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BREAST CANCER AND REPRODUCTION

SIR,-Lowe and MacMahon have presented data fromSouth Wales as part of an international collaborative studyfrom seven areas in different countries. Reports by Wein-berg and others earlier this century 2-4 suggest a significantfeature of breast cancer in younger age-groups-namely,that the disease shows higher incidence among ever-

married women than for single women. Lowe and Mac-Mahon seem to disregard this point.The main achievement of the authors is their evaluation

of the risk of breast cancer associated with age at first

pregnancy: women aged over 35 at first pregnancy were atmore than twice the risk of breast cancer than women under20 at first pregnancy. However, when they state that thedifference in risk between nulliparous and highly parouswomen was present whatever the age at which breast cancerwas diagnosed, they disregard one of their own results.Their table IV shows that, contrary to most other age-groups, ever-married women aged below 40 and para 1 havea relative risk of 1’43, while only one other group shows avalue over 1 (1.03).However small the numbers in this group in the South

Wales series, this finding is not without significance. Onmortality data Dorn 5 and Duffield and Jacobson 6 found ahigher risk for married women up to 34 years, and Logan 7for married women with children up to 35 years. On

morbidity data for metropolitan areas Dorn and Cutler 8found equal or even higher risk for married than for un-married women in the United States, and Clemmesen 9

reported a higher risk for married women up to age 40 inDenmark, as did Deelman 4 in Amsterdam in 1920.The higher risk of breast cancer for young married

women in comparison with single women at the same age,therefore. seems worth considering.

Danish Cancer Registry,Finsen Institute,Copenhagen 2100,

Denmark. JOHANNES CLEMMESEN.

LEVODOPA AND MIGRAINE

SIR,-A 48-year-old woman was referred to hospital in1962 with a history of migraine attacks since the age of 12.Crises were typical, monthly, and lasted 1 or 2 days. Asister and a cousin (daughter of an identical twin of thepatient’s mother) also had a history of migraine. Neuro-logical examination showed no abnormality, and electro-encephalography revealed a right occipital slow-wave dys-rhythmia. She was put on phenobarbitone and ergotaminetartrate. The intensity of pain was partially relieved byergotamine, but the frequency of crises was not influenced.

In 1967, she complained of tremor in left upper limb,and weakness in left lower limb. In 1968 Parkinson’sdisease was diagnosed and she was put on benzhexol andbenztropine with poor results. In January, 1970, she wasadmitted to a clinical trial with levodopa (L-dopa). At thattime she had a well-developed parkinsonian picture(akinesia and rigidity, practically no tremor). In themonths before the trial she had migraine attacks weeklyand sometimes even twice a week. All drugs were dis-continued. During the first week, on 1 g. levodopa per day,she had a typical migrainous attack. She had no more

migraine during the next 7 months, and the neurological

1. Lowe, C. R., MacMahon, B. Lancet, 1970, i, 153.2. Weinberg, W., Gastpar, K. Z. Krebsforsch. 1904, 2, 195.3. Weinberg, W. ibid. 1912, 11, 302.4. Deelman, H. T. ibid. 1920, 17, 164.5. Dorn, H. Hum. Biol. 1943, 15, 73.6. Duffield, T. J., Jacobson, P. H. J. nat. Cancer Inst. 1945, 6, 103.7. Logan, W. P. D. Lancet, 1953, ii, 1199.8. Dorn, H. F., Cutler, S. U.S. publ. Hlth Monogr. 1955, no. 29.9. Clemmesen, J. Acta path. microbiol. scand. 1965, suppl. no. 174.

recovery, on 2·5 g. levodopa per day, was rather good. In

August, when levodopa was replaced by a placebo, attacksreturned. The patient was not told that levodopa had beenwithdrawn and was surprised at the relapse.

This case, together with a similar one personally reportedto us by Dr. Melvin Yahr (unpublished), prompts us tosuggest that the role of levodopa in migraine warrantsfurther attention.

Department of Neurology,Lisbon Faculty of Medicine. J. LOBO ANTUNES.

Department of Neurology,Hospitais Civis de Lisboa. CARLOS MACEDO.

Department of Psychiatry,Lisbon Faculty of Medicine,Lisbon, Portugal. ANTÓNIO R. DAMÁSIO.

AUSTRALIA (HEPATITIS) ANTIGEN INSARCOIDOSIS

SIR,- In the past few years several reports have providedevidence for the association of Australia antigen (hepatitis-associated antigen) with viral hepatitis, and its increasedincidence in Down’s syndrome, acute and chronic lympho-cytic leukaemia, chronic renal disease, and lepromatousleprosy. 1-6 In lepromatous leprosy depression of delayed-type hypersensitivity is indicated by an inability to respondto tuberculin antigen and the failure of lymphocyte trans-formation in response to phytohæmagglutinin stimulation.It has been suggested that the presence of Australiaantigen in patients with lepromatous leprosy may berelated to an inadequate immune response and suscep-tibility to various illnesses, including lepromatous leprosy. 6

Sarcoidosis is another disorder in which the cardinalimmunological defect is depression of delayed-type hyper-sensitivity.7 As in patients with lepromatous leprosy, thosewith sarcoidosis have tuberculin anergy and poor lympho-cyte transformation in the presence of phytohæmagglutinin.7In order to explore further the relation of Australia antigento defective immune response, we have tested the sera from45 histologically proven cases of sarcoidosis for this antigen.The method used for detecting antigen was the immuno-diffusion technique as modified by Ashcavai et al. by whichthe test serum is concentrated tenfold by use of polyacryl-amide gel and antigen wells are overfilled. This methoddetects 0-3% antigenæmia in a normal population of theLos Angeles area and 80% antigenxmia in patients in theearly stage of serum hepatitis. 8

In this study we failed to find any evidence of the

presence of Australia antigen in patients with histologicallyproven sarcoidosis and depression of delayed-type hyper-sensitivity.

Pulmonary Disease Service,Department of Medicine andDepartment of Pathology,

University of Southern California,School of Medicine,2025 Zonal Avenue,

Los Angeles, California 90033.

OM P. SHARMAR. L. PETERSMARY ASHCAVAIOSCAR J. BALCHUM.

1. Blumberg, B. S., Alter, H. J., Visnich, S. J. Am. med. Ass. 1965,191, 541.

2. Blumberg, B. S., Gerstley, B. J. S., Huntingford, D. A., London,W. T., Sutnick, A. I. Ann intern. Med. 1967, 66, 924.

3. Blumberg, B. S., Sutnick, A. I., London, W. T. Bull N.Y. Acad.Med. 1968, 44, 1566.

4. London, W. T., Sutnick, A. I., Ziegenfuss, J., Blumberg, B. S. Clin.Res. 1968, 16, 567.

5. London, W. T., DiFiglia, M., Sutnick, A. I., Blumberg, B. S.New Engl. J. Med. 1969, 281, 571.

6. Blumberg, B. S., Melantin, L., Lechat, M., Guinto, R. S. Lancet,1967, ii, 173.

7. Sharma, O. P. Thorax, 1969, 24, 510.8. Ashcavai, M., Peters, R. L. Am. J. clin. Path. (in the press).