ANALGESIC EFFECTS OF ORAL FLECAINIDE

420 RELAPSE AND DISEASE-FREE SURVIVAL

the addition of desmopressin (’DDAVP’, Ferring) to the regimen resulted in an almost normal bleeding time. A 36-year-old woman with medullary cystic disease treated by haemodialysis since 1975 complained of nosebleeds and subcutaneous haematomas. Kidney transplantation in 1977 and de-transplantation in 1982 were by severe blood losses and large deep haematomas, and the patient needed 10 packed red-cell transfusions and 15 platelet concentrates. The only abnormal haemostatic test was increased bleeding time ("Simplate", Organon Technika). Von Willebrand factor, platelet aggregation by ADP and collagen, thrombin and ristocetin times, and prothrombin and partial prothromboplastin times were normal. Although bleeding time remained high (table), the nosebleeds were occasionally controlled,1,2 either by desmopressin infusion (0-3 3 Ilg/kg) or by oestrogen. The steroid could not be used more than once because of menorrhagia two weeks after the injection. The patient has been receiving rHu-EPO since 1986 (haemoglobin [Hb] 8-4 g/dl), with a weekly dose of 192 U/kg3 (Hb in December, 1987, 11-5 g/dl), with incomplete improvement of bleeding time and nosebleeds. The addition of desmopressin then made bleeding time nearly normal. Under this combined regimen subtotal parathyroidectomy was done without any abnormal blood loss.

complicated

in all transplantation series. In our prospective multicentre study all patients will have transplants within 3 months of diagnosis to avoid

this bias. Stem cell dose (CFU-GM) is important too.8,9 Our recent experience with patients who had low levels of PBSC very early in remission is that sufficient stem cells can be collected after consolidation with 2 days of daunorubicin 60 mg/m2 and 5 days of intravenous cytarabine 100 mg/m2 12-hourly and oral thioguanine 100 mg/m2 12-hourly. In two such patients four aphereses yielded 84 x 104 and 107 x 104 CFU-GM/kg body weight. While our intention remains to use cells collected during the recovery after induction chemotherapy-because of the simplicity of this approach and its ability to shorten the total treatment phase-the feasibility of post-consolidation PBSC collection will allow the technique to be used in more patients. The post-consolidation stem cell collections may also have lower leukaemic contamination, as suggested by Laporte et al. We agree that the number ofleukaphereses done should be as few as possible. With the assistance of the Baxter Centre for Medical Reseach, we hope to refme the collection technique to make it possible to collect an adequate stem cell dose with two or three

aphereses. C. A. JUTTNER Division of Haematology, Institute of Medical

and Veterinary Science, Adelaide, South Australia 5000

P. G. DYSON L. B. TO J. Q. K. HO D. N. HAYLOCK M. M. ROBERTS

AJ, Hamblin TJ, Oscier DG. Circulating stem cell autograft. Bone Marrow Transpl 1986; 1: 103-10. 2. Reiffers J, Bernard Ph, Marit G, et al. Collection of blood-derived haemopoietic stem cells and applications for autologous transplantation. Bone Marrow Transpl 1986;1 (suppl 1): 371-72. 3. Tilly H, Bastit D, Lucet JC, Esperou H, Monconduit M, Piguet H. Haemopoietic reconstitution after autologous peripheral blood stem cell transplantation m acute leukaemia. Lancet 1986; ii. 154. 4. Castaigne S, Calvo F, Douay L, et al. Successful haematopoietic reconstitution using autologous peripheral blood mononucleated cells in a patient with acute promyelocytic leukaemia. Br J Haematol 1986; 63: 209-11. 5. Santos GW, Tutschka PJ, Brookmeyer R, et al Marrow transplantation for acute non-lymphocytic leukaemia after treatment with busulfan and cyclophosphamide. N Engl J Med 1983; 22: 1347-53. 6. Yeager AM, Kaizer H, Santos GW, et al. Autologous bone marrow transplantation in patients with acute non-lymphocytic leukaemia, using ex vivo marrow treatment with 4-hydroperoxycyclophosphamide. N Engl J Med 1986; 315: 141-47. 7. Tutschka PJ, Copelan EA. Bone marrow transplantation following a new busulfan and cyclophosphamide regimen-results after 3 years of observation. Exp Hematol 1987; 15: 601 (abstr). 8. To LB, Dyson PG, Juttner CA. Cell-dose effect in circulating stem cell autografting. 1. Bell

Lancet 1986; i 404-05 9. To LB, Juttner CA

for AML?

Peripheral blood stem cell autografting: a new therapeutic option Br J Haematol 1987, 66: 285-88.

ADDITION OF DESMOPRESSIN TO RECOMBINANT HUMAN ERYTHROPOIETIN IN TREATMENT OF HAEMOSTATIC DEFECT OF URAEMIA

SIR,-Dr Moia and colleagues report (Nov 28,

p

1227)

improvement in the haemostatic defect plus correction of anaemia in uraemic patients treated with recombinant human erythropoietin (rHu-EPO, Cilag-Ortho-Amgen). Their patient 7 only partly responded. We have seen a similar case. In our patient on rHu-EPO treatment we noticed incomplete correction of bleeding time, but

December,

EFFECTS OF DRUGS AND rHu-EPO ON BLEEDING TIME

(MIN)

The improvement of bleeding time during treatment with rHu-EPO might be related either to the correction of anaemia and/or to the qualitative improvement of red cells. A possible effect of rHu-EPO on megakaryocytes has also been reported.’ However, both Moia and colleagues’ experience and our case indicate that the correction is incomplete in a few patients. Our observation suggests that supplementary administration of demopressin may achieve normal bleeding time in these patients. r’...... T.

"-’r>....-.-,",""-’

CH JACQUOT

AURA Haemodialysis Centre, 75015 Paris, France; and Hôpital Broussais, Paris

J. P. MASSELOT J. M. BERTHELOT

CILAG Laboratories

F. PETERLONGO J. P. CASTAIGNE

PM, Remuzzi G, Pusineri F, et al. Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia. N Engl J Med 1983; 308: 8-12. 2. Liu YK, Kosfeld RE, Marcum SG. Treatment of uraemic bleeding with conjugated oestrogen. Lancet 1984; ii: 887-90. 3. Jacquot Ch, Ferragu-Haguet M, Lefebvre A, Berthelot J-M, Peterlongo F, Castaigne JP. Recombinant erythropoietin and blood pressure. Lancet 1987; ii: 1083. 4. Ishibashi T, Koziol JA, Burstein SA. Human recombinant erythropoietin promotes differentiation of murine megakaryocytes in vitro. J Clin Invest 1987; 79: 286-89. 1. Mannucci

ANALGESIC EFFECTS OF ORAL FLECAINIDE

SIR,-Dr Dejgard and colleagues (Jan 2/9, p 9) show that mexilitine was superior to placebo in relieving the pain of chronic diabetic neuropathy. This finding supports the potential role of membrane-stabilising agents in the management of pain associated with damage to the nervous system. There is another important clinical application of these findings, namely the control of pain associated with malignant infiltration of nerves. We have treated 17 patients with oral flecainide, 100 mg twice daily. These patients have had pain in one or more dermatomes, associated with sensory changes in the painful area. The patients have had malignant infiltration of brachial plexus (6), lumbar plexus (4), sacral plexus (2), or individual nerve roots (2); 1 patient had pain associated with paraneoplastic peripheral neuropathy. 2 patients had coeliac plexus involvement. The patients had either been unsuitable for or had failed nerve blocks; some had refused to have nerve blocks. 15 patients were already receiving morphine and still had severe pain. 6 patients had complete analgesia, lasting until death 1-26 weeks later. 4 patients are alive and pain-free after up to 8 months on

421 5 patients had some relief, achieving mild levels of pain. 2 patients had no response after 10 days’ treatment. 2 patient who were receiving morphine were able to reduce the dose of opioid. treatment.

Support Care Team, St Bartholomew’s Hospital London EC1A 7BE, and Department of Clinical Pharmacology, St Bartholomew’s Hospital

ROBERT DUNLOP ROBERT J. DAVIES JOSEPHINE HOCKLEY PAUL TURNER

RESUMPTION OF HIV ANTIGEN PRODUCTION DURING CONTINUOUS ZIDOVUDINE TREATMENT

SiR,—Zidovudine is a potent inhibitor of human immunodeficiency virus (HIV) replication in vitro,l and treatment of patients with AIDS or AIDS-related complex with zidovudine has resulted in a fall in HIV antigen levels in serum.2.3 An in-vitro study has lately demonstrated resumption of virus production in HIVinfected T lymphocytes in the continued presence of initially highly inhibitory doses of zidovudine.4 As indicated by HIV antigen levels in two patients we have treated (figure), a similar resumption of antigen production may occur in vivo after prolonged zidovudine treatment. Both were HIV-Ag seropositive (Abbott enzyme immunoassay) AIDS patients and were treated with 200 mg zidovudine 4-hourly. Serum HIV-Ag concentrations fell rapidly

HIV TESTING ON ALL PREGNANT WOMEN

SIR,-We are surprised by the reasons for not pursuing antenatal testing for HIV antibody, given in the report from the Royal College of Obstetricians and Gynaecologists referred to by Mr Hudson and colleagues (Jan 30, p239). This shows a serious misunderstanding of the procedures used by the regional blood transfusion services and by the Public Health Laboratory Service. Screening tests do give occasional positive results which cannot be confirmed so a patient should never be alerted to a "provisionally positive result". Indeed no intimation even of suspicion should be given without true positivity being established by a reference laboratory using several different tests. The reporting of falsepositive results therefore is not a real problem. We are also concerned about the perceived difficulties in maintaining confidentiality. Complete confidentiality has been exercised for many years with respect to both syphilis and hepatitis B where they are detected by routine antenatal screening. It should therefore be no more difficult to assure confidentiality of HIV results. We do agree that in an ideal clinical setting, pregnant women should be informed of all tests being asked of them, with an option to decline. Obstetric practice already involves counselling for many pregnancy-related problems: rubella neural tube defects, Down’s syndrome, and other fetal malformations, and haemolytic disease of the newborn, to name but a few. The implication of testing for syphilis, hepatitis B, and now HIV is that these disorders will inevitably be added to this list. Regional Blood Transfusion Centre, John Radcliffe Hospital, C. C. ENTWISTLE Oxford OX3 9DU PHLS Laboratory, Oxford J. B. SELKON

ADDICTED MOTHERS AND PRETERM BABIES: A DISASTROUS OUTCOME discussion of drug and alcohol addiction during SIR,-The pregnancy has focused on fetal growth and development;1-3 follow-up studies are scarce. The baby born to an addicted mother faces an uncertain futureespecially when the baby is bom preterm. We took the opportunity offered by the Project on Preterm and Small-for-gestational-age Infants in The Netherlands 1983 (POPS),’,6 of a virtually complete cohort of liveborn infants with gestational age under 32 weeks. and/or birthweight below 1500 g, to evaluate the outcome of these problem pregnancies (table). There were 14 very preterm and/or very low birth weight (VLBW) babies born to drug and/or alcohol addicted mothers. 5 died during the first 4 weeks of life. 2 others died after discharge Serum HIV antigen levels in

two

AIDS patients

on

home; in 1, bronchopulmonary dysplasia partly explained the death, but both deaths were sudden and unexpected. Of the 7

zidovudine.

below the cut-off level for the assay. However, despite continuation of the same drug regimen and patient compliance with the therapy, HIV-Ag serum levels subsequently rose in both patients. Neither had diarrhoea or clinical evidence of malabsorption. Further investigations are needed to establish the frequency and clinical relevance of this resumption of viral production in vivo during zidovudine treatment and the mechanisms involved. PETER REISS Departments of Internal Medicine and Virology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, Netherlands

1

JOEP M. A. LANGE CHARLES A. BOUCHER SVEN A. DANNER JAAP GOUDSMIT

Mitsuya H, Weinhold KJ, Furman PA, et al. 3’-azido-3’-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc Natl Acad Sci USA 1985; 82: 7096-100. RE, Allain J-P, Leuther M, Volberding PA. Significant changes in HIV antigen level in the serum of patients treated with azidothymidine. N Engl J Med

2 Chaisson

1986; 315: 1610-11. 3 Fischl MA, Richmann DD, Gneco MH, et al The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS related complex. N Engl J Med 1987; 317: 185-91 MS, Bnan EL, Pagano JS. Resumption of virus production immunodeficiency virus infection of T lymphocytes in the azidothymidine. J Virol 1987; 61: 3769.

4 Smith

after human presence

of

survivors 3 have a major handicap at age 2 years, 1 due to fetal alcohol syndrome, 1 to cerebral palsy probably of perinatal origin, and 1 mainly due to a severely deficient parent-infant interaction. The fourth child is suspected of non-accidental injury and has serious psychosocial problems. The remaining 3 children are normal as far as is known: 1 has sickle cell trait, 1 did not attend follow-up visits but was normal at the child health clinic, 1 was normal at the age of 1 year and moved abroad. These last 3 children were all bom to mothers who used soft drugs only (eg, marijuana). In only 1 case were the social services involved; no child has been in a foster home or has otherwise been taken out of the direct care of the

parent(s). We conclude that, in contrast to the generally. favourable prognosis for VLBW infants, the outlook for VLBW babies born to OUTCOME IN 14 VERY LOW BIRTHWEIGHT INFANTS BORN TO MOTHERS ADDICTED TO HARD OR SOFT DRUGS OR ALCOHOL