John Wright, 1983. Restless leg syndrome in pregnancy. We agree with Mr Jonathan D S Goodman and colleagues (29 October, p 1101), that restless legs.
Such a prospective study is currently being undertaken by a postgraduate clinical psychologist using standardised psychological techniques. Adjuvant systemic treatment benefits a small number of women. We prefer to use it only in those who will be likely to benefit, and a prospective trial in patients with an extremely poor prognosis, as determined by multiple receptor analysis, is also currently in progress. Ductal carcinoma in situ does pose a considerable problem of management: a quarter of cases subsequently develop into invasive cancer in the ipsilateral breast after excisional biopsy. In just over half of cases (55%) the disease is multicentric. Occult invasion of the breast tissue and axillary nodes occur. Definitive treatment is, therefore, required. This has been given by mastectomy, wide local excision, or wide local excision followed by radiotherapy. In a series reported by Lippman et al the only treatment associated with no subsequent invasion was mastectomy.' Further evidence of the unsuitability of radiotherapy for premalignant lesions is given by Wang.2 In premalignant lesions of the vocal cords the results of radiotherapy are not as good as those for TINOMO invasive carcinomas. This may be due either to radioinsensitivity of the lesion or perhaps more probably to a second primary arising in an area of field change. In the light of the above, albeit limited, evidence and the difficulties we believe are associated with a randomised trial of two very different methods of treatment our advice after discussion of the above with patients is that mastectomy seems to offer a more satisfactory result than other treatment. In the future we may well alter our views if ongoing studies produce the evidence that the above advice is not satisfactory. We are delighted that one of the main messages of the paper -that the option to have a mastectomy must remain available to women-has the support of Professor Baum and his colleagues. P J D K DAWES ALISON HART R C WILSON Newcastle General Hospital, Newcastle upon Tyne NE4 6BE
1 Swain SM, Lippman ME. In: Lippman ME, Lichter AS, Danforth DN, eds. Diagnosis and management of breast cancer. Philadelphia: Saunders, 1988. 2 Wang CC. Radiation therapv for head and neck neoplasms. Boston: John Wright, 1983.
missed as an unimportant complaint as some patients will need drug treatment, and carbamazepine should at least be considered. PETER McPARLAND
J MALCOLM PEARCE Department of Obstetrics and Gynaecology, St George's Hospital Medical School, London SW17 ORE 1 Ekbom KA. Restless legs. Acta Med Scand 1945;158(suppl): 1-123. 2 Telstad W, Sorensen 0, Larsen S, Lillewold P, Stenrud P, Nyberg-Hansen R. Treatment of the restless legs syndrome with carbamazepine: a double blind study. BrMedJ 1984;288: 444-6. 3 Handwerker JV, Palmer RF. Clonidine in the treatment of restless legs syndrome. N Engli Med 1985;313: 1228-9.
Brainstorming the postviral fatigue syndrome Jane Dawson's report of the recent Ciba Foundation meeting referred to muscle fatigue, widely felt to be a hallmark of the condition (5 November, p 1151). Muscle metabolism is profoundly deranged in the syndrome of chronic habitual hyperventilation via four mechanisms: (a) reduction in tissue alkali buffer reserves, (b) increased sodium and water retention, (c) depleted intracellular potassium and magnesium, and (d) increased intracellular ionised calcium (promoting muscle cramps). It surprises us greatly that people discussing myalgic encephalomyelitis-postviral fatigue syndrome do not consider the above, which has been well recognised since Sir Thomas Lewis's studies in 1916.' As we have reported,2 all the patients (a total so far of 68) previously diagnosed by physicians as suffering from myalgic encephalomyelitis or postviral fatigue and then referred to us have turned out to have effort syndrome (exhaustion and hyperventilation).2 When appropriately managed by rehabilitation under the aegis of occupational therapists-the muscle symptoms have disappeared within three weeks with full restoration of health very soon afterwards. S D ROSEN JENNY KING P G F NIXON
Cardiac Department, Charing Cross Hospital, London W6 8RF
that neopterin concentrations rose earlier during the course of HIV infection.' Neopterin and 12 microglobulin may share some characteristics. Human macrophages release neopterin and, to a lesser extent, 12 microglobulin on stimulation with y interferon.4 All other nucleated cells, however, may shed significant amounts of 12 microglobulin but not neopterin when being activated or while proliferating-for example, B lymphocytes express a high density of major histocompatibility complex antigens on their surface, and increased spontaneous B cell activation was shown in patients with HIV infection.5 Thus 132 microglobulin probably also reflects an increased turnover of the B cell compartment. Simple laboratory tests are particularly important for monitoring patients during trials of treatment. Single variables allow close follow up of patients. One can measure 12 microglobulin, HIV antigen, or neopterin concentrations in extremely small sample volumes, which renders these tests better than, for example, CD4 lymphocyte counting. Moreover, in terms of infectivity serum estimation has considerable advantages over whole blood estimation. Neopterin concentrations in urine are also representative. Urine sampling is more convenient to patients, and the risk of getting infected by HIV or other pathogens via urine samples is almost negligible. DIETMAR FUCHS MANFRED P DIERICH HELMUT WACHTER Institutes of Medical Chemistry and Biochemistry and of Hygiene, University of Innsbruck, and Ludwig Boltzmann Institute for AIDS-Research, 6020 Innsbruck, Austria 1 Fuchs D, Banekovich M, Hausen A, et al. Neopterin estimation compared with the ratio of T-cell subpopulations in persons infected with human immunodeficiency virus 1. Clin Chem (in press). 2 Bogner JR, Matuschke A, Heinrich B, Eberle E, Goebel FD. Serum neopterin levels as predictor of AIDS. Klin Wochenschr 1988;66: 1015-8. 3 Kofler H, Fuchs D, Hintner H, Wachter H, Fritsch P. Urinary neopterin: an early marker of HIV infection. Eur J Clin Microbiol 1987;6:698-9. 4 Nachbaur K, Troppmair J, Bieling P, Kotlan B, Konig P, Huber Ch. Cytokines in the control of P2-microglobulin release. In sivo studies on various haemopoietic cells. Immunobiology
1988;177:55-65. 5 Amadori A, De Rossi A, Faulkner-Valle GP, Chieco-Bianchi L.
Spontaneous production of virus-specific antibody by lymphocytes from HIV-infected subjects. Clin Immunol Immunopathol (in press).
I Lewis T. Breathlessness in soldiers suffering from irritable heart.
Restless leg syndrome in pregnancy We agree with Mr Jonathan D S Goodman and colleagues (29 October, p 1101), that restless legs syndrome in pregnancy is common-indeed, this has been shown before'-but because it is poorly understood it is often dismissed as a trivial complaint. Simple reassurance on the benign nature of the disease, in addition to massage, flexion-extension movements, and walking, will control symptoms in most patients. Occasionally, however, symptoms may be severe and lead to anxiety, sleep disruption, and depression. We have seen two such cases recently which did not respond to simple measures. Many therapeutic approaches have been advocated, but only two double blind studies have been published, both in non-pregnant people; both carbamazepine2 and clonidine3 were significantly more effective than placebo. Both of our patients had been prescribed diazepam, temazepam, and phenobarbitone with no benefit. Within 48 hours of starting carbamazepine, however, both patients had dramatic relief of their symptoms. Treatment was continued until shortly after delivery. Neither patient suffered a relapse in the puerperium. Restless legs in pregnancy should not be dis-
BMJ VOLUME 297
10 DECEMBER 1988
BrMedj 1916;i:517-9. 2 Rosen SD, King JC, Nixon PGF. Magnetic resonance muscle studies.JR Soc Med 1988;81:676. 3 King JC. Hyperventilation-a therapist's point of view: discussion paper. J R Soc Med 1988;81:532-5.
Predicting AIDS Dr A R Moss reviewed four candidate predictors of the onset of AIDS in patients infected with human immunodeficiency virus (HIV). We would like to add to his discussion. When comparing homosexuals with and without established HIV infection urinary neopterin excretion is of higher sensitivity and specificity than T cell subset analyses, including ratios. ' Independent studies comparing serum neopterin concentrations with CD4 counts, CD8 counts, lymphocytes, y globulin, platelets, haemoglobin, and erythrocyte sedimentation rate2 and urinary neopterin excretion with CD4 counts, CD8 counts, and their ratio in seropositive homosexuals (A Kraemer et al and D Fuchs et al, unpublished) show neopterin to be independently the best predictor of AIDS onset. So far no study has directly compared the predictive value of neopterin concentrations with P2 microglobulin concentrations, but we found
Hope for broken hips? We were surprised by the optimistic conclusions drawn in This Week in the BMJ about the management of proximal femoral fractures (29 October). Two randomised trials were published in the same issue, but only the "positive" results of Dr David C Kennie and coauthors (p 1083) were mentioned. We believe that these positive results were caused by unintentional bias and not by a true difference. This first study included two groups each of 54 patients and reported a 64% improvement (41 v 25) in physical function in the group transferred to the designated rehabilitation ward. Some patients were not assessed (7 v 10). Unfortunately there was a difference between the two groups in age (median 79 v 84) and mental state at entry to the study. The subgroup analyses did not give the numbers in each group, but it was clear that the mentally intact and mildly impaired had a better functional outcome than the moderately or severely impaired. The treatment group started with 42 intact or mildly impaired people, whereas the control group started with 29. We suspect that these differences in age and mental state at entry to the study accounted for the apparent improvement in function, inpatient stay, and discharges home.
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