985
Adult Schönlein-Henoch purpura after
lisinopril SIR,-Dr Moots and colleagues (Aug 1, p 304) report a case of adult Schonlein-Henoch purpura after treatment with enalapril. We have seen a similar case in a 52-year-old man treated with another angiotensin-converting enzyme (ACE) inhibitor, lisinopril, which, like enalapril, does not contain the thiol group. He was admitted in April, 1992, for recent purpuric rash on the legs, ileus, and low-grade fever. He had had chronic polyarthritis of knees and ankles for 8 months with a recent acute episode, and could not walk more than 5 m. Schonlein-Henoch purpura was diagnosed on the basis of no infection, accelerated erythrocyte sedimentation rate (75 mm/h), mild proteinuria (0-39 g/1), microscopic haematuria, normal platelet count, hypergammaglobulinaemia with polyclonal rise in IgA (6-82 g/1), normal serum complement, leucocytoclastic vasculitis with deposition of IgA and complement on skin biopsy, and negative searches for rheumatoid factor, antinuclear antibodies, and antineutrophils cytoplasm antibodies. He had a 3-year history of hypertension and had been taking lisinopril (20 mg per day) since February, 1991. 6 months later, in August, 1991, articular symptoms started in knees and progressively increased, and chondrocalcinosis or gout were considered. 8 months later, in April, 1992, he had an acute purpuric eruption and skin biopsy showed fibrinoid necrosis. A vasculitis syndrome and possible aetiologic role of drugs (lisinopril, aspirin, nicardipine) were then suspected. After withdrawal of lisinopril alone in May, 1992, he improved strikingly, with regression of the purpuric rash after 1 month and of polyarthritis after 3 months (which presently persists only in the left knee), with persistence of a moderate microscopic haematuria 3 months later. The toxic reaction to lisinopril was estimated as 12 (possible), according to the French method of evaluation.1 As far as we are aware, no case of lisinopril-associated vasculitis has been recorded. Our case and that of Moots’ confirms that absence of a thiol group in ACE inhibitors, such as in enalapril or lisinopril, does not prevent severe skin side-effects and vasculitis
syndromes. PATRICK DISDIER JEAN-ROBERT HARLÉ DENIS VERROT
JACQUELINE JOUGLARD PIERRE-JEAN WEILLER
JC, Jouglard J, Lagier G. Unexpected or toxic drug reaction (imputation): actualization of the method used in France. Therapie 1985; 40: 111-18.
Bégaud B,
inconclusive results. Evidence is accumulating that a year or so of adjuvant 5-FU based systemic therapy can moderately improve the survival of colorectal cancer patients.2 Continuing studies may establish whether this small benefit of systemic 5-FU can be enhanced either by folinic acid or by levamisole. In the meantime, we urgently need AXIS to reach its recruitment target to obtain final and definitive evidence on whether similar benefits can be achieved with much more convenient perioperative 5-FU infusion therapy. This information on just a few thousand patients would then help guide the treatment of the 2 million or so colorectal cancer patients worldwide who will have their disease diagnosed in the 1990s. AXIS is sponsored jointly by the Cancer Research Campaign, Imperial Cancer Research Fund, and the Medical Research Council. International participation is welcome and further details, including an information pack and explanatory video, are available from L. G. MRC Cancer Trials Office, 1 Brooklands Avenue, Cambridge CB2 2BB, UK
Evreux
assessment
Intraportal 5-fluorouracil for colorectal cancer:
the AXIS trial
SIR,-Professor Fielding and colleagues report (Aug 29, p 502) a randomised trial of portal vein infusion of 5-fluorouracil (5-FU) after curative resection for colorectal adenocarcinoma. They suggest that there may be some beneficial effect of therapy after the third year of follow-up in patients with stage III (Dukes’ C) disease but propose that a much larger trial is necessary to elucidate the effect of this treatment on survival. They recommend that the AXIS trial of the UK Coordinating Committee on Cancer Research-addressing this same question-should be supported vigorously. As co-organisers of this study, we concur with this view and present a brief update on AXIS’s progress. AXIS aims to confirm or refute reliably any worthwhile benefit obtainable from a one-week postoperative portal vein infusion of 5-FU for patients with any stage of cancer of the colon or rectum. (The trial also makes use of a factorial design to evaluate perioperative radiotherapy for patients with rectal tumours.) Unfortunately, to detect reliably the realistically moderate difference in survival that may be achievable with adjuvant therapy in colorectal cancer, several thousand patients must be investigated. AXIS is therefore aiming to recruit 4000 patients and, thanks to the collaboration of more than 100 surgeons and radiotherapists in the UK and continental Europe, 1400 patients have been entered in the first three years. Preliminary analyses confirm the findings of Fielding et al and others that intraportal 5-FU infusion is a widely
LORE GARTEN SALLY STENNING
ICRF/MRC Clinical Trial Service Unit, Radcliffe 1.
2.
Service du Professeur Weiller, Hôpital de la Timone, 13385 Marseille, France 1.
practicable, inexpensive procedure with minimum toxicity that is only very rarely associated with serious postoperative complications. It is too early to present data on outcome, but results are available from six other studies that have attempted to confirm the striking benefit of intraportal 5-FU reported by Taylor et al.l A metaanalysis of the published data from these confirmatory studies suggests that intraportal 5-FU may reduce the risk of death by about a quarter.2 However, many randomised but ineligible patients were excluded from the published reports and a systematic overview of the individual patient data from ten infusion studies-including data on the ineligible patients-is now under way to try to confirm the meta-analysis results. But, with just 3000 patients in the mature studies, this overview may produce promising but still
RICHARD GRAY
Infirmary, Oxford
Taylor I, Machin D, Muliee M. A randomized controlled trial of adjuvant portal-vein cytotoxic perfusion in colorectal cancer. Br J Surg 1985; 72: 359-63. Gray R, James R, Mossman J, Stenning S. UK Coordinating Committee on Cancer Research Colorectal Cancer Subcommittee. AXIS: Br J Cancer 1991; 63: 841-45.
a
suitable
case
for
treatment.
Transmission of de-novo mutation associated with facioscapulohumeral muscular dystrophy muscular dystrophy (FSHD) is a neuromuscular disorder with autosomal dominant inheritance pattern. The gene for FSHD has been localised to chromosome 4q35 by linkage studies.1,2 In addition, isolated patients with a negative family history have been described frequently, and are most likely due to new mutations. We have described a probe, pl3E-11, detecting de-novo DNA rearrangements in EcoRI digested DNA in new FSHD patients.3 These rearranged fragments might be due to deletions and are usually shorter than 30 kb, whereas the normal fragments can be as large as 150 kb. The relation between FSHD and these newly mutated DNA fragments was established by association analysis. Here we show strong additional genetic evidence by reporting a de-novo rearrangement that is subsequently transmitted to the next
SIR,-Facioscapulohumeral
common
generation. We studied an FSHD family with only one affected branch. After clinical examination of the complete family, the proband (figure, arrow) was diagnosed as a new FSHD patient; the parents did not have any symptoms of the disease and Southern blotting with probe pl3E-1demonstrated a rearranged EcoRI fragment of 16.5 kb in this individual, which was not present in either parent. Nonpaternity was excluded by analysing different random microsatellite markers and the two VNTR markers, D4S 163 and D4S 139, which are closely linked to the FSHD gene.2 One of the two children of the proband also has FSHD. Analysis with p 13E-11demonstrated that the rearranged EcoRl fragment of the proband had been transmitted to the affected child, whereas it has not been transmitted to the healthy child. The findings demonstrate.that the appearance of FSHD in the proband is due to a new mutation, characterised by a deletion
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...".
Adult Schönlein-Henoch purpura after
lisinopril SIR,-Dr Moots and colleagues (Aug 1, p 304) report a case of adult Schonlein-Henoch purpura after treatment with enalapril. We have seen a similar case in a 52-year-old man treated with another angiotensin-converting enzyme (ACE) inhibitor, lisinopril, which, like enalapril, does not contain the thiol group. He was admitted in April, 1992, for recent purpuric rash on the legs, ileus, and low-grade fever. He had had chronic polyarthritis of knees and ankles for 8 months with a recent acute episode, and could not walk more than 5 m. Schonlein-Henoch purpura was diagnosed on the basis of no infection, accelerated erythrocyte sedimentation rate (75 mm/h), mild proteinuria (0-39 g/1), microscopic haematuria, normal platelet count, hypergammaglobulinaemia with polyclonal rise in IgA (6-82 g/1), normal serum complement, leucocytoclastic vasculitis with deposition of IgA and complement on skin biopsy, and negative searches for rheumatoid factor, antinuclear antibodies, and antineutrophils cytoplasm antibodies. He had a 3-year history of hypertension and had been taking lisinopril (20 mg per day) since February, 1991. 6 months later, in August, 1991, articular symptoms started in knees and progressively increased, and chondrocalcinosis or gout were considered. 8 months later, in April, 1992, he had an acute purpuric eruption and skin biopsy showed fibrinoid necrosis. A vasculitis syndrome and possible aetiologic role of drugs (lisinopril, aspirin, nicardipine) were then suspected. After withdrawal of lisinopril alone in May, 1992, he improved strikingly, with regression of the purpuric rash after 1 month and of polyarthritis after 3 months (which presently persists only in the left knee), with persistence of a moderate microscopic haematuria 3 months later. The toxic reaction to lisinopril was estimated as 12 (possible), according to the French method of evaluation.1 As far as we are aware, no case of lisinopril-associated vasculitis has been recorded. Our case and that of Moots’ confirms that absence of a thiol group in ACE inhibitors, such as in enalapril or lisinopril, does not prevent severe skin side-effects and vasculitis
syndromes. PATRICK DISDIER JEAN-ROBERT HARLÉ DENIS VERROT
JACQUELINE JOUGLARD PIERRE-JEAN WEILLER
JC, Jouglard J, Lagier G. Unexpected or toxic drug reaction (imputation): actualization of the method used in France. Therapie 1985; 40: 111-18.
Bégaud B,
inconclusive results. Evidence is accumulating that a year or so of adjuvant 5-FU based systemic therapy can moderately improve the survival of colorectal cancer patients.2 Continuing studies may establish whether this small benefit of systemic 5-FU can be enhanced either by folinic acid or by levamisole. In the meantime, we urgently need AXIS to reach its recruitment target to obtain final and definitive evidence on whether similar benefits can be achieved with much more convenient perioperative 5-FU infusion therapy. This information on just a few thousand patients would then help guide the treatment of the 2 million or so colorectal cancer patients worldwide who will have their disease diagnosed in the 1990s. AXIS is sponsored jointly by the Cancer Research Campaign, Imperial Cancer Research Fund, and the Medical Research Council. International participation is welcome and further details, including an information pack and explanatory video, are available from L. G. MRC Cancer Trials Office, 1 Brooklands Avenue, Cambridge CB2 2BB, UK
Evreux
assessment
Intraportal 5-fluorouracil for colorectal cancer:
the AXIS trial
SIR,-Professor Fielding and colleagues report (Aug 29, p 502) a randomised trial of portal vein infusion of 5-fluorouracil (5-FU) after curative resection for colorectal adenocarcinoma. They suggest that there may be some beneficial effect of therapy after the third year of follow-up in patients with stage III (Dukes’ C) disease but propose that a much larger trial is necessary to elucidate the effect of this treatment on survival. They recommend that the AXIS trial of the UK Coordinating Committee on Cancer Research-addressing this same question-should be supported vigorously. As co-organisers of this study, we concur with this view and present a brief update on AXIS’s progress. AXIS aims to confirm or refute reliably any worthwhile benefit obtainable from a one-week postoperative portal vein infusion of 5-FU for patients with any stage of cancer of the colon or rectum. (The trial also makes use of a factorial design to evaluate perioperative radiotherapy for patients with rectal tumours.) Unfortunately, to detect reliably the realistically moderate difference in survival that may be achievable with adjuvant therapy in colorectal cancer, several thousand patients must be investigated. AXIS is therefore aiming to recruit 4000 patients and, thanks to the collaboration of more than 100 surgeons and radiotherapists in the UK and continental Europe, 1400 patients have been entered in the first three years. Preliminary analyses confirm the findings of Fielding et al and others that intraportal 5-FU infusion is a widely
LORE GARTEN SALLY STENNING
ICRF/MRC Clinical Trial Service Unit, Radcliffe 1.
2.
Service du Professeur Weiller, Hôpital de la Timone, 13385 Marseille, France 1.
practicable, inexpensive procedure with minimum toxicity that is only very rarely associated with serious postoperative complications. It is too early to present data on outcome, but results are available from six other studies that have attempted to confirm the striking benefit of intraportal 5-FU reported by Taylor et al.l A metaanalysis of the published data from these confirmatory studies suggests that intraportal 5-FU may reduce the risk of death by about a quarter.2 However, many randomised but ineligible patients were excluded from the published reports and a systematic overview of the individual patient data from ten infusion studies-including data on the ineligible patients-is now under way to try to confirm the meta-analysis results. But, with just 3000 patients in the mature studies, this overview may produce promising but still
RICHARD GRAY
Infirmary, Oxford
Taylor I, Machin D, Muliee M. A randomized controlled trial of adjuvant portal-vein cytotoxic perfusion in colorectal cancer. Br J Surg 1985; 72: 359-63. Gray R, James R, Mossman J, Stenning S. UK Coordinating Committee on Cancer Research Colorectal Cancer Subcommittee. AXIS: Br J Cancer 1991; 63: 841-45.
a
suitable
case
for
treatment.
Transmission of de-novo mutation associated with facioscapulohumeral muscular dystrophy muscular dystrophy (FSHD) is a neuromuscular disorder with autosomal dominant inheritance pattern. The gene for FSHD has been localised to chromosome 4q35 by linkage studies.1,2 In addition, isolated patients with a negative family history have been described frequently, and are most likely due to new mutations. We have described a probe, pl3E-11, detecting de-novo DNA rearrangements in EcoRI digested DNA in new FSHD patients.3 These rearranged fragments might be due to deletions and are usually shorter than 30 kb, whereas the normal fragments can be as large as 150 kb. The relation between FSHD and these newly mutated DNA fragments was established by association analysis. Here we show strong additional genetic evidence by reporting a de-novo rearrangement that is subsequently transmitted to the next
SIR,-Facioscapulohumeral
common
generation. We studied an FSHD family with only one affected branch. After clinical examination of the complete family, the proband (figure, arrow) was diagnosed as a new FSHD patient; the parents did not have any symptoms of the disease and Southern blotting with probe pl3E-1demonstrated a rearranged EcoRI fragment of 16.5 kb in this individual, which was not present in either parent. Nonpaternity was excluded by analysing different random microsatellite markers and the two VNTR markers, D4S 163 and D4S 139, which are closely linked to the FSHD gene.2 One of the two children of the proband also has FSHD. Analysis with p 13E-11demonstrated that the rearranged EcoRl fragment of the proband had been transmitted to the affected child, whereas it has not been transmitted to the healthy child. The findings demonstrate.that the appearance of FSHD in the proband is due to a new mutation, characterised by a deletion
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...".
