Every practitioner in Tropical Countries knows how frequently cases of fever occur in which it is impossible to arrive at a definite diagnosis.

Much light has been thrown on the subject of long-continued fevers by the researches of Leishman, Donovan, Manson, Rogers, etc., especially with regard to Kala-azar. Moreover, the work of Wright, Lamb, and others, has shown that some other forms of long-continued tropical fevers represent cases of Malta fever.

Owing to the somewhat contradictory results which have been obtained by various investigators as to the nature of the Micrococcus neoformans and the relation which this organism bears to malignant disease, we have thought it advisable to place on record our observations in a large number of cases of carcinomata, sarcomata and certain cases of anaemia which are known to run a fatal course. Doyen (1886), in a preliminary note communicated to the Academy of Sciences of Paris, stated that he had found small spherical bodies in malignant and other growths which he regarded as micro-organisms. In 1902, at the Surgical Congress, at Berlin, he stated further that he had isolated a micro-organism from simple and malignant growths which, when inoculated into animals, gave rise to neoplastic formations. To this organism he gave the name M. neoformans. In his opinion new growths resulted from an infection of the body with this organism. Since then he has published a number of observations showing the beneficial effects which may be obtained by the employment of a vaccine or serum against the M. neoformans in malignant disease.

In view of the importance of a pure milk supply, we considered that it might be of interest to examine chemically, microscopically, and bacteriologically, a number of specimens of milk coming into the Metropolis for which purpose we decided to select samples from the various counties, the milk of which is consigned to London. We found that milk so consigned comes from about twenty-six counties extending from Derby in the North, to Hampshire and Devonshire in the South and South-West, and from Hereford in the West, to Norfolk in the East.

Though milk has often been considered the medium by means of which outbreaks of diphtheria have been propagated, the diphtheria bacillus has only on rare occasions been isolated from the milk in a virulent form.

When the blood serum of one animal is injected into an animal of a different species the injected animal in many instances appears to take no hurt. If however after a certain interval the experiment is repeated, it has been noted that the injected animal may speedily show evidence of physical disturbance. Its breathing becomes rapid: its heart-beat grows feeble: its limbs move spasmodically and general convulsions may ensue. These phenomena have been taken to indicate that the injected animal has been supersensitized—or rendered abnormally sensitive—to the serum employed. They may attain such gravity that the animal dies. It has been suggested that the same untoward issue is possible in the case of man, and that the death of patients under treatment for diphtheria is to be apprehended in certain circumstances as the result of repeated injections of antidiphtherial serum, for the reason that the serum in question is derived not from the human subject but from the horse. A suggestion which assails the prestige of the antitoxin treatment of diphtheria cannot be viewed with indifference: it must either be sustained or rejected.

Since the close of the period which furnished the data for the preceding paper regarding the effects of repeated injections of horse serum, two cases have been observed in the practice of Belvidere Fever Hospital which have special bearing on the subject of abnormal rashes after suitably repeated doses of antidiphtherial serum.

1. During the immunisation of a horse which ultimately failed to yield high grade antitoxic serum, the globulin-content of the total proteid showed no tendency to increase. The slight rise in total proteid which occurred was due to an increase in the albumin fraction. It is probable that the failure of this horse to yield high grade antitoxin was in some way connected with the initial high globulin-content of the serum.

2. During the immunisation of a goat, the rise in total proteid affected mainly the albumin fraction and the globulin fraction in lesser degree.

3. During the immunisation of a horse which ultimately yielded high grade antitoxic serum, the percentage globulin-content of the total proteid, progressively increased. This increase affected the euglobulin fraction more than the pseudoglobulin fraction.

4. In the horse the pseudoglobulin contains the greater part if not all the antitoxin but it seems probable that this relationship holds good only when the antitoxin-content of the serum is steadily rising.

5. In the goat the antitoxin-content of the euglobulin and pseudoglobulin fractions may vary at different periods in the course of immunisation.

It must be clear then from the above data on the horse and goat that the inoculation of diphtheria toxin produces a definite leucocytic reaction of polynuclear type. In fact the detailed evidence speaks more clearly in favour of a leucocytic reaction than Besredka's own results on the goat which he immunised. The question then arises: How are we to interpret the contradictory conclusions reached by Nicolas and Courmont? Metchnikoff (1905), while referring to the work of these authors in his Immunity in Infectious Diseases, maintains that a slight leucocytic reaction is apparent from their own figures and especially from the figures obtained in the early hours succeeding an injection. Of course, Nicolas and Courmont considered these slight changes to be negligible.

It seems to me, that the reason must be sought in the method of immunisation employed.

Nicolas and Courmont immunised their animals with very small doses many times repeated, and by such a method it was doubtless possible to reduce local swelling to a minimum. With no local reaction it would seem quite reasonable to expect an absence of general leucocytic reaction, but, as Metchnikoff maintains, such local tumefaction is never absent in horses which are subjected to increasing doses of toxin and which ultimately develop high grade antitoxin.

Throughout the immunisation of the animals detailed in the foregoing paper local swelling and oedema invariably followed the injections except in the earlier stages of immunisation when small doses were being given.

There is no doubt that, in order to produce a high degree of immunity in an animal, the stimulation must be sufficient. A certain small degree of immunity may always be reached without much leucocytic change, as was apparent in the early stages of “Plug's” immunisation.

It must be admitted, however, that, though the leucocytic reaction may be extremely marked after large doses of toxin, it does not necessarily follow that the antitoxin development will be correspondingly influenced.

Such a phenomenon was apparent in the case of "Plug," a relatively refractory horse.

In the more responsive horses, a parallelism between leucocytic reaction after large doses and increased antitoxin development would certainly be expected, without, however, inferring a causal relationship between these two phenomena. We cannot therefore admit the general applicability of Nicolas and Courmont's views, which merely indicate that cells subjected to small oft-repeated doses lose their power of reaction.

On the other hand there is probably no justification for the criticism brought forward by Besredka with regard to the results of Nicolas and Courmont, viz. that in the absence of antitoxin development, an absence of leucocytic reaction was to be expected.

We may therefore conclude that the leucocytic reaction of polynuclear type which follows the injection of large and increasing doses of diphtheria toxin is merely an evidence of efficient cellstimulation and may not necessarily be accompanied by increased antitoxin development.

Ehrlich had not long announced his theory of immunity, when Wassermann and Takaki (1898) published their discovery, that the brain matter of the guinea-pig was capable of neutralising tetanus toxin. This was taken as a demonstration of the existence of Ehrlich's receptors in the cells of the normal brain.

For years we have been vainly striving to find some method of treatment capable of preventing or cutting short the relapses so constantly present in Mediterranean fever. Though certain drugs have for a time seemed successful, their beneficial effects are usually uncertain and transient, so that the treatment of the disease has come to be almost entirely symptomatic. Many germicides have been tried; among these “cyllin” has lately been said to shorten the course of the fever. In my hands this has not been the case. Burney Yeo's chlorine and quinine mixture has here occasionally produced very satisfactory results when given with a rising temperature, apparently cutting short a wave of pyrexia, which from experience we had expected to last ten days or more; but its action is very uncertain.

The Micrococcus catarrhalis was first isolated by Kirchner (1890) from cases of influenza-like illness. Since then several epidemics of acute catarrh and bronchitis associated with this organism have been recorded.

In view of the observations made of late years on the action of red light in variola, it was thought that it might be of interest to ascertain, if possible, whether the red, or other rays of daylight, exerted any influence in cases of vaccinia; that is to say, with a disease the specific virus of which differs from that of variola probably only in that its pathogenic capabilities are modified, while vaccinia presents clinically many points of resemblance to variola.