kind.
.4 Died. Snake
4:0 The efficacy of the serum was tested in the Venom. usual way by determining the amount required to neutralise the effects of a known amount of venom upon test animals. The experiments Death
-4 Died. performed by injecting mixtures Adder
4.0 of venom and serum into rabbits In order
Venom. to prevent the
misleading inferences which might result from partial
It will be seen from this table that .4cc. of tralisation, the amount of venom given was the serum per kilo. body weight sufficed to pro10 times the quantity required to kill the tect against the tiger snake venom, whereas ten rabbits. As the result of a long series of obser- times this amount, viz., 4cc, failed to protect vations, which, indeed, have not yet been against the other venoms tested. It is obvious, carried to finality, it was found that the follow- therefore, that, although an effective serum has ing quantities represent approximately the been obtained, its action is specific, being smallest doses which on subcutaneous injection operative only against the particular kind of could be relied upon to certainly cause the venom used in its production. death of the rabbits :
From the fact that ·4cc. of the serum proved Tiger snake venom, *00005 gramme per kilo of rabbit
effective against the tenfold lethal dose of .0005 Brown snake *0002
gramme of the venom, it was to be inferred Death adder -0002
that •04cc. would protect against the single Black snake 0006
lethal dose of .00005 gramme of the venom. These amounts are, therefore, what may be The validity of this inference is demonstrated called the minimal lethal doses of the venoms. by the data contained in the following table, The tests were made with 10 times the above
expressing the results of two confirmatory exmentioned quantities, to which were added periments in which were used the single lethal different amounts of serum, and the solution | dose of venom, and equivalent quantity of injected immediately after mixture to avoid any chemical changes that might occur after long contact.
Per kilo, body weight. In the first series the mixtures were injected subcutaneously, and the results obtained with the four different kinds of venom tested are briefly expressed in the following tabular statement:-
Serum in cubic
Per kilo body weight.
It is therefore concluded that .04cc. of the serum is the quantity which will entirely neutralise the effects of 00005 gramme of tiger snake venom, the two being measured per kilo. of rabbit, and injected subcutaneously immediately after their mixture in vitro.
By a further series of experiments, it was ascertained that this same value for the serum held good when the mixtures were injected directly into the veins of rabbits. As a preliminary, it was necessary to determine the certain minimal lethal dose of venom for this method of administration. The series of experiments performed to this end gave :000005 gramme of tiger snake venom per kilo as the smallest that could be relied upon to cause death after intravenous injection into rabbits. As in the previous experiment, ten times this minimal lethal quantity was
used as the
standard dose of venom. It will be observed 1000 times, the efficient quantity of the serum that the minimal lethal intravenous dose of the locally prepared by means of tiger snake venom happens to be one-tenth of the minimal venom, lethal subcutaneous dose; consequently, in making the tests the serum pitted against it
Per Kilo Body Weight. was correspondingly reduced. The following table shows the results obtained by injecting mixtures of .00005 gramme of tiger snake venom and 04 cc. of serum per kilo of the body weight into the jugular vein of rabbits :
Subcutaneous in- / 1 *00005 -04 Died jection of Single 2
.4 Per kilo body weight.
Mode of Adminis.
Result. Venom in
From the series of observations just conThat these results apply also when single doses sidered, it will be apparent that whilst the are used is shown by the results expressed in serum prepared in this laboratory with tiger the following table :
possesses a high neutralising
potency against this same venom, it utterly Per kilo body weight.
failed to exhibit appreciable protection against the venoms of the brown and black snakes and
that of the death adder. To extend the series Venom in
of observations, I have forwarded a quantity of the serum to Captain G. Lamb, of the Parel
Laboratory, Bombay, who has kindly consented 1 .000005 ·004 Survived.
to test it against the venoms of Indian snakes. 3
In the meantime, the outcome of the experiments already performed is such as to indicate
that the serum is specific in its action, operative It will be seen, therefore, that the serum is, only against the venom by means of which it at least, no less efficacious when the mixtures was prepared. In view of this issue, it seems are injected intravenously than when they are reasonable to
suppose that the value of injected subcutaneously. Taking the two Calmette's serum against cobra venom, and its series of results together, it becomes clear that lack of efficacy against daboia and tiger snake as mixed and tested upon rabbits in the man- venoms are to be explained on the grounds of ner described, 04cc. of the serum possesses the specificity. However much in keeping with power of neutralising the effects of .00005 scientific theories and beliefs, this specificity is gramme of tiger snake venom, irrespective unfortunate from the point of view of practical of the mode in which the mixture is adminis- serotherapy, since there is the prospect that we tered.
need a special serum for each kind of snake. By way of completion, attention may be Whether or not this complication can be called to correspouding experiments performed overcome by immunisation with a judicious with Calmette's serum and tiger snake venoin, mixture of venoms must be left for the future the results of which are shown in the table on to decide. the next column.
In conclusion, it may be pointed out that In these experiments every advantage is given the experimentally ascertained neutralising to the serum by the use of only single lethal potency of the serum prepared in this laboradoses of the venom; nevertheless the results tory by no means indicates the degree of its failed to indicate the possession of the power possible value for the treatment of tiger snake of even partial neutralisation, although the bite in practice. The establishment of this subcutaneous dose of Calmette's serum reached point is beset with difficulties, and the observa100 times, and the intravenous dose reached tions so far made with respect to it are too
incomplete to permit of any valid inference. may be the means of spreading the disease was However, the work is in progress, and I hope evidently not made easier of solution—at least to be in a position to make some further com for the time. And the question has always been munication upon this subject in the course of a answered in a somewhat uncertain way. The few months.
infective period was supposed to last till the Sydney, April 11th, 1902.
temperature had definitely fallen to the normal
point, till convalescence was established, or till NOTES ON A MILK EPIDEMIC OF TYPHOID.
an assumed ulceration could be supposed to have ILLUSTRATING
healed up finally. Clearly there were THE
certainties in all these respects, and so authorINFECTIVITY.
ities had a way of avoiding positive expressions By James Jamieson, M.D., Health Officer, of opinion on this most important point. As City of Melbourne.
it became known that the bacillus either ceases
to occur in the fæces, or can with difficulty be As is often the case with new knowledge, the detected, it was also clearly shown that it gaining of more exact information about the may remain lodged in the body for quite long intimate nature of the acute infective diseases, periods after recovery from an attack of the seems for a time to bring in almost as much disease. In his Goulstonian lectures, published doubt as certainty. It may be, of course, that in the Lancet in March and April, 1900, Dr. the old supposed certainty was based on real F. Horton-Smith discussed very fully the ignorance, and that the new doubt marks only evidence as to the persistence of the bacillus a temporary halting place on the path of after recovery and notably in the urine. His scientific progress. This is notably true in the own observations showed that the urine may case of diphtheria. For, while exactness has contain the bacilli, in enormous numbers, at been given to diagnosis by the discovery of the least as late as the seventieth day of the bacillus of Læffler, it is also true that in cases disease, and he makes reference to a case in which look like diphtheria clinically, the real which they were believed to have persisted for bacillus may not be found, and further, that several years. His own belief was that seventy the bacillus is not uncommonly discovered days by no means marked the maximum durawhere there are not clinical signs of the disease. tion. In the present state of our knowledge, In respect of prophylaxis the gain is unmis- therefore, we seem to be driven to the opinion takably great.
that the disease is more liable to be spread by With regard to typhoid the present position contaminated urine than by fæcal discharges, is distinctly an interesting one. The relation especially at a late period of an attack, and of Eberth's bacillus to the disease is definitely after apparent establishment of full accepted, although the distinctive characters of convalescence. the organism, as against varieties of the Colon But though observations such as those rebacillus, are not easily definable. It is corded by Dr. Horton-Smith and others carry especially, however, in respect to the duration conviction to a very large extent, it is both of the period of infectivity, that fresh light interesting and important to get evidence of was needed, and has to some extent lately actual infection, as helping to fix the duration come. It is owing largely to the strenuous of the period of infectivity. advocacy of Budd that the doctrine as to the A series of cases occurring among
the spread of infection mainly, if not solely, by customers of a dairy in the City of Melbourne, means of the stools of patients suffering from the supplies some points of interest in this connecdisease came to be almost universally accepted. tion. S.B., the keeper of the dairy was The demonstrated presence of the bacillus in removed to the hospital on 6th December, 1900, the structures of the intestinal wall, and in the on what was considered to be the sixth day of fæcal contents went to establish the contention bis illness. He remained in hospital till the of Budd and his followers, which had been 15th day of January, 1901, the trade having based on practical observation. But difficulties in the meantime been carried on, after prearose, and there came to be agreement among cautions taken, and without any consumers of bacteriologists that, while the bacillus is very the milk having been reported as affected. He frequently discoverable in the fæces at an early went home from the hospital, and declared stage of the disease, it is difficult or impossible that he did no work about the dairy for to identify it at a later period. That being so, several weeks. On the 11th of March the the old question about the length of time first of a series of six cases was reported, the during which the stools of typhoid patients, others occurring in pretty rapid succession,
The calculated dates of attack were the 4th,
CASES OF GASTRIC FISTULÆ. 5th, 11th, 12th, 19th, and 21st March, the
R. Humphrey Marten, M.B., B.C. Cantab, last case being that of a brother of the proprietor
M.R.C.S Eng., L.R.C.P. Lond , Adelaide who lived and worked on the premises. In the time which elapsed between the first and last of these notifications, only sixteen other cases Cases of gastric fistulæ are apparently not of were reported from the whole district with a frequent occurrence. Sydney Martin, in his population of about 67,000. There was another book on “ Diseases of the Stomach,” does not circumstance which made more definite the mention their existence, but Robson and attribution of the outbreak to the milk supply. Moynihan in their work on the “Surgery of A list of the customers was obtained shewing the stomach” devote a chapter to the condition. that 154 households were supplied, and it The fistulæ may be internal, i.e., between the was found that in most instances the milk was stomach and some other abdominal or thoracic scalded before delivery, but that 22 house organ, or open externally. They are either holders preferred to obtain the milk fresh. All traumatic or due to a perforating ulcer, simple the cases outside of the dairy occurred among or malignant. I am doubtful whether my first persons belonging to these households
case should come under the heading of this In various ways the history of this small paper, as I made an opening myself into a outbreak was an interesting one. The man subphrenic abscess which afterwards became a who is assumed to have distributed the infection fistula. The history of the first case is as had not an unusually severe attack, judging follows : from the period of stay in hospital, though Miss G., vet. 25, from Grunthal, who had his ability to take up work was delayed by an consulted me several times previously for attack of pleurisy. His illness apparently anæmia, called on February 6th, 1899, and it began on 1st December, and the last cases was then noted that she looked ill, and comamong his customers occurred on 11th, 12th, plained of pain in the left hypochondriac region, and 19th March, so that even allowing fourteen made worse by taking food or breathing. She days of incubation, full three months elapsed came again on March 1st, and was then much between the beginning of his illness and actual better. Dr. C. Mainwaring saw her for me on infection in these cases. As soon as suspicion April 13th, and she then complained of pain was excited, precautions were at once taken, and after food and between her shoulders, but no when the second case occurred on 21st March, vomiting. She was brought down on April these were rene
newed, and the outbreak, so far 27th, having driven 18 miles in a buggy. She as concerned this focus of infection, was at an was greatly collapsed, with i feeble, thready end. And warning was further taken, and pulse, and a dusky expression and a temperareturn to work on the part of this patient was ture of 103° F., and gave a history that, whilst prohibited for three months after discharge vomiting the night before, she had experienced from the hospital. This was, perhaps, a straining a sudden, violeat, pelvic pain. The breathing of powers, since the maximum time of seclusion, was so difficult that I was afraid she would die contemplated by the Victorian Health Act, is in my consulting room, and I had the greatest fixed at three months. It is not stated, of trouble in persuading her friends to leave her course, at what date or stage of illness the in the private hospital, as they were most period of three months begins to count, and anxious to take her back the long drive. advantage may thus be taken of this
vagueness. Dr. Poulton saw her with me in the afterWith the knowledge we now have of the noon, and we found the abdomen distended and duration of infectivity, in more than one of tender over the region of the appendix, and the infectious diseases, it is apparent that the although we did not think the symptoms limit of three months, whether from the pointed altogether to a perforation of that beginning of the attack or from the establish- organ, we bore that in mind. She recovered ment of convalescence, does not err on the side from the collapse and the abdominal distention of over-strictness.
gradually receded, but never actually flattened. (Read at the Intercolonial Medical Congress at Hobart.)
The temperature rose each night to 101° F. or At the meeting of the Benevolent Asylum
102° F., and on May 4th she developed a (Melbourne) committee on April 4th, the chairman parotitis on the right side, followed by a simisaid the committee should consider what should be lar condition on the left ; these went down, but done in the matter of the £25,000 legacy recently left her temperature still remained high at high. to the institution by the late Mr. J. Hingston. The committee should decide whether the building was to
On May 9th there was tenderness below the be removed from its present site or not. It was decided left rib cartilages, and I thought a fullness ; but that the matter be considered at next meeting.
a few hours afterwards neither Dr. Poulton nor
myself could find any physical signs in this Borthwick, nine weeks ago, and has been in bed region. Impaired resonance now appeared in ever since; but she does not think that she has the left axilla as high as the eighth rib, but lost much flesh. The swelling became much this dulness was most peculiar, as it would be larger after Dr. Borthwick saw it, and he absolutely dull in the morning and hypere recommended exploration, but the proposal was sonant in the afternoon. On May 13th it was refused. Six weeks ago she had rigors followed decided to explore here under an anæsthetic, by night sweats, and fourteen days ago a foul and Dr. G. Hayward having administered gas smelling discharge of pus occurred from the and ether, a hollow needle was inserted in the umbilicus. Her present state showed a pale eighth interspace in the mid-axiliary line, and face, but fairly well nourished body. There about Zii. of foul-smelling pus withdrawn. An was a swelling about the size of a fætal head at inch of the ninth rib was then resected, and a term, placed above the umbilicus, tender in the small flat cavity entered, which contained foul upper portion, with a fulness to be traced below pus. The cavity could be extended inwards the umbilicus on the left side. The swelling by gently insinuating the finger, and appeared was movable laterally under an anesthetic. . to be going below the arch of the diaphragm and The umbilicus presented a central perforation, above the stomach and spleen. A tube was which admitted a probe for one inch, and disinserted and a dry dressing applied. The nurse charged a thin, foul smelling pus. Nothing else was told to look out for the contents of the abnormal could be detected in the abdomen, stomach on the dressing, and they appeared at and the lungs were healthy. The heart's apex the first changing.
beat could not be felt, the sounds were clear at On the following morning, on removing the the apex and base, but a systolic murmur could dressing and giving the patient milk to drink, it be heard over the xipho-sternal articulation. immediately came out through the drainage The urine was of a good colour, acid, 1020, with tube, shewing a perforation of the stomach no albumen, sugar or bile. The axillary teminto a subphrenic abscess. The patient gradu- perature was 99-6° F. The pulse 116, soft and ally improved, but the stomach contents still compressible. She was admitted to the private escaped from the wonnd, but in varying quanti hospital on the evening of September 4th, and ties, and on May 24th it was noted that if the anæsthetized on the morning of the 5th by Dr. patient remained on her back or on the left Cudmore, Dr. Poulton assisting me, and Dr. side the fluid contents of the stomach escaped, Borthwick being present. The umbilical fistula but if the patient lay on the right side she was enlarged and the finger entered a stinking, soon suffered a peculiar dull pain, only re- soft pultaceous mass. This could be fairly well lieved by turning on her back and allowing outlined by the finger in the mass and the hand the drain to act. On June 4th it was ob- outside. Gas of a foul-smelling odour escaped served that the patient was becoming decidedly on opening the umbilicus ; the cavity was emaciated. with a high evening temperature, washed out and two drainage tubes inserted. and her friends took her home to the country, The soft pultaceous material that came away where she lingered for a few weeks and died was more like broken-down brain substance practically of starvation. Unfortunately no than anything else, and it was noted that it post-mortem examination could be obtained. showed very little tendency to bleed. On
The second case was Mrs. A., æt. 64, seen at September 6th it was observed that there had Burnside with Dr. Borthwick on September been a fair discharge of foul-smelling pus; the 4th, 1901. The patient was a very anæmic temperature was normal and the patient had and somewhat emaciated woman, complaining passed a fairly good night and seemed better. of a discharging sinus at the umbilicus. Her On September 7th a glass drainage tube was past history was good; seven years before she inserted in place of an indiarubber one, and had been operated upon by the lato Dr. Way through it the contents of the stomach, such as for varicose veins. Her present illness dated milk and porridge, escaped, along with foul
. back two years, when she first noticed an un- smelling pus. On September 8th a large comfortable sensation in the upper abdomen, quantity of highly acid fluid escaped through which was soon followed by increasing weak- the tube, bile-stained and smelling like vomit.
There had never been any vomiting of In this fluid were pieces of partially-digested blood or coffee grounds, and only a few attacks egg and bread. The glass tube was removed of retching. A swelling in the abdomen in the and a short indiarubber one inserted. The neighbourhood of the umbilicus was first noted patient appeared much better in herself. about a year ago, but only became painful during The contents of the stomach continued to the last few weeks.
seen by Dr. ! escape for several days, together with pus, but