1346
have been alarmed by the development of tumours at an early age in 2 of these 4 children. Both children had humoral and cellular immunodeficiency. The first child developed B-cell non-Hodgkin lymphoma with widespread abdominal disease and involvement of the lung, bones, and one kidney at the age of 5 - 5 years after 5 months of rhGH. Remission was obtained with standard-dose induction chemotherapy, but the child died due to massive gastrointestinal bleeding and overwhelming septicaemia. The second child developed a stem-cell leukaemia with chromosomal abnormalities suggestive of underlying myelodysplasia at the age of 13 years, after 44 months on rhGH. A modified, reduced-dose myeloid leukaemia induction protocol was given. The child went into partial remission and is now receiving low-dose cytosine arabinoside. rhGH has been withdrawn in all patients with Bloom’s syndrome. Several reports now point to a relation between development of leukaemia in children and treatment with rhGH.sAlthough no direct proof exists, our observations suggest that, at least in children with Bloom’s syndrome, treatment with rhGH may lead to we
neoplastic change. PENELOPE R. BROCK FRANCIS DE ZEGHER Department of Paediatrics, University Hospital Gasthuisberg, MARIA CASTEELS-VAN DAELE 3000 Leuven, Belgium M. VANDERSCHUEREN-LODEWEYCKX 1. Bloom D.
Congenital telangiectatic erythema resembling lupus erythematosus
in
dwarfs. Am J Dis Child 1954; 88: 754-58. 2. Bloom D. The syndrome of congenital telangiectatic erythema and stunted
growth. J Pediatr 1966; 68: 103-13. 3. German J, Passarge E. Bloom’s syndrome: XII. Report from the registry for 1987. Clin Genet 1989; 35: 57-69. 4. Van Kerkhove CW, Ceuppens JL, Vanderschueren-Lodeweyckx M, Eggermont E, Vertessen S, Stevens EAM. Bloom’s syndrome; clinical features and immunologic abnormalities of four patients. Am J Dis Child 1988; 142: 1089-93. 5. Stahnke N, Zeisel HJ. Growth hormone therapy and leukemia. Eur J Pediatr 1989; 148: 591-96.
HHV-6 reactivation in chronic
fatigue
syndrome SiR,—Chronic fatigue syndrome (CFS) is a well-recognised syndrome of chronic illness typically beginning suddenly after an acute, apparently infectious illness (often influenza-like), lasting 6 months or longer. Patients experience debilitating fatigue, lowgrade fevers, muscle and joint pains, adenopathy, difficulties with concentration, paraesthesiae, photophobia, reactive mood disorders, and other symptoms.1,2 A variety of immunological and other laboratory abnormalities have been described.3 Antibody levels to human herpesvirus-6 (HHV-6), a lymphotropic and gliotropic ViruS,4,5 are raised in patients with CFS. We have looked for HHV-6 reactivation in patients who met the Centers for Disease control
definition for CFS.1 Peripheral blood mononuclear cells from seven CFS patients and two healthy donors were cultured in vitro. The cells were maintained in ’RPMI-1640’ containing fetal calf serum for the first 48 h of culture.4,5 Unusual medium-to-large refractile cells similar to those seen in HHV-6 infected cultures4 were observed within 72 h in cultures of three of the seven patients. At 10 days, the cultures HHV-6 positive cells by indirect contained 8-30% immunofluorescence assays, with monoclonal antibodies directed to HHV-6 strain GS7 (table). DNAs prepared from the 10-day cultures from these patients were highly positive by Southern blot analysis with HHV-6 specific probe ZVH14:8 strong signals were seen with autoradiographic exposure times of less than 10 min (figure). Each lane contained 15 ug of restriction-enzyme-digested DNA. The amount of viral specific DNA was nearly equal in all the DNAs, as displayed in typical BglII and EcoRI banding patterns.5 Three patients whose peripheral blood mononuclear cells contained HHV-6 antigen positive cells were very lethargic and had severe cerebral dysfunction, exemplified by cognitive or memory difficulties. They had mild-to-severe anterior cervical adenopathy. Patient 1 had severe submandibular adenopathy and mild bilateral axillary adenopathy, and patient 2 had severe posterior cervical adenopathy and moderate axillary adenopathy. Patient 1 had case
Detection of HHV-6 DNA in DNA from 10-day cultures of peripheral blood lymphocytes of CFS patients Lane numbers correspond to patient. Restriction enzymes were Bglll (a) and EcoRl (b). Sizes of EcoRl fragments indicated in kilobase pairs Probe is ZVHL 4.1
antibody to Epstein-Barr virus capsid antigen at a titre of 5000, and cytomegalovirus and varicella zoster virus antibody titres of 20 and 64, respectively. She was seronegative (titre < 10) to Epstein-Barr nuclear antigen, suggesting acute EBV infection; however, isolation of EBV from throat washings was not attempted. (Titres to the above three viruses on the other patients were not determined.) Patient 2 had an increased CD4/CD8 ratio and IgG subclass deficiency at the time peripheral blood lymphocyte cultures were set up. IgG titres to HHV-6 were increased at 320-640 in all except patient 5. The two healthy control titres were 80 and 160, within the range for the normal healthy populationNo HHV-6 antigen expressing cells were detected with any of the monoclonal antibodies in the four other patients or the controls (table). The facile propagation of HHV-6 from CFS patients reported here is in contrast to negative results obtained with normal healthy donors4 even though HHV-6 has been isolated from the saliva of PRESENCE OF HHV-6ANTIGEN EXPRESSING CELLS IN SHORT-TERM CULTURES OF LYMPHOCYTES FROM CFS PATIENTS AND IgG ANTIBODY TITRES TO HHV-6 LATE CAPSID ANTIGENS*
*Penpheral blood mononuclear cellcultures were monitored for viralantigens for at least 15 days post infection. tMonoclonal antibodies used were detected agamst HHV-6 strain GS, and included 9A5D12 (p42), 7A2 (gp105), and 12B32G4 (p135)’7 < 1 % - none detected
1347
healthy donors.9 Thus, HHV-6 reactivation in these CFS patients is indicated, suggesting that HHV-6 may be contributing in the
pathogenesis of CFS. Short-term culture assays, as done here, may prove to be a reliable test for reactivation of HHV-6. Any symptomatic involvement of HHV-6 in CFS should be evaluable with the development of viral inactivation or intervention therapy. Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda
S. F. JOSEPHS*
Department of Microbiology, University of Nevada, Reno
B. HENRY
Department of Microbiology and Immunology, University of Kansas Medical School
N. BALACHANDRAN
Department of Neoplastic Disease, Hahnemann University, Philadelphia
D. STRAYER
Incline Village
D. PETERSON
Flecainide may have a useful role in the management of resistant
neuralgic pain in advanced malignant disease. Increasing the dose from 100 to 200 mg twice daily may increase the likelihood of achieving a good and sustained response.
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892, USA
CLAIRE SINNOTT
Department of Palliative Medicine, St Thomas’ Hospital, London SE1 7EH, UK, and Royal Marsden Hospital, London SW3 1.
Division of General Medicine, Brigham and Women’s Hospital, Harvard University School of Medicine, Boston
POLLY EDMONDS IAN CROPLEY GEOFFREY HANKS
Dunlop R, Davies RJ, Hockley J, Turner P. Analgesic effects of oral flecainide. Lancet
1988; i: 420. 2. Cardiac arrhythmia suppression trial (CAST) investigators. Preliminary report: effect of encamide and flecainide on mortality in a randomised trial of arrhythmia suppression after myocardial infarction. N Engl J Med 1989; 321: 406-12.
SjR,—Following our open study A. L. KOMAROFF
D. V. ABLASHI
*Present address Universal Biotechnology Inc, Rockville, Maryland 1. Holmes GP, Kaplan JE, Gantz NM, et al. Chronic fatigue syndrome: a working case definition. Ann Intern Med 1988; 108: 387-89. 2. Komaroff AL. Chronic fatigue syndromes: relationship to viral infections. J Virol Methods 1988; 21: 1-18. 3. Buchwald D, Komaroff AL. Review of laboratory findings for patients with chronic fatigue syndrome. Rev Infect Dis 1991; 13: S12-S18. 4 Salahuddm SZ, Ablashi DV, Markham PD, et al. Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science 1986; 234: 596-601. 5. Ablashi DV, Lusso P, Hung C-L, et al. Utilization of human hemapoeitic cell lines for the propagation and characterization of HBLV (human herpesvirus-6). Int J Cancer 1988; 42: 787-91. 6. Ablashi DV, Zompetta C, Lease C, et al. Human herpesvirus-6 (HHV-6) in chronic fatigue syndrome (CFS). In: Rozee KR, ed. Proceedings of the Chronic Fatigue Workshop (Toronto, 1989). Can Dis Wkly Rep 1991; 17 (suppl): 33-37. 7. Balachandran N, Amelse RE, Zhou WW, et al. Identification of proteins specific for human herpesvirus-6 infected human T cells. J Virol 1989; 63: 2835-40. 8 Josephs SF, Salahuddin SZ, Ablashi DV, et al. Genomic analysis of the human B-lymphotrophic virus (HBLV). Science 1986; 234: 601-03. 9. Levy JA, Ferro F, Greenspan D, Lennett ET. Frequent isolation of HHV-6 from saliva and the seroprevalence to the virus in the population. Lancet 1990; 335: 1047-50.
Flecainide in
following a study in myocardial infarction.2 However, this is a very different population and none of our patients have had any difficulties. 2 had ischaemic heart disease (of whom 1 experienced the side-effects noted above).
cancer nerve
pain
SIR,-Neuropathic pain associated with advanced malignant disease is often very difficult to manage. In a preliminary study1 flecainide showed promise, and following this report we used the drug in 21 patients (8 males and 13 females; aged 17-75 years [median 55]). In most cases flecainide was second-line therapy when anticonvulsant therapy had failed due to inadequate response (8) or unacceptable drowsiness (6). All patients were also on opioids. Flecainide was started at a dose of 100 mg twice daily. 9 patients responded well, this effect being sustained for 1-14 weeks (table). Only 1 patient had side-effects (confusion and nocturnal hallucinations) on flecainide therapy, which resolved when the drug was discontinued. Antiarrhythmic drugs can be proarrhythmic in some circumstances and concern has been voiced about flecainide
flecainide in
with
of the
analgesic effect of oral pain1 we embarked on a
patients double-blind, placebo-controlled trial. Patients cancer
nerve
were
invited
to
participate if they had cancer-related nerve pain that had not been treated with radiography or chemotherapy within the previous month and which had not responded to conventional analgesia. We were aware of the proarrhythmic potential of flecainide and patients were excluded if they had evidence of heart disease on the basis of history, physical examination, ECG, chest X-ray, and, if necessary, echocardiography or gated-blood-pool scintigraphy. The trial received ethical committee approval. Results from the CAST study were released shortly after our trial began.2 This study showed an increased incidence of sudden death in patients with symptom-free ventricular arrhythmias treated with flecainide after myocardial infarction. In view of the advice to discontinue the flecainide, we felt that a preliminary review of our results was appropriate. The 2 patients who received flecainide 100 mg 12-hourly both experienced complete relief of pain. 4 patients had received placebo; 1 patient had experienced some relief while others had not and required rescue analgesia. After further consideration of the CAST study our ethical committee permitted the trial to continue. We were then disappointed to learn that the supply of flecainide had been discontinued by the pharmaceutical company. Others (see above letter) have confirmed our initial observations about the efficacy of flecainide and we believe strongly that it is important to complete a controlled trial. A wide variety of medications have been recommended for cancer-related nerve pain but few have been subjected to rigorous trial.
South Auckland Hospice, Auckland, New Zealand
Department of Palliative Medicine, St Bartholomew’s Hospital, London EC1
Department of Clinical Pharmacology, St Bartholomew’s Hospital Medical College, London EC1A 7BE, UK
ROBERT J. DUNLOP
JOSEPHINE M. HOCKLEY TERESA TATE
PAUL TURNER
Dunlop R, Davies RJ, Hockley J, Turner P. Analgesic effects of oral flecainide. Lancet 1988; i: 420. 2. Cardiac arrhythmia suppression trial (CAST) investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomised trial of arrhythmia 1989; 321: 406-12. J suppression after myocardial infarction N Engl Med 1.
RESPONSE TO FLECAINIDEIN 9 PATIENTS
Treatment of childhood fevers SIR,-Dr Kramer and colleagues’ (March 9, p 591) report has aroused considerable comment in the UK lay and medical press. Despite their caveats, others have made sweeping generalisations that this proves that anti-pyresis for childhood fever is no better than placebo. The data as published show that the children given active analgesia/anti-pyretic show a statistically significant improvement in activity and alertness with a pronounced but non-significant improvement in mood and eating. The children given placebo had a reported increase in drinking that Kramer et al interpret as evidence of improved fluid balance-but this
have been alarmed by the development of tumours at an early age in 2 of these 4 children. Both children had humoral and cellular immunodeficiency. The first child developed B-cell non-Hodgkin lymphoma with widespread abdominal disease and involvement of the lung, bones, and one kidney at the age of 5 - 5 years after 5 months of rhGH. Remission was obtained with standard-dose induction chemotherapy, but the child died due to massive gastrointestinal bleeding and overwhelming septicaemia. The second child developed a stem-cell leukaemia with chromosomal abnormalities suggestive of underlying myelodysplasia at the age of 13 years, after 44 months on rhGH. A modified, reduced-dose myeloid leukaemia induction protocol was given. The child went into partial remission and is now receiving low-dose cytosine arabinoside. rhGH has been withdrawn in all patients with Bloom’s syndrome. Several reports now point to a relation between development of leukaemia in children and treatment with rhGH.sAlthough no direct proof exists, our observations suggest that, at least in children with Bloom’s syndrome, treatment with rhGH may lead to we
neoplastic change. PENELOPE R. BROCK FRANCIS DE ZEGHER Department of Paediatrics, University Hospital Gasthuisberg, MARIA CASTEELS-VAN DAELE 3000 Leuven, Belgium M. VANDERSCHUEREN-LODEWEYCKX 1. Bloom D.
Congenital telangiectatic erythema resembling lupus erythematosus
in
dwarfs. Am J Dis Child 1954; 88: 754-58. 2. Bloom D. The syndrome of congenital telangiectatic erythema and stunted
growth. J Pediatr 1966; 68: 103-13. 3. German J, Passarge E. Bloom’s syndrome: XII. Report from the registry for 1987. Clin Genet 1989; 35: 57-69. 4. Van Kerkhove CW, Ceuppens JL, Vanderschueren-Lodeweyckx M, Eggermont E, Vertessen S, Stevens EAM. Bloom’s syndrome; clinical features and immunologic abnormalities of four patients. Am J Dis Child 1988; 142: 1089-93. 5. Stahnke N, Zeisel HJ. Growth hormone therapy and leukemia. Eur J Pediatr 1989; 148: 591-96.
HHV-6 reactivation in chronic
fatigue
syndrome SiR,—Chronic fatigue syndrome (CFS) is a well-recognised syndrome of chronic illness typically beginning suddenly after an acute, apparently infectious illness (often influenza-like), lasting 6 months or longer. Patients experience debilitating fatigue, lowgrade fevers, muscle and joint pains, adenopathy, difficulties with concentration, paraesthesiae, photophobia, reactive mood disorders, and other symptoms.1,2 A variety of immunological and other laboratory abnormalities have been described.3 Antibody levels to human herpesvirus-6 (HHV-6), a lymphotropic and gliotropic ViruS,4,5 are raised in patients with CFS. We have looked for HHV-6 reactivation in patients who met the Centers for Disease control
definition for CFS.1 Peripheral blood mononuclear cells from seven CFS patients and two healthy donors were cultured in vitro. The cells were maintained in ’RPMI-1640’ containing fetal calf serum for the first 48 h of culture.4,5 Unusual medium-to-large refractile cells similar to those seen in HHV-6 infected cultures4 were observed within 72 h in cultures of three of the seven patients. At 10 days, the cultures HHV-6 positive cells by indirect contained 8-30% immunofluorescence assays, with monoclonal antibodies directed to HHV-6 strain GS7 (table). DNAs prepared from the 10-day cultures from these patients were highly positive by Southern blot analysis with HHV-6 specific probe ZVH14:8 strong signals were seen with autoradiographic exposure times of less than 10 min (figure). Each lane contained 15 ug of restriction-enzyme-digested DNA. The amount of viral specific DNA was nearly equal in all the DNAs, as displayed in typical BglII and EcoRI banding patterns.5 Three patients whose peripheral blood mononuclear cells contained HHV-6 antigen positive cells were very lethargic and had severe cerebral dysfunction, exemplified by cognitive or memory difficulties. They had mild-to-severe anterior cervical adenopathy. Patient 1 had severe submandibular adenopathy and mild bilateral axillary adenopathy, and patient 2 had severe posterior cervical adenopathy and moderate axillary adenopathy. Patient 1 had case
Detection of HHV-6 DNA in DNA from 10-day cultures of peripheral blood lymphocytes of CFS patients Lane numbers correspond to patient. Restriction enzymes were Bglll (a) and EcoRl (b). Sizes of EcoRl fragments indicated in kilobase pairs Probe is ZVHL 4.1
antibody to Epstein-Barr virus capsid antigen at a titre of 5000, and cytomegalovirus and varicella zoster virus antibody titres of 20 and 64, respectively. She was seronegative (titre < 10) to Epstein-Barr nuclear antigen, suggesting acute EBV infection; however, isolation of EBV from throat washings was not attempted. (Titres to the above three viruses on the other patients were not determined.) Patient 2 had an increased CD4/CD8 ratio and IgG subclass deficiency at the time peripheral blood lymphocyte cultures were set up. IgG titres to HHV-6 were increased at 320-640 in all except patient 5. The two healthy control titres were 80 and 160, within the range for the normal healthy populationNo HHV-6 antigen expressing cells were detected with any of the monoclonal antibodies in the four other patients or the controls (table). The facile propagation of HHV-6 from CFS patients reported here is in contrast to negative results obtained with normal healthy donors4 even though HHV-6 has been isolated from the saliva of PRESENCE OF HHV-6ANTIGEN EXPRESSING CELLS IN SHORT-TERM CULTURES OF LYMPHOCYTES FROM CFS PATIENTS AND IgG ANTIBODY TITRES TO HHV-6 LATE CAPSID ANTIGENS*
*Penpheral blood mononuclear cellcultures were monitored for viralantigens for at least 15 days post infection. tMonoclonal antibodies used were detected agamst HHV-6 strain GS, and included 9A5D12 (p42), 7A2 (gp105), and 12B32G4 (p135)’7 < 1 % - none detected
1347
healthy donors.9 Thus, HHV-6 reactivation in these CFS patients is indicated, suggesting that HHV-6 may be contributing in the
pathogenesis of CFS. Short-term culture assays, as done here, may prove to be a reliable test for reactivation of HHV-6. Any symptomatic involvement of HHV-6 in CFS should be evaluable with the development of viral inactivation or intervention therapy. Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda
S. F. JOSEPHS*
Department of Microbiology, University of Nevada, Reno
B. HENRY
Department of Microbiology and Immunology, University of Kansas Medical School
N. BALACHANDRAN
Department of Neoplastic Disease, Hahnemann University, Philadelphia
D. STRAYER
Incline Village
D. PETERSON
Flecainide may have a useful role in the management of resistant
neuralgic pain in advanced malignant disease. Increasing the dose from 100 to 200 mg twice daily may increase the likelihood of achieving a good and sustained response.
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892, USA
CLAIRE SINNOTT
Department of Palliative Medicine, St Thomas’ Hospital, London SE1 7EH, UK, and Royal Marsden Hospital, London SW3 1.
Division of General Medicine, Brigham and Women’s Hospital, Harvard University School of Medicine, Boston
POLLY EDMONDS IAN CROPLEY GEOFFREY HANKS
Dunlop R, Davies RJ, Hockley J, Turner P. Analgesic effects of oral flecainide. Lancet
1988; i: 420. 2. Cardiac arrhythmia suppression trial (CAST) investigators. Preliminary report: effect of encamide and flecainide on mortality in a randomised trial of arrhythmia suppression after myocardial infarction. N Engl J Med 1989; 321: 406-12.
SjR,—Following our open study A. L. KOMAROFF
D. V. ABLASHI
*Present address Universal Biotechnology Inc, Rockville, Maryland 1. Holmes GP, Kaplan JE, Gantz NM, et al. Chronic fatigue syndrome: a working case definition. Ann Intern Med 1988; 108: 387-89. 2. Komaroff AL. Chronic fatigue syndromes: relationship to viral infections. J Virol Methods 1988; 21: 1-18. 3. Buchwald D, Komaroff AL. Review of laboratory findings for patients with chronic fatigue syndrome. Rev Infect Dis 1991; 13: S12-S18. 4 Salahuddm SZ, Ablashi DV, Markham PD, et al. Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science 1986; 234: 596-601. 5. Ablashi DV, Lusso P, Hung C-L, et al. Utilization of human hemapoeitic cell lines for the propagation and characterization of HBLV (human herpesvirus-6). Int J Cancer 1988; 42: 787-91. 6. Ablashi DV, Zompetta C, Lease C, et al. Human herpesvirus-6 (HHV-6) in chronic fatigue syndrome (CFS). In: Rozee KR, ed. Proceedings of the Chronic Fatigue Workshop (Toronto, 1989). Can Dis Wkly Rep 1991; 17 (suppl): 33-37. 7. Balachandran N, Amelse RE, Zhou WW, et al. Identification of proteins specific for human herpesvirus-6 infected human T cells. J Virol 1989; 63: 2835-40. 8 Josephs SF, Salahuddin SZ, Ablashi DV, et al. Genomic analysis of the human B-lymphotrophic virus (HBLV). Science 1986; 234: 601-03. 9. Levy JA, Ferro F, Greenspan D, Lennett ET. Frequent isolation of HHV-6 from saliva and the seroprevalence to the virus in the population. Lancet 1990; 335: 1047-50.
Flecainide in
following a study in myocardial infarction.2 However, this is a very different population and none of our patients have had any difficulties. 2 had ischaemic heart disease (of whom 1 experienced the side-effects noted above).
cancer nerve
pain
SIR,-Neuropathic pain associated with advanced malignant disease is often very difficult to manage. In a preliminary study1 flecainide showed promise, and following this report we used the drug in 21 patients (8 males and 13 females; aged 17-75 years [median 55]). In most cases flecainide was second-line therapy when anticonvulsant therapy had failed due to inadequate response (8) or unacceptable drowsiness (6). All patients were also on opioids. Flecainide was started at a dose of 100 mg twice daily. 9 patients responded well, this effect being sustained for 1-14 weeks (table). Only 1 patient had side-effects (confusion and nocturnal hallucinations) on flecainide therapy, which resolved when the drug was discontinued. Antiarrhythmic drugs can be proarrhythmic in some circumstances and concern has been voiced about flecainide
flecainide in
with
of the
analgesic effect of oral pain1 we embarked on a
patients double-blind, placebo-controlled trial. Patients cancer
nerve
were
invited
to
participate if they had cancer-related nerve pain that had not been treated with radiography or chemotherapy within the previous month and which had not responded to conventional analgesia. We were aware of the proarrhythmic potential of flecainide and patients were excluded if they had evidence of heart disease on the basis of history, physical examination, ECG, chest X-ray, and, if necessary, echocardiography or gated-blood-pool scintigraphy. The trial received ethical committee approval. Results from the CAST study were released shortly after our trial began.2 This study showed an increased incidence of sudden death in patients with symptom-free ventricular arrhythmias treated with flecainide after myocardial infarction. In view of the advice to discontinue the flecainide, we felt that a preliminary review of our results was appropriate. The 2 patients who received flecainide 100 mg 12-hourly both experienced complete relief of pain. 4 patients had received placebo; 1 patient had experienced some relief while others had not and required rescue analgesia. After further consideration of the CAST study our ethical committee permitted the trial to continue. We were then disappointed to learn that the supply of flecainide had been discontinued by the pharmaceutical company. Others (see above letter) have confirmed our initial observations about the efficacy of flecainide and we believe strongly that it is important to complete a controlled trial. A wide variety of medications have been recommended for cancer-related nerve pain but few have been subjected to rigorous trial.
South Auckland Hospice, Auckland, New Zealand
Department of Palliative Medicine, St Bartholomew’s Hospital, London EC1
Department of Clinical Pharmacology, St Bartholomew’s Hospital Medical College, London EC1A 7BE, UK
ROBERT J. DUNLOP
JOSEPHINE M. HOCKLEY TERESA TATE
PAUL TURNER
Dunlop R, Davies RJ, Hockley J, Turner P. Analgesic effects of oral flecainide. Lancet 1988; i: 420. 2. Cardiac arrhythmia suppression trial (CAST) investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomised trial of arrhythmia 1989; 321: 406-12. J suppression after myocardial infarction N Engl Med 1.
RESPONSE TO FLECAINIDEIN 9 PATIENTS
Treatment of childhood fevers SIR,-Dr Kramer and colleagues’ (March 9, p 591) report has aroused considerable comment in the UK lay and medical press. Despite their caveats, others have made sweeping generalisations that this proves that anti-pyresis for childhood fever is no better than placebo. The data as published show that the children given active analgesia/anti-pyretic show a statistically significant improvement in activity and alertness with a pronounced but non-significant improvement in mood and eating. The children given placebo had a reported increase in drinking that Kramer et al interpret as evidence of improved fluid balance-but this
