855
NCEPOD and UK specialist training SiR,—Dr Fielden states (Aug 29, p 554) that the National Enquiry into Perioperative Deaths condemned the long training in the UK. We would be grateful if he would supply us Confidential
with the reference
to
this
statement
in the report. E. A. CAMPLING H. B. DEVLIN R. W. HOILE J. N. LUNN
NCEPOD, 35 Lincolns Inn Fields, London WC2 3PN, UK
* Thisletter has been shown follows.-ED. L.
Dr
to
Fielden, whose repl3
SIR,-I did not refer to particular parts of the NCEPOE (National Confidential Enquiry into Perioperative Deaths) repon because I, and other junior doctor representatives, believe that the whole report contains important, constructive criticisms of tht training, education, supervision, and application of knowledge oj doctors in the UK. The difference of opinion may be partly due tc interpretation, and editorial interpretation of my original letter may have contributed-my original wording (lst line, paragraph 3: being "The prolonged training, by a process of osmosis whilst halj asleep, has been frequently condemned, most recently by NCEPOD". It should be stated that supervision is an essential aspect of training and that education should not cease once seni01 status is achieved. "Condemnation by NCEPOD", I believe, is a concise description of the many instances where inadequacies oi UK training are reported. The following NCEPOD references are criticisms of our present system that allows junior doctors to undertake unsupervised procedures beyond their ability (pp 120, 126 [b], 188,189, 216, 273. 283). "Lack of supervision or improper delegation can result in junior and inexperienced surgeons doing inappropriate surgery. The patients’ demise was directly related to this in 18 cases" (187); "Presence or availability of a Consultant in only 42% of cases" (216); "It is inappropriate for this grade of surgeon to be left unsupervised in this type of case" (233). With respect to criticisms of poor judgment or lack of expertise, could these not be rectified by better training? (pp 126 a, c, d, e, 127. 186, 192, 261); "there is no place for the occasional oesophageal surgeon (194); "inappropriate use of resources" (211); "Had this surgeon been experienced in the appropriate specialty he might have reconsidered the indication to operate in the first place" (252); "inappropriate operations and grade of operating surgeon" (265). The report mentions inappropriate techniques (188): "are junior surgeons being actively taught the management of patients with complications of hernias?" (240), and refers to lack of involvement of seniors (230) and poor pre-operative assessment and treatment (surely a basic aspect of surgical and anaesthetic training?) (271, 296). I hope that the debate about specialist medical training continues, so as to help to overcome many of our present difficulties. National audits such as NCEPOD are vital for the improvement of both training and practice in the UK; I, many juniors, and the public are indebted to NCEPOD. To quote NCEPOD, "we hope to encourage and promote the maintenance of a standard of care in which we all feel pride" (p 126)-so do all junior doctor representatives involved in the wide ranging review of specialist
medical
training.
-
J.
9
Highbury Place, Camden, Bath BA1 6DU, UK
The NHS
as a
-
-
M.
-
FIELDEN,
Honorary Secretary, Wessex Junior Doctors Committee
market for research
developing
year’s meeting of the British Oncology Association provided an opportunity to hear Professor Peckham outline the Department of Health’s overall strategy for structured research and development. His plans give grounds for optimism that research has a high priority. Indeed, we were introduced to a vision of a world in which research and development will flower as never before. In the past the NHS has provided an enviable environment for research, but support has been patchy and results often not fully implemented. Market forces could prove a potent ally in gaining wider acceptance of the need for prospective clinical trials. Limited resources make it essential to identify the most efficient methods of improving care. Trials of treatment efficacy provide the best experimental environment in which to measure quality of life and cost/benefit endpoints. They therefore offer a better investment than blindly buying new treatments and expensive technological toys. If purchasers can be convinced of their value, then many of the existing difficulties associated with funding, recruitment, and implementation might be removed. Dare we hope that the new purchaser/provider arrangements might actually facilitate and encourage participation in randomised trials? The declared NHS goals of equity, effectiveness, responsiveness, efficiency, and appropriateness fit well into a structured research and development programme. Following state-of-the-art protocols offers both clinicians and patients assurance of the delivery of a uniform standard of optimum care. Patients may demand to be managed according to protocol and accept the need to have treatment chosen at random where resources are limited (as in AIDS trials). The less socially motivated can go and purchase potentially toxic therapy of unproven benefit from the private sector. Within the NHS, the ability of a centre to follow the appropriate protocol will help determine the need for specialist rather than local management. Research will become an integral part of the health service, and only protocols making a substantial contribution to the overall health and wealth of the Nation will be undertaken, thus assuring clinical interest and participation. The Government’s generous budget will support research without detracting from other services. We will all have access to the best computing and communications technology for data collection, analysis, and information transfer. Trial results will be rapidly assimilated into medical practice thus enabling everyone to live long, healthy, productive, and tax-paying lives. CRC Trials Unit, Queen Elizabeth Hospital,
LINDA WARD,
Birmingham B15 2TH,
CRC Trials Unit Coordinator
UK
SIR,-The "purchaser-provider" split in the new NHS reared its an unusual way recently. I received an inquiry from a fund-holding general practitioner (GP) about whether his practice would be charged for each attendance of one of their patients at a cardiac rehabilitation trial we are running (twice weekly visits for 6 weeks). The inquiry was to allow the GP to decide on the financial consequences of their patient’s participation in the study and to head in
allow for this in their budget. Implicit in this inquiry was the possibility that if it did not suit the practice, they may not "allow" their patient’s participation. It would be a great shame if clinical trials in the future needed not only the informed consent of the patient, but also the permission of the patient’s (fund holding) GP before recruitment. Will randomised, double-blind clinical trials be possible-with the advances in therapy they bring-in the new NHS? Chesterfield and North Derbyshire Royal Hospital, Chesterfield, Derbyshire S44 5BL, UK
D. A. SANDLER
cancer
SiR,—My medical colleagues are full of gloomy predictions over the effects of National Health Service (NHS) reform on the clinical trials "industry". Is it true that new arrangements for contracting services and the emergence of trust-status hospitals are killing the freedom to undertake prospective research? To run successful trials in the current environment is certainly proving more difficult than before. The symposium on cost-effectiveness in cancer care at this
Smoking
as a on
contributory cause of death death certificates
SiR,—The conclusions of a joint working party of the Royal Colleges of Pathologists, Physicians, and Surgeons (of England) on the use of necropsy in relation to clinical audit were published in booklet form.’ In view of serious discordance between clinical diagnosis before necropsy and diagnosis post mortem (eg, only 75 % agreement that malignant disease was the cause of death of
856
individuals thought on clinical grounds to have died from such diseases, and only 56% accuracy by clinicians in identifying the primary site in cancer cases), the working party concluded that mortality statistics that are not supported by necropsy examinations should be viewed with caution. This conclusion is of serious concern at a time when overall necropsy rates have fallen to less than 20%, and the rates for older people in whom there is no suspicion of occupational or unnatural cause are even lower. Against this background does it really make sense for doctors to be encouraged to put smoking as a cause of death on death certificates? Is the British Medical Association justified in concluding that this new development will "improve the quality and accuracy of statistics on tobacco-related death"?2 If there is no necropsy, and the doctor signing the death certificate gets the cause of death wrong, will it improve the accuracy of statistics if he then opines that smoking contributed to the cause of death? Has any demonstrable benefit emerged in those North American states (ie, Oregon, Utah, Colorado, Washington, and Wisconsin) where certifying doctors have been asked "Did tobacco use contribute to death?"? Doctors, some of whom are far from punctilious in the way they complete death certificates, are likely to vary greatly in how they take advantage of this new facility. Fortunately, the Office of Population Censuses and Surveys will continue to require that certificates identify the disease that constituted the underlying cause of death and smoking will not be accepted as a disease for this purpose. However, whether or not smoking appears on death certificates in the future is likely to depend greatly on the knowledge, whims, and prejudices of individual practitioners. 19 Marryat Road, London SW19 5BB, UK
FRANCIS
J. C. ROE
FETAL AND MATERNAL CARDIOVASCULAR CHANGES IN RESPONSE TO SUBLINGUAL GLYCERYLTRINITRATE
Mean (SE) shown *p =006 and t p=0 018, vs resting value
trinitrate
directly affects the placental circulation in vitro.’Z Moreover, in our patients there were no significant changes in fetal heart rate, suggesting that any general circulatory effects in the fetus were minimum. Further work is needed to find out whether drugs such as glyceryl trinitrate, which cause nitric oxide release and thereby produce vasodilation, will benefit those fetuses with increased resistance in the fetal placental vasculature. We thank Prof Peter Fletcher, John Hunter Hospital, for advice about the dose of glyceryl trinitrate.
Discipline of Reproductive Medicine, University of Newcastle, and Department of Obstetrics and Gynaecology, John Hunter Hospital, Newcastle, New South Wales 2305, Australia
WARWICK GILES STEPHEN O’CALLAGHAN ALAN BOURA WILLIAM WALTERS
joint working party of the Royal College of Pathologists, the Royal College of Physicians of London and the Royal College of Surgeons of England. London: Royal College of Pathologists, 1991: 1-24. Beecham L. Smoking accepted on death certificates. BMJ 1992; 305: 543
NM, King RG, Brennecke SP. Role of endothelium-derived nitric oxide in low fetal vascular resistance in placenta. Lancet 1990; 336: 1589-90. 2. Myatt L, Brewer A, Brockman DE. The action of nitric oxide in the perfused human fetal-placental circulation. Am J Obstet Gynecol 1991; 164: 687-92. 3. Pinto A, Sorrentino R, Sorrentino P, et al. Endothelial-derived relaxing factor released
Reduction in human fetal umbilical-placental vascular resistance by glyceryl trinitrate
endothelial cells of human umbilical vessels and its impairment in pregnancyinduced hypertension. Am J Obstet Gynecol 1991; 164: 507-13. 4 Giles W, Trudinger B, Baird P. Fetal umbilical artery flow velocity waveforms and placental resistance. pathological correlation. Br J Obstet Gynaecol 1985; 92: 31-38. 5. Trudinger BJ, Cook CM, Giles WB, et al. Fetal umbilical artery velocity waveforms and subsequent neonatal outcome. Br J Obstet Gynaecol 1991; 98: 378-84 6. Harper A, Murnaghan GA. Maternal and fetal haemodynamics in hypertensive pregnancies during maternal treatment with intravenous hydralazine or labetalol Br J Obstet Gynaecol 1991; 98: 453-59.
1. Gude
1. The autopsy and audit: report of the
2.
maintenance of
by
SIR,-Nitric oxide may have an important role in the maintenance of low basal fetal vascular tone in the placenta at term.’ Glyceryl trinitrate, which generates nitric oxide, vasodilates the human fetal placental circulation in vitro,2 and nitric oxide release from endothelial cells of umbilical vessels in women with pregnancy-induced hypertension is reduced.3 Placental tertiary stem villous arterial obliteration4 is associated with poor fetal and neonatal outcomes.5 The index of placental vascular resistance most often used is the umbilical arterial systolic/diastolic velocity ratio. We report the effect of glyceryl trinitrate on the human fetal placental circulation in vivo. Five pregnant women aged 21-31 years (mean 25 SD 4-3) were studied at 34-38 (36-4, 1-53) weeks’ gestation. All had been admitted with abnormal umbilical artery velocity ratios, two had pregnancy-induced hypertension, and three had normal blood pressure but impaired fetal growth. All delivered infants with birthweights that were less than the 10th centile for gestational age. After a rest in the supine position for 15 min, initial doppler umbilical artery systolic/diastolic velocity ratios were obtained, after which each woman received 300 (ig glyceryl trinitrate sublingually. The change in velocity ratio in each woman was important because the ratios are dependent on gestational age. At 10 min, umbilical artery systolic/diastolic velocity ratio decreased from baseline by 17%; after 20 min, the mean reduction was 21 %, with a return to baseline after 30 min (Minitab ANOVA p 0-006). There was no change in fetal heart rate or maternal mean arterial blood pressure, nor did the women have side-effects. There was an accompanying increase in mean maternal pulse of 20 per min =
(p = 0018). Reports of other drugs said to affect the fetal-placental circulation have been criticised on the grounds that these agents primarily affect other parts of the fetal circulation.6 On the other hand, glyceryl
Acamprosate as cause of erythema multiforme contested SIR,-Dr Fortier-Beaulieu and colleagues report (April 18,
991) the possible association of erythema multiforme with acamprosate in an alcohol-abusing patient with liver cirrhosis and recent vulvar herpes, suggesting that acamprosate was the cause of this skin reaction. Up to 75 % of all cases of erythema multiforme are often preceded by an attack of herpes simplex virus (HSV 1 or 2), and such cutaneous manifestation may or may not be recurrent. 1,2 We were therefore alarmed by the implication of acamprosate in the development of erythema multiforme in this patient who had had a documented vulvar herpes attack 2-3 weeks earlier. We believe that such implied double pathology needs firm factual evidence, apart from coincidental use, before being accepted as such. We were also concerned about whether this patient did in fact have erythema multiforme. We accordingly obtained the complete hospital records, the original histological report, and the histological slides for this patient from the reporting doctors in Rouen, France, to enable us to review this case with the assistance of some independent experts. Dr A. B. Ackerman, of New York Medical Center, reviewed the slides and reported that several factors argued against a diagnosis of erythema multiforme. From a histopathological view the presence of mounds of parakeratosis visible in the biopsy specimen were evidence against the diagnosis, since these mounds are hardly ever seen in an early evolving lesion of erythema multiforme. He also stated that almost always erythema multiforme lesions affect the p
NCEPOD and UK specialist training SiR,—Dr Fielden states (Aug 29, p 554) that the National Enquiry into Perioperative Deaths condemned the long training in the UK. We would be grateful if he would supply us Confidential
with the reference
to
this
statement
in the report. E. A. CAMPLING H. B. DEVLIN R. W. HOILE J. N. LUNN
NCEPOD, 35 Lincolns Inn Fields, London WC2 3PN, UK
* Thisletter has been shown follows.-ED. L.
Dr
to
Fielden, whose repl3
SIR,-I did not refer to particular parts of the NCEPOE (National Confidential Enquiry into Perioperative Deaths) repon because I, and other junior doctor representatives, believe that the whole report contains important, constructive criticisms of tht training, education, supervision, and application of knowledge oj doctors in the UK. The difference of opinion may be partly due tc interpretation, and editorial interpretation of my original letter may have contributed-my original wording (lst line, paragraph 3: being "The prolonged training, by a process of osmosis whilst halj asleep, has been frequently condemned, most recently by NCEPOD". It should be stated that supervision is an essential aspect of training and that education should not cease once seni01 status is achieved. "Condemnation by NCEPOD", I believe, is a concise description of the many instances where inadequacies oi UK training are reported. The following NCEPOD references are criticisms of our present system that allows junior doctors to undertake unsupervised procedures beyond their ability (pp 120, 126 [b], 188,189, 216, 273. 283). "Lack of supervision or improper delegation can result in junior and inexperienced surgeons doing inappropriate surgery. The patients’ demise was directly related to this in 18 cases" (187); "Presence or availability of a Consultant in only 42% of cases" (216); "It is inappropriate for this grade of surgeon to be left unsupervised in this type of case" (233). With respect to criticisms of poor judgment or lack of expertise, could these not be rectified by better training? (pp 126 a, c, d, e, 127. 186, 192, 261); "there is no place for the occasional oesophageal surgeon (194); "inappropriate use of resources" (211); "Had this surgeon been experienced in the appropriate specialty he might have reconsidered the indication to operate in the first place" (252); "inappropriate operations and grade of operating surgeon" (265). The report mentions inappropriate techniques (188): "are junior surgeons being actively taught the management of patients with complications of hernias?" (240), and refers to lack of involvement of seniors (230) and poor pre-operative assessment and treatment (surely a basic aspect of surgical and anaesthetic training?) (271, 296). I hope that the debate about specialist medical training continues, so as to help to overcome many of our present difficulties. National audits such as NCEPOD are vital for the improvement of both training and practice in the UK; I, many juniors, and the public are indebted to NCEPOD. To quote NCEPOD, "we hope to encourage and promote the maintenance of a standard of care in which we all feel pride" (p 126)-so do all junior doctor representatives involved in the wide ranging review of specialist
medical
training.
-
J.
9
Highbury Place, Camden, Bath BA1 6DU, UK
The NHS
as a
-
-
M.
-
FIELDEN,
Honorary Secretary, Wessex Junior Doctors Committee
market for research
developing
year’s meeting of the British Oncology Association provided an opportunity to hear Professor Peckham outline the Department of Health’s overall strategy for structured research and development. His plans give grounds for optimism that research has a high priority. Indeed, we were introduced to a vision of a world in which research and development will flower as never before. In the past the NHS has provided an enviable environment for research, but support has been patchy and results often not fully implemented. Market forces could prove a potent ally in gaining wider acceptance of the need for prospective clinical trials. Limited resources make it essential to identify the most efficient methods of improving care. Trials of treatment efficacy provide the best experimental environment in which to measure quality of life and cost/benefit endpoints. They therefore offer a better investment than blindly buying new treatments and expensive technological toys. If purchasers can be convinced of their value, then many of the existing difficulties associated with funding, recruitment, and implementation might be removed. Dare we hope that the new purchaser/provider arrangements might actually facilitate and encourage participation in randomised trials? The declared NHS goals of equity, effectiveness, responsiveness, efficiency, and appropriateness fit well into a structured research and development programme. Following state-of-the-art protocols offers both clinicians and patients assurance of the delivery of a uniform standard of optimum care. Patients may demand to be managed according to protocol and accept the need to have treatment chosen at random where resources are limited (as in AIDS trials). The less socially motivated can go and purchase potentially toxic therapy of unproven benefit from the private sector. Within the NHS, the ability of a centre to follow the appropriate protocol will help determine the need for specialist rather than local management. Research will become an integral part of the health service, and only protocols making a substantial contribution to the overall health and wealth of the Nation will be undertaken, thus assuring clinical interest and participation. The Government’s generous budget will support research without detracting from other services. We will all have access to the best computing and communications technology for data collection, analysis, and information transfer. Trial results will be rapidly assimilated into medical practice thus enabling everyone to live long, healthy, productive, and tax-paying lives. CRC Trials Unit, Queen Elizabeth Hospital,
LINDA WARD,
Birmingham B15 2TH,
CRC Trials Unit Coordinator
UK
SIR,-The "purchaser-provider" split in the new NHS reared its an unusual way recently. I received an inquiry from a fund-holding general practitioner (GP) about whether his practice would be charged for each attendance of one of their patients at a cardiac rehabilitation trial we are running (twice weekly visits for 6 weeks). The inquiry was to allow the GP to decide on the financial consequences of their patient’s participation in the study and to head in
allow for this in their budget. Implicit in this inquiry was the possibility that if it did not suit the practice, they may not "allow" their patient’s participation. It would be a great shame if clinical trials in the future needed not only the informed consent of the patient, but also the permission of the patient’s (fund holding) GP before recruitment. Will randomised, double-blind clinical trials be possible-with the advances in therapy they bring-in the new NHS? Chesterfield and North Derbyshire Royal Hospital, Chesterfield, Derbyshire S44 5BL, UK
D. A. SANDLER
cancer
SiR,—My medical colleagues are full of gloomy predictions over the effects of National Health Service (NHS) reform on the clinical trials "industry". Is it true that new arrangements for contracting services and the emergence of trust-status hospitals are killing the freedom to undertake prospective research? To run successful trials in the current environment is certainly proving more difficult than before. The symposium on cost-effectiveness in cancer care at this
Smoking
as a on
contributory cause of death death certificates
SiR,—The conclusions of a joint working party of the Royal Colleges of Pathologists, Physicians, and Surgeons (of England) on the use of necropsy in relation to clinical audit were published in booklet form.’ In view of serious discordance between clinical diagnosis before necropsy and diagnosis post mortem (eg, only 75 % agreement that malignant disease was the cause of death of
856
individuals thought on clinical grounds to have died from such diseases, and only 56% accuracy by clinicians in identifying the primary site in cancer cases), the working party concluded that mortality statistics that are not supported by necropsy examinations should be viewed with caution. This conclusion is of serious concern at a time when overall necropsy rates have fallen to less than 20%, and the rates for older people in whom there is no suspicion of occupational or unnatural cause are even lower. Against this background does it really make sense for doctors to be encouraged to put smoking as a cause of death on death certificates? Is the British Medical Association justified in concluding that this new development will "improve the quality and accuracy of statistics on tobacco-related death"?2 If there is no necropsy, and the doctor signing the death certificate gets the cause of death wrong, will it improve the accuracy of statistics if he then opines that smoking contributed to the cause of death? Has any demonstrable benefit emerged in those North American states (ie, Oregon, Utah, Colorado, Washington, and Wisconsin) where certifying doctors have been asked "Did tobacco use contribute to death?"? Doctors, some of whom are far from punctilious in the way they complete death certificates, are likely to vary greatly in how they take advantage of this new facility. Fortunately, the Office of Population Censuses and Surveys will continue to require that certificates identify the disease that constituted the underlying cause of death and smoking will not be accepted as a disease for this purpose. However, whether or not smoking appears on death certificates in the future is likely to depend greatly on the knowledge, whims, and prejudices of individual practitioners. 19 Marryat Road, London SW19 5BB, UK
FRANCIS
J. C. ROE
FETAL AND MATERNAL CARDIOVASCULAR CHANGES IN RESPONSE TO SUBLINGUAL GLYCERYLTRINITRATE
Mean (SE) shown *p =006 and t p=0 018, vs resting value
trinitrate
directly affects the placental circulation in vitro.’Z Moreover, in our patients there were no significant changes in fetal heart rate, suggesting that any general circulatory effects in the fetus were minimum. Further work is needed to find out whether drugs such as glyceryl trinitrate, which cause nitric oxide release and thereby produce vasodilation, will benefit those fetuses with increased resistance in the fetal placental vasculature. We thank Prof Peter Fletcher, John Hunter Hospital, for advice about the dose of glyceryl trinitrate.
Discipline of Reproductive Medicine, University of Newcastle, and Department of Obstetrics and Gynaecology, John Hunter Hospital, Newcastle, New South Wales 2305, Australia
WARWICK GILES STEPHEN O’CALLAGHAN ALAN BOURA WILLIAM WALTERS
joint working party of the Royal College of Pathologists, the Royal College of Physicians of London and the Royal College of Surgeons of England. London: Royal College of Pathologists, 1991: 1-24. Beecham L. Smoking accepted on death certificates. BMJ 1992; 305: 543
NM, King RG, Brennecke SP. Role of endothelium-derived nitric oxide in low fetal vascular resistance in placenta. Lancet 1990; 336: 1589-90. 2. Myatt L, Brewer A, Brockman DE. The action of nitric oxide in the perfused human fetal-placental circulation. Am J Obstet Gynecol 1991; 164: 687-92. 3. Pinto A, Sorrentino R, Sorrentino P, et al. Endothelial-derived relaxing factor released
Reduction in human fetal umbilical-placental vascular resistance by glyceryl trinitrate
endothelial cells of human umbilical vessels and its impairment in pregnancyinduced hypertension. Am J Obstet Gynecol 1991; 164: 507-13. 4 Giles W, Trudinger B, Baird P. Fetal umbilical artery flow velocity waveforms and placental resistance. pathological correlation. Br J Obstet Gynaecol 1985; 92: 31-38. 5. Trudinger BJ, Cook CM, Giles WB, et al. Fetal umbilical artery velocity waveforms and subsequent neonatal outcome. Br J Obstet Gynaecol 1991; 98: 378-84 6. Harper A, Murnaghan GA. Maternal and fetal haemodynamics in hypertensive pregnancies during maternal treatment with intravenous hydralazine or labetalol Br J Obstet Gynaecol 1991; 98: 453-59.
1. Gude
1. The autopsy and audit: report of the
2.
maintenance of
by
SIR,-Nitric oxide may have an important role in the maintenance of low basal fetal vascular tone in the placenta at term.’ Glyceryl trinitrate, which generates nitric oxide, vasodilates the human fetal placental circulation in vitro,2 and nitric oxide release from endothelial cells of umbilical vessels in women with pregnancy-induced hypertension is reduced.3 Placental tertiary stem villous arterial obliteration4 is associated with poor fetal and neonatal outcomes.5 The index of placental vascular resistance most often used is the umbilical arterial systolic/diastolic velocity ratio. We report the effect of glyceryl trinitrate on the human fetal placental circulation in vivo. Five pregnant women aged 21-31 years (mean 25 SD 4-3) were studied at 34-38 (36-4, 1-53) weeks’ gestation. All had been admitted with abnormal umbilical artery velocity ratios, two had pregnancy-induced hypertension, and three had normal blood pressure but impaired fetal growth. All delivered infants with birthweights that were less than the 10th centile for gestational age. After a rest in the supine position for 15 min, initial doppler umbilical artery systolic/diastolic velocity ratios were obtained, after which each woman received 300 (ig glyceryl trinitrate sublingually. The change in velocity ratio in each woman was important because the ratios are dependent on gestational age. At 10 min, umbilical artery systolic/diastolic velocity ratio decreased from baseline by 17%; after 20 min, the mean reduction was 21 %, with a return to baseline after 30 min (Minitab ANOVA p 0-006). There was no change in fetal heart rate or maternal mean arterial blood pressure, nor did the women have side-effects. There was an accompanying increase in mean maternal pulse of 20 per min =
(p = 0018). Reports of other drugs said to affect the fetal-placental circulation have been criticised on the grounds that these agents primarily affect other parts of the fetal circulation.6 On the other hand, glyceryl
Acamprosate as cause of erythema multiforme contested SIR,-Dr Fortier-Beaulieu and colleagues report (April 18,
991) the possible association of erythema multiforme with acamprosate in an alcohol-abusing patient with liver cirrhosis and recent vulvar herpes, suggesting that acamprosate was the cause of this skin reaction. Up to 75 % of all cases of erythema multiforme are often preceded by an attack of herpes simplex virus (HSV 1 or 2), and such cutaneous manifestation may or may not be recurrent. 1,2 We were therefore alarmed by the implication of acamprosate in the development of erythema multiforme in this patient who had had a documented vulvar herpes attack 2-3 weeks earlier. We believe that such implied double pathology needs firm factual evidence, apart from coincidental use, before being accepted as such. We were also concerned about whether this patient did in fact have erythema multiforme. We accordingly obtained the complete hospital records, the original histological report, and the histological slides for this patient from the reporting doctors in Rouen, France, to enable us to review this case with the assistance of some independent experts. Dr A. B. Ackerman, of New York Medical Center, reviewed the slides and reported that several factors argued against a diagnosis of erythema multiforme. From a histopathological view the presence of mounds of parakeratosis visible in the biopsy specimen were evidence against the diagnosis, since these mounds are hardly ever seen in an early evolving lesion of erythema multiforme. He also stated that almost always erythema multiforme lesions affect the p
