986
collected on the day of first perfusion and before infusion in 98; at 3 weeks after the last perfusion in 26; and from 3 to 6 months later in 43 patients and from 6 to 25 months later in the other 55. All the post-treatment samples were screened for anti-HCV by secondgeneration ELISA (Ortho). Samples that were positive were tested by RIBA-2. When the post-treatment sample was scored as reactive, the corresponding pretreatment samples were tested similarly. In the last post-treatment samples, 94 were negative by ELISA and 4 were reactive. The pretreatment samples from these 4 patients were also anti-HCV positive with the same profile by RIBA as that observed in the late sample (ie, two bands for 1 and a C22 band for the other 3). Of the 26 patients tested 3 weeks after treatment, transient positive results were observed in 6. 5 of these 6 had received Gammagard. Samples collected several months after treatment were anti-HCV negative. To sum up, no anti-HCV seroconversion was observed in these patients. This prospective study showed that the method of production of these IVIGs is safe with regard to the transmission of HCV. Perinatal Haematology Centre, 53 Boulevard Diderot, 75012 Paris, France, Obstetrics and Gynaecology Service, Hôpital Saint Antoine,
Paris;
Southern
blot containing EcoRl digested DNA after hybridisation with probe p13Ep-11. Both the proband (large arrow) and his affected son (filled symbols) have a 165 kb fragment (small arrows) that is absent in parents of the
and National Blood Transfusion Institute, Paris 1. Lane RS.
proband. 2.
fragment of 16kb. In addition, the transmission of this deletion, together with FSHD, to the next generaton confirms the association between the development of FSHD and de-novo DNA rearrangements. The detection of such rearranements by probe pl3E-11 will improve the diagnosis in new FSHD patients and in small families in which a new mutation can be demonstrated.
3. 4.
5.
C. WIJMENGA O. F. BROUWER G. W. PADBERG R. R. FRANTS
MGC Department of Human Genetics and Department of Neurology, Leiden University, 2333 Leiden, Netherlands 1.
Wijmenga C, Frants RR, Brouwer OF, Moerer P, Weber JL, Padberg GW. Location of facioscapulohumeral muscular dystrophy gene on chromosome 4. Lancet 1990; 336: 651-53.
Regional mapping of facioscapulohumeral muscular dystrophy gene on 4q35: combined analysis of an international consortium. Am J Hum Genet 1992; 51: 396-403. 3. Wijmenga C, Hewitt JE, Sandkuijl LA, et al. Chromosome 4q DNA rearrangements associated with facioscapulhumeral muscular dystrophy. Nature Genet 1992; 2: 2. Sarfarazi M, Wigmenga C, Upadhyaya M,
et
al.
26-30.
Intravenous immunoglobulins and hepatitis C transmission in healthy pregnant women SIR,-Human intravenous immunoglobulins (IVIG) are widely patients with humoral immunodeficiency, autoimmune disorders, prophylaxis of infections, and in rhesus-negative women to prevent haemolytic disease of the newborn. There have been reports of transmission of non-A, non-B hepatitis to hypogammaglobulinaemic or agammaglobulinaemic patients receiving large amounts of IVIG, including several cases of severe liver damage and death. 1,5 We have assessed the frequency of hepatitis C virus (HCV) infection in healthy women who received high doses of IVIG to prevent recurrence of spontaneous abortion. 98 women with a history of three or more previous spontaneous abortions were treated during the next pregnancy with four perfusions of 500 mg/kg IVIG after 5-13 weeks’ amenorrhoea.6 The IVIG was Gammagard (Baxter) in 5 and different batches of Biotransfusion IVIG (France) in 94. IVIG was prepared with Cohn cold ethanol fractionation from pooled plasmas of more than 1000 donors; and diethaminoethyl-Sephadex adsorption for Gammagard, and proteolysis by pepsin pH 4 for Biotransfusion IVIG. Most of this IVIG was prepared from a pool of plasma not tested for anti-HCV. Samples of sera from the patients were used in
M. F. REZNIKOFF-ETIEVANT Y. DE LACHAUX L. MARPEAU A. COUROUCÉ
6.
Non-A, non-B hepatitis from intravenous immunoglobulin. Lancet 1983; ii: 974-75. Lever AML, Webster ADB, Brown D, Thomas HC. Non-A, non-B hepatitis occuring in agammaglobulinaemic patients after intravenous immunoglobulin. Lancet 1984; ii: 1062-64. Ochs HD, Fischer SH, Virant FS, Lee MI, Kingdon HS, Wedgewood RJ. Non-A, non-B hepatitis and intravenous immunoglobulin. Lancet 1986; i: 967-77. Bjorkander J, Cunningham-Rundles C, Lundin P, Olsson R, Söderström R, Hanson LA. Intravenous immunoglobulin prophylaxis causing liver damage in 16 of 77 patients with hypogammaglobulinaemia or IgG subclass deficiency. Am J Med 1988; 84: 107-11. Williams PE, Yap PL, Gillon J, Crawford RJ, Galea G, Cuthberttson B. Non-A, non-B hepatitis transmission by intravenous immunoglobulin. Lancet 1988; ii: 501. Reznikoff-Etievant MF, Jarraya MH, de Lachaux VL, Marpeau L, Papiernick E, Netter A. Interruptions spontanées de grossesse: aspects actuels des mécanismes et traitements. Actual Gynecol 1991; 25: 159-71.
Dog days and antiandrogens SiR,—Ireport a 26-year-old female patient with severe facial hirsutism. All relevant investigations were negative and I put her on antiandrogen therapy with cyproterone acetate 100 mg daily, taken from day 5 to day 15 of each menstrual cycle, together with Dianette (2 mg cyproterone acetate and ethinyloestradiol 35 pg). I saw the patient 4 months after initiating this therapy, when her hirsutism was beginning to improve. However, she complained that her male Rottweiler would not leave her alone and repeatedly tried to mount her during the 10 days that she was taking the increased dose of cyproterone acetate. This behaviour ended once the higher dose was finished, after the 15th day of her cycle. Ultimately, the dog’s behaviour became so embarrassing that it was castrated and since that time my patient has been able to take her antiandrogen therapy without any further interference by the dog. Cyproterone acetate is a progestogen and Kloek1 showed that police dogs can smell progesterone on an object briefly held by a pregnant woman. Dermatology Department, General Infirmary at Leeds. Leeds LS1 3EX, UK
J. A. COTTERILL
J. The smell of some steroid sex hormones and their metabolites. Reflections and experiments concerning the significance of smell from the mutual relation of the sexes. Psychiat Neurol Neurochir 1961; 64: 309-44.
1. Kloek
CORRECTION Mumps meningitis and measles, mumps, and rubella vaccine.-In this letter by Dr Colville and Dr Pugh (Sept 26, p 786) paragraph 3 line 5 should have read "... (CSF) of 6 children following MMR...".
collected on the day of first perfusion and before infusion in 98; at 3 weeks after the last perfusion in 26; and from 3 to 6 months later in 43 patients and from 6 to 25 months later in the other 55. All the post-treatment samples were screened for anti-HCV by secondgeneration ELISA (Ortho). Samples that were positive were tested by RIBA-2. When the post-treatment sample was scored as reactive, the corresponding pretreatment samples were tested similarly. In the last post-treatment samples, 94 were negative by ELISA and 4 were reactive. The pretreatment samples from these 4 patients were also anti-HCV positive with the same profile by RIBA as that observed in the late sample (ie, two bands for 1 and a C22 band for the other 3). Of the 26 patients tested 3 weeks after treatment, transient positive results were observed in 6. 5 of these 6 had received Gammagard. Samples collected several months after treatment were anti-HCV negative. To sum up, no anti-HCV seroconversion was observed in these patients. This prospective study showed that the method of production of these IVIGs is safe with regard to the transmission of HCV. Perinatal Haematology Centre, 53 Boulevard Diderot, 75012 Paris, France, Obstetrics and Gynaecology Service, Hôpital Saint Antoine,
Paris;
Southern
blot containing EcoRl digested DNA after hybridisation with probe p13Ep-11. Both the proband (large arrow) and his affected son (filled symbols) have a 165 kb fragment (small arrows) that is absent in parents of the
and National Blood Transfusion Institute, Paris 1. Lane RS.
proband. 2.
fragment of 16kb. In addition, the transmission of this deletion, together with FSHD, to the next generaton confirms the association between the development of FSHD and de-novo DNA rearrangements. The detection of such rearranements by probe pl3E-11 will improve the diagnosis in new FSHD patients and in small families in which a new mutation can be demonstrated.
3. 4.
5.
C. WIJMENGA O. F. BROUWER G. W. PADBERG R. R. FRANTS
MGC Department of Human Genetics and Department of Neurology, Leiden University, 2333 Leiden, Netherlands 1.
Wijmenga C, Frants RR, Brouwer OF, Moerer P, Weber JL, Padberg GW. Location of facioscapulohumeral muscular dystrophy gene on chromosome 4. Lancet 1990; 336: 651-53.
Regional mapping of facioscapulohumeral muscular dystrophy gene on 4q35: combined analysis of an international consortium. Am J Hum Genet 1992; 51: 396-403. 3. Wijmenga C, Hewitt JE, Sandkuijl LA, et al. Chromosome 4q DNA rearrangements associated with facioscapulhumeral muscular dystrophy. Nature Genet 1992; 2: 2. Sarfarazi M, Wigmenga C, Upadhyaya M,
et
al.
26-30.
Intravenous immunoglobulins and hepatitis C transmission in healthy pregnant women SIR,-Human intravenous immunoglobulins (IVIG) are widely patients with humoral immunodeficiency, autoimmune disorders, prophylaxis of infections, and in rhesus-negative women to prevent haemolytic disease of the newborn. There have been reports of transmission of non-A, non-B hepatitis to hypogammaglobulinaemic or agammaglobulinaemic patients receiving large amounts of IVIG, including several cases of severe liver damage and death. 1,5 We have assessed the frequency of hepatitis C virus (HCV) infection in healthy women who received high doses of IVIG to prevent recurrence of spontaneous abortion. 98 women with a history of three or more previous spontaneous abortions were treated during the next pregnancy with four perfusions of 500 mg/kg IVIG after 5-13 weeks’ amenorrhoea.6 The IVIG was Gammagard (Baxter) in 5 and different batches of Biotransfusion IVIG (France) in 94. IVIG was prepared with Cohn cold ethanol fractionation from pooled plasmas of more than 1000 donors; and diethaminoethyl-Sephadex adsorption for Gammagard, and proteolysis by pepsin pH 4 for Biotransfusion IVIG. Most of this IVIG was prepared from a pool of plasma not tested for anti-HCV. Samples of sera from the patients were used in
M. F. REZNIKOFF-ETIEVANT Y. DE LACHAUX L. MARPEAU A. COUROUCÉ
6.
Non-A, non-B hepatitis from intravenous immunoglobulin. Lancet 1983; ii: 974-75. Lever AML, Webster ADB, Brown D, Thomas HC. Non-A, non-B hepatitis occuring in agammaglobulinaemic patients after intravenous immunoglobulin. Lancet 1984; ii: 1062-64. Ochs HD, Fischer SH, Virant FS, Lee MI, Kingdon HS, Wedgewood RJ. Non-A, non-B hepatitis and intravenous immunoglobulin. Lancet 1986; i: 967-77. Bjorkander J, Cunningham-Rundles C, Lundin P, Olsson R, Söderström R, Hanson LA. Intravenous immunoglobulin prophylaxis causing liver damage in 16 of 77 patients with hypogammaglobulinaemia or IgG subclass deficiency. Am J Med 1988; 84: 107-11. Williams PE, Yap PL, Gillon J, Crawford RJ, Galea G, Cuthberttson B. Non-A, non-B hepatitis transmission by intravenous immunoglobulin. Lancet 1988; ii: 501. Reznikoff-Etievant MF, Jarraya MH, de Lachaux VL, Marpeau L, Papiernick E, Netter A. Interruptions spontanées de grossesse: aspects actuels des mécanismes et traitements. Actual Gynecol 1991; 25: 159-71.
Dog days and antiandrogens SiR,—Ireport a 26-year-old female patient with severe facial hirsutism. All relevant investigations were negative and I put her on antiandrogen therapy with cyproterone acetate 100 mg daily, taken from day 5 to day 15 of each menstrual cycle, together with Dianette (2 mg cyproterone acetate and ethinyloestradiol 35 pg). I saw the patient 4 months after initiating this therapy, when her hirsutism was beginning to improve. However, she complained that her male Rottweiler would not leave her alone and repeatedly tried to mount her during the 10 days that she was taking the increased dose of cyproterone acetate. This behaviour ended once the higher dose was finished, after the 15th day of her cycle. Ultimately, the dog’s behaviour became so embarrassing that it was castrated and since that time my patient has been able to take her antiandrogen therapy without any further interference by the dog. Cyproterone acetate is a progestogen and Kloek1 showed that police dogs can smell progesterone on an object briefly held by a pregnant woman. Dermatology Department, General Infirmary at Leeds. Leeds LS1 3EX, UK
J. A. COTTERILL
J. The smell of some steroid sex hormones and their metabolites. Reflections and experiments concerning the significance of smell from the mutual relation of the sexes. Psychiat Neurol Neurochir 1961; 64: 309-44.
1. Kloek
CORRECTION Mumps meningitis and measles, mumps, and rubella vaccine.-In this letter by Dr Colville and Dr Pugh (Sept 26, p 786) paragraph 3 line 5 should have read "... (CSF) of 6 children following MMR...".
