252
Managing hypertension
in the
elderly
SiR,—The STOP-Hypertension trial (Nov 23, p 1281) compared four different once-daily medications for hypertension (atenolol, hydrochlorothiazide plus amiloride, metoprolol, and pindolol) with matching placebos, but in the report the results of the active treatments are lumped together. We are not even told how many patients received each treatment. Did the active treatments differ in their therapeutic or in their unwanted effects? I would certainly expect differences in the adverse effect profiles. And why was
this information omitted?
9 Park Crescent, London N3 2NL, UK
ANDREW HERXHEIMER
** This letter has been shown to Dr Dahlof and colleagues, whose reply follows.-ED. L. SIR,-A clearly stated aim in the STOP study was to evaluate "active treatment" versus placebo. An analysis of the effects of each of the four active regimens separately on hard end-points was never intended. It would be scientifically inappropriate to make such a post-hoc subgroup analysis, a procedure that regrettably is not uncommon in studies of this kind. The fact that 68% of all patients on active therapy were on combined treatment with one of the three
P-blockers
and the diuretic does not increase
our
urge to do the
subgroup analysis proposed. Department of Medicine, University of Gothenburg, Ostra Hospital, S-146 85 Gothenberg, Sweden, Health Sciences Centre, University of Lund, Dalby, and Department of Medicine, University Hospital, Umeå
B. DAHLÖF L. H. LINDHOLM L. HANSSON B. SCHERSTÉN T. EKBOM P. O. WESTER
SiR,—Your editorial commenting on the SHEP and STOPHypertension trials (Nov 23, p 1299) concludes that previous concerns about treating elderly hypertensive patients are unwarranted. But there is a new risk in treating older hypertensive patients which needs attention. Brandt et aP recently reported a group of old patients with severe systemic hypertension who were found to have hypertrophic cardiomyopathy with left-ventricular outflow obstruction (demonstrated by an isoproterenol test). Recognition of this group is clinically important because use of afterload-reducing agents, such as arterial vasodilators and angiotensin-converting-enzyme inhibitors or/and preloadreducing agents such as diuretics and nitrates, both of which may aggravate left-ventricular outflow obstruction of the dynamic variety, will be harmful. The frequency with which this group is met in clinical practice needs further study. Department of Medicine, George Washington University, Washington, DC 20037, USA 1. Brandt
TSUNG O. CHENG
CM, Boulenc JM, Carriere T, Verdun A, Imbs JL Myocardiopathie du ventncule gauche
hypertrophique avec syndrome d’obstruction dynamique chez l’adulte hypertendu. Presse Méd 1991; 20: 1923-26.
contact, the immediate environment, or some other route does not affect the validity of the notion of separation of a potential source of infection from those at risk of acquisition of that infection. For 4 years our policy has been geographical separation of colonised and non-colonised patients in our CF clinic of over 100 adults, both as inpatients and outpatients, through the use of separate wards and clinics. Despite these measures, in 1991 we noted 5 new cases of Ps cepacia infection. Ribotyping of the organisms isolated from these 5 patients revealed that 3 have strains that are indistinguishable. These 3 patients had had no contact with each other within the hospital environment or with patients known to be colonised with Ps cepacia. However, inquiry into their social contacts outside the hospital environment has revealed episodes of contact between these 3 patients and other CF individuals whose microbiological status is not known to us. We believe that this provides further evidence of the possibility of person-to-person transmission of Ps cepacia among the CF community outside the hospital environment.s We now advise our patients that, although the level of risk remains to be defmed, there may be transmission of Ps cepacia through social as well as hospital contact and that social contact should be kept to a minimum. We suggest that until Ps cepacia can be shown not to be infectious, and that it does not lead to accelerated deterioration or premature death in some patients, then we should err on the side of safety. There are clearly important issues arising from such advice which can only be addressed in consultation with individual patients. The adoption of this advice has been very difficult for some patients, their families, and members of the CF team. However, we have been heartened by their response to open discussion of these difficulties. We thank Dr Ty Pitt for
ribotype analysis of Ps cepacia strains.
I, Corey M, et al. Pseudomonas cepacia infection in cystic fibrosis: an emerging problem. J Pediatr 1984, 104: 206-10. 2. Simmonds EJ, Conway SP, Ghoneim ATM, Ross H, Littlewood JM. Ps cepacia. a new pathogen in patients with cystic fibrosis referred to a large centre m the United Kingdom Arch Dis Child 1990; 65: 874-77. 3. Gilligan PH. Microbiology of airways disease in patients with cystic fibrosis. Clin 1. Isles A, Maclusky
Microbiol Rev 1991; 4: 35-51. 4. Tablan OC, Martone WJ, Doershuk CF, et al. Colonisation of the respiratory tract with Ps cepacia in cystic fibrosis: risk factors and outcomes. Chest 1987; 91: 527-32 5. LiPuma JJ, Dasen SE, Nielson DW, Stem RC, Stull TL. Person-to-person transmission of Ps cepacia between patients with cystic fibrosis. Lancet 1990; 336: 1094-96. 6. Rabkin CS, Jarvis WR, Anderson RL, et al. Ps cepacia typing systems: collaborative study to assess their potential in epidemiological investigations. Rev Infect Dis 1989, 11: 600-07 7. Gilligan PH, Gage PA, Bradshaw LM, Schidlow DV, Decicco BT. Isolation medium for the recovery of Ps cepacia from the respiratory secretions of patients with cystic fibrosis. J Clin Microbiol 1985, 22: 5-8. 8 Thomassen MJ, Demko CA, Klinger JD, Stem RC. Ps cepacia colonisation amongst patients with cystic fibrosis: a new opportunist. Am Rev Respir Dis 1985; 131: 791-96.
Childhood leukaemia
Pseudomonas cepacia infection in cystic fibrosis SiR,—Dr Nelson and colleagues (Dec 14, p 1525) report success in isolating Pseudomonas cepacia from the immediate environment of two colonised cystic fibrosis (CF) patients in hospital. They rightly point out the importance of the use of selective media and comment that their results confirm the potential for indirect transmission of Ps cepacia between patients. They do not, however, reach any firm conclusions about some aspects of the management of colonised patients either from their own work or from the publications that they cited Our experience and that of others’-4,8 is that acquisition of Ps cepacia for some patients with CF heralds the onset of increased morbidity and unexpected early death. Although the precise mode of transmission remains unknown, evidence suggests that colonised patients are a potential source for transmission to non-colonised patients. Whether transmission is via droplet spread, physical
D. L. SMITH E. G. SMITH L. B. GUMERY D. E. STABLEFORTH
Adult Cystic Fibrosis Unit and Department of Microbiology, East Birmingham Hospital, Birmingham B9 5ST, UK
on
Greek Islands
SIR,—Ur Petridou and colleagues (Nov 9, p 1204) raise when
an
interesting possibility they imply that mass tourism may involve the type of population mixing that is conducive to an increase of childhood leukaemia, as found in rural new towns in Britain and in keeping with my hypothesis.’ However, those towns experienced increases only in the first decade of their existence, after which there was no excess. Still more limited in time was the increase of childhood leukaemia recorded near large military encampments in England and Wales early in the period of post-war national military service.2 Petridou and colleagues were able to study leukaemia mortality on Greek islands only in a period starting in 1976--ie, about 15 years after the start of large-scale tourism there. Since no excess of childhood leukaemia was observed in new towns in the corresponding period, it is incorrect to state that the Greek results "do not seem compatible with" my hypothesis. Petridou and colleagues acknowledge that the population mixing involved in tourism may not be comparable with that in British new
253
in their period of rapid growth. Much more comparable to the latter were the large population movements in mainland Greece from rural areas to the towns during its civil war, the 1950s and beyond, and about which much has been written. Indeed, the recent urbanisation of Greece has been more rapid than in most countries at a comparable stage of socioeconomic development. In consequence, for example, whereas 27% of the nation lived below an altitude of 100 m in 1951, this had risen to 55% in 1961.3 This could be investigated by examining mortality from childhood leukaemia in Greece in relation to that of other countries in the 1960s, when modem therapy had not yet affected national rates. towns
Department of Public Health and Primary Care, CRC Cancer Epidemiology Research Group, University of Oxford, Radcliffe Infirmary, Oxford 0X2 6HE, UK 1. Kinlen
L. J. KINLEN
LJ, Clarke K, Hudson C. Evidence from population mixing in British new
1946-85 of an infective basis for childhood leukaemia. Lancet 1990; 336: 577-82. 2 Kinlen LJ, Hudson C. Childhood leukaemia and poliomyelitis in relation to military encampments m England and Wales in the period of national military service 1950-63 Br Med J 1991; 303: 1357-62. 3. Carter FW. In Clout HD, ed. Regional development of Western Europe. London: David Fulton, 1987: chap 18. towns
Fashions in
breastfeeding
SiR,-It is often amazing what medical publications are noticed and how their findings are implemented. A new fashion in breastfeeding in Australia is that mothers are being told to feed from only one breast at each feed. The most extreme example of this type of advice was a woman with twins who was told to feed both babies from the same (one) breast at each feed. This fashion seems to come from overinterpretation of studies such as that by Woolridge and Fisher.1 They suggested that failure to thrive in some babies might have resulted from a lack of higher-energy hind-milk if the mother follows the timed feeds on each side routine. But in fact Woolridge and Fisher’ actually stated that the baby should "come off the breast spontaneously before being offered the second breast should the baby still show signs of hunger". Moreover, a recent study has shown that the amount of milk in a breast varies before each feed and that the fat content of breastmilk does not increase substantially until the breast is 40% empty.2Therefore this new fashion will probably have little effect on the average infant’s fat intake at any particular feed whereas it may lead to discomfort for the mother. We seem to have replaced one dogma with another, equally unfounded. Department of Public Health, University of Sydney, NSW 2006, Australia
DOROTHY MACKERRAS
1. Woolridge MW, Fisher C. Colic, "overfeeding", and symptoms of malabsorption in the breast-fed baby: a possible artifact of feed management? Lancet 1987; ii: 382-84. 2 Daly SEJ, Kent JC, Atwood CS, et al. Breastmilk fat content increases with the degree of breast emptying. Proc Nutr Soc Aust 1991; 16: 126.
Catamenial an
epilepsy and goserelin
SIR,-Dr Haider and Professor Barnett (Dec 14, p 1530) report improvement in seizure frequency in catamenial epilepsy treated
with goserelin. They suggest that reduction of serum oestradiol concentrations with this gonadotropin releasing hormone (GnRH) analogue might explain the improvement. We propose that the abolition of cyclical fluctuations of sex steroids might be the mechanism. In premenstrual syndrome (PMS), menstrual migraine, and catamenial epilepsy, the cause of the cyclical features remains elusive. It is recognised, however, that complete suppression of ovarian activity can abolish these symptoms.1,2 The hypo-oestrogenic state induced by GnRH therapy indicates effective ovarian suppression and the clinical improvement described could be due to the elimination of cyclical changes in ovarian hormones. We would caution against long-term therapy with a GnRH analogue, which effectively creates a medical oophorectomy. Prolonged hypo-oestrogenism significantly increases the risk of osteoporosis and cardiovascular disease.3,4Additionally, patients
commonly experience flushing, vaginal dryness, and dyspareunia.5 replacement therapy (HRT) can prevent such complications, and we have reported the long-term use of goserelin with continuous combined HRT in a patient with severe endometriosis.6 We used goserelin 3-6 mg every 4 weeks with medroxyprogesterone acetate (’Provera’) 5 mg and conjugated Hormone
(’Premarin’) 0625 mg, both taken daily and continuously. The endometriosis resolved, she remained amenorrhoeic, and preservation of bone-mineral density was confirmed by dual-energy X-ray absorptiometry. No hypooestrogenic symptoms were seen during 12 months of treatment. We propose that continuous combined HRT supplementation6 will not negate the benefits of goserelin. Cyclical changes of ovarian hormones rather than their absolute concentrations are now widely believed to be important in the genesis of menstrually related disorders. Thus, it is not surprising that the combined oral contraceptive pill, with its seven day pill-free interval, was not effective. Premarin 0 625 mg daily is a bone-conserving doseand might protect the cardiovascular system.’ oestrogens
Department of Obstetrics and Gynaecology, St Mary’s Hospital Medical School, London W2 1PG, UK
B. A. REID K. F. GANGAR
Magos A. Advances in the treatment of the premenstrual syndrome. Br J Obstet Gynaecol 1990; 97: 7-11 2. Magos AL, Zilkhar KJ, Studd JWW. Treatment of menstrual migraine by oestradiol implants. J Neurol Neurosurg Psychiatry 1983, 46: 1044. 3. Dodm S, Lemay AS, Maheux R, Dumont M, Turcot-Lemay L. Bone mass in endometriosis patients treated with GnRH agonist implant or danazol. Obstet Gynecol 1991, 77: 410-15. 4. Stampfer MJ, Colditz GA, Willett WC, et al. Postmenopausal estrogen therapy and cardiovascular disease: ten year follow-up from the nurses’ health study. N Engl J Med 1991; 325: 756-62. 5. Shaw RW. LHRH analogue in the treatment of endometriosis: comparative results with other treatment. Ballière’s Clin Obstet Gynaecol 1988; ii: 659-75. 6. Reid BA, Gangar KF, Beard RW. Severe endometriosis treated with gonadotrophin releasing hormone agonist and continuous combined hormone replacement therapy. Br J Obstet Gynaecol (in press). 7. Stevenson JC, Cust MP, Gangar KF, Hillard TC, Lees B, Whitehead MI. Effects of transdermal versus oral hormone replacement therapy on bone density in spine and proximal femur in postmenopausal women. Lancet 1990; 336: 265-69. 1.
Post-transfusion fulminant hepatitis B after screening for hepatitis B virus core antibody SIR,-Since November, 1989, Japanese Red Cross Blood Centres have screened blood for units with high-titre (2) antibody to hepatitis B virus core antigen (HBcAb) in addition to hepatitis B surface antigen (HBsAg) and surface antibody (HBsAb). The aim of the introduction of the additional HBcAb screening is to reduce the frequency of post-transfusion hepatitis B infection, especially of the fulminant type. The Japanese Red Cross Non-A, Non-B Hepatitis Research Group report (Oct 26, p 1040) complete protection from post-transfusion hepatitis B since the introduction of screening for HBcAb. We have seen the first case of posttransfusion fulminant hepatitis B since the start of this screening. A 70-year-old man was admitted to Showa University Fujigaoka Hospital on Sept 19, 1991, because of fever and jaundice. He had undergone resection of the entire transverse colon because of carcinoma on April 12 of that year. At operation he received four units of blood from four donors. His liver disease began with a slight fever and urine colour change at the beginning of September. On admission he was jaundiced, and liver atrophy was confirmed by ultrasonography. Total bilirubin was 110 mg/dl, aspartate aminotransferase 821 U/1, alanine aminotransferase 940 U/1, and prothrombin time (PT) 43-8%. He was positive for HBsAg, HBeAg, IgM HBcAb, and HBV DNA (by polymerase chain reaction (PCR), and negative for HBsAb, HBeAg, IgM HAVAb, and HCVAb (anti-Cl00). Subsequently PT became undetectable, and grade IIcoma developed on Oct 21. He was immediately placed on liver-support treatment, consisting of plasma exchange and haemofiltration.1 After three such treatments he regained clear consciousness with recovery of liver functions. He continued to improve and was discharged on October 26. The original serum samples from the four blood donors were not available for HBV DNA assay by PCR. The donors, however, were traced by the Japanese Red Cross Kawasaki Blood Centre, and they
Managing hypertension
in the
elderly
SiR,—The STOP-Hypertension trial (Nov 23, p 1281) compared four different once-daily medications for hypertension (atenolol, hydrochlorothiazide plus amiloride, metoprolol, and pindolol) with matching placebos, but in the report the results of the active treatments are lumped together. We are not even told how many patients received each treatment. Did the active treatments differ in their therapeutic or in their unwanted effects? I would certainly expect differences in the adverse effect profiles. And why was
this information omitted?
9 Park Crescent, London N3 2NL, UK
ANDREW HERXHEIMER
** This letter has been shown to Dr Dahlof and colleagues, whose reply follows.-ED. L. SIR,-A clearly stated aim in the STOP study was to evaluate "active treatment" versus placebo. An analysis of the effects of each of the four active regimens separately on hard end-points was never intended. It would be scientifically inappropriate to make such a post-hoc subgroup analysis, a procedure that regrettably is not uncommon in studies of this kind. The fact that 68% of all patients on active therapy were on combined treatment with one of the three
P-blockers
and the diuretic does not increase
our
urge to do the
subgroup analysis proposed. Department of Medicine, University of Gothenburg, Ostra Hospital, S-146 85 Gothenberg, Sweden, Health Sciences Centre, University of Lund, Dalby, and Department of Medicine, University Hospital, Umeå
B. DAHLÖF L. H. LINDHOLM L. HANSSON B. SCHERSTÉN T. EKBOM P. O. WESTER
SiR,—Your editorial commenting on the SHEP and STOPHypertension trials (Nov 23, p 1299) concludes that previous concerns about treating elderly hypertensive patients are unwarranted. But there is a new risk in treating older hypertensive patients which needs attention. Brandt et aP recently reported a group of old patients with severe systemic hypertension who were found to have hypertrophic cardiomyopathy with left-ventricular outflow obstruction (demonstrated by an isoproterenol test). Recognition of this group is clinically important because use of afterload-reducing agents, such as arterial vasodilators and angiotensin-converting-enzyme inhibitors or/and preloadreducing agents such as diuretics and nitrates, both of which may aggravate left-ventricular outflow obstruction of the dynamic variety, will be harmful. The frequency with which this group is met in clinical practice needs further study. Department of Medicine, George Washington University, Washington, DC 20037, USA 1. Brandt
TSUNG O. CHENG
CM, Boulenc JM, Carriere T, Verdun A, Imbs JL Myocardiopathie du ventncule gauche
hypertrophique avec syndrome d’obstruction dynamique chez l’adulte hypertendu. Presse Méd 1991; 20: 1923-26.
contact, the immediate environment, or some other route does not affect the validity of the notion of separation of a potential source of infection from those at risk of acquisition of that infection. For 4 years our policy has been geographical separation of colonised and non-colonised patients in our CF clinic of over 100 adults, both as inpatients and outpatients, through the use of separate wards and clinics. Despite these measures, in 1991 we noted 5 new cases of Ps cepacia infection. Ribotyping of the organisms isolated from these 5 patients revealed that 3 have strains that are indistinguishable. These 3 patients had had no contact with each other within the hospital environment or with patients known to be colonised with Ps cepacia. However, inquiry into their social contacts outside the hospital environment has revealed episodes of contact between these 3 patients and other CF individuals whose microbiological status is not known to us. We believe that this provides further evidence of the possibility of person-to-person transmission of Ps cepacia among the CF community outside the hospital environment.s We now advise our patients that, although the level of risk remains to be defmed, there may be transmission of Ps cepacia through social as well as hospital contact and that social contact should be kept to a minimum. We suggest that until Ps cepacia can be shown not to be infectious, and that it does not lead to accelerated deterioration or premature death in some patients, then we should err on the side of safety. There are clearly important issues arising from such advice which can only be addressed in consultation with individual patients. The adoption of this advice has been very difficult for some patients, their families, and members of the CF team. However, we have been heartened by their response to open discussion of these difficulties. We thank Dr Ty Pitt for
ribotype analysis of Ps cepacia strains.
I, Corey M, et al. Pseudomonas cepacia infection in cystic fibrosis: an emerging problem. J Pediatr 1984, 104: 206-10. 2. Simmonds EJ, Conway SP, Ghoneim ATM, Ross H, Littlewood JM. Ps cepacia. a new pathogen in patients with cystic fibrosis referred to a large centre m the United Kingdom Arch Dis Child 1990; 65: 874-77. 3. Gilligan PH. Microbiology of airways disease in patients with cystic fibrosis. Clin 1. Isles A, Maclusky
Microbiol Rev 1991; 4: 35-51. 4. Tablan OC, Martone WJ, Doershuk CF, et al. Colonisation of the respiratory tract with Ps cepacia in cystic fibrosis: risk factors and outcomes. Chest 1987; 91: 527-32 5. LiPuma JJ, Dasen SE, Nielson DW, Stem RC, Stull TL. Person-to-person transmission of Ps cepacia between patients with cystic fibrosis. Lancet 1990; 336: 1094-96. 6. Rabkin CS, Jarvis WR, Anderson RL, et al. Ps cepacia typing systems: collaborative study to assess their potential in epidemiological investigations. Rev Infect Dis 1989, 11: 600-07 7. Gilligan PH, Gage PA, Bradshaw LM, Schidlow DV, Decicco BT. Isolation medium for the recovery of Ps cepacia from the respiratory secretions of patients with cystic fibrosis. J Clin Microbiol 1985, 22: 5-8. 8 Thomassen MJ, Demko CA, Klinger JD, Stem RC. Ps cepacia colonisation amongst patients with cystic fibrosis: a new opportunist. Am Rev Respir Dis 1985; 131: 791-96.
Childhood leukaemia
Pseudomonas cepacia infection in cystic fibrosis SiR,—Dr Nelson and colleagues (Dec 14, p 1525) report success in isolating Pseudomonas cepacia from the immediate environment of two colonised cystic fibrosis (CF) patients in hospital. They rightly point out the importance of the use of selective media and comment that their results confirm the potential for indirect transmission of Ps cepacia between patients. They do not, however, reach any firm conclusions about some aspects of the management of colonised patients either from their own work or from the publications that they cited Our experience and that of others’-4,8 is that acquisition of Ps cepacia for some patients with CF heralds the onset of increased morbidity and unexpected early death. Although the precise mode of transmission remains unknown, evidence suggests that colonised patients are a potential source for transmission to non-colonised patients. Whether transmission is via droplet spread, physical
D. L. SMITH E. G. SMITH L. B. GUMERY D. E. STABLEFORTH
Adult Cystic Fibrosis Unit and Department of Microbiology, East Birmingham Hospital, Birmingham B9 5ST, UK
on
Greek Islands
SIR,—Ur Petridou and colleagues (Nov 9, p 1204) raise when
an
interesting possibility they imply that mass tourism may involve the type of population mixing that is conducive to an increase of childhood leukaemia, as found in rural new towns in Britain and in keeping with my hypothesis.’ However, those towns experienced increases only in the first decade of their existence, after which there was no excess. Still more limited in time was the increase of childhood leukaemia recorded near large military encampments in England and Wales early in the period of post-war national military service.2 Petridou and colleagues were able to study leukaemia mortality on Greek islands only in a period starting in 1976--ie, about 15 years after the start of large-scale tourism there. Since no excess of childhood leukaemia was observed in new towns in the corresponding period, it is incorrect to state that the Greek results "do not seem compatible with" my hypothesis. Petridou and colleagues acknowledge that the population mixing involved in tourism may not be comparable with that in British new
253
in their period of rapid growth. Much more comparable to the latter were the large population movements in mainland Greece from rural areas to the towns during its civil war, the 1950s and beyond, and about which much has been written. Indeed, the recent urbanisation of Greece has been more rapid than in most countries at a comparable stage of socioeconomic development. In consequence, for example, whereas 27% of the nation lived below an altitude of 100 m in 1951, this had risen to 55% in 1961.3 This could be investigated by examining mortality from childhood leukaemia in Greece in relation to that of other countries in the 1960s, when modem therapy had not yet affected national rates. towns
Department of Public Health and Primary Care, CRC Cancer Epidemiology Research Group, University of Oxford, Radcliffe Infirmary, Oxford 0X2 6HE, UK 1. Kinlen
L. J. KINLEN
LJ, Clarke K, Hudson C. Evidence from population mixing in British new
1946-85 of an infective basis for childhood leukaemia. Lancet 1990; 336: 577-82. 2 Kinlen LJ, Hudson C. Childhood leukaemia and poliomyelitis in relation to military encampments m England and Wales in the period of national military service 1950-63 Br Med J 1991; 303: 1357-62. 3. Carter FW. In Clout HD, ed. Regional development of Western Europe. London: David Fulton, 1987: chap 18. towns
Fashions in
breastfeeding
SiR,-It is often amazing what medical publications are noticed and how their findings are implemented. A new fashion in breastfeeding in Australia is that mothers are being told to feed from only one breast at each feed. The most extreme example of this type of advice was a woman with twins who was told to feed both babies from the same (one) breast at each feed. This fashion seems to come from overinterpretation of studies such as that by Woolridge and Fisher.1 They suggested that failure to thrive in some babies might have resulted from a lack of higher-energy hind-milk if the mother follows the timed feeds on each side routine. But in fact Woolridge and Fisher’ actually stated that the baby should "come off the breast spontaneously before being offered the second breast should the baby still show signs of hunger". Moreover, a recent study has shown that the amount of milk in a breast varies before each feed and that the fat content of breastmilk does not increase substantially until the breast is 40% empty.2Therefore this new fashion will probably have little effect on the average infant’s fat intake at any particular feed whereas it may lead to discomfort for the mother. We seem to have replaced one dogma with another, equally unfounded. Department of Public Health, University of Sydney, NSW 2006, Australia
DOROTHY MACKERRAS
1. Woolridge MW, Fisher C. Colic, "overfeeding", and symptoms of malabsorption in the breast-fed baby: a possible artifact of feed management? Lancet 1987; ii: 382-84. 2 Daly SEJ, Kent JC, Atwood CS, et al. Breastmilk fat content increases with the degree of breast emptying. Proc Nutr Soc Aust 1991; 16: 126.
Catamenial an
epilepsy and goserelin
SIR,-Dr Haider and Professor Barnett (Dec 14, p 1530) report improvement in seizure frequency in catamenial epilepsy treated
with goserelin. They suggest that reduction of serum oestradiol concentrations with this gonadotropin releasing hormone (GnRH) analogue might explain the improvement. We propose that the abolition of cyclical fluctuations of sex steroids might be the mechanism. In premenstrual syndrome (PMS), menstrual migraine, and catamenial epilepsy, the cause of the cyclical features remains elusive. It is recognised, however, that complete suppression of ovarian activity can abolish these symptoms.1,2 The hypo-oestrogenic state induced by GnRH therapy indicates effective ovarian suppression and the clinical improvement described could be due to the elimination of cyclical changes in ovarian hormones. We would caution against long-term therapy with a GnRH analogue, which effectively creates a medical oophorectomy. Prolonged hypo-oestrogenism significantly increases the risk of osteoporosis and cardiovascular disease.3,4Additionally, patients
commonly experience flushing, vaginal dryness, and dyspareunia.5 replacement therapy (HRT) can prevent such complications, and we have reported the long-term use of goserelin with continuous combined HRT in a patient with severe endometriosis.6 We used goserelin 3-6 mg every 4 weeks with medroxyprogesterone acetate (’Provera’) 5 mg and conjugated Hormone
(’Premarin’) 0625 mg, both taken daily and continuously. The endometriosis resolved, she remained amenorrhoeic, and preservation of bone-mineral density was confirmed by dual-energy X-ray absorptiometry. No hypooestrogenic symptoms were seen during 12 months of treatment. We propose that continuous combined HRT supplementation6 will not negate the benefits of goserelin. Cyclical changes of ovarian hormones rather than their absolute concentrations are now widely believed to be important in the genesis of menstrually related disorders. Thus, it is not surprising that the combined oral contraceptive pill, with its seven day pill-free interval, was not effective. Premarin 0 625 mg daily is a bone-conserving doseand might protect the cardiovascular system.’ oestrogens
Department of Obstetrics and Gynaecology, St Mary’s Hospital Medical School, London W2 1PG, UK
B. A. REID K. F. GANGAR
Magos A. Advances in the treatment of the premenstrual syndrome. Br J Obstet Gynaecol 1990; 97: 7-11 2. Magos AL, Zilkhar KJ, Studd JWW. Treatment of menstrual migraine by oestradiol implants. J Neurol Neurosurg Psychiatry 1983, 46: 1044. 3. Dodm S, Lemay AS, Maheux R, Dumont M, Turcot-Lemay L. Bone mass in endometriosis patients treated with GnRH agonist implant or danazol. Obstet Gynecol 1991, 77: 410-15. 4. Stampfer MJ, Colditz GA, Willett WC, et al. Postmenopausal estrogen therapy and cardiovascular disease: ten year follow-up from the nurses’ health study. N Engl J Med 1991; 325: 756-62. 5. Shaw RW. LHRH analogue in the treatment of endometriosis: comparative results with other treatment. Ballière’s Clin Obstet Gynaecol 1988; ii: 659-75. 6. Reid BA, Gangar KF, Beard RW. Severe endometriosis treated with gonadotrophin releasing hormone agonist and continuous combined hormone replacement therapy. Br J Obstet Gynaecol (in press). 7. Stevenson JC, Cust MP, Gangar KF, Hillard TC, Lees B, Whitehead MI. Effects of transdermal versus oral hormone replacement therapy on bone density in spine and proximal femur in postmenopausal women. Lancet 1990; 336: 265-69. 1.
Post-transfusion fulminant hepatitis B after screening for hepatitis B virus core antibody SIR,-Since November, 1989, Japanese Red Cross Blood Centres have screened blood for units with high-titre (2) antibody to hepatitis B virus core antigen (HBcAb) in addition to hepatitis B surface antigen (HBsAg) and surface antibody (HBsAb). The aim of the introduction of the additional HBcAb screening is to reduce the frequency of post-transfusion hepatitis B infection, especially of the fulminant type. The Japanese Red Cross Non-A, Non-B Hepatitis Research Group report (Oct 26, p 1040) complete protection from post-transfusion hepatitis B since the introduction of screening for HBcAb. We have seen the first case of posttransfusion fulminant hepatitis B since the start of this screening. A 70-year-old man was admitted to Showa University Fujigaoka Hospital on Sept 19, 1991, because of fever and jaundice. He had undergone resection of the entire transverse colon because of carcinoma on April 12 of that year. At operation he received four units of blood from four donors. His liver disease began with a slight fever and urine colour change at the beginning of September. On admission he was jaundiced, and liver atrophy was confirmed by ultrasonography. Total bilirubin was 110 mg/dl, aspartate aminotransferase 821 U/1, alanine aminotransferase 940 U/1, and prothrombin time (PT) 43-8%. He was positive for HBsAg, HBeAg, IgM HBcAb, and HBV DNA (by polymerase chain reaction (PCR), and negative for HBsAb, HBeAg, IgM HAVAb, and HCVAb (anti-Cl00). Subsequently PT became undetectable, and grade IIcoma developed on Oct 21. He was immediately placed on liver-support treatment, consisting of plasma exchange and haemofiltration.1 After three such treatments he regained clear consciousness with recovery of liver functions. He continued to improve and was discharged on October 26. The original serum samples from the four blood donors were not available for HBV DNA assay by PCR. The donors, however, were traced by the Japanese Red Cross Kawasaki Blood Centre, and they
