962 tory conditions of the digestive tract, such as oesophagitis,’o and ulcerative colitis (see p. 988), in which over-
production of prostagiandinS41 51 may play a part. NEURONAL LOSS IN INFANCY IN general, morbidity-rates tend to parallel respective mortality-rates, and this is especially true in infancy where the stresses of perinatal events, trauma, infection, and nutritional deprivation represent the main threats to wellbeing as well as to survival. The neuraxis is particularly at hazard, and it is the lagging neurodevelop-
mental progress after otherwise successful treatment of an acute illness which advertises the saddest sequelae. With improved obstetric and perinatal care, not only perinatal death but also mental and physical handicap have become less frequent among those infants whose delivery and neonatal care has been exceptionally demanding. The declining frequency of handicapping conditions in certain areas of London during the past two years may in addition reflect changing contraceptive practice and the working of abortion legislation. Since neuraxial tissue seems particularly susceptible to adverse toxic, biochemical, and infective insults in the first two years, the concept of "vulnerability" seems apt. This has been developed, hitherto, mostly in relation to the nutritional demands of the developing brainy It could now be applied in relation to infective processes, either through toxic/metabolic or neuro-allergic effects, which likewise are more damaging in early life-and to psychosocial aspects as well. A survey from Seattle.53 of the sequelae of enterovirus infections emphasises the frequency of long-term deficits in children whose original illness was predominantly neurological. Unfortunately the series is small, with only 19 patients traced out of 40 in whom enterovirus infections were diagnosed between 1966 and 1972. Their ages ranged from 7 to 64 months at the time of presenting illness; 9 had aseptic meningitis, 9 had meningoencephalitis, and 1 had acute cerebellar ataxia. Of these, 3 had definite and 9 others had possible neurological deficits on follow-up. Of particular interest is the observation that those children whose original illness was in the first year of life had significantly smaller mean head circumference, lower mean measured intelligence, and poorer language skills than matched controls. These results will surprise no-one responsible for management of acute illness in infancy: there is a continuing challenge from maladies and organisms which as yet can only be treated symptomatically. Although in the Seattle series specifically neurotropic characteristics of the viruses may have largely contributed to neuronal loss, careful management of the acute illness, with control of seizures and of fluid and electrolyte balance and with treatment of brain swelling, may limit handicapping sequelae. Anxieties about giving steroids in the presence of virus infection should not be a bar to dexamethasone administration, to reduce cerebral oedema, in those acute neurological illnesses with an inflammatory component. 50. Medical Research Council Annual Report, 1973-1974; p. 71. H. M. Stationery Office, 1974. 51. Bennett, A. in Advances in Prostaglandin and Thromboxane Research (edited by B. Sammuelsson and R. Paoletti); p. 547. New York, 1976. 52. Dobbing, J. in Applied Neurochemistry (edited by A. N. Davison and J Dobbing); chap. vii. Oxford, 1968. 53. Sells, C. J., Carpenter, R. L., Ray, C. G. New Engl. J. Med. 1975, 293, 1.
MELIOIDOSIS MELIOIDOSIS is
disease caused by the Pseudomonas pseudomallei. gram-negative bacillus, Whitmore’ first recognised the disease at a post-mortem examination in 1911 at Rangoon.’ The main endemic area is South-East Asia,2 and a few cases have originated in other places between the 200 north and south parallels of latitude.3 During the past 35 years many cases occurred in Servicemen in South-East Asia, but a few patients developed the disease on return to the Western Hemisphere, sometimes after many years’ latency. Pre-existing conditions such as trauma, burns, 4 and diabetes mellitus feature in some case-reports.2 Melioidosis has rarely been described in women or children, though just lately three cases have been reported in children.56 Initially man was thought to be infected via food contaminated by rat excreta, but rats seldom harbour the causal organism.7 8 Ps. pseudomallei seems to occur naturally in soil and surface water in Vietnam,9 Malaysia,’O Singapore," and northern Australia,’2 and the organism probably infects man by entering the body through open skin lesions or by inhalation.z2 Melioidosis may be acute (and frequently fulminating and fatal), less acute, chronic, or it may be mild or subclinical.There is no specific clinical feature." The acutely ill patient is confused and toxic, with signs of sepan uncommon
ticsemia, pneumonia, and severe diarrhoea. Skin sepsis, purulent arthritis, meningitis, hepatomegaly, and lymphadenopathy may occur.14 Less acutely ill patients show signs of chest infection, but radiographic appearances
are not
diagnostic and may mimic tubercu-
losis.14 Persistent or recurrent abscesses are prominent in chronic cases. Lesions have been reported in all tissues except bowel; microscopically they vary from suppurat-
ing abscesses to pseudo-caseous granulomas. 15 Melioidosis should be borne in mind in the differential
diagnosis of septicxmia, chest infection, or other febrile illness in any patient who is in, or who has visited, an endemic area. It may be suspected at the bedside, but the diagnosis can only be established in the laboratory; Ps. pseudomallei is easily isolated from pus and has been found in almost all body fluids except fxces. Ps. pseudomallei grows well on ordinary media and specimens from all septic lesions, and blood in acute cases, should be sent to the laboratory for culture. Nutrient agar incorporating 3% glycerol and 1/200 000 crystal-violet is a useful selective medium. Serological tests are valuable for diagnosis, the haemagglutination test being more specific than the simple agglutination or complement-fixation techniques. 1. Whitmore, A., Krishnaswamy, C. S. Ind. med. Gaz. 1912, 47, 262 2. Thin, R. N. T., Brown, M., Stewart, J. B., Garret, C. J. Q Jl Med 1970,
39, 115. 3. Howe, C., Sampath, A., Spotnitz, M. J. infect Dis. 1971, 124, 598 4. Greenawald, K. A., Nash, G., Foley, F. D. Am. J. clin. Path. 1969, 52, 188 5. Buse, P. J., Henderson, A., White, M. Med. J. Aust. 1975, ii, 476. 6. Pattamasukon, P., Pihyangkura, C., Fischer, G. W. Trop Pediat 1975, 87,
133. 7. Stanton, A. T., Fletcher, W. Studies from the Institute for Medical Research, Federated Malay States, no. 21, London, 1932. 8. Strauss, J. M., Ellison, D. W., Gan, E., Jason, S., Marcarelli, J L., Rapmund, G. Med. J. Malaysia, 1969, 24, 94. 9. Chambon, L. Ann Inst. Pasteur, 1965, 89, 229. 10. Strauss, J. M., Groves, M. G., Mariappan, M., Ellison, D. W. Am. J trop Med. Hyg. 1969, 18, 698. 11. Thin, R. N. T., Groves, M., Rapmund, G.,Mariappan, M. Singapore med J
1971, 12, 181. 12. Laws, L., Hall, W. T. K. Aust. vet. J. 1964, 40, 309. 13. Lancet, 1970, 1, 761. 14. Weber, D. R., Douglas, L. E., Brundage, W. G., Stalkhamp, T C Am Med. 1969, 46, 234. 15. Piggott, J. A., Hochholzer, L. Archs. Path. 1970, 90, 101.
J
963 vital for treating melioidosis. On disc Ps. sensitivity tests, pseudomallei is usually sensitive to chloramphenicol, tetracycline, sulphadiazine, and novobiocin, and resistant to the penicillins. Quantitative assays show more complex patterns; colonies from one specimen may show different sensitivities,2 and sensitivity may vary between consecutive specimens taken from one patient. 14 Careful laboratory investigations are essential for good antibiotic treatment, and the best regimen for acute melioidosis has yet to be established. Huge intravenous doses of chloramphenicol and novobiocin plus intramuscular kanamycin have cured such cases.’6 In less acute forms 2-4 g of oral chloramphenicol and/or tetracycline daily will probably suffice. Ps. pseudomallei may be isolated for several days after the start of therapy and antibiotics should be continued for several weeks after clinical improvement. A minimum of four weeks’ treatment has been suggested.2 In-vitro Ps. pseudomallei is sensitive to co-trimoxazole 17 18 and this was used successfully with kanamycin in a case reported from Papua-New Guinea.s South-East Asia is an important tourist and trading area, and with air travel patients suffering from melioidosis may present anywhere in the world.
Antibiotics
are
THE COLD FACTS OF CHILDBIRTH
CHILDBIRTH is an emotional subject, and in the past few weeks some intelligent mothers have been expressing passionate views on the psychological deprivation imposed by some obstetric practices. The other, and colder,
side of the argument is presented by the latest Report on Confidential Enquiries into Maternal Deathl-a reminder that deaths still occur in this young at-risk age-group and that those who advocate any move away from organised obstetric teams should be careful not to lead less well-informed women into danger. Although the number of maternal deaths is declining, a report like this deserves as much public attention as that lately given to consumer-satisfaction surveys. Maternal deaths are examined one by one so as to identify avoidable factors. No individuals are incriminated, but the mistakes of others show how maternity care may be improved. The first of these reports, eighteen years ago, related to 1410 maternal deaths. The current one covers 606. This striking fall owes something to advances in scientific obstetrics, something to previous reports, and something to improved health in the population, limitations in family size, and the habit of having babies in hospital. With the reduction in maternal deaths the proportions of the major causes are altering. Abortion, pulmonary embolism, and toxaemia still head the list, but hxmorrhage (27 deaths) has now been overtaken by ectopic pregnancy (34) and sepsis (32). This may reflect better obstetrics, but still over half the group who died after antepartum or postpartum haemorrhage have an avoidable factor. The deaths after abortion were about equally divided between illegal and legal terminations of pregnancy, with very few after a spontaneous abortion. Sheehy, T W., Deller, J. J., Weber, D. R. Ann intern. Med 1967, 67, 897 17 Beaumont. R. J. Med. J. Aust. 1970, ii, 1123. 18 Everett, E. D., Kishimoto, R. A. J. infect. Dis. 1973, 128, 796. 1 Report on Confidential Enquiries into Maternal Deaths, 1970-72. Rep. Hlth
16
Soc
Subj. no. 11. £1.80
In the triennium, deaths from criminal abortion fell to half the number in the previous report, while those folrose; however, more detailed breakdown of deaths after legal abortion shows a progressive drop in death-rate inside the three-year period. While the deaths from sepsis after abortion were reduced there is little drop in those associated with delivery. Anaesthetics fatalities are down in number, but still three-quarters were judged to have an avoidable factor. Overall, the number of deaths with an avoidable factor is now down to 34%. As a critical self-appraisal carried out by practising obstetricians and the Department of Health, this medical audit might be an example to other branches of medicine, who could examine similarly the effectiveness of their work and its usefulness towards the health of the nation.
lowing legal procedures
ECTOPIC PREGNANCY AND THE I.U.D. IN some of the early reports on Confidential Enquiries into Maternal Deaths ectopic pregnancy did not receive special attention, and the incidence seemed to be declining. But the 1970s have seen a worrying increase in this complication of pregnancy, and some 9% of maternal deaths are now due to this cause. So many factors, social and medical, have changed in the obstetric scene in the past few years that it might be thought impossible to sort out which, if any, have contributed to the increase in ectopic pregnancies. However, there seems little doubt that a woman who conceives despite using an intrauterine device (i.u.D.) or taking a progestagen-only oral contraceptive does have a greater than usual risk of an ectopic pregnancy. In a large American study of over 1000 LV.D. failures 4.3% of the unplanned pregnancies were ectopic1 and this experience has been confirmed on a smaller scale by others.2 3 Rather less is known about the failures of progestagen-only oral contraceptives, but the pointers are to a substantial increase in the risk of ectopic pregnancy,4 perhaps of the same order of magnitude as that for LU.D. users.s In England and Wales it is too early to judge the impact of progestagen-only oral contraception, but Beral, in a convincing attempt to estimate the contributions of both long-established and new-found associations with ectopic pregnancy, suggests that much of the recent increase in the incidence of this complication can be laid at the door of the r.U.D.;6 and of the many different devices, she singles out the copperbased ones for special attention. Such calculations require statistics, broken down by age, for ectopic pregnancies, the incidence of ectopic pregnancy among i.u.D. users, and the prevalence of l.U.D. use in the general population of women over the years. Until the third of these variables is known with greater certainty and further work has been done indictment of the LU.D. must be qualified, but Beral’s paper does highlight the need for urgent action when an LU.D. patient misses a
period. 1. Lehfeldt, H., Tietze, C., Gorstein, J. Am. J. Obstet. Gynec 1970, 108, 1005 2. Vessey, M. P., Johnson, B., Doll, R., Peto, R. Lancet, 1974, i, 495. 3. Steven, J. D., Fraser, I. S. J. Obstet. Gynœc. Br. Commonw. 1974, 81, 282. 4. Smith, M., Vessey, M. P., Bounds, W., Warren, J Br. med. J. 1974, iv, 104. 5. Bergsjo, P., Langengen, H., Aas, J. Acta obstet. gynœc. scand. 1974, 53, 377. 6. Beral, V. Br. J. Obstet. Gynœc. 1975, 82, 775.
.’
production of prostagiandinS41 51 may play a part. NEURONAL LOSS IN INFANCY IN general, morbidity-rates tend to parallel respective mortality-rates, and this is especially true in infancy where the stresses of perinatal events, trauma, infection, and nutritional deprivation represent the main threats to wellbeing as well as to survival. The neuraxis is particularly at hazard, and it is the lagging neurodevelop-
mental progress after otherwise successful treatment of an acute illness which advertises the saddest sequelae. With improved obstetric and perinatal care, not only perinatal death but also mental and physical handicap have become less frequent among those infants whose delivery and neonatal care has been exceptionally demanding. The declining frequency of handicapping conditions in certain areas of London during the past two years may in addition reflect changing contraceptive practice and the working of abortion legislation. Since neuraxial tissue seems particularly susceptible to adverse toxic, biochemical, and infective insults in the first two years, the concept of "vulnerability" seems apt. This has been developed, hitherto, mostly in relation to the nutritional demands of the developing brainy It could now be applied in relation to infective processes, either through toxic/metabolic or neuro-allergic effects, which likewise are more damaging in early life-and to psychosocial aspects as well. A survey from Seattle.53 of the sequelae of enterovirus infections emphasises the frequency of long-term deficits in children whose original illness was predominantly neurological. Unfortunately the series is small, with only 19 patients traced out of 40 in whom enterovirus infections were diagnosed between 1966 and 1972. Their ages ranged from 7 to 64 months at the time of presenting illness; 9 had aseptic meningitis, 9 had meningoencephalitis, and 1 had acute cerebellar ataxia. Of these, 3 had definite and 9 others had possible neurological deficits on follow-up. Of particular interest is the observation that those children whose original illness was in the first year of life had significantly smaller mean head circumference, lower mean measured intelligence, and poorer language skills than matched controls. These results will surprise no-one responsible for management of acute illness in infancy: there is a continuing challenge from maladies and organisms which as yet can only be treated symptomatically. Although in the Seattle series specifically neurotropic characteristics of the viruses may have largely contributed to neuronal loss, careful management of the acute illness, with control of seizures and of fluid and electrolyte balance and with treatment of brain swelling, may limit handicapping sequelae. Anxieties about giving steroids in the presence of virus infection should not be a bar to dexamethasone administration, to reduce cerebral oedema, in those acute neurological illnesses with an inflammatory component. 50. Medical Research Council Annual Report, 1973-1974; p. 71. H. M. Stationery Office, 1974. 51. Bennett, A. in Advances in Prostaglandin and Thromboxane Research (edited by B. Sammuelsson and R. Paoletti); p. 547. New York, 1976. 52. Dobbing, J. in Applied Neurochemistry (edited by A. N. Davison and J Dobbing); chap. vii. Oxford, 1968. 53. Sells, C. J., Carpenter, R. L., Ray, C. G. New Engl. J. Med. 1975, 293, 1.
MELIOIDOSIS MELIOIDOSIS is
disease caused by the Pseudomonas pseudomallei. gram-negative bacillus, Whitmore’ first recognised the disease at a post-mortem examination in 1911 at Rangoon.’ The main endemic area is South-East Asia,2 and a few cases have originated in other places between the 200 north and south parallels of latitude.3 During the past 35 years many cases occurred in Servicemen in South-East Asia, but a few patients developed the disease on return to the Western Hemisphere, sometimes after many years’ latency. Pre-existing conditions such as trauma, burns, 4 and diabetes mellitus feature in some case-reports.2 Melioidosis has rarely been described in women or children, though just lately three cases have been reported in children.56 Initially man was thought to be infected via food contaminated by rat excreta, but rats seldom harbour the causal organism.7 8 Ps. pseudomallei seems to occur naturally in soil and surface water in Vietnam,9 Malaysia,’O Singapore," and northern Australia,’2 and the organism probably infects man by entering the body through open skin lesions or by inhalation.z2 Melioidosis may be acute (and frequently fulminating and fatal), less acute, chronic, or it may be mild or subclinical.There is no specific clinical feature." The acutely ill patient is confused and toxic, with signs of sepan uncommon
ticsemia, pneumonia, and severe diarrhoea. Skin sepsis, purulent arthritis, meningitis, hepatomegaly, and lymphadenopathy may occur.14 Less acutely ill patients show signs of chest infection, but radiographic appearances
are not
diagnostic and may mimic tubercu-
losis.14 Persistent or recurrent abscesses are prominent in chronic cases. Lesions have been reported in all tissues except bowel; microscopically they vary from suppurat-
ing abscesses to pseudo-caseous granulomas. 15 Melioidosis should be borne in mind in the differential
diagnosis of septicxmia, chest infection, or other febrile illness in any patient who is in, or who has visited, an endemic area. It may be suspected at the bedside, but the diagnosis can only be established in the laboratory; Ps. pseudomallei is easily isolated from pus and has been found in almost all body fluids except fxces. Ps. pseudomallei grows well on ordinary media and specimens from all septic lesions, and blood in acute cases, should be sent to the laboratory for culture. Nutrient agar incorporating 3% glycerol and 1/200 000 crystal-violet is a useful selective medium. Serological tests are valuable for diagnosis, the haemagglutination test being more specific than the simple agglutination or complement-fixation techniques. 1. Whitmore, A., Krishnaswamy, C. S. Ind. med. Gaz. 1912, 47, 262 2. Thin, R. N. T., Brown, M., Stewart, J. B., Garret, C. J. Q Jl Med 1970,
39, 115. 3. Howe, C., Sampath, A., Spotnitz, M. J. infect Dis. 1971, 124, 598 4. Greenawald, K. A., Nash, G., Foley, F. D. Am. J. clin. Path. 1969, 52, 188 5. Buse, P. J., Henderson, A., White, M. Med. J. Aust. 1975, ii, 476. 6. Pattamasukon, P., Pihyangkura, C., Fischer, G. W. Trop Pediat 1975, 87,
133. 7. Stanton, A. T., Fletcher, W. Studies from the Institute for Medical Research, Federated Malay States, no. 21, London, 1932. 8. Strauss, J. M., Ellison, D. W., Gan, E., Jason, S., Marcarelli, J L., Rapmund, G. Med. J. Malaysia, 1969, 24, 94. 9. Chambon, L. Ann Inst. Pasteur, 1965, 89, 229. 10. Strauss, J. M., Groves, M. G., Mariappan, M., Ellison, D. W. Am. J trop Med. Hyg. 1969, 18, 698. 11. Thin, R. N. T., Groves, M., Rapmund, G.,Mariappan, M. Singapore med J
1971, 12, 181. 12. Laws, L., Hall, W. T. K. Aust. vet. J. 1964, 40, 309. 13. Lancet, 1970, 1, 761. 14. Weber, D. R., Douglas, L. E., Brundage, W. G., Stalkhamp, T C Am Med. 1969, 46, 234. 15. Piggott, J. A., Hochholzer, L. Archs. Path. 1970, 90, 101.
J
963 vital for treating melioidosis. On disc Ps. sensitivity tests, pseudomallei is usually sensitive to chloramphenicol, tetracycline, sulphadiazine, and novobiocin, and resistant to the penicillins. Quantitative assays show more complex patterns; colonies from one specimen may show different sensitivities,2 and sensitivity may vary between consecutive specimens taken from one patient. 14 Careful laboratory investigations are essential for good antibiotic treatment, and the best regimen for acute melioidosis has yet to be established. Huge intravenous doses of chloramphenicol and novobiocin plus intramuscular kanamycin have cured such cases.’6 In less acute forms 2-4 g of oral chloramphenicol and/or tetracycline daily will probably suffice. Ps. pseudomallei may be isolated for several days after the start of therapy and antibiotics should be continued for several weeks after clinical improvement. A minimum of four weeks’ treatment has been suggested.2 In-vitro Ps. pseudomallei is sensitive to co-trimoxazole 17 18 and this was used successfully with kanamycin in a case reported from Papua-New Guinea.s South-East Asia is an important tourist and trading area, and with air travel patients suffering from melioidosis may present anywhere in the world.
Antibiotics
are
THE COLD FACTS OF CHILDBIRTH
CHILDBIRTH is an emotional subject, and in the past few weeks some intelligent mothers have been expressing passionate views on the psychological deprivation imposed by some obstetric practices. The other, and colder,
side of the argument is presented by the latest Report on Confidential Enquiries into Maternal Deathl-a reminder that deaths still occur in this young at-risk age-group and that those who advocate any move away from organised obstetric teams should be careful not to lead less well-informed women into danger. Although the number of maternal deaths is declining, a report like this deserves as much public attention as that lately given to consumer-satisfaction surveys. Maternal deaths are examined one by one so as to identify avoidable factors. No individuals are incriminated, but the mistakes of others show how maternity care may be improved. The first of these reports, eighteen years ago, related to 1410 maternal deaths. The current one covers 606. This striking fall owes something to advances in scientific obstetrics, something to previous reports, and something to improved health in the population, limitations in family size, and the habit of having babies in hospital. With the reduction in maternal deaths the proportions of the major causes are altering. Abortion, pulmonary embolism, and toxaemia still head the list, but hxmorrhage (27 deaths) has now been overtaken by ectopic pregnancy (34) and sepsis (32). This may reflect better obstetrics, but still over half the group who died after antepartum or postpartum haemorrhage have an avoidable factor. The deaths after abortion were about equally divided between illegal and legal terminations of pregnancy, with very few after a spontaneous abortion. Sheehy, T W., Deller, J. J., Weber, D. R. Ann intern. Med 1967, 67, 897 17 Beaumont. R. J. Med. J. Aust. 1970, ii, 1123. 18 Everett, E. D., Kishimoto, R. A. J. infect. Dis. 1973, 128, 796. 1 Report on Confidential Enquiries into Maternal Deaths, 1970-72. Rep. Hlth
16
Soc
Subj. no. 11. £1.80
In the triennium, deaths from criminal abortion fell to half the number in the previous report, while those folrose; however, more detailed breakdown of deaths after legal abortion shows a progressive drop in death-rate inside the three-year period. While the deaths from sepsis after abortion were reduced there is little drop in those associated with delivery. Anaesthetics fatalities are down in number, but still three-quarters were judged to have an avoidable factor. Overall, the number of deaths with an avoidable factor is now down to 34%. As a critical self-appraisal carried out by practising obstetricians and the Department of Health, this medical audit might be an example to other branches of medicine, who could examine similarly the effectiveness of their work and its usefulness towards the health of the nation.
lowing legal procedures
ECTOPIC PREGNANCY AND THE I.U.D. IN some of the early reports on Confidential Enquiries into Maternal Deaths ectopic pregnancy did not receive special attention, and the incidence seemed to be declining. But the 1970s have seen a worrying increase in this complication of pregnancy, and some 9% of maternal deaths are now due to this cause. So many factors, social and medical, have changed in the obstetric scene in the past few years that it might be thought impossible to sort out which, if any, have contributed to the increase in ectopic pregnancies. However, there seems little doubt that a woman who conceives despite using an intrauterine device (i.u.D.) or taking a progestagen-only oral contraceptive does have a greater than usual risk of an ectopic pregnancy. In a large American study of over 1000 LV.D. failures 4.3% of the unplanned pregnancies were ectopic1 and this experience has been confirmed on a smaller scale by others.2 3 Rather less is known about the failures of progestagen-only oral contraceptives, but the pointers are to a substantial increase in the risk of ectopic pregnancy,4 perhaps of the same order of magnitude as that for LU.D. users.s In England and Wales it is too early to judge the impact of progestagen-only oral contraception, but Beral, in a convincing attempt to estimate the contributions of both long-established and new-found associations with ectopic pregnancy, suggests that much of the recent increase in the incidence of this complication can be laid at the door of the r.U.D.;6 and of the many different devices, she singles out the copperbased ones for special attention. Such calculations require statistics, broken down by age, for ectopic pregnancies, the incidence of ectopic pregnancy among i.u.D. users, and the prevalence of l.U.D. use in the general population of women over the years. Until the third of these variables is known with greater certainty and further work has been done indictment of the LU.D. must be qualified, but Beral’s paper does highlight the need for urgent action when an LU.D. patient misses a
period. 1. Lehfeldt, H., Tietze, C., Gorstein, J. Am. J. Obstet. Gynec 1970, 108, 1005 2. Vessey, M. P., Johnson, B., Doll, R., Peto, R. Lancet, 1974, i, 495. 3. Steven, J. D., Fraser, I. S. J. Obstet. Gynœc. Br. Commonw. 1974, 81, 282. 4. Smith, M., Vessey, M. P., Bounds, W., Warren, J Br. med. J. 1974, iv, 104. 5. Bergsjo, P., Langengen, H., Aas, J. Acta obstet. gynœc. scand. 1974, 53, 377. 6. Beral, V. Br. J. Obstet. Gynœc. 1975, 82, 775.
.’
