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as a primary paratyphoid B meningitis. Infants arepeculiarly liable to meningitis during the invasion periodof infections which in older children and adults usuallylocalise elsewhere primarily. The evidence that the caseis primary lies in the history, the presence of normalstools from which repeated cultures were negative andthe low positive agglutination titre. A supporting pointis the fact that there were 3 other children and 2 adultsliving mainly in one room under very dirty conditionsand yet all remained well. The apparent rarity of eithertype of paratyphoid B meningitis has already beencommented on. In paratyphoid B fever the organismsare even more numerous in the blood than in typhoidfever, and suppurative lesions are not uncommon.Purulent meningitis is, therefore, always a possibilityand it is not unlikely that it is commoner than recordsshow, particularly where the enteric infections are

endemic.Clinically there were no special features in .relation to

the meningitis except that the onset was less acute thanone would have expected and that neither patientappeared as ill as the CSF revealed that they were. Thismade the assessment of benefit derived from chemo-therapy difficult, but it is noteworthy that both patientsrecovered from a disease of notoriously high mortalityand that two members of the sulphonamide group ofdrugs were tried in each case. Drug and dosage were amatter of experiment. It is true that claims have beenmade in support of chemotherapy in typhoid and para-typhoid fevers but bearing in mind the natural variabilityin the course and duration of both diseases the resultsare not convincing. In addition, the danger of agranulo-cytosis in these leucopenic fevers has been emphasised.Generally speaking in diseases for which the sulphen-amides have proved of value the response to adequatedosage is prompt and striking. I decided, therefore, togive a fairly big dose but not to prolong the course ifthere was no obvious benefit. From the temperaturerecords it may seem that the therapy was effective, butthis was not supported by the condition of the patients.It was possible to culture the organism from the CSFin both cases after a course of sulphapyridine and sulpha-thiazole, and in case 1 the fluid only became normal 6weeks later. It is reasonable to argue that the amountof sulphathiazole given (7 g. to case 1 and 3 g. to case 2)was inadequate. Serial estimations of blood and cerebro-spinal sulphonamide levels and periodic leucocyte countswould have been of value in estimating if the dose wasadequate and safe. The only leucocyte count done wasin case 1, 24 hours after stopping treatment, when it was9400.The relapse of case 2 is interesting ; similar recrudesc-

ence is known to occur in other diseases for which thesulphonamides are almost specific. The reason usuallygiven is inadequate dosage. Katsampes and Bradford(1940) gave 1 g. of sulphapyridine daily for 19 days to aninfant a month old with salmonella meningitis, yet arelapse occurred 3 months after the onset of the originalattack.Though it is becoming customary to reduce the number

of lumbar punctures to a minimum 9 punctures were donein case 1 and 7 in case 2. Repeated examination of theCSF, particularly in case 1, was found to help consider-ably in judging progress and guiding convalescence.

SUMMARY

Published reports of paratyphoid B meningitis are few :only 7 could be found. The condition is probablycommoner than records show. The fatality in salmonellameningitis generally is high.A primary and a secondary case of paratyphoid B

meningitis are reported here. Both patients, one aged8 years and the other 5 months, recovered.

Sulphapyridine and sulphathiazole were used in bothcases. Neither drug appeared in any way specific ascompared with the effects of sulphonamides in someforms of meningitis, but sulphathiazole is probably to bepreferred until some better compound is discovered.

REFERENCES

Bahrenburg, J. H. and Ecker, E. E. (1937) J. infect. Dis. 60, 81.Caselli, E. G. (1939) Arch. argent. Pediat. 10, 416.Hageman, P. O. (1938) Amer. J. med. Sci. 195, 487.Katsampes, C. P. and Bradford, W. L. (1940) J. ped. 16, 79.Osler, W., McCrae, T. (1907) System of Medicine, London, p. 157.Storey, W. E. (1938) J. med. Ass. Ga. 27, 472.

Medical Societies

ROYAL SOCIETY OF MEDICINEAT the annual general meeting of the section of

medicine on May 26, with Dr. GEOFFREY MARSHALL, thepresident, in the chair, a discussion onMineral and Vitamin Requirements and War-time

Dietarywas opened by Dr. R. A. MCCANCE. Net requirementsof minerals, he said, had not been altered by the war ;the question therefore was : are diets today adequate,as satisfactory as before the war and likely to remain so ?Only calcium and iron need be considered. Before thewar it had been fashionable to represent people as allliving on the verge of calcium starvation ; a good manywomen and children and certain men were certainlynot getting enough. Diets had been much altered bythe war. Before the war they had been regulated bypreference and price ; now they were a matter ofplanned distribution. Milk had been taken out of themilk-bars and redistributed, practically free, to children,so that adults were short. Some experiments showed

. that the calcium intake in certain women and childrenwas slightly higher now than before the war ; men weregetting slightly less. The only children likely to bedeficient were those leaving school at 14 and not gettingtheir school milk. The position about iron was much thesame ; there was less meat but far more iron in the bread.The question was : were these minerals as well absorbedas before the war ? Experiments had suggested thatcalcium was not. Brown bread had been suspected ofpreventing calcium absorption. On diets in which40-50% of the calories were provided by bread thesubject invariably showed a drop in calcium absorptionwhen brown bread was substituted for white. Thelaxative action had been eliminated as a cause : theother possibility was the presence of phytic acid whichprecipitated the calcium. Mellanby had shown thatcereals, and notably brown flour, encouraged rickets inpuppies. In 1939 Harrison and Mellanby had shownthat rickets could be produced by adding sodiumphytate to a puppy’s diet. War-time experiments onman indicated that if phytate were added to whitebread there was a big drop in calcium absorption-evensometimes a negative absorption was produced, withmore calcium in the faeces than in the food. Magnesiumwas affected in the same way. Iron, especially ferriciron, had also a very insoluble phytate ; and the samedrop in absorption appeared in changing from whitebread to brown. There was an enormous increase inintake and an enormous drop in absorption. Thiswork required repetition, but the result with calciumwas quite certain. Addition of calcium carbonate tobread precipitated all the phytic acid and further calciumadded became available for absorption. It was not easyto remove the phytic acid, but it was possible. Whenbread so treated was eaten the absorption of calciumwas improved, but was never so good as from whitebread, because the phosphates remaining interferedwith the absorption of calcium. If the phosphates wereremoved as well as the phytic acid the calcium absorptionclosely approached that from white bread. Magnesiumalways did the same thing as calcium. Dephytinisingwas not commercially possible for the whole country,though it was practicable for patent foods. Additionof calcium to bread therefore seemed the only solution.The present 85% loaf had about half as much phyticacid as the 92% bread used in the experiments. Theaddition of calcium did not seem to call for discussion ;the evidence for it was sound. It was pathetic tothink that arteriosclerotics could have so little judgmentas to-think this measure would affect them unfavourably.

Prof. R. A. PETERS showed X rays illustrating theeffect on a man of 53 of 13 months consumption of an85% loaf with prepared chalk added ; no evidence ofcalcification was present.Mr. L. J. HARRIS, D.Sc., said he had tested groups of

people to ascertain if their nutritional status had deterior-ated or not since the war. He had particularly used thesaturation test, with a view to establishing a quantitativeindex. It was now possible to demonstrate the effects

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of subclinical deficiencies. Changes in individualswere not seen, but the analysis of the group as a wholerevealed statistical differences. The minimal absorptionof a vitamin produced obvious clinical symptoms, theoptimal promoted maximal health, and there was anappreciable gap between the two. In animals vitamin-C deficiency short of scurvy produced diminished growthrate, failure in production of new tissues (e.g., teeth orwound healing) and increased liability to infection.These applied also to human beings, although this wasa controversial issue. One thing against it was the workof Fox, in South Africa, who studied a group of minerson 12-25 mg. of ascorbic acid a day. A few of theseactually developed scurvy, but there was no evidencethat the health of the group as a whole was worse thanthat of another group receiving supplementary vitaminC over a 7 months period. The second argument wasCrandon’s experiment on himself, in which he showedno failure to heal artificial wounds and developed noinfection on a vitamin-C-free diet for several months.But this was only one subject; another on a dietdeficient in vitamin C developed whooping-cough withsevere complications. A number of recent publicationsat home and abroad supported the belief that additionof vitamin C to the diet led to better growth and increasedresistance to infection. Tonsillitis was cut short and itscomplications did not arise, and dental and surgicalwounds healed better. Tests to measure the level ofnutrition were valuable because vitamin deficiencymight appear suddenly if the levels were not beingwatched, and because general levels of nutrition inwar-time could be followed. Test doses of vitamin weregiven to see how many days the subject took to reachthe plateau of excretion. There was relatively littlescatter ; delay was proportional to the deficiency in theprevious diet. Children of well-conducted institutionswere still better off than children in poor homes, butthere was a drop all round in vitamin C, owing to theshortage of fruit. After the summer, however, nearlyall groups were up to a satisfactory figure. Care wasneeded in providing vitamin C during the winter. Dark-adaptation could be made a specific and reliable test forvitamin-A deficiency ; about 9% of the children in aninstitution, about 15% of children in homes, and 18%in village homes had a subclinical deficiency which couldbe put right by administering vitamin A. Slit-lampexamination of the cornea for vascularisation of thelimbus showed that 6% of Cambridge children had- riboflavin deficiency, but children showed this sign lessthan adults.

Dr. H. M. SINCLAIR thought the whole subject wasvery difficult as there was so much conflicting evidenceto be weighed up. He asked whether the iron situationwas satisfactory. We regularly threw away a greatdeal of iron by separating plasma at blood-transfusioncentres : could not some of that be added to bread ?

Dr. A. P. MEIKLEJOHN also asked about addition ofiron, as he thought haemoglobin levels were now, com-monly rather low. In a recent survey in Lancashirea random sample of young married women had a levelof about 76%. He also asked Dr. Harris to define sub-clinical deficiency more precisely. There was un-

doubtedly a period of vague ill health between theinstitution of an inadequate diet and the appearance ofdefinite deficiency symptoms, but it seemed dangerousto assume that a patient in a state of suboptimal nutri-tion was necessarily suffering therefrom. It was easyto collect a groups of people with lassitude and insomnia ;they had no bromide in the urine but were not neces-sarily suffering from bromide deficiency. It was verydifficult in practice to apply vitamin-deficiency tests.Correlation between results of test-dose experimentsand the clinical side was needed.

Dr. HARRIS replied that the balance of evidence sug-gested that resistance to infection was affected ; thefact that one group did not show this was neither herenor there. A negative result did not necessarily proveanything, whereas a positive result did. A group hadsubclinical deficiency if, as a group, they showed improve-ment on increased vitamin dosage ; individuals mightnot show anything. The saturation test enabled theobserver to determine the relative position of the group ;he had never said that saturation was necessary.

Dr. R. A. MURRAY ScoTT, speaking as a generalpractitioner among specialists, said that his committeein Leeds had been seeking effects of faulty war-timediet. They had decided that anaemia was the most easilyidentified defect. There seemed to be a definite increasein anaemia in the country, especially among women.Medical students had shown 100-105% haemoglobin asthe commonest reading for six years before the war ;last year the largest group had been 90-95%.

Dr. GEOFFREY EVANS believed there was a certainamount of mineral and vitamin deficiency today, evenallowing for the psychological action of vitamin ad-ministration. He had been struck by the response ofacne rosacea with conjunctivitis and keratitis to ribo-flavin, 3-6 mg. daily. Some who suffered from lack ofpower of concentration found real benefit from vitaminB. He was much impressed by the number of peoplewho had low haemoglobin values-80% or less-and theobvious benefit conferred by bringing it to a morenormal level. We should not be iron-conscious, vitamin-conscious and so on, but food-conscious. Differentpeople, and perhaps different families too, had differentpowers of assimilating these substances. He knew onefamily of six with definite evidence of muscular hypotoniaon a diet undoubtedly adequate in vitamins ; there hadbeen much improvement in many directions from givingcalcium and vitamin D. Enormous doses of the fat-soluble vitamins could cause real poisoning : therapeuticdoses must be given.

Prof. J. R. MARRACK had estimated the vitamin Cin many meals in British Restaurants and canteens.In the former he found over 20 mg. per meal in London,but in Bishop’s Stortford in March it never reached thatand was under 10 mg. in a third of the meals. In theschools, a third of the dinners supplied under 10 mg. anda third over 20 mg., with a maximum of over 60 ing.Saturation tests confirmed the meal analyses. The testwas comparable with the urea-concentration test.The worst vitamin-C supply was in a school with a ratherpoor cook where the headmaster grew potatoes only.In the school with best meals the headmaster was aenthusiastic gardener, and there were large supplies ofgreen vegetables. On the full diet in a hospital he hadinvestigated patients managed fairly well, but the lightdiets in the same hospital supplied less than 10 mg. ofascorbic acid on five days out of twelve, and never morethan 30 mg. daily. He had been surprised to find him-self feeling better and less tired on a diet high in vitamin C.

Dr. H. E. MAGEE said that the word minimum didnot appear in the League of Nations recommendations.The Ministry of Health had been criticised, especi-ally with reference to cod-liver oil. On the adviceof the Medical Research Council it had accepted theLeague’s 1938 standards. The standards had been setup by methods which were not clear-cut and definite, asprotein and mineral standards had been. It was not amatter of balance where intake and output were de-termined, but of the recognition of diseased states. Thestandards were therefore speculative, and much signi-ficance should not be attached to specific figures.

Mr. W. R. G. ATKINS, Sc.D., F.R.S., pointed out thatthere were traces of nearly all the elements in seawater,and food coming from the sea might be expected tocontain substances not present in inland foods. Therealso might be substances in the soil, such as manganese,preventing the absorption of iron. He had carried outexperiments on a number of men. In one case 50 menfed from the same kitchen showed differences of satura-tion according to whether they had their vitamin tabletsbefore or after breakfast. How long did it take for achange from one diet to another to affect a man ? Of 100men tested lately, 40 had been done ten months ago andleft saturated then. Yet these 40 showed no quickersaturation than the others. Obviously if they normallystored 7-8 g. this would not be so. It appeared thatthe man who had a big supply got rid of it very quickly.

Mr. A. L. BACHARACH, B.Sc., thought only one logicalconclusion could be drawn from Fox’s experiments:that ascorbic acid reduced the risk of scurvy and didnothing else. That, however, did not prove that thevitamin had no other effects. The state of nutrition ofthese natives was such that the only thing vitamin Ccould do for them was to reduce the incidence of scurvy.

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The other things depended on other factors of nutritionas well. An increase of 5 mg. of iron per day per personin this country would only require an extraction of 80tons a year of iron ore, and would be entirely simple.A person in a state of permanent unsaturation must bemore likely to step over into deficiency than anotherperson ; no more could be or had been claimed. Theindividual prewar brown bread consumer was notrelevant ; brown bread was not necessarily war bread.The most popular brown bread was a mixture of whiteHour and wheatgerm, and most of the phytin was in thebran, not in the germ. There was a good deal of looseterminology in this sphere. Brown bread must not beidentified with wholemeal bread or even with bread ofhigh extraction.

Dr. McCANCE, in reply, said that requirements hadto be defined in terms of the diet and particularly of thecereal eaten, and individuals varied enormously. Hehad never been in calcium balance during a two years’diet of brown bread. It was easy to find out an indi-vidual’s calcium requirements but very difficult to assessthe requirements of a population. Calcium could beadded to brown bread to make it a neutral product,like white bread, or to make it a source of calcium. Thepresent proposal did the former only. Evidence fromindividuals was useless ; a man who got 70% of hiscalcium from other sources naturally would never

show calcium deficiency as a result of changing fromwhite bread to wholemeal. -

SOCIETY OF MEDICAL OFFICERS OF HEALTHAT a meeting of the Fever Hospital Medical Service

group of the Society of Medical Officers of Health onMay 8, with Dr. E. H. R. HARRIES in the chair, a dis-cussion on

Recent Improvements in the Preparation of Antitoxinswas opened by Mr. L. F. HEWITT, Ph.D. He recalledthat unprocessed antitoxic serum with its low potencyand its tendency to produce severe serum reactions wasfirst superseded by antitoxic globulins from which aconsiderable amount of inert protein fractions had beenremoved. With this material and the improvementsintroduced from time to time more potent antitoxinsbecame available and the incidence of severe serumreactions was greatly reduced. More recently enzyme-treated antitoxins have been developed, in which notonly have inert proteins been removed but the antitoxicproteins themselves have been split into active and inertfractions. This result was obtained by proteolyticenzymes such as pepsin acting under conditions inwhich the proteins were disaggregated into smallermolecules without allowing true digestion into peptonesand amino-acids. The antitoxin thus produced was ofhigh potency and possessed other advantages, includingrapidity of absorption, slow disappearance from thebody and a reduced tendency to cause serum reactionsor sensitisation even when administered in massivedoses. There is no evidence of the absence of anyessential factor from this enzyme-treated material.Recent laboratory work on diphtheria has failed toreveal any other antibody necessary for treatment-forexample, late diphtheritic paralysis in animals has beenshown to be due to ordinary diphtheritic toxin and to beprevented by early administration of antitoxin. Factorshave recently come to light explaining the high toxi-genicity of gravis strains of Corynebacterium diphtheriœin patients and their comparatively low toxigenicity in theusual artificial culture media. The culture media usuallyemployed are deficient in iron and strains other thangravis produce potent toxins, but when the iron contentof the medium is increased to a level comparable to thatobtaining in the throat the toxigenicity of gravis is stillconsiderable while that of other strains is greatlyreduced, thus providing an explanation of the clinicalfindings. Dr. Hewitt urged the importance of obtainingclinical reports on the new antitoxin preparations.

Dr. E. H. R. HARRIES said that reactions so rarelyfollow the injection of these refined products that it isdifficult to find serum rashes to demonstrate to students.He is coming to the conclusion that, provided all orpart is injected intravenously, doses in excess of 50,000units are seldom required.

Dr. H. J. PARISH said that experiments in the labora-tory have shown that there are wide differences betweenstrains of C. diphtheriœ in respect of toxigenicity andvirulence. These variations may explain why anti-toxin is more effective in some cases than in others.It is not always realised that many valuable hours canbe gained and expense saved by administering anti-toxin intravenously. A relatively small dose givenintravenously so as to be immediately available is moreuseful than many times the unitage given intramuscu-larly. Antitoxin neutralises toxin in the circulationbut cannot deal with toxin already fixed to the cellsof the body. Is antitoxin less effective unit for unittoday than before the introduction of refined serum,and has it become qualitatively different since the earlydays of serum therapy ? Dr. Parish recalled that therewas a tendency some years ago to employ a very hightherapeutic dosage-e.g., 300,000 units intravenously-but he was told that in one hospital equally good resultswere obtained with 50,000 units or less. This does notsuggest that antitoxin has become " weaker," but is itgeneral experience ?

Dr. L. J. M. LAURENT said that with modern con-centrated antitoxin there are still two problems requiringsolution : first, the rigors after intravenous injectionswhich are not due to serum hypersensitiveness and-seemassociated with certain batches of antitoxin; secondly,the delayed response of some severe cases of diphtheriato antitoxin, even when adequate intravenous doses aregiven early. Variations in the infecting strain, in thepatient’s susceptibility and in some hypothetical" avidity " factor in antitoxin have been put forward inexplanation, but no explanation accounts for all thefacts. This occasional delayed response to antitoxinwas well known twenty years ago when only naturalserum was used. His experience of those days did notbear out the view that improvement was then morerapid than it is now.

Dr. H. S. BANKS said that serum sickness as well asthe anaphylactoid reaction following intravenous injec-tion are practically abolished by the use of " digest "concentrated antitoxin. The thermal reaction whicharises about half an hour after intravenous injectionwas produced by earlier batches but not by those nowin use. Some recent cases of apparently simple tonsillardiphtheria treated with as much as 40,000 units intra-venously on admission progressed to the " bull-neck "stage with extensive palatal membrane and oedemawithin 12-24 hours. Such cases are, however, rapidlycontrolled by a further injection of 100,000-150,000 unitsintravenously. Although there is sometimes a time lagin its action, large intravenous doses of the new anti-toxin, repeated if necessary, can be relied on to effect arapid cure of the early hypertoxic case of diphtheria,often without paresis or other complications.

Dr. MAURICE MiTMAN said that for some years he hasregarded thermal reactions-rigor and collapse-asfundamentally different from the antigen-antibodyreaction responsible for serum disease, chiefly because aserum rash may appear 7-10 days after the administra-tion of serum to a patient who had a rigor 20 minutesafter the injection. If thermal reactions have materi-ally diminished in frequency with protein disaggregatedserum some light may be thrown on their aetiology. Indiphtheria he does not regard the extension of localmanifestations within 24 hours of the administration ofserum as positive proof of the failure of serum. Theappearance of membrane is an end-result of a biologicalprocess which may have begun before the serum wasgiven; at the time of administration there may belittle or no clinical evidence that the mucosa is affected.He thought some generally acceptable simple nomencla-ture for the different sera is desirable ; such terms as"refined sera " are being used for both concentratedand protein disaggregated sera and there may beconfusion.

’

Mr. C. G. POPE, B.Sc., drew attention to the differencein time required to purify and concentrate antitoxicsera by the old ammonium sulphate method comparedwith the newer enzyme-heat denaturatiom method. Inthe old method, technical difficulties due to poor filtra-tion of the ammonium sulphate fractions made theprocess a lengthy one and some degree of bacterial