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journey and where the transfusion had stopped running)have been due to the absence of an orderly, so that theflow had not been adjusted during the journey.

SUMMARY

1. The average severity of wounds and the degree ofwound shock are apt to be unusually great in desertwarfare.

2. This view is borne out by figures showing theaverage amounts of blood and plasma given in two periodsof severe fighting, in desert and in hill country.

3. The harmful effect of an ambulance journey on analready embarrassed or recently resuscitated circulationis emphasised.

4. A technique has been elaborated in the WesternDesert, whereby it has been possible to evacuate 200casualties by ambulance with a transfusion of blood orplasma in progress.My thanks are due to Brigadier J. Walker, late DDMS

Eighth Army, and to Lieut.-Colonel G. A. H. Buttle, adviserin blood transfusion, MEF, for their constant encouragementin these experiments, and to all transfusion officers in EighthArmy, whose help and suggestions enabled the travellingtransfusion to become a reality.

’

EHRLICH’S MEGALOBLASTSASSOCIATED WITH LOW MEAN CORPUSCULAR VOLUME

AND RED CELL DIAMETER

HENRY FOY, MA OXFDDIRECTOR OF THE WELLCOME

TRUST RESEARCH LABORA-

TORIES, THESSALONIKI

ATHENA KONDI, MDCLINICAL RESEARCH

WORKER

(From the Wellcome Trust Research Laboratories, and SouthAfrican Institute for Medical Research, Johannesburg)DURING the course of a nutritional anaemia, survey in

the Bechuanaland Protectorate, Africa, we came acrossa case of chronic untreated amoebic dysentery in a9 months’ pregnant negress, who had been suffering frompersistent diarrhoea for the whole of her pregnancy.The bone-marrow on examination was found to

contain typical Ehrlich’s megaloblasts, exactly similarto those in the nutritional macrocytic anaemias ofIndia (Wills 1932) and Macedonia (Fairley et al. 1938,Foy and Kondi 1939) and in untreated cases of perniciousanaemia.The megaloblasts found in this case are not to be

confused with the megaloblasts of the American workers(Sabin 1921, Doan et al. 1925). The cells we describehere are the typical Ehrlich’s megaloblasts, with finenetwork open nuclei, and smooth hsemoglobinisedcytoplasm described by Turnbull (1936), Schulten (1937)and Israels (1939b). They are characteristic of perni-cious anaemia and of the nutritional macrocytic anaemiaof India and Macedonia. Our wide experience of thesecells, which were first introduced to us by Dr. LucyWills, as being similar to her Indian ones, leaves noroom for doubt as to their existence in the present case.In addition to these there were also present in the bone-marrow pathological white cells-the typical giantstab-cells (Riesen-Stabkern of Schulten)-which are alsocharacteristic of both pernicious anaemia and nutritionalmacrocytic anaemia of Macedonia (Foy and Kondi1939).Jones (1937), Tempka and Braun (1932), and Dameshek

and Valentine (1937) have given excellent accounts ofthese cells, and the last state that whatever deficiency isresponsible for abnormal maturation of the red cellsalso affects white-cell maturation, with production ofbizarre forms of " metamyelocytes " (giant stab-cells).These, they consider, may give rise to the hypersegmentedpolymorphs found in the peripheral blood of many, ifnot all, macrocytic anaemias.

Giant stab-cells are typically 1811. to 32µ in diameter,and contain large U-shaped nuclei, coarsely netted andporous in appearance. There may be chromatin con-densation in the nucleus but there is never any pyknosis.The cytoplasm is much more immature than the nucleus,finely or coarsely granular, and weakly basopnilic whenstained in Leishman and Giemsa and buffered withwater at pH 68. In our opinion these cells are just ascharacteristic of the macrocytic anaemias as are the

megaloblasts of Ehrlich, and we have found them notonly in pernicious anaemia, but also in tropical sprue,and the nutritional macrocytic ansemias reported fromMacedonia. It is interesting to note that the deficiencyresponsible for the production of these abnormal red andwhite cells affects the two series differently: in the red-cell series resulting in the megaloblast, with mature-cytoplasm and immature nucleus ; in the white-cellseries in the giant stab-cell, with immature cytoplasm-and a mature nucleus.The presence of Ehrlich megaloblasts in associationwith normal mean corpuscular diameters, volumes andthicknesses, raises the question of their ultimate fate.Bock and Malamos (1939), Jones (1937), Fieschi (1938)

and Naegeli (1935) state that in their opinion these megalo-blasts are present in the marrow of pernicious anaemia andgive rise, after treatment with liver, to the megalocytes foundin the peripheral blood. If this view is correct, then theterm " megalocytic anaemia " should be used to define large-cell anaemias occurring in conjunction with megaloblasts inthe marrow. On the other hand Schulten (1937), Doan(1938), Henning (1936) and Schartum-Hansen (1937) considerthat the megaloblasts in the marrow are transformed, aftertreatment, into normal-size red cells. Israels (1939a) believesthat megaloblasts occur in the marrow of all " PA-factordeficient anaemias " and that all such anaemias are megalocytic,but that not all large-cell anaemias have megaloblasts in themarrow.

The present case seems to indicate that megaloblastscan occur in the marrow without giving rise to a megalo-cytic anaemia. Precisely how this can happen is notclear. It is possible that we may have caught this caseat such an early stage that although megaloblasts werepresent in the marrow sufficient time had not elapsedfor the production of a megalocytic blood-picture,though this view would be difficult to fit in with the lowblood-count. Or perhaps the exit of these large cellsfrom the marrow was hindered in some unknown way,analogous to that operating in pernicious anaemia,where leucopenia is associated with a hyperplasticmarrow. If, as some claim, marrow megaloblasts areconverted after liver treatment into normal-size redcells, then other things besides liver might facilitatethis maturation of megaloblasts-just as thyroid doesin myxcedema. Probably the antipernicious-anaemiafactor exerts its effects somewhere at the pro-erythroblaststage, thus preventing the formation of megaloblastsand pushing the bell maturation along normal lines.None of these explanations accounts for the large-cellanaemias which occur in the absence of megaloblasts inthe marrow.The interest of the present case is that megaloblasts

and giant stab-cells were found in association with amean corpuscular volume (MCV) of 69µ, and a meanred-cell diameter of 6.75µ as shown by Price-Jonescurve (see figure). -

CASE-HISTORY

The woman was brought to us suffering from weakness andanaemia, and with a history of 9 months continuous diarrhoea.She was emaciated, about 30 years old, and 9 months preg-nant. She had a palpable and tender liver; spleen not felt.There was no glossitis, though the gums showed the blotchyhaemorrhages common among these natives. Her teethwere very bad, and her gums soggy. Her skin was dry andcheeks sunken. Reflexes were normal ; there was no signof an icteric tinge in the whites of her eyes. There was no

history of nose-bleeding or chronic haemorrhages. Her

temperature and pulse-rate were normal. We did a haema-

tological examination on May 28, 1942, with the followingresults.: red cells 2,627,000 (± 3%) per e.mm.; Hb. 7% ;colour-index 0-92 ; white cells 3440; hæmatocrit 18%;MCV 69µ; reticulocytes 0.5%; haemobilirubin 0-6 mg. % ;mean corpuscular average thickness 1 9 9jJL; mean corpuscularHb. = 26.9&ggr;&ggr;; mean corpuscular concentration 38-9%.A marrow biopsy done at the same time showed a very activemarrow, containing typical Ehrlich’s megaloblasts, giantstab-cells, and early and late erythroblasts. No malariaparasites were found; there is hardly any malaria in thisarea where the spleen rate is about 0-5%. A fæcal examina-tion showed abundant Amœba histolytica cysts.We were unable to follow up the case or to do a gastric

test, but have since heard that the woman made an

506

uneventful recovery after having emetine injections, andgiving birth to a live child. This history rules outpernicious ansemia.

REVIEW OF METHODS

Our first reaction to the finding of megaloblasts in themarrow, associated with such hsematological findings,was that our haematocrit value had gone astray. Wetherefore repeated the examination, getting the sameresults. In addition we carried out an examinationusing exactly similar methods on a known normalBechuana native and found the marrow normal in

Price-Jones earre.-Arithmetic mean 6.75; standard deviation 0.658 ; ;coefficient of variation 9-7%.

every respect and the blood as follows : red cells5,700,000 (± 3%)1; Hb. 14-5%; CI 1-0; hæmatocrit46.6%; MCV 80µ3; MCHb. 25.4&ggr;&ggr;; iVICHb. con-

centration 31.5 % ; reticulocytes 03 % ; hæmobilirubin0-4 mg. %.The red cells were counted in standardised pipettes and

chambers, and a thousand cells counted, thus stabilising theerror at =b 3% (Ponder 1934). It will be noticed that thered-cell diameters as ascertained by Price-Jones curve (seefigure) were in harmony with the MCV as calculated from thehæmatocrit. The slide for the Price-Jones curve was takenfrom peripheral blood, and after drying in air was immediatelyfixed in Leishman for 1 minute, dried and immediatelycounter-stained in 1 % aqueous eosin for 1 minute. This is thestandard method used for all our curves, and is the onerecommended by Price-Jones (1936). If such methods arealways adopted then any change in cell diameters are constant.The hæmoglobin was done by the standard method of New-comer using a Duboscq colorimeter.

DISCUSSION

This is’the first time we have seen Ehrlich’s megalo-blasts associated with anything but macrocytic anaemias.Other authors have described such cells in cases ofchronic diarrhoea and prostatitis, but none so far aswe are aware has given the haematological findingsassociated with them. Our case emphasises that oneshould not rely on a single index in diagnosing macro-cytic ansemias. For the diagnosis of such anaemias weregard as essential: a mean corpuscular volume ofabove 100µ taken at low reticulocyte level; a colour-indexabove 1-0 based on haemoglobin estimated by somereliable method ; the presence of Ehrlich’s megaloblastsand stab-cells in the bone-marrow ; and response to aknown potent liver preparation. We have seen manypapers describing macrocytic anaemias diagnosed on

only one of the above criteria. In particular. it iscommon to find diagnoses made on mean corpuscularvolumes alone, with no mention of the percentage ofreticulocytosis, which can itself give a macrocytosis.Diagnoses are also quite commonly made on sternal-puncture findings only, the danger of which is illustratedin the present case. The increasing popularity ofsternal punctures may lead to confusion among workersnot fully aware of the difficulties of identifying megalo-blasts, and of the importance of proper staining methodsand differentiation ; in many parts of the world wehave seen diagnoses made on marrow smears in which it

1. The altitude of this Native Reserve is about 3500 feet.

was impossible to identify anything with certainty onaccount of faulty staining. A further cause of confusionwhich we have constantly met with is the failure to differen-tiate between early erythroblasts, and the megalo-blasts of Ehrlich-a state worse confounded by someAmerican authors who call erythroblasts megaloblasts,and of some English textbooks on hsematology, whichrefer to the haemocytoblasts of Vaughan, Turnbull, andothers; as megaloblasts. Vaughan has given an excellentaccount of this confusion in her textbook which shouldbe consulted.

It will be noticed from the figure that there is little aniso-cytosis in the present case, the coefficient of variationbeing 9-7 %. Probably in this case the long-continueddiarrhcea, by preventing the absorption of substancesnecessary for haemopoiesis, was the factor behind thehaemopoietic failure.We wish to thank Dr. Bernard Squires of the Bechuanaland

Medical Service for putting us into contact with this case ;and Miss Hales of the London Missionary Society for her help.Our thanks are also due to the Principal Medical Officer ofBechuanaland.

REFERENCES

Bock, H. E. and Malamos, B. (1939) Folia hœmat., Lpz. 62, 408.Dameshek, W. and Valentine, E. H. (1937) Arch. Path. 23, 159.Doan, C. A. (1938) in Downey’s Handbook of Hematology, New York,

vol. III, p. 1839.Doan, C. A., Cunningham, R. S. and Sabin, F. R. (1925) Contr. Embryol.

Carneg. Inst. 16, 163.Fairley, N. H., Bromfield, R. J., Foy, H. and Kondi, A. (1938) Trans.

R. Soc. trop. Med. Hyg. 32, 132.Fieschi, A. (1938) Biblioteca " Hæmatologica," Pavia, vol. VI.Foy, H. and Kondi, A. (1939) Lancet, ii, 360.Henning, N. (1936) Med. Klin. 32, 542.Israëls, M. C. G. (1939a) J. Path. Bact. 49, 231; (1939b) Ibid, 52, 17.Jones, O. P. (1937) Arch. intern. Med. 60, 1002.Naegeli, O. (1935) Wien. klin. Wschr. 48, 225.Ponder, E. (1934) The Mammalian Red Cell, and the Properties of Hemo-

lytic Systems, Berlin.Price-Jones, C. (1936) Red Blood-cell Diameters, London.Sabin, F. R. (1921) Bull. Johns Hopk. Hosp. 32, 314.Schartum-Hansen, H. (1937) Folia hœmat., Lpz. 58, 145.Schulten, H. (1937) Die Sternalpunktion als diagnostische Methode,

Leipzig.Tempka, T. and Braun, B. (1932) Folia hœmat., Lpz. 48, 355.Turnbull, H. M. (1936) In Vaughan’s Anæmias.Vaughan, J. (1936) The Anæmias, London.Wills, L. (1932) Proc. R. Soc. Med. 25, 128.

POSTERIOR SUBASTRAGALOID

ARTHRODESIS IN FRACTURED OS CALCIS

J. R. ARMSTRONG, MD, M CH BELF, FRCSWING-COMMANDER RAF; REGISTRAR, METROPOLITAN HOSPITAL,

AND FRACTURE CLINIC, CHARING CROSS HOSPITAL

FRACTURES of the os calcis now occupy the place onceheld by adduction fractures of the neck of the femur.Many surgeons have become so dissatisfied with theresults of treatment by the recognised methods thatthey advocate and practise measures which, in effect,consist of ignoring the fracture and treating the patient,and in certain types of these injuries their results arecertainly no worse than those produced by treatment inaccordance with the accepted principles of reductionfollowed by immobilisation until firm bony union hasoccurred.

All types of os calcis fracture are not equally crippling.Generally speaking the ultimate function is much betterif the subastragaloid joints are not directly involved inthe fracture. When these joints are directly involved itappears to me that any treatment which does notinclude an immediate arthrodesis of the affected joint isfutile. As with any other weight-bearing joint reductionof a fracture involving the articular surface must beabsolutely accurate to be effective, and any persistingirregularity will produce subsequent arthritis. Theusual methods of traction and lateral compressionproduce, at best, only an approximately accuratereduction. The articular surface of the os calcis remainsirregular, and the articular cartilage of the os calcis andastragalus is contused and crushed. Not only is sub-sequent arthritis inevitable, but, as joint movementunder any circumstances is prevented in the early stagesby pain, intra-articular adhesions produced by organisingblood-clot become well established. These changesmust occur with any form of conservative treatment,although the use of a transfixion pin, with a subsequentlow-grade infection of the pin track spreading to the