1. The problem of assessing nutritional state

This paper emphasizes the need for measurement in diagnosis and recognizes two distinct problems, those of:

(a) Diagnosing specific diseases in the sense of distinct pathological conditions.

(b) Assessing general malconditions where there is no sharp dividing line between the normal and the subnormal.

It suggests a programme of research designed to overcome some of the difficulties inherent in (b) in the case of nutritional assessment.

2. Establishing general health standards

The first requirement is the scientific standardization of the elements making up the concept of health and good physique. This is a complex matter requiring all the help which statistical procedures can give. Moreover, we must check the reliability of the assessors and the indicators which they use before we can place any reliance on results purporting to relate to the population studied.

Provisionally we begin by collecting a battery of indicators of general health; each is then given a graded assessment for each child (and the assessment is repeated to obtain its reliability), and by employing the statistical device of factor analysis we can determine what combination of symptoms will give the highest agreement with the criterion of general health abstracted from these individually imperfect measures. We are actually making explicit the stages which are normally telescoped in the method of ‘general impression’ (which is the method usually adopted in assessing general health, state of nutrition, etc., despite evidence of its unreliability). In this method a number of individual characteristics are fused together without ensuring that different observers will attach equal importance to the signs or even that they will take into account the same ones. The emphasis to be given to each symptom in the final mark is determined statistically by its agreement with the aggregate result. Some indicators may give results so unrelated to the others that they must be eliminated. Other tests, whether physiological, functional or anatomical, may later be added to the battery to reinforce it. A point of practical importance is that some readily assessable symptom or index may be found which gives results in close enough agreement with those of the standard battery to enable it to be used as a substitute, thus shortening the task of diagnosis without appreciably lessening its accuracy.

An alternative criterion could, as we have seen, be the weighted combination of doctors' assessments, for by weighting the results according to each doctor's agreement with his colleagues we were able to increase the agreement between the team result and the hypothetical true mark. However, since the ordinary methods of assessment are unreliable, even the pooled results of the team do not give as good a standard as the standardized battery of tests.

A third standard is sometimes possible in the form of an objective accurately measurable physiological laboratory test or anatomical index. If this is inconvenient to apply generally, any single symptom or pool may be tested by correlation with it to see if the agreement is close enough for practical purposes.

3. Study of more specific nutritional defects

Factor analysis can be used to discover and assess more limited similarities than those covering the whole range of observers or test symptoms. For example, the doctors tended to show group affinities (depending possibly on their different emphasis in diagnosis) in addition to their somewhat low general conformity. Applying similar analytic methods to the study of symptoms, we might isolate specific nutritional deficiencies or it is possible that group factors may be revealed corresponding to the effects of recent or early adverse nutritional conditions respectively.

Whilst the examples of analytic techniques have here been applied to illustrative cases in nutritional and general health assessment, they are equally applicable to other fields of medicine, in particular to endocrinology and to the study of predisposing conditions of disease.

My thanks are due to Prof. Burt and Dr E. H. Wilkins for their suggestions for modifying my original draft. However, this in no way commits them to agreement with the views expressed here.

[Note added in Proof.] Since writing this article I have had an opportunity of correlating and analysing some results of nutritional surveys involving clinical and biochemical signs of malnutrition. The evidence so far obtained indicates a rather weak general factor for clinical signs identifiable with general nutritional state. I hope to be able to give the full results when the material becomes available for publication.

In the records of the Registrar-General of England and Wales prior to the year 1940, diabetes was accorded by the rules of classification a high preference over other causes mentioned in association with it upon death certificates, the only important causes preferred to it being the infective diseases cancer, rheumatic fever, sequelae of syphilis, injuries, poisoning, acute intestinal obstruction and puerperal sepsis. It was ascertained from a sample of 123,000 deaths during 1921–30 that 91 % of all death certificates with mention of diabetes were classified to diabetes; in other words the death-rates represented 91 % of the total mortality suffered by persons recognized as diabetics and recorded on certificates as such. It is important to keep this fact in mind when seeking explanations for the trends of mortality at different ages between the years 1860 and 1940.

The experiments here described proved that preparations made from widely different classes of bacteria are capable of inducing immunity in mice against pneumococci. The success of these preparations was found to depend on the differential separation of an active immunizing antigen from another bacterial constituent—an ‘opposition factor’—which interferes with immunization. Further investigation and comparison depend largely on the discovery of a really effective method for the isolation and purification of the active antigen. Until its chemical nature is determined, the identity of the pneumococcal species antigen with similarly acting substances found in other bacteria remains unproved.

Pathogenic bacteria depend for their virulence and invasiveness on certain products individual to the species or type, and specific immunity is due to the development of the appropriate antibodies. But chemotherapy, as in the case of the sulphonamides, interferes with a less specialized metabolic process of the microbes and is neither species nor type specific in action. It is reasonable to infer that bacteria may possess in common a vital process associated with the presence of a common constituent which may be antigenic. ‘Species antigen’ may be a substance of this nature.

In view of the wide distribution of ‘species antigen’ among bacteria generally, it is probable that this constituent has already been separated and named in accordance with its presence in a particular species, but irrespective of its potential immunizing capacity.

So far as pneumococci are concerned, there is good evidence that species antigen may be identical with the species C carbohydrate. Tillett (1927) found that rabbits injected with successive courses of heat-killed pneumococci, whether of types I, II, III or of avirulent rough strains, developed an equal increase of resistance to infection by type III Pneumococcus. In 1936 Enders, Wu & Shaffer varied the procedure, and by injections of rough pneumococci prepared an antiserum which gave passive protection to rabbits against infection by type III Pneumococcus. This antiserum lost its protective power after absorption with the species C carbohydrate.

Sample frequency distributions are given of height and weight measurements of London elementary school children made during the period 1935–8. In addition these measurements have been analysed in order to determine the seasonal fluctuation in rates of growth. The rate of increase in height appears to reach a maximum in the latter part of spring and a minimum in the middle of autumn. The rate of increase in weight appears to reach a maximum in the latter part of autumn and a minimum in the middle of spring. Tables and graphs are given showing, for each sex, the variation in the rates of growth throughout the calendar year. I wish to thank the County Medical Officer of Health, W. Allen Daley, M.D., F.R.C.P., for permission to publish this paper and for encouragement in its preparation; Mr L. Coward, F.I.A., and Mr E. Lewis Faning, Ph.D., for statistical criticism; and Mr J. H. Farrar for drawing the diagrams.

The London County Council takes no responsibility for the views expressed in this paper which are personal only.

An apparatus which prevents the distribution of infective droplets into the air of the laboratory during the intranasal inoculation of mice is described.

Experiments using Chr. prodigiosum as indicator organism are described to show the extent and duration of the droplet dissemination by inoculated mice, and the effect of the apparatus in reducing this dissemination.

We wish to express our thanks to Dr R. B. Bourdillon for many suggestions in the design of the apparatus, and to Mr C. D. Sutton for the photographs.

1. Serological methods for the determination of smallpox immunity are briefly discussed, and it is concluded that they are unlikely to provide a diagnostic method of sufficient accuracy.

2. Experimental work is recorded which shows certain differences in the response of previously vaccinated individuals, revaccinated simultaneously with a standard vaccine lymph and an elementary body suspension (vaccinia) of high potency. The significance of these differences is discussed.

3. The results indicate that although the advantage of the e.b. suspension over vaccine lymph is relatively insignificant, that of two insertions over one is very marked. In revaccination the routine use of one insertion only may result in a certain number of semi-immunes (vaccinoids) being erroneously reported as immunes.

4. It is concluded that if the two insertion technique be practised, persons showing immune reactions (negatives) may be considered, in all probability, as possessing full immunity to vaccinia-variola virus.

Some concentration of the carcinogenic material in a Venezuelan spindle grade oil has been affected by simultaneous molecular distillation, and further concentration has also been accomplished by subjecting one of the more carcinogenic of these distillates to chromatographic adsorption. Animal experiments revealed that this distillate was about twice as carcinogenic as the oil from which it was derived. Two small fractions obtained from this distillate by chromatographic adsorption were painted on the skin of a few mice and both appeared to be appreciably more carcinogenic than the distillate from which they were derived. Further experiments with one of these fractions and the distillate, not yet completed, indicate that this fraction is at least five times as strong as the distillate from which it was derived. Thus by a combination of molecular distillation and chromatographic adsorption processes we have obtained a fraction about ten times as strong as the original oil. During the chromatographic adsorption process large quantities of colourless, low index, inert or almost inert material of relatively low viscosity have been separated from the highly coloured active remainder. It would appear that the most active material is highly viscous at room temperature, but its activity may be due to the presence in it of crystalline solids.

In conclusion we wish to express our thanks to our steward, Mr L. Norburn, for his valuable assistance in the practical work.

Signs and symptoms attributed to a disturbed function of the parathyroid glands as a result of the protracted action of small quantities of fluorine have been described elsewhere (Spira, 1942c). It was shown that the lesions on the teeth known as ‘mottled enamel’ were frequently accompanied by lesions on the skin and its appendages, the nails and hair. The object of the present communication is to give some details of the changes produced in the finger- and toe-nails in chronic fluorine poisoning (fluorosis).

Some recent advances in the subject of bacterial variation and cytology are:

(1) The white race of Bact. coli-mutabile contains lactase, inhibited by some cause unknown (Deere et al. 1939). Deere (1939) suggests that the cells of the white race may be impermeable to lactose while the lactase system is intracellular.

(2) Variation from non-lactose-fermenter to lactose fermenter in Bact. coli-mutabile takes place on lactose only (Stewart, 1942).

(3) The nucleus of Myxococcus xanthus consists of definite chromatin masses. A process resembling karyokinesis and autogamic conjugation precedes spore formation (Beebe, 1941).

(4) The nucleus of vegetative bacterial cells consists of a pair of dumbbell-shaped chromatinic bodies, which split longitudinally before cell division. The dumbbell bodies are comparable to the chromosomes of animals and plants (Robinow, 1942).

(5) Careful plating provides unquestionably pure lines in the coliform group (Stewart, 1942).

Like the skin and its appendages, the teeth, nails and hair, so also other tissues of ectodermal origin are here shown to be affected by fluorine. The action of fluorine consists in lowering the level of the calcium in the blood and tissues. The epithelia of the mouth and the salivary glands, of the nasopharynx, the conjunctivae and the lachrymal glands may be affected. Signs and symptoms are thus produced which are closely similar to those usually attributed primarily to infection. It is suggested that an infection accompanying chronic fluorine poisoning is of a secondary nature, and that it is brought about by the loss of calcium in the body.

The modern study of the problem of fluorosis (chronic fluorine poisoning) became possible when an Italian, Stefano Chiaie, described, as quoted by Eager (1901), an unsightly dental dystrophy, now known as ‘mottled teeth’. The efforts to trace its aetiology have been ceaselessly continued ever since, mainly by American investigators. Outstanding amongst these were Black & McKay (1916), pioneers whose researches led to the discovery made by Smith, Lantz & Smith (1931) that it was the fluorine, contained in drinking water, in a concentration of not less than 1 part per million (1 p.p.m.) and ingested during the period of calcification of the teeth, which was the direct cause of the dental dystrophy. This result was soon followed up by a number of observers, mainly in the United States under the leadership of the dental profession, amongst them physiologists, experimental pathologists, pharmacologists, veterinary surgeons, geologists and analytical chemists. The gate for further research, which in view of its magnitude and importance must be considered as being still in its infancy, has thus been thrown wide open.

Experiments are described for determining the effect of hypochlorite mists and hypochlorous acid gas on aerosols of influenza A virus.

The virus aerosol is shown to be at least as easily killed by hypochlorite mists as Streptococcus salivarius. It is also killed by liberating hypochlorous acid gas itself into the atmosphere. A concentration of 1 vol. of gas in 2 million vol. of air is probably effective in destroying 99% or more of virus particles when the proportion of these in the air is small.

Preliminary experiments on mice and cats are recorded which failed to reveal any toxic effects produced by inhaling the gas in relatively high concentrations or for prolonged periods. Acute irritation of mucous membranes only was found. This did not appear to lead to any increased susceptibility of mice to subsequent infection with influenza.

We wish to acknowledge our indebtedness to the late Sir Patrick Laidlaw and to Dr R. J. V. Pulvertaft in co-operation with whom the earlier experiments were made. We also wish to thank Dr W. J. Elford, Dr F. C. MacIntosh, Dr R. K. Callow and Dr T. S. Work for their assistance and advice in parts of the investigation.

Dystrophies due to chronic fluorine poisoning in organs regulated by the parathyroid glands, namely the skin and its appendages, the nails, teeth and hair, and also in bones, are here shown to be unusually common in this country. They should be regarded as easily detectable signs of a serious disturbance of the calcium metabolism of the body. Fluorine is a poison of which the action, in many respects, is similar to that of arsenic. It is the task of the authorities responsible for the health of the nation to search for ways and means capable of minimizing its effect.

I wish to express my sincere thanks to the Librarian of the Royal Society of Medicine and his staff for their never-failing courtesy and help.

1. A general survey of diphtheria in Glasgow during 1934–42 has been made. Over 11,000 strains of C. diphtheriae have been typed and the incidence of the types is recorded.

2. The period has been marked by a change in the predominant type of organism from intermedius to gravis, and gravis infections are now responsible for most of the mortality, though the average case fatality rate due to them is not high.

3. Diphtheria on the whole has been mild and complications relatively few, but some shift in the death-rate incidence to the higher age periods with increase in the corresponding case fatality rate has taken place. A small shift in the age incidence of diphtheria is noted.

4. Some account of the effect of immunization is given.

5. Comment is made upon colony variation among the types of C. diphtheriae.

In continuation of previous work involving accentuated effects of perspiration on chrome upper leather, the present paper records observations of such effects in more complicated conditions.

Thus, effects were studied at varying temperatures and pH of tans, buffered tans, buffered perspiration, buffered perspiration coupled with tans, buffering material itself and soap solutions.

Particular reference is made to the influence of basicity on the stability of the chrome complex against perspiration in such buffered chemical systems. Brown grain leathers are considered as well as box and willow calf.

A method is evolved for minimizing spueing risks or the formation of Glauber's salts in the vamps of worn footwear, by appropriate treatment of the skins before cutting up into shoe upper components.

Finally, some foot-bath experiments and the dark, cracky grain of worn insoles are discussed from the general point of view of perspiratory action on footwear.

The writer acknowledges with thanks the assistance of Messrs L. P. Huggett, B.Sc., A.I.C., and W. H. F. Jackman, B.Sc., A.I.C., in the routine analytical work. His best thanks are also due to the Director and Council of the Research Association for permission to publish.

The colloid material (S.D. 2), which contains as active constituents 30 % tetrachlorethylenum and 10 % oleum pini, was prepared and supplied by Mr J. F. Moseley of Altrincham for tests on the skin. It is claimed that this material had benefited considerably certain forms of dermatitis, including that produced by mineral oil. We were therefore interested to discover whether its effect on tumour production in mice would resemble our lanolin-olive oil ointment.

During the discussion following the late Sir Henry Japp's paper on ‘Prevention of compressed air illness’, read at a meeting of the Institute of Structural Engineers on 28 March 1935, I suggested an extension of Haldane's system of decompression which might prove of considerable practical value in tunnel and caisson work (Japp, 1935). Briefly the proposed extension consisted in making use of Dalton's theory of the partial pressure of gases in such a manner that denitrogenization of the blood might be brought about while the workers were still under full pressure, namely, by making them breathe before entering the decompressing chamber an artificial atmosphere containing no nitrogen.

A form of Pirani vacuum gauge is described for obtaining a continuous record of the total residual pressure in a high-vacuum serum-drying cylinder of the Greaves-Adair type. The circuit incorporates an automatic relay which breaks the electric current heating the frozen serum if the pressure rises to a dangerous level, and so delays materially the onset of fusion of the serum.