705
hydrophone surface or directly within the fetal head, on skull and ear ossicle structures. The cochlea responds to vibrations not pressure as such. The fetal cochlea is insensitive to sounds travelling through the body and will have poor sensitivity to the sound generated in the maternal tissues. In contrast, sounds generated within the fetal head may be more efficiently conducted to the cochlea. The sound sensation would be unfamiliar, and fluctuate in a random manner as the ultrasound operator altered the beam position. It could thus act to stimulate the fetus whenever the transducer was applied for observations including the head. This effect should not be present in systems such as those used for fetal monitoring in labour because the force will be several orders of magnitude smaller and is unmodulated.
on the
We acknowledge helpful discussions with Dr Johan Liljencrants (Royal Institute of Technology, Stockholm), Dr Roy Preston (National Physical Laboratory, London), and Dr Francis Duck (Regional Medical Physics
Service, Bath, UK). Department of Obstetrics and Gynaecology, National University Hospital, Singapore 0511
S. ARULKUMARAN
Institute of Obstetrics and London W6, UK
D. G. TALBERT
Gynaecology,
Huddinge Hospital, Karolinaka Institute, Huddinge, Sweden
M. NYMAN M. WESTGREN
Department of Physics, National University Hospital, Singapore
T. S. HSU
Department of Obstetrics and Gynaecology, National University Hospital, Singapore
S. S. RATNAM
1. Nymen M, Arulkumaran S, Hsu TS, Ratnam SS, Till O, Westgren M. Vibroacoustic stimulation and intrauterine sound pressure levels. Obstet Gynecol (m press).
1. Nichols C, Roth B, Williams S, et al. Cardiovascular complications of chemotherapy for testicular cancer Proc Am Soc Clin Oncol 1990; 9: 132. 2. Hansen SW, Olsen N Raynaud’s phenomenon in patients treated with cisplatin, vinblastine and bleomycin for germ cell cancer- measurement of vasocontrictor responses to cold. J Clin Oncol 1989; 7: 940-42. 3. Licciardello JTW, Moake JL, Rudy CK, et al. Elevated plasma von Willebrand factor levels and arterial occlusive complications associated with cisplatin-based chemotherapy Oncology 1985; 42: 296-300. 4. Lewis GD, Campbell WB, Johnson AR. Inhibition of prostaglandin synthesis by glucocorticoids in human endothelial cells. Endocrinology 1986; 119: 62-69. 5. Pepine CJ, Hirsfeld JW, Macdonald RG, et al. A controlled trial of corticosteroids to prevent restenosis after coronary angioplasty, M-HEART Group. Circulation
1990; 81: 1753-61.
Hypersensitivity to thiomersal in hepatitis
B
vaccine SIR,-Dr Seal and colleagues (Aug 3, p 315) report hypersensitivity to thiomersal. Rietschel and Adams’ reported reactions to thiomersal in 2 patients receiving hepatitis B vaccination. A further case has lately been seen at this hospital. A 27-year-old man received a first dose of hepatitis B vaccine (’Engerix B’) and a further dose five months later. After the second inoculation a severe local reaction developed, lasting four weeks. Patch testing showed delayed-type hypersensitivity to thiomersal and he was advised not to complete the course of vaccination. Two months later his
serum
anti-HBs titre
was more
than 100
IU/1,
indicating satisfactory immunity despite an incomplete course of vaccine. Monitoring of antibody titres is planned. Thiomersal is used as a preservative2 in diphtheria, tetanus, and pertussis vaccines and both hepatitis B vaccines available in the UK (engerix B and ’H-B-Vax’). In addition, it can be a component of eardrops and ophthalmic solutions, and there have been reports of ocular allergy in soft contact-lens wearers.3 Thiomersal in hepatitis B vaccine can induce severe cutaneous reactions,’ and .
hypersensitivity with other vaccines has been recorded.4 We agree with Seal and colleagues that the pharmaceutical
Cisplatin-based chemotherapy and acute cerebrovascular events SiR,—The case Dr Gerl and colleagues describe (Aug 10, p 385) raises concern about the appearance of cerebrovascular thrombotic events after cisplatin-based chemotherapy for testicular cancer. The clinical importance of this complication would be further ascertained from randomised studies comparing treated with untreated patients. A large trial by the Testicular Cancer Study Group failed to find an increased incidence of strokes among patients receiving short-term cisplatin regimens. Furthermore, we believe that the arguments presented by Gerl et al do not give clear support for a causative role of cisplatin in this complication. Cisplatin-induced hypomagnesaemia has not been previously related to thrombotic events in these patients, and even its potential role in long-term Raynaud’s phenomenon has been disregarded in recent series The reference Gerl et al cite in relation to endothelial damage after cisplatin therapy3 is taken from an older population with some evidence of pretreatment vascular disease, as indicated by high levels of von Willebrand factor. There is no evidence of such findings in healthy young patients with testicular cancer. We also disagree that antiemetic steroids might contribute to chemotherapy-induced vascular complications. Glucocorticoids inhibit prostaglandin synthesis in human endothelial cells.4 The potentially beneficial effects of steroids on the vascular wall have encouraged the assay of short-term methylprednisolone, a commonly used antiemetic compound in cisplatin therapy, as an aid in the prevention of recurrence in certain arterial thromboses.5 Prednisone has never been associated with the well-known cerebrovascular events induced by asparaginase, although both drugs are frequently used together in the induction therapy of .
lymphoblastic leukaemia. Services of Oncology and Hospital de Navarra, 31008 Pamplona, Spain
Neurology,
J. J. ILLARRAMENDI J. GALLEGO
industry should reconsider its use of thiomersal in view of the severe delayed hypersensitivity reactions that may arise. Since wider use of hepatitis B vaccine is being advocated with repeat vaccination after 3-5 years,s the prevalence of hyersensitivity reactions will probably increase unless a thiomersal-free vaccine is produced. Dryburn Hospital, Durham DH1 5TW, UK
I. NOEL A. GALLOWAY F. A. IVE
1. Rietschel RL, Adams RM. Reactions to thiomerosal in hepatitis B vaccines. Dermatol Clin 1990; 8: 161-64. 2. Cox NH, Forsyth A. Thiomersal allergy and vaccination reactions. Contact Dermatitis 1988; 18: 229-33. 3. Tosti A, Tosti G. Thiomerosal: a hidden allergen in ophthalmology. Contact Dermatitis 1988; 18: 268-73 4. Forstrom L, Hannuksela M, Kousa M, Lehmuskallio E. Merthiolate hypersensitivity and vaccination. Contact Dermatitis 1980; 6: 241-45. 5. Department of Health. Immunisation against infectious disease. London: HM Stationery Office, 1990.
Allergic reactions to mesna SIR,-Dr Seidel and Professor Gross and their colleagues report allergic reactions to mesna (Aug 10, p 381). We have also noted these effects although the frequency of serious adverse reactions has not been high. In the past four years we have treated 83 patients with intravenous cyclophosphamide-45 with lupus nephritis, 30 with systemic vasculitis, and 8 with polymyositis/dermatomyositis. Our usual regimen consists of 500 mg cyclophosphamide in 250 ml normal saline given over 30 min. Mesna (’Uromitexan’) is given intravenously 100 mg at the start of the pulse, and 200 mg is given orally 4 and 8 h afterwards. The oral doses were divided into aliquots from the uromitexan ampoules and mixed with fruit juice. A total of 372 pulses were given, mesna being used in 349 of these. The patients received a mean of 45 (SD 4-6) pulses of cyclophosphamide (range 2-22), with the systemic vasculitis patients receiving the most pulses (mean 6-0 [5’3] per patient).
hydrophone surface or directly within the fetal head, on skull and ear ossicle structures. The cochlea responds to vibrations not pressure as such. The fetal cochlea is insensitive to sounds travelling through the body and will have poor sensitivity to the sound generated in the maternal tissues. In contrast, sounds generated within the fetal head may be more efficiently conducted to the cochlea. The sound sensation would be unfamiliar, and fluctuate in a random manner as the ultrasound operator altered the beam position. It could thus act to stimulate the fetus whenever the transducer was applied for observations including the head. This effect should not be present in systems such as those used for fetal monitoring in labour because the force will be several orders of magnitude smaller and is unmodulated.
on the
We acknowledge helpful discussions with Dr Johan Liljencrants (Royal Institute of Technology, Stockholm), Dr Roy Preston (National Physical Laboratory, London), and Dr Francis Duck (Regional Medical Physics
Service, Bath, UK). Department of Obstetrics and Gynaecology, National University Hospital, Singapore 0511
S. ARULKUMARAN
Institute of Obstetrics and London W6, UK
D. G. TALBERT
Gynaecology,
Huddinge Hospital, Karolinaka Institute, Huddinge, Sweden
M. NYMAN M. WESTGREN
Department of Physics, National University Hospital, Singapore
T. S. HSU
Department of Obstetrics and Gynaecology, National University Hospital, Singapore
S. S. RATNAM
1. Nymen M, Arulkumaran S, Hsu TS, Ratnam SS, Till O, Westgren M. Vibroacoustic stimulation and intrauterine sound pressure levels. Obstet Gynecol (m press).
1. Nichols C, Roth B, Williams S, et al. Cardiovascular complications of chemotherapy for testicular cancer Proc Am Soc Clin Oncol 1990; 9: 132. 2. Hansen SW, Olsen N Raynaud’s phenomenon in patients treated with cisplatin, vinblastine and bleomycin for germ cell cancer- measurement of vasocontrictor responses to cold. J Clin Oncol 1989; 7: 940-42. 3. Licciardello JTW, Moake JL, Rudy CK, et al. Elevated plasma von Willebrand factor levels and arterial occlusive complications associated with cisplatin-based chemotherapy Oncology 1985; 42: 296-300. 4. Lewis GD, Campbell WB, Johnson AR. Inhibition of prostaglandin synthesis by glucocorticoids in human endothelial cells. Endocrinology 1986; 119: 62-69. 5. Pepine CJ, Hirsfeld JW, Macdonald RG, et al. A controlled trial of corticosteroids to prevent restenosis after coronary angioplasty, M-HEART Group. Circulation
1990; 81: 1753-61.
Hypersensitivity to thiomersal in hepatitis
B
vaccine SIR,-Dr Seal and colleagues (Aug 3, p 315) report hypersensitivity to thiomersal. Rietschel and Adams’ reported reactions to thiomersal in 2 patients receiving hepatitis B vaccination. A further case has lately been seen at this hospital. A 27-year-old man received a first dose of hepatitis B vaccine (’Engerix B’) and a further dose five months later. After the second inoculation a severe local reaction developed, lasting four weeks. Patch testing showed delayed-type hypersensitivity to thiomersal and he was advised not to complete the course of vaccination. Two months later his
serum
anti-HBs titre
was more
than 100
IU/1,
indicating satisfactory immunity despite an incomplete course of vaccine. Monitoring of antibody titres is planned. Thiomersal is used as a preservative2 in diphtheria, tetanus, and pertussis vaccines and both hepatitis B vaccines available in the UK (engerix B and ’H-B-Vax’). In addition, it can be a component of eardrops and ophthalmic solutions, and there have been reports of ocular allergy in soft contact-lens wearers.3 Thiomersal in hepatitis B vaccine can induce severe cutaneous reactions,’ and .
hypersensitivity with other vaccines has been recorded.4 We agree with Seal and colleagues that the pharmaceutical
Cisplatin-based chemotherapy and acute cerebrovascular events SiR,—The case Dr Gerl and colleagues describe (Aug 10, p 385) raises concern about the appearance of cerebrovascular thrombotic events after cisplatin-based chemotherapy for testicular cancer. The clinical importance of this complication would be further ascertained from randomised studies comparing treated with untreated patients. A large trial by the Testicular Cancer Study Group failed to find an increased incidence of strokes among patients receiving short-term cisplatin regimens. Furthermore, we believe that the arguments presented by Gerl et al do not give clear support for a causative role of cisplatin in this complication. Cisplatin-induced hypomagnesaemia has not been previously related to thrombotic events in these patients, and even its potential role in long-term Raynaud’s phenomenon has been disregarded in recent series The reference Gerl et al cite in relation to endothelial damage after cisplatin therapy3 is taken from an older population with some evidence of pretreatment vascular disease, as indicated by high levels of von Willebrand factor. There is no evidence of such findings in healthy young patients with testicular cancer. We also disagree that antiemetic steroids might contribute to chemotherapy-induced vascular complications. Glucocorticoids inhibit prostaglandin synthesis in human endothelial cells.4 The potentially beneficial effects of steroids on the vascular wall have encouraged the assay of short-term methylprednisolone, a commonly used antiemetic compound in cisplatin therapy, as an aid in the prevention of recurrence in certain arterial thromboses.5 Prednisone has never been associated with the well-known cerebrovascular events induced by asparaginase, although both drugs are frequently used together in the induction therapy of .
lymphoblastic leukaemia. Services of Oncology and Hospital de Navarra, 31008 Pamplona, Spain
Neurology,
J. J. ILLARRAMENDI J. GALLEGO
industry should reconsider its use of thiomersal in view of the severe delayed hypersensitivity reactions that may arise. Since wider use of hepatitis B vaccine is being advocated with repeat vaccination after 3-5 years,s the prevalence of hyersensitivity reactions will probably increase unless a thiomersal-free vaccine is produced. Dryburn Hospital, Durham DH1 5TW, UK
I. NOEL A. GALLOWAY F. A. IVE
1. Rietschel RL, Adams RM. Reactions to thiomerosal in hepatitis B vaccines. Dermatol Clin 1990; 8: 161-64. 2. Cox NH, Forsyth A. Thiomersal allergy and vaccination reactions. Contact Dermatitis 1988; 18: 229-33. 3. Tosti A, Tosti G. Thiomerosal: a hidden allergen in ophthalmology. Contact Dermatitis 1988; 18: 268-73 4. Forstrom L, Hannuksela M, Kousa M, Lehmuskallio E. Merthiolate hypersensitivity and vaccination. Contact Dermatitis 1980; 6: 241-45. 5. Department of Health. Immunisation against infectious disease. London: HM Stationery Office, 1990.
Allergic reactions to mesna SIR,-Dr Seidel and Professor Gross and their colleagues report allergic reactions to mesna (Aug 10, p 381). We have also noted these effects although the frequency of serious adverse reactions has not been high. In the past four years we have treated 83 patients with intravenous cyclophosphamide-45 with lupus nephritis, 30 with systemic vasculitis, and 8 with polymyositis/dermatomyositis. Our usual regimen consists of 500 mg cyclophosphamide in 250 ml normal saline given over 30 min. Mesna (’Uromitexan’) is given intravenously 100 mg at the start of the pulse, and 200 mg is given orally 4 and 8 h afterwards. The oral doses were divided into aliquots from the uromitexan ampoules and mixed with fruit juice. A total of 372 pulses were given, mesna being used in 349 of these. The patients received a mean of 45 (SD 4-6) pulses of cyclophosphamide (range 2-22), with the systemic vasculitis patients receiving the most pulses (mean 6-0 [5’3] per patient).
