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Annotations

CHRISTMAS IN THE MEDICAL FAMILYDAILY bread is a fine thing, but much improved by

butter ; and if this year we must spread the butterrather thin it should help us to remember that in manycountries today, and even in some homes in England, itis spread even thinner. The Royal Medical BenevolentFund has a special concern with the butterless bread ofone group of people at Christmas. Sir Arnold Lawson’sletter will have recalled to readers that the Fund triesto give a substantial Christmas present to medical menor their families who find. themselves in need, and thatlast year it was possible to give a cheque of E4 to eachrecipient. He asks that this year the profession will makethe same gift possible by sending the Fund 2000. Last

year his appeal was exceeded by more than :E100, andthis year, they tell us, we all have more to spend andless to spend it on. Most doctors will gladly do a kindnessif reminded. This is the reminder.

PARÆSTHESIÆ IN THE LEGS

PERVERTED sensations in the limbs-numbness, ting-ling, prickings, burnings, and so on-are a common

symptom, and their causation in the hand has beenclarified by the differentiation of the syndromes ofcostoclavicular compression and of lateral prolapse ofcervical intervertebral disks. Similar symptoms in thelegs and feet may be the .manifestations of organicneurological diseases such as peripheral neuritis andsubacute combined degeneration of the cord, or of

deficiency of some factor of the vitamin-B complex,a condition often seen among prisoners-of-war andinternees in the Far East 1 ; but there are cases wherethe cause remains obscure. Ekhom 2 in Scandinavia,Allison 3 in Canada, and Martin 4 in London havedrawn attention to parsesthesise in the feet and legs(" restless legs," or " leg jitters ") which wake thesufferers at night and may keep recurring for years with-out signs of organic neurological or vascular disease

developing.Now Schepers 5 in Johannesburg has approached the

problem afresh by studying 100 patients in an institutionfor chronic diseases who suffered from parsesthesise inthe legs, and excluding cases of frank organic neuro-logical disease or manifest psychoneurosis.’ There werefive main groups among these cases. The largest group(47%) were suffering from organic diseases of the lowerabdominal viscera-ureteritis associated with prosta-titis or cervicitis, salpingo-oophoritis, or chronic colitis.In these patients there were areas of hyperaesthesia onthe thighs, lower part of the legs, and feet, the distribu-tion to some extent depending on the abdominalcondition. The explanation offered for the sensorydisorder in these cases is either spread of inflammationto the lumbosacral plexus or involvement of the auto-nomic nerves and retrograde reflex irritation of spinalcord segments. The second main group (28%) werecases of macrocytic hyperchromic anemia in whichthere was either impaired superficial sensation in thedistal parts of the legs, thought to be due to degenerationof the termination of the peripheral nerves, or spread ofthe sensory impairment up the back of the thigh andbuttock in the distribution of the sacral dermatomes.In this group Schepers suggests that ischemia of thespinal cord plays a part in causation, and the paraes-thesise always disappeared when the ansemia was

corrected ; it seems possible that they were early casesof subacute combined degeneration. In two groups, one

1. Lancet, Oct. 12, p. 545. The Fund’s address is 1, Balliol House,Manor Fields, London, S.W.15.

1. Cruickshank, E. K. Lancet, Sept. 14, p. 369.2. Ekhom, K. A. Acta. med. scand. 1945, suppl. 158.3. Allison, F. G. Canad. med. Ass. J. 1943, 48, 36.4. Martin, J. P. Brit. med. J. 1946, i, 307.5. Schepers, G. W. H. S. Afr. med. J. 1946, 20, 437.

associated with gravitational oedema (9%), often onlyslight, and the other with peripheral vascular spasm(4%), ischemia of the nerve-endings was thought to bethe cause. Finally there were 12 cases of " masked "

hypothyroidism, in which scattered patches of hyper-and hypo-sesthesia on the legs disappeared with adequatesubstitution therapy. Here the terminal parts of the

peripheral nerves were thought to be constricted as

they pierced the deep fascia, either because of increasedturgidity in the nerves or because the fascia became"

fluid-logged " and rigid as a result of the endocrinedefect.

O AND ANTI-O

THE groups of human red blood cells are determinedby the presence or absence of two specific antigens,A and B. Thus the four main blood-groups are AB,A, B, and 0 (i.e., zero, neither A nor B). Yon Dungernand Hirszfeld 1 postulated that the inheritance of theA and B factors depended on two independent pairs ofallelic genes, A and a (not A) and B and b (not B).But Bernstein 2 demonstrated mathematically that thisview was not supported by statistical data, which did,however, fit in with a theory assuming three allelicgenes-A, B, and 0 (or R), where A and B are dominantover 0. This theory has now been generally accepted.It differs from that of von Dungern and Hirszfeld insupposing that group 0 is determined by a positiveantigen. The discovery of sera which will react withgroup-0 red cells has lent additional weight to Bern-stein’s hypothesis.Twenty years ago Landsteiner and Levine 3 found

irregular iso-agglutinins in some rare human sera of

groups AIB and At> which, though weak and actingonly in the cold, would agglutinate red cells of groupsA and 0. Since then more potent iso-sera have beendescribed in two persons of group Al 45 5 and two of AB.’ rIn three of these four cases iso-immunisation by trans-fusion or pregnancy may have increased the activityof the atypical iso-agglutinin, so that it became activeagainst the appropriate cells at body temperature.The serum of the latest example with group AIB,described this year by Henry, agglutinated not only0 and A2 red cells but also, though less strongly, somered cells of groups Ai, B, and A2B.

Schiff 8 showed in 1927 that cattle sera sometimescontained an agglutinin which would agglutinate humangroup-0 red cells. Eisler, by immunisation with

Shiga bacilli, produced in goats an antibody which alsowould agglutinate group-0 red cells. Both the naturalox sera and the immune goat sera agglutinate all humanred cells, but those of groups 0 and A2 much more stronglythan those of groups AI, B, and A1B. Furthermore, evenas some individuals of groups A and B secrete in their

body fluids-notably the saliva and gastric juice-substances which have great A and B activity as measuredby inhibition of anti-A and anti-B sera, so some indi-viduals of group 0 secrete a substance capable ofinhibiting anti-O sera.’ 0 Morgan and van Heyningen 1have noted that an even better source than saliva ofA, B, and 0 active substances is the material from

pseudomucinous ovarian cysts. However, whereas" secretors " of A and B substances usually secrete intheir saliva not only A or B but also 0 active substance,cyst fluid from A and B persons has not, except in one1. von Dungern, E., Hirszfeld, L. Z. ImmunForsch. 1910, 6, 284.2. Bernstein, F. Klin. Wschr. 1924, 3, 1495.3. Landsteiner, K., Levine, P. J. Immunol. 1926, 12, 441 ; Ibid.

1929, 17, 1.4. Morzycki, J. Z. ImmunForsch. 1935, 84, 80.5. Davidsohn, L. J. Amer. med. Ass. 1942, 120, 1288.6. Wiener, A. S., Oremland, B. H., Hyman, M. A., Samwick, A. A.

Amer. J. clin. Path. 1942, 11, 102.7. Henry, N. R. Med. J. Aust. 1946, i, 395.8. Schiff, F. Klin. Wschr. 1927, 6, 303.9. Eisler, M. Z. ImmunForsch. 1930, 67, 38.

10. Schiff, F., Sasaki, H. Klin. Wschr. 1932, 11, 1426.11. Morgan, W. T. J., van Heyningen, R. Brit. J. exp. Path.

1944, 25, 5.

913

instance, shown significant 0 activity. Morgan andWaddell,12 using purified 0 active material from ovariancysts, have immunised rabbits and obtained a serumwith anti-0 activity stronger than the natural anti-Oserum obtained by selection from over 100 cattle sera.The titres against A2 and 0 red cells of both this immuneserum and of good ox serum were high ; some B redcells reacted as strongly as A2 red cells, and the reactionof Al red cells varied.On the Bernstein theory, it might be expected that all

heterozygous A and B red cells (i.e., AO and BO) wouldbe agglutinated by powerful anti-O sera ; but Hirszfeldand Amzel,13 using a powerful immune goat serum

as anti-O, could find no evidence of this. And Aloureaii 14has reported a family AB x AB with 10 children-4 with AA, 2 with BB, and 4 with AB-in all of whom thered cells reacted with anti-0 serum. Hirszfeld and Amzelregard the receptor 0 as almost ubiquitous in the humanspecies and therefore almost a species factor (cf. Witebskiand Oka,be 15). Matta 16 has rejected the theory thatanti-O is a species antibody, since some AB, A, and Bcells cannot completely absorb from a powerful anti-Oserum all its a,nti-O activity, and anti-human sera donot agglutinate 0 cells more strongly than red cells ofother groups. Wiener and Karowe 17 appear to acceptthe theory that anti-O is a. species antibody, and attemptto explain diagrammatically why this serum reacts with0 cells and heterozygous AI> A2, and B cells ; but theydo not explain its reactions with A2A2 and A2B cells,which were found to be positive by Wiener.18 Wienerexplains this by comparing anti-O to anti-Hr’ (anti-c),and the 0 and A2 agglutinogens to H-r’ antigens (c),which appear in the rh and Rh", Rho, and Rh2 genesof the Rh series-in other words, the genes contain acommon antigen. The apparent presence of 0 antigenin Shiga bacilli, hog-gastric mucin, and probably otheranimal tissues excludes the possibility of its beinga species-specific antigen. The bulk of evidence goes toshow that it is almost universally present in human tissuesbut that it varies in quantity. It could be argued thatit is a heterophile antigen. Eisler has shown that it isnot the Forssman antigen, but it may be of similar

type, originally universally present and still practicallyubiquitous in human red cells, as described by Hirszfeldand Amzel. These workers describe a descending degreeof reaction with anti-O serum, from 0 to A5 to A4 to A8to A2 and to four grades of Al (Am, Ar, Aj, and AQ),and a similar descending degree from 0 to B2, Bm,Br, and Bj : they postulate the presence of Bg, B4,and B3 at one end of the scale and B at the other.They suppose that in each case, by mutation throughthese stages, 0 is converted to A or B ; thus, theyargue, there is only a quantitative difference betweenthe subgroups of A. Wiener 19 and Boorman et al.,20however, claim to have shown that there is a qualitativedifference at least between A2 and AI, in that personsof group A2 can have an anti-A! iso-agglutinin in theserum, capable of agglutinating in vitro and haemolysingin vivo red cells of subgroup A,.

It is possible to fit all the facts into a hypothesiswhich assumes that the 0 is a fundamental antigen,that the common A is a separate antigen, and that theAl antigen develops by mutation from 0. Thus all AIand 0 cells would react strongly with anti-0, and Alred cells would react according to the degree of mutationof 0 to Ai. When mutation was complete, anti-O could12. Morgan, W. T. J., Waddell, M. B. R. Ibid, 1945, 26, 387.13. Hirszfeld, L., Amzel, R. Ann. Inst. Pasteur, 1940, 65, 251, 386.14. Moureau, P. Sang. 1935, 9, 484.15. Witebski, E., Okabe, K. Klin. Wschr. 1927, 6, 1095.16. Matta, D. Egyptian University, Faculty of Medicine, Publica-

tion no. 11, 1937.17. Wiener, A. S., Karowe, H. E. J. Immunol. 1944, 49, 51.18. Wiener, A. S. Science, 1944, 100, 595.19. Wiener, A. S. J. Immunol. 1941, 41, 181.20. Boorman, K. E., Dodd, B. E., Loutit, J. F., Mollison, P. L.

Brit. med. J. 1946, i, 751.

appear in the serum of such a blood without infringingLandsteiner’s law. A similar postulate would be neededfor group B, although as yet no qualitative differencebetween human R antigens has been proved. Whateverthe hypothesis favoured, there is sufficient evidencethat the 0 antigen detected with these many anti-Osera. differs from that of Bernstein’s hypothesis. Thisdoes not disprove that hypothesis ; it does, however,necessitate a revision of terminology, unless we revertto the use of R as the third antigen to A and B in Bern-stein’s hypothesis ; but this might lead to confusionsince the Rh antigen is sometimes known as R. Beforenew theories and terminologies are accepted it mustbe established that all these various anti-O sera have thesame specificity.

MORE EXCITING GIVING

THE first proposals for the nationalisation of the

hospitals under the now Act seemed to many to endangermuch that was of value in the voluntary system. Butthe chairman at the annual meeting of King Edward’sHospital Fund for London last week, Lord Catto,said that the concessions made by the Minister inthe process of transmuting the Bill into an Act have

gone a long way to allay misgivings. Indeed he suggestedthat for the first time in the history of the hospitals it hasbecome possible to give " without the mental reservationthat the gift may be swallowed up in routine expenses."The changes about to take place in the organisation

of medicine will give scope to courageous pioneers, andthe King’s Fund are determined to make the most oftheir opportunities. Their influence is widening, for theabolition of the distinction between voluntary and

municipal hospitals will allow them for the first time tohelp all the hospitals of London. Among the thingson which the Fund propose to continue to spend money,Lord Catto mentioned the improvement of hospitalcatering, the recruitment of nurses and the provision ofpreliminary training schools for them, and the provisionof special equipment and amenities. The Fund are also

interesting themselves in accommodation for convales-cents, and have lately appointed a committee which,with the Institute of Hospital Almoners, is surveyingthe needs and possibilities of these homes.

In proposing the vote of thanks to the chairman,Sir Herbert Eason, F.R.c.s., pointed out that the Fundduring its existence had adapted itself to the varyingneeds of the voluntary hospitals, and he was confidentthat it would also adapt itself to the needs of the future.

TUBERCULOSIS IN NEWFOUNDLAND

IN July, 1945, the Newfoundland government invitedDr. T. O. Garland and Dr. D’Arcy Hart to investigatetuberculosis on the island. Their-report 1 shows a serious’state of affairs. About half the population of 320,000live on the Avalon peninsula (including St. John’s, thecapital city of 50,000), while the rest live in tiny scatteredsettlements on the very long coastline. Radiographicsurveys of samples indicate an average of about 35%of active cases of tuberculosis (adding previously knownactive cases to those newly discovered), but great varia-tions were found in different places, suggesting localpockets or epidemics. Although the tuberculosis death-rate decreased from 236 per 100,000 in 1926 to 143 in1943, it is still’ nearly three times that of Canada orGreat Britain ; in fact, Newfoundland is now where

England and Wales were in 1910. The rate of decline inrecent years has been approximately the same in thethree countries, with the significant exception that inNewfoundland it started rising in 1932 and reached apeak in 1937, this rise coinciding with the years ofsevere economic depression. More women than men die

1. Tuberculosis in Newfoundland. Department of Public Healthand Welfare, St. John’s, Newfoundland. 1946. Pp. 58.