274
their effects by combining with specific cellsurface receptors. Non-primate growth hormones show weak or undetectable binding to extracellular prolactin receptors. The Genentech researchers began their investigations by cloning the binding domain of the human prolactin receptor and then established that 50 jmol/1 zinc chloride enhanced the binding affinity of human growth hormone (hGH) for this extracellular receptor 8000-fold. Binding of hGH to the hGH receptor and of human prolactin to the prolactin receptor was not zinc dependent. Probable zinc ligands were shown to be a three-residue clusterHis, HisZl, and Glul74-in the hGH receptor and Hisl88 in the human prolactin receptor; non-primate growth hormones contain His21 and Glu 174 but instead of HisI8 they have Gln18. The hormone receptor zinc sandwich not only explains why non-primate growth hormones do not have lactogenic activity but also may shed light on other endocrine effects of zinc-eg, the link between zinc deficiency and growth retardation. Since growth hormone and prolactin receptors belong to the same family as peptide regulatory factor receptors, zinc may mediate receptor interaction of the interleukins, erythropoietin, and colony stimulating factors. exert
1.
Cunningham BC, Bass S, Fuh G, Wells JA. Zinc mediation of the binding of human growth hormone to the human prolactin receptor.
Science 1990; 250: 1709-12. 2. Evans RM. The steroid and thyroid hormone receptor superfamily. Science 1988; 240: 889-95. 3. Editorial. Zinc fingers and vitamin D resistance. Lancet 1989; i: 478.
Placental localisation in early pregnancy When women undergo ultrasound scanning in early pregnancy to clarify the gestational age or to screen for structural malformation in the fetus, an incidental finding may be a low-lying placenta-the placenta reaches or overlies the cervical os in 5%1,2 to 26 %of cases. That the frequency is lower if the initial scan is conducted at 20 weeks than if it is done early4 does not seem to explain all of this variation. Different criteria may have been used to categorise cases; researchers who describe a placenta as low lying only if it is seen to cover the cervical os, at least partly, report a frequency of 5-6%.12 Very few of the women identified in this way will have placenta praevia at delivery, presumably because growth of the uterus outstrips that of the placenta. Nevertheless, it has been arguedl,2,4-6 that they should be rescanned for placental site in the third trimester, at 28-36 weeks. This argument is based on a delivery frequency of placenta praevia of 2’3%4 to 16-9% in this group, compared with the population frequency of less than 1%. It is not clear why there should be such a large variation in the rate at which the condition is present at delivery in women diagnosed initially as high risk.
Other workers who have carried out prospective studies have concluded that, because so few women found to have a low placenta on the first scan still manifest the condition at delivery (2%,’ 0%1-3%), third-trimester scanning for this group cannot be justified unless there are clinical indications such as vaginal bleeding or unstable lie. These studies also provided data on whether all the clinical cases of placenta praevia noted in hospital had been diagnosed by the booking scan. Mc Clure and Doman,3 who conducted the largest and most recent study (also the one with the highest rate of low-lying placenta on initial ultrasound scanning), found that only 18 of 30 clinical cases had been so predicted, and agreed with previous proposals that a low-lying placenta on the initial scan should be ignored. Because of the high morbidity associated with placenta praevia and because bleeding does not necessarily occur before the onset of labour,l the possibility of early detection is attractive. However, the sensitivity and specificity of low-lying placenta on the first scan, as a test for clinical placenta praevia at delivery, are very poor. Many women, informed of the result and asked to reattend, become unduly worried that, if the repeat scan still shows a low-lying placenta, they may be advised to restrict activity, or be admitted. Placental localisation is important in women who have appreciable or recurrent vaginal bleeding and in those with an unstable lie in late pregnancy. The index of suspicion should be higher in older women of high parity, especially if there is a history of caesarean section9-11 (because such patients have an enhanced risk of placenta praevia and placenta accreta) and in those with a history of placenta praevia.12 Placental localisation at the initial scan cannot be recommended, and when a low placenta is noted incidentally, it is not necessary routinely to order a third-trimester scan. N, Doran TA, Miskin M, Benzie RJ, Ford JA. Natural history of placenta previa ascertained by diagnostic ultrasound. Am J Obstet Gynecol 1979; 133: 287-91. 2. Varma TR. The implications of low implantation of the placenta detected by ultrasonography in early pregnancy. Acta Obstet Gynaecol Scand 1. Rizos
1981; 60: 265-68. 3. McClure N, Dornan JC. Early identification of placenta praevia. Br J Obstet Gynaecol 1990; 97: 959-61. 4. Comeau J, Shaw L, Marcell CC, Lavery JP. Early placenta previa and delivery outcome. Obstet Gynecol 1983; 61: 577-80. 5. Royal College of Obstetricians and Gynaecologists. Report of the RCOG Working Party on Routine Ultrasound Examination in Pregnancy. London: RCOG, 1984. 6. Langlois SL, Miller AG. Placenta praevia: a review with emphasis on the role of ultrasound. Aust NZ J Obstet Gynaecol 1989; 29: 110-16. 7. Ruparelia BA, Chapman MG. Early low-lying placentae—ultrasonic assessment, progress and outcome. Eur J Obstet Gynecol Reprod Biol 1985; 20: 209-13. 8. Anderson ES, Steinke NM. The clinical significance of asymptomatic midtrimester low placenta diagnosed by ultrasound. Acta Obstet Gynaecol Scand 1988; 67: 339-41. 9. Singh PM, Rodrigues C, Gupta AN. Placenta praevia and previous caesarean section. Acta Obstet Gynaecol Scand 1981; 292: 371-72. 10. Breen JL, Neubecker R, Gregori CA, Franklin JE. Placenta accreta, increta and percreta: a survey of 40 cases. Obstet Gynecol 1977; 49: 43-47. 11. Clark SL, Koonings PP, Phelan JP. Placenta previa/accreta and prior cesarean section. Obstet Gynecol 1985; 66: 89-92. 12. Godoreski IG, Bahari CM, Schachter A, Neri A. Recurrent placenta previa. Eur J Obstet Gynecol Reprod Biol 1981; 12: 7-11.
their effects by combining with specific cellsurface receptors. Non-primate growth hormones show weak or undetectable binding to extracellular prolactin receptors. The Genentech researchers began their investigations by cloning the binding domain of the human prolactin receptor and then established that 50 jmol/1 zinc chloride enhanced the binding affinity of human growth hormone (hGH) for this extracellular receptor 8000-fold. Binding of hGH to the hGH receptor and of human prolactin to the prolactin receptor was not zinc dependent. Probable zinc ligands were shown to be a three-residue clusterHis, HisZl, and Glul74-in the hGH receptor and Hisl88 in the human prolactin receptor; non-primate growth hormones contain His21 and Glu 174 but instead of HisI8 they have Gln18. The hormone receptor zinc sandwich not only explains why non-primate growth hormones do not have lactogenic activity but also may shed light on other endocrine effects of zinc-eg, the link between zinc deficiency and growth retardation. Since growth hormone and prolactin receptors belong to the same family as peptide regulatory factor receptors, zinc may mediate receptor interaction of the interleukins, erythropoietin, and colony stimulating factors. exert
1.
Cunningham BC, Bass S, Fuh G, Wells JA. Zinc mediation of the binding of human growth hormone to the human prolactin receptor.
Science 1990; 250: 1709-12. 2. Evans RM. The steroid and thyroid hormone receptor superfamily. Science 1988; 240: 889-95. 3. Editorial. Zinc fingers and vitamin D resistance. Lancet 1989; i: 478.
Placental localisation in early pregnancy When women undergo ultrasound scanning in early pregnancy to clarify the gestational age or to screen for structural malformation in the fetus, an incidental finding may be a low-lying placenta-the placenta reaches or overlies the cervical os in 5%1,2 to 26 %of cases. That the frequency is lower if the initial scan is conducted at 20 weeks than if it is done early4 does not seem to explain all of this variation. Different criteria may have been used to categorise cases; researchers who describe a placenta as low lying only if it is seen to cover the cervical os, at least partly, report a frequency of 5-6%.12 Very few of the women identified in this way will have placenta praevia at delivery, presumably because growth of the uterus outstrips that of the placenta. Nevertheless, it has been arguedl,2,4-6 that they should be rescanned for placental site in the third trimester, at 28-36 weeks. This argument is based on a delivery frequency of placenta praevia of 2’3%4 to 16-9% in this group, compared with the population frequency of less than 1%. It is not clear why there should be such a large variation in the rate at which the condition is present at delivery in women diagnosed initially as high risk.
Other workers who have carried out prospective studies have concluded that, because so few women found to have a low placenta on the first scan still manifest the condition at delivery (2%,’ 0%1-3%), third-trimester scanning for this group cannot be justified unless there are clinical indications such as vaginal bleeding or unstable lie. These studies also provided data on whether all the clinical cases of placenta praevia noted in hospital had been diagnosed by the booking scan. Mc Clure and Doman,3 who conducted the largest and most recent study (also the one with the highest rate of low-lying placenta on initial ultrasound scanning), found that only 18 of 30 clinical cases had been so predicted, and agreed with previous proposals that a low-lying placenta on the initial scan should be ignored. Because of the high morbidity associated with placenta praevia and because bleeding does not necessarily occur before the onset of labour,l the possibility of early detection is attractive. However, the sensitivity and specificity of low-lying placenta on the first scan, as a test for clinical placenta praevia at delivery, are very poor. Many women, informed of the result and asked to reattend, become unduly worried that, if the repeat scan still shows a low-lying placenta, they may be advised to restrict activity, or be admitted. Placental localisation is important in women who have appreciable or recurrent vaginal bleeding and in those with an unstable lie in late pregnancy. The index of suspicion should be higher in older women of high parity, especially if there is a history of caesarean section9-11 (because such patients have an enhanced risk of placenta praevia and placenta accreta) and in those with a history of placenta praevia.12 Placental localisation at the initial scan cannot be recommended, and when a low placenta is noted incidentally, it is not necessary routinely to order a third-trimester scan. N, Doran TA, Miskin M, Benzie RJ, Ford JA. Natural history of placenta previa ascertained by diagnostic ultrasound. Am J Obstet Gynecol 1979; 133: 287-91. 2. Varma TR. The implications of low implantation of the placenta detected by ultrasonography in early pregnancy. Acta Obstet Gynaecol Scand 1. Rizos
1981; 60: 265-68. 3. McClure N, Dornan JC. Early identification of placenta praevia. Br J Obstet Gynaecol 1990; 97: 959-61. 4. Comeau J, Shaw L, Marcell CC, Lavery JP. Early placenta previa and delivery outcome. Obstet Gynecol 1983; 61: 577-80. 5. Royal College of Obstetricians and Gynaecologists. Report of the RCOG Working Party on Routine Ultrasound Examination in Pregnancy. London: RCOG, 1984. 6. Langlois SL, Miller AG. Placenta praevia: a review with emphasis on the role of ultrasound. Aust NZ J Obstet Gynaecol 1989; 29: 110-16. 7. Ruparelia BA, Chapman MG. Early low-lying placentae—ultrasonic assessment, progress and outcome. Eur J Obstet Gynecol Reprod Biol 1985; 20: 209-13. 8. Anderson ES, Steinke NM. The clinical significance of asymptomatic midtrimester low placenta diagnosed by ultrasound. Acta Obstet Gynaecol Scand 1988; 67: 339-41. 9. Singh PM, Rodrigues C, Gupta AN. Placenta praevia and previous caesarean section. Acta Obstet Gynaecol Scand 1981; 292: 371-72. 10. Breen JL, Neubecker R, Gregori CA, Franklin JE. Placenta accreta, increta and percreta: a survey of 40 cases. Obstet Gynecol 1977; 49: 43-47. 11. Clark SL, Koonings PP, Phelan JP. Placenta previa/accreta and prior cesarean section. Obstet Gynecol 1985; 66: 89-92. 12. Godoreski IG, Bahari CM, Schachter A, Neri A. Recurrent placenta previa. Eur J Obstet Gynecol Reprod Biol 1981; 12: 7-11.
