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The group of non-White children who died of Ewing’ssarcoma consisted of 10 Negroes, 1 American Indian, and1 Oriental. The low mortality among non-Whites probablyreflects a low incidence, since it is unlikely that thetumour is less lethal or selectively under-reported in thisgroup.

In the tumour registries of Uganda and Jamaica, Ewing’ssarcoma seems to be uncommon relative to other bonetumours of childhood." 12 Though the numbers of neo-plasms reported are small, the ratio of Ewing’s sarcoma toosteogenic sarcoma is similar to that observed amongNegroes in the U.S. Thus it would seem that Negroes aregenetically resistant to Ewing’s sarcoma. This observation,like others on racial and geographical variations in cancer,would be clarified, as Davies has proposed,13 by a compara-tive study of childhood cancer using data from tumourregistries in various parts of the world.

JOSEPH F. FRAUMENI, JR.ANDREW G. GLASS.

Epidemiology Branch,National Cancer Institute,Bethesda, Maryland 20014.

ORAL CONTRACEPTIVES AND SERUM-PROTEINS

SIR,-I should like to comment on the paper by Dr.Horne and his colleagues (Jan. 10, p. 49) on the effect ofcombined oestrogen-progestagen oral contraceptives on

serum levels of cx2-macroglobulin, transferrin, albumin,and IgG.

In the proteins of cervical mucus, a progestationalinfluence has been shown to cause an increase in total-protein content and the appearance of prominent bandsof transferrin and immunoglobulin. 14,15 In these circum-stances the mucus acts as a barrier to the entry of sper-matozoa into the upper genital tract.16 The changes in theproteins of cervical mucus suggest that these proteins maycontribute to the cross-linking mechanism between theglycoprotein fibrils of cervical mucus in a similar way tothat which occurs in the bondings between mucopoly-saccharides.17,ls Thus, measurement of cervical-mucus

proteins provides a useful means of evaluating low-doseprogestagens which are being developed as locally actingoral contraceptives.The findings of Dr. Horne and his colleagues suggest

that studies of serum-proteins may provide an indicationof general progestational effects. It would be useful toexamine these measurements in parallel, in order to seewhether a local effect can be achieved without generalprogestational changes in the body, such as have beenfound in the case of chlormadinone acetate in beagles.19The adverse nature of generalised progestational effectshas not been well documented. The suggestion of Dr. Horneand his colleagues, that the increase of «2-macroglobulin asan effect of progestagens could be related to the increasedtendency to thrombosis with combined oral contraceptives,does not agree with the view of Poller and Thomson,20 whoreport a decreased clotting tendency in women who changedfrom an oestrogen-containing oral contraceptive to one

containing only a 17-acetoxy-progestagen.

MAX ELSTEIN.

Department of Obstetrics and Gynæcology,Charing Cross Hospital Medical School,

London W.C.2.

11. Brown, R. E., Wright, B. I. Clin. Pediat. (Phila), 1967, 6, 106.12. Bras, G., Cole, H., Ashmeade-Dyer, A., Watler, D. C. J. Natn.

Cancer Inst. 1969, 43, 417.13. Davies, J. N. P. Rec. Results Cancer Res. 1968, 13, 13.14 Elstein, M, Pollard, A. C. Nature, Lond. 1968, 219, 612.15. Elstein, M. J. Obstet. Gynœc. Br. Commonw. (in the press).16. Elstein, M., MacDonald, R. R. Unpublished.17. Partridge, S. M., Davis, H. F. in Chemistry and Biology of

Mucopolysaccharides; p. 93. Ciba Fdn Symp. London, 1958.18 Mathews, M. B., Lozaityte, I. Archs Biochem. 1958, 74, 158.19 Times, Jan 24, 1969.20. Poller, L., Thomson, J. M. Br. med. J. 1969, ii, 822.

ABORTION CAPITAL

Sm,ňIn their preliminary assessment of the 1967Abortion Act in practice, Mr. Diggory and his colleagues(Feb 7, p. 287), commenting upon exaggerated and ill-informed ideas that London has become the abortion

capital of the world, rely upon an official estimate that" The number of women terminated whose permanentplace of residence is abroad amounted to 7°o of the firstyear’s total and even this figure will include nurses andau pairs working in Britain ".But it may be worth pointing out that this estimate of

7% is itself quite unreliable, being based only uponpatients’ statements in the returns submitted to the Ministryof Health under the Abortion Regulations 1968. These

require the certifying practitioners to give the pregnantwoman’s " usual place of residence ", but not her

nationality; and any patient who wished not to reveal hertrue home address for an official form, as many might inthe circumstances, would not be committing even a

technical offence if she preferred to give only her lastaddress in Britain however temporary. Nor is there anyreason to expect either the doctor or the nursing-homeconcerned to take any special trouble to make sure thatwhat a prospective patient tells them is true.

C. B. GOODHARTGonville and Caius College,

Cambridge.

BOVINE LEUKOSIS AND HUMAN CANCER

SIR,-Several reports have suggested that there maybe time-space clustering of bovine leukosis and human

leukeemia-lymphoma 1,2 or human cancer generally.sTwo other studies,4,5 however, have not revealed suchclustering. We report here a prospective study of canceramong individuals living on dairy farms where bovineleukosis had occurred and had been histologically confirmed.

In 1962-65, 130 such farms were identified in a 19-

county area in central Michigan.6 At the same time a mailcensus was made of the cattle population of dairy farms inthe area. Total mortality and cancer mortality from Jan. 1,

OBSERVED AND EXPECTED* MORTALITY ON MICHIGAN FARMS WITHAND WITHOUT BOVINE LEUKOSIS (JANUARY, 1961 TO JUNE, 1969)

* Based on age and sex distribution of the survey population.

1961 to June 30, 1969, in farm households in the leukosisseries was compared with those of households in the samecounty matched for herd size but with no reported casesof bovine leukosis. (Each leukosis farm was matched withtwo control farms.) The populations at risk and mortalitywere determined through mail questionaries to which 75%in the case series and 83% in the control series responded.Death certificates were obtained from the State health

1. Heller, H. Lancet, 1961, ii, 314.2. Wolska, A. ibid. 1968, i, 1155.3. Aleksandrowicz, I., Wolska, A. Pol. Tyk. Lek, 1968, 23, 1468.4. Lavorkovskii, L. I., Pinus, A. G., Orlova, L. D., Sushchenko, I. B.,

Zaitseva, M. V., Malanina, V. N., Launsleinis, E. la, Dzenis,V. A. Probl. Gemat. 1968, 13, 35. (Carcinogenesis Abstracts, 1969,7, 378.)

5. Ringertz, N. Bull. int. Acad. Path. 1967, 8, 30.6. Conner, G. H., La Belle, J. A., Langham, R. F., Crittenden, M.

J. natn. Cancer Inst. 1966, 36, 383.

368

departments for individuals reported to have died duringthe period under study.Among the 98 reporting farms with leukosis there were

4108 person-years at risk as compared with 7968 person-years at risk on the 212 reporting control farms. Thesurvey data were used to obtain expected mortality from allcauses, including cancer and leukaemia-Iymphoma, adjustedfor age and sex, for the case and control series (see accom-panying table). There were no statistically significantdifferences in observed-versus-expected values. In a

study of this magnitude there is a 95 °o probability ofdetecting a 2 4-fold or greater increase in human cancermortality associated with bovine leukosis. The data forhuman leukaEmia-lymphoma was too sparse to permitestimation of an upper limit on risk. However, the singledeath in this category did occur in the control rather thanthe leukosis series.

WILLIAM A. PRIESTERARTHUR OLEINICK.

Epidemiology Branch,National Cancer Institute,

Bethesda, Maryland 20014.

GABEL H. CONNER.

College of Veterinary Medicine,Michigan State University,

East Lansing, Michigan 48823.

CASE OF JUVENILE CHRONIC MYELOIDLEUKÆMIA

SIR,-I wish to report an atypical case of the rare

" juvenile form " of chronic myeloid leukaemia.A boy aged 2l/, years presented in December, 1968,

with arthritis which began in the left foot, spread after48 hours to the right, and next day involved the proximalinterphalangeal joints of the left hand. An erythematousnodular eruption on the soles and on the dorsum of theaffected hand accompanied the joint disturbance. Physicalexamination and laboratory investigations on admissionto hospital disclosed no abnormality except an occasionalmyelocyte in the circulating blood. There was littlemalaise, and after a few days’ observation he was dis-

charged, symptoms and signs having resolved.In mid-February he was readmitted with a florid

violaceous eruption on both feet, spontaneous bruising ofboth lower limbs, and an erythematous rash on the cheeks.He had had two arthritic episodes similar to the presentingillness, the second of which was accompanied by a vesicu-lating erythema on the arms and desquamation of thearthritic great toe. Investigations were essentially negativeapart from 200 metamyelocytes in a total white-blood-cellcount of 9500 per c.mm. At the end of May he wasreadmitted because of progressive but relatively mildmalaise. In the interim he had two further recurrencesof florid but nonspecific rashes, and also an episode ofbruising of the buttocks, abdominal pain, and melwhich resembled anaphylactoid purpura. Further haema-

tological investigations had revealed no abnormalities, butjust before admission he developed moderate hepato-splenomegaly with the erythematous facial rash, palatalpetechix, and widespread spontaneous bruising.The total leucocyte-count was now 10,200 per c.mm.,

with an abnormal differential of 66°n neutrophils, 16%lymphocytes, 12"u monocytes, and 6"u myelocytes; plateletswere reduced to 117,000 per c.mm. A marrow biopsyshowed granulocyte hyperplasia with no abnormal cells.No other investigations produced abnormal results.On the first day of this admission he had convulsions,

but these were later attributed to prodromal measles, forhe developed a characteristic morbilliform rash 3 dayslater and was discharged. By mid-June his lower-limb

arthralgia was such that he was unable to walk at all, andpainful purple nodules appeared intermittently on thesoles. The splenomegaly became minimal. He was givenprednisolone 20 mg. daily, with dramatic symptomatic

improvement which was maintained for 2 months. Thesteroid dose was reduced weekly and was down to 25 mg.daily in mid-August. There was then a recurrence ofmalaise and rashes, and investigations revealed a risingteucocyte-count of 23,200 per c.mm., with 19°o o meta-myelocytes and an occasional blast-cell in the peripheralblood. There was no response to prednisolone in theoriginal dosage.

10 months after his presentation he was admitted tohospital for the fourth and last time. He was by nowclearly a very ill child; in addition to flitting joint painsthere was spontaneous bruising, considerable facialerythema, and gross hepatosplenomegaly. There was noperipheral lymphadenopathy. The correct diagnosis wassuspected and confirmed when 43% of the haemoglobinwas found to be of fetal type (Hb F.). Bone-marrow washypercellular with granulocyte proliferation. Haemo-globin fell to 69 g. per 100 ml., and there was a pro-gressive leucocytosis with circulating blast-cells. Leuco-cyte-alkaline-phosphatase score was 8 per 100 cells.Despite blood-transfusions, increased amounts of predni-solone, and 6-mercaptopurine he deteriorated and died inearly October. Permission for necropsy was withheld.The clinical history was dominated by the joint and

skin complaints; whilst these may be expected in any typeof leukaemia, they produced a puzzling picture in theabsence of specific haematological abnormalities, and a

tentative diagnosis of allergic vasculitis was maintainedfor 7 months. Although the curious facial erythema is afeature of most descriptions of this condition, a case withpredominantly arthritic symptoms has not hitherto beenrecorded; the clinician faced with a similar problem inpractice would do well to recall this condition, and haveearly recourse to the simple procedure of fetal-hsemo-globin detection.

Whilst fetal-haemoglobin levels up to 10% may befound in any variety of leukaemia, levels from 40-70% arecharacteristic and virtually pathognomonic of the juvenileform of chronic myeloid disease. A progressive reductionin red-cell carbonic anhydrase toward the levels found invery early life has been recorded in this condition, andthe occurrence of two independent examples of reversiontoward the fetal state within the red-cell seems to sup-port the suggestion that this unique form of leukaemiais essentially a congenital disorder. So, perhaps, does its

apparent restriction to children under 5, and peak incidenceunder 3 years of age, in contrast to the later distributionin the unusual but more frequently reported cases of the" adult type

" of chronic myeloid leukaemia in childhood.It is unfortunate that in our case early blood-transfusionand unexpectedly sudden death prevented red-cell enzymestudies.The distinction between " adult " and "

juvenile "

types of chronic myeloid leukaemia 2 is further emphasisedby the absence from the latter of the Philadelphia chro-mosome 3 (was in this case), as well as the tendency forred-cell precursors to be found in the peripheral blood,and the lower total leucocyte and platelet counts at

presentation. These juvenile cases usually respond, if atall, to 6-mercaptopurine rather than to busulphan.The severe arthritic features of this case recall the

12-year-old described by Shuster et al.. whose haemotyticanaemia, associated with a fetal-haemoglobin level of 1910,developed into acute myeloid leukaemia characterised bythrombocytopaenia and arthropathy. Philadelphia-nega-tive chronic myeloid leukaemia in adults has been de-

1. Weatherall, D. J., Edwards, J. A., Donohoe, W. T. Br med. J.1968, i, 679.

2. Hardisty, R. M., Speed, D. E., Till, M. Br. J. Hœmat. 1964,

10, 551.3. Reisman, L. E., Trujillo, J. M. J. Pediat. 1963, 62, 710.4. Shuster, S., Jones, J. H., Kilpatrick, G. S. Br. med. J. 1960, ii,

1556.