1. The effect of virulent bovine tubercle bacilli on rabbit tissue in vitro was studied.

2. When normal spleen cultures were infected in vitro the cells actively phago- cyted the bacilli. At first the phagocytes tolerated the organisms, and in the course of their wanderings spread the infection throughout the tissue. Some infected cells even underwent mitotic division.

3. Eventually the infected cells broke down, and the freed bacilli continued to grow in the tissue. Fourteen days after infection, outgrowth had usually ceased and the explants were almost completely replaced by bacilli.

4. Actively growing spleen cultures were unable to suppress even a slight infection with virulent bovine bacilli.

5. No tubercles were formed in the cultures.

6. There were no indications ofan exotoxic action of the bacilli on the cells in tissue culture, an densely infiltrated explants were often surrounded by a large zone ofoutgrowth.

In many hospital wards it is usual to have a certain proportion of the beds separately accommodated in single-bed rooms. Current practice shows a great variety not only in the availability of separate accommodation but also in the use made of such a facility. A clear understanding of both the demand and the way in which it can be met is of great importance in the theory and practice of ward design. This problem has been discussed in a recent paper by J. W. D. Goodall (1951), who, using purely medical criteria for the need for separate accommodation, considered that present practice was on the whole largely inadequate. He found it convenient to divide patients into two groups. First, those who have to be kept under close observation, such as dying cases, infants under 2 years, cases of posttraumatic psychosis, patients requiring special treatment, and so on. These are called type A patients, and their beds must be situated for easy observation and attention. Secondly, there are those who need to be separated but who do not require constant nursing supervision, such as patients who are liable to infect others or who are peculiarly susceptible to infection, burns cases and physically unpleasant patients, etc. These are of type B and need not be placed in such immediately accessible parts of the ward. Goodall obtained data from many different hospital wards showing the day-to-day demand for single rooms over, in most cases, at least a month.

A study was made of the reaction of the white blood corpuscles in bovines at parturition.

Graphs made from the differential total counts of the white blood corpuscles from shortly before calving and at intervals through the period of parturition and for 24–48 hr. after calving show a definite absolute lymphopoenia with a rise in the neturophils.

The type of graph produced resembles that found in bovines when cortisone is injected.

The peak of the white blood cell reaction usually takes place about 5–9 hr. after the delivery of the calf. This is also the period of the peak reaction in the cellular relations after injection of cortisone.

The observations recorded seem to afford positive evidence that C 11 hydroxy steroids (cortisone) are poured out in the last stage of parturition in the normal bovine. The desensitization of the skin in animals which were sensitized to Trichomonas foetus an which was found at this time is considered to be connected with the action of the hormone.

1. Rabbits were infected with virulent bovine tubercle bacilli in three ways: by (1) intravenous, (2) intrasplenal and (3) intrapulmonary injection. In series (1) and (2) part of the spleen, and in series (3) part of the draining lymph glands were sectioned for histological examination, and usually explants for tissue culture were made from the rest of the organ.

2. A histological study of the infected spleens and lymph glands fixed after different periods of infection showed the usual picture of progressive tuberculous infection; acid-fast bacilli were rare and often difficult to find.

3. After a few days' cultivation in vitro, explants of the infected spleens often became densely infiltrated with bacilli.

4. Previous investigators have expressed the view that acid-fast bacilli are so few in tuberculous lesions in vivo, because large numbers become unstainable. If this is true, and if the unstained bacilli remain viable, it would readily account for the extraordinarily rapid bacillary infiltration of tissue cultures of infected organs. Alternatively, it must be assumed that the few scattered acid-fast rods in the original tissue grow at a prodigious rate under the conditions of life in vitro.

5. These alternatives and other theoretical implications of the results are discussed.

The Cambridge University Health Service started work in October 1948. So far it has been restricted to preventive measures and has been confined to new entrants to the University on an entirely voluntary basis. The Service provides a clinical examination and a chest X-ray. A general survey of the scope of the Service and the results obtained have been given in the annual reports of the Senior Health Service Officer, Sir Alan Rook (1950, 1951). In addition to the original clinical records a Hollerith punched-card record system has been used since the inception of the Service to facilitate detailed investigations. In Appendix I to the first annual report mentioned above (Rook, 1950) I gave a few preliminary results on various physical measurements for the first 900 men examined. It has now been possible to complete a much more extensive investigation, the results of which are given in the present paper. In some cases this has been based on the completed records for the year 1948–9, while in others the records for the two years 1948–50 have been utilized. I have already given a brief summary of the contents of this paper in Appendix I to the second annual report (Rook, 1951).

Discrete, Feulgen-positive granules, attached to the periphery of bacterial spores, were described by Pietschmann & Rippel (1931), who considered them to be residual cytoplasmic structures; by Stille (1937), who was apparently in doubt as to their nature; and by others, including Robinow (1945), who at first described them as the natural appearance of the spore nucleus. Delaporte (1950) figured the spore nucleus as a less discrete, crescentic body lying against one side of the spore, and in a later study Robinow (1951) accepted this view, and presented evidence to prove that the appearance of the discrete body was an artefact, caused by the hydrolysis with HC1 which was employed in staining. Robinow, in this later study, employed nitric acid instead of hydrochloric acid, and claimed that it gave a truer picture. Both Delaporte and Robinow observed a central, stainable body, which they considered to be cytoplasmic.

1. Type F1 will appear in old Dorset egg cultures of Type F2 after storage for months or years at room temperature in the dark.

2. It is probable that a similar change is responsible for the appearance of Types F1 and F2 in the same carrier and outbreak of typhoid fever.

3. The two types are stable when growing logarithmically in the pure state.

4. There is also evidence that the two types are stable under ordinary field conditions.

5. Logarithmic growth of F1 in the presence of F2 results in the disappearance of F1.

6. This change is caused by a phago carried by F2, which converts F1 into F2.

7. The significance of these observations is discussed. It is suggested that the two types retain their status in the typing scheme.

A series of thirty-five patients suffering from diphtheria, who had been previously fully inoculated against the disease and from whom toxigenic diphtheria bacilli were isolated, were investigated and compared with seventeen patients who had not been inoculated. There were smaller groups of those patients who had had incomplete courses of immunization and of those who had had previous attacks of the disease.

Two-thirds of the infections in the inoculated were due to Corynebacterium diphtheriae, intermedius type. Intermedius infections were proportionately more numerous in the inoculated than in the uninoculated, whereas gravis infections were less frequent.

Estimations of the antitoxin in the blood were made on admission. The inoculated patients had levels of antitoxin below, or in the neighbourhood of, that believed to confer protection.

In the inoculated group severity did not appear to be influenced by the level of antitoxin in the blood on admission.

Antitoxin in the blood was found to have increased after recovery from the disease in all except one patient; the increase was considerable in those who had been inoculated previously.

From 23·5% of all cases of clinical diphtheria investigated only non-toxigenic diphtheria bacilli (gravis, intermedius and mitis types) were isolated. These cases were considered separately. On admission the majority had in their blood considerable amounts of antitoxin, which did not increase after recovery. No other pathogenic organisms were regularly found. The possibility is discussed that under certain conditions non-toxigenic C. diphtheriae may be able to cause a diphtherialike disease.

1. The most virulent strains of Salmonella typhi are those that develop both the Vi and O antigens in maximum quantities.

2. The Vi antigen is not a particularly toxic substance; it is less toxic for the mouse than the O antigen.

3. The main biological function of the Vi antigen is to protect the O antigen against the action of the natural or immune O antibody, thereby protecting the bacterial cell against phagocytosis and the bactericidal action of the serum.

4. The relative virulence for mice of freshly isolated strains of Salmonella typhi reflects their virulence for man.

It is suggested that routine tests for infectious mononucloosis in a large number of apparently unrelated syndromes would disclose a frequent common aetiology and perhaps modify the present conception of the course of the disease.

A technique is suggested for a simple test involving tho demonstration of ox cell haemolysins which would make the testing of large numbers of sera practicable.

The results in sixty cases of infectious mononucleosis and 200 controls are evaluated. The test does not reduce significantly the proportion of serologically negative cases but may confirm the diagnosis before the characteristic sheep cell agglutinins are demonstrable.

The test is as sensitive and as specific as other serological tests for infectious mononucleosis and is very much easier to perform.

The main clinical and pathological features of the naturally occurring canine virus hepatitis were reproduced in dogs, using four strains of virus from different parts of the world and by various routes of inoculation. Young puppies seemed to be most susceptible. A kitten was also infected. An unusual type of kerato-conjunctivitis occurred after both intraocular and intraperitoneal injection.

Specific antigen was detected in the blood for short periods at irregular intervals during the acute stages of the illness and up to 6 months after complete clinical recovery.

Specific antibodies were detected in the blood of recovered animals 3 to 10 weeks after the inoculation and 2–6 weeks after the onset of clinical illness.

The four strains of virus were similar in their serological and immunological characters.

Evidence is presented that virus can persist for some months in recovered animals.

Virus was demonstrated in lice collected from affected dogs.

The importance of clinically inapparent infections is stressed.

An investigation of the survival rate of bacteria after drying in vacuo by the ' spin–freeze' method showed that one of the most important factors was the fluid in which the bacteria were suspended. Broth or nutrient gelatin gave a moderate survival rate, but in various other protein solutions, even though there might be a fair survival immediately after drying, a large fall occurred in the viable count after storage. The addition of glucose to the suspending fluid in concentrations of between 5 and 10% greatly increased the survival rate both immediately and after storage. Some experiments showed that, without added glucose, the longer the drying process was continued the lower was the survival rate, and it is thought that glucose acts by automatically retaining a small amount of water which is necessary for survival. Lactose appears to produce the same effect.

It is shown that the highest death-rate generally occurs during the early stages of drying, the further drop after 24 hr. being small if glucose is used in the suspending fluid. Very young cultures (4½–6 hr.) seem to be far more sensitive to drying than older ones (18–24 hr.). The bacteria that survive drying are not more resistant to subsequent drying.

Most of these results have been obtained with one strain of paracolon bacillus, but a limited number of other experiments show that the same principles hold good for other organisms such as Salmonella typhi-murium, staphylococci, streptococci, Neisseria gonorrhoeae and Vibrio cholerae. In the case of the last two species the percentage survival is much lower than with the others, but survivals up to 1% have been obtained after storage for from 1 to 3 years.

Intraperitoneal inoculation of the mouse has been employed for many years as a means of assaying the virulence of different strains of Salmonella typhi or of detecting alterations in virulence in the same strain occurring from time to time in the laboratory. Such changes are usually in the nature of loss of virulence resulting from antigenic change. Occasionally, however, there may be increase of virulence, either as a result of mouse passage or simply from a more strict observance of nutritional requirements and improvements in the method of cultivation. Where cultures of typhoid organisms are to be used for vaccine production the detection of these antigenic changes and the associated loss of virulence is obviously of the greatest practical importance.

A new method of titrating the infectivity of egg-adapted influenza virus suspensions is described.

For this purpose a plastic tray has been made, drilled with one hundred conical cups. In each cup a small piece of chorio-allantoic membrane from a chick embryo is suspended in a buffered salt solution. To these surviving tissue suspensions virus dilutions are added, and the tray is put in an incubator and rocked mechanically for 60 hr.

In those cups in which the inoculum has been sufficiently large, the membrane becomes infected by the virus which multiplies within the cells and, bursting out, builds up by infection of other cells a high concentration of virus in the suspending fluid. The virus multiplication is detected by removing the pieces of tissue and adding to the cups a drop of washed chicken erythrocytes. The presence of virus in the cup is shown by the pattern of the sedimented erythrocytes, and virus multiplication is inferred because the original seed virus is too dilute to be detectable by haemagglutination.

The method has been compared with in ovo titration. As a means of detecting egg-adapted infective virus, the tissue suspension is between 20 and 80 times less sensitive; as a titration system, however, approximately one cup is equivalent to one egg, so that by using sufficient replicates accurate assays of infective virus can be made.

The technique is readily adaptable to the titration of serum-neutralizing antibodies.

In addition to haemagglutination, the infectivity end-point of the titration can also be estimated by a specific complement fixation test, and it is suggested that, with modifications, the new technique may be applicable to the titration of a large number of other viruses.

Cylinder-model vacuum cleaners cause no bacterial contamination of the air, whereas even on oiled floors domestic brooms caused statistically significant contamination of the air when compared with a vacuum cleaner.

The Hoover model 402 was the only machine tested whose bag is never removed, a theoretical as well as a practical advantage. Domestic brooms can destroy an otherwise efficient barrier nursing system and should bo avoided in hospital wards.

A bacteriophage is described which attacks almost exclusively strains of Bacillus anthracis, and attacks all the strains of this species which have been tested.

As well as attacking typical strains of this species it attacks atypical variants.

Strains of B. anthracis are not attacked by this phage when they are in a muciod state.

A few strains of B. anthracis are only feebly attacked by this phage. Some experiments, conducted in an attempt to discover the reason for this, are described.

The results are discussed and arguments in favour of regarding B. anthracis as a valid species are put forward.

1. A series of 110 patients with staphylococcal infections has been investigated. From 43 patients a penicillin-resistant staphylococcus was isolated: in cultures from 38 patients all staphylococcal colonies tested were penicillin resistant and in five both sensitive and resistant strains were isolated. Seven patients yielded a streptomycin-resistant staphylococcus.

2. Of the 84 strains of staphylococci which could be phage typed, 33 belonged to the group of phages 6/7/47 and 32 were of type 52 A. Of the 32 typable penicillin- resistant strains 18 belonged to the group of phages 6/7/47, and 13 were type 52 A.

3. Of the 115 strains isolated 110 were α-lysinogenic.

4. These results are compared with those found a year previously and the significant changes are discussed.