- Email: [email protected]
PRENATAL SCREENING FOR CONGENITAL NEPHROSIS
991
multiple pregnancy. Amniocentesis (on 0.63% of the total) would yield 68 cases of N.T.D. and 9 of congenital nephrosis, assuming that
minal intracardial puncture of twin 1 was done in the 24th week of pregnancy. A 0-8x80 mm needle was used. After two attempts the fetal heart stopped. Twin 2 did not seem to be affected. Serial ultrasound scans showed that the biparietal diameter of twin 2 increased, whereas that of twin 1 got smaller (fig. 2). Examination of amniotic cells of twin 1 obtained at cardiac puncture ("2nd amniocentesis") confirmed the diagnosis of Hurler’s disease (fig. lB, table). Labour contractions started in the 33rd week of pregnancy. An attempt to inhibit contractions by p-mimetic drugs was unsuccessful. The remnants of the dead fetus were delivered vaginally. The living fetus, however, was delivered by a caaarean section due to a transverse position. This was done without
or
N.T.D. would be open, and 84% of open defects would have a maternal serum-A.F.p. over 2.5 times the normal medianFetal losses due to amniocentesis (1%) might number 6. If the amniotic-fluid-A.F.P. cut-off were set at 5 S.D. above the normal mean the N.T.D. yield might be 61, while that for congenital nephrosis would be 9. In the first 212 samples from 125 pregnancies there were 4 pregnancies in which the maternal serum-A.F.P. was above 2.5
90% of
times the normal median. Repeat assay confirmed this increase in 3; 2 were multiple pregnancies (ultrasonography). Amniocentesis was done in the remaining case where the maternal serum-A.F.P. had been 259 ng/ml at 17 weeks, or 9-6 times the normal median. The amniotic-fluid A.F.P. was 227 ug/ml, which is 51 S.D. above the normal mean for 18 weeks. This pregnancy was terminated, and congenital nephrosis was verified by light and electron miscroscopy of the fetal kidneys.4 The previous pregnancy of this woman had ended in stillbirth. Since our previous report5 our accumulated experience now includes 27 pregnancies of women who were considered to be at 25% risk of having another child with congenital nephrosis. 7 had maternal serum-A.F.p.s over the normal 97-5 percentile, and in 9 cases the amniotic-fluid A.F.P. level was 12-137 s.D. above the normal mean. The 9 cases with raised amniotic-fluid A.F.P.S were terminated, and congenital nephrosis was identified in all. A healthy child was born in all those cases where the amniotic-fluid A.F.P. was normal.4 The early experience from our screening programme is encouraging. Although rare, congential nephrosis has been encountered in most parts of the world, and this condition should be borne in mind whenever a pregnancy is terminated on the basis of raised A.F.P. values and the fetus shows no overt malformation.
any complications. After the delivery of twin 2, a girl, an analysis of cultured fibroblasts showed a normal mucopolysaccharide metabolism (fig. lc) and an oc-L-iduronidase activity of 64% of normal (table), thus confirming the prenatal tests. In view of the large variation of a-L-iduronidase activity in normal fibroblast cultures we cannot say whether twin 2 is a Hurler heterozygote. However, as Hurler’s disease is an autosomal recessive trait, this question is of no consequence to the child’s health. The girl, now 8 months old, shows normal psychomotor development.
Under certain favourable conditions it may be possible to avoid abortion of an unaffected twin when prenatal diagnosis has revealed one normal fetus, the other being affected with a serious disease. The procedure is technically simple, and should carry no risk for the healthy co-twin. When one twin fetus dies spontaneously it is gradually resorbed, and at delivery a fetus papyraceus or even no remnants may be found. In a monozygous twin pair there may be a risk of brain damage in the co-twin due to disseminated intravascular coagulation.5 In dizygous twins, however, there are no data, to our knowledge, suggesting that the living twin may be harmed by the dead co-twin. Mother and child are in perfect health.
Department of Obstetrics and Gynæcology, University Central Hospital, 70100 Kuopio 10, Finland
The expert technical assistance of Dr Dan Erik Wicklund, Mrs Christa Becker, Mrs Renate Hellmann, and Miss HelgardMesser is gratefully acknowledged. Part of this work was supported by a grant from the Deutsche Forschungsgemeinschaft.
Department of Obstetrics and Gynæcology, University Hospital, Lund
Department of Clinical Genetics, University Hospital,
ANDERS
Department of Pædiatrics, University of Mainz, Mainz, West Germany
Hospital,
University
of Helsinki
J. RAPOLA
Department of Obstetrics and Gynæcology, and Laboratory of Prenatal Genetics University of Helsinki
ÅBERG
P. AULA M. SEPPÄLÄ
REVERSAL OF HYPNOSIS-INDUCED ANALGESIA BY NALOXONE
FELIX MITELMAN
S-221 85 Lund, Sweden
Children’s
M. RYYNÄNEN O. CASTREN
SiR,—The neurological basis of hypnosis is obscure. This letter describes a preliminary investigation into the mechanism of hypnotic pain relief. Naloxone is a pure opiate antagonist6 with no pain-enhancing properties in moderate doses.7 These
MICHAEL CANTZ
JÜRGEN GEHLER
properties
make it ideal to detect those situations
in
whicn
implicated in endogenous opioid peptides (endorphins) pain suppression. By this means the analgesia induced by acupuncture8 or placeb07.9 have been shown to be endorphin mediated. I gave naloxone single-blind within a series of saline injections and found that, after a short latency, hypnosisinduced analgesia seemed to be reversed. A 53 kg healthy young adult consented to the study. This volunteer was known to be able to sustain a deep hypnotic trance with eyes open ("somnambulistic state"). The pain stiare
PRENATAL SCREENING FOR CONGENITAL NEPHROSIS
SIR,-We wish to report the first prenatal diagnosis of congenital nephrosis based on maternal serum-A.F.p. (alpha-fetoprotein) screening. In June, 1978, we started a screening programme for congenital nephrosis and other A.F.p.-related fetal disorders in an area of Finland where the incidence of congenital nephrosis is high. We expected that such a programme, when applied to 100 000 pregnancies at 16-18 weeks, would allow the prenatal diagnosis of 9 cases with congenital nephrosis and 61 ’
cases
.
mulus was hand. The
a sharp sterile needle pressed onto the back of the pain-rating scale was a 10 cm horizontal line on a
of neural-tube defect.
This estimate is based on the assumed incidence of 0-12 per 1000 for congenital nephrosis and 0.90 per 1000 for neural-tube defects in the whole of Finland.’2 These 100 000 pregnancies might be expected to yield 3377 with a maternal serum-A.F.p. more than 2.5 the normal median. Of these, 2747 would not come to amniocentesis because a repeat A.F.P. measurement was normal or because of an error in dates
1. Huttunen, N.-P. Archs Dis. Childh. 2. Saxén, L., Klemetti, A., Härö, A. S.
1976, 51, 344.
Am. J. Epidem. 1974, 100, 297.
Report of U. K. Collaborative Study. Lancet, 1977, i, 1323. Aula, P., Rapola, J., Karjalainen, O., Lindgren, J., Hartikainen, A.-L., Seppälä, M. Am. J. Dis. Child. (in the press). 5. Seppälä, M., Aula, P., Rapola, J., Karjalainen, O., Huttunen, N.-P., Ruoslahti, E. Lancet, 1976, ii, 123. 6. Blumberg, H., Dayton, H. B. in Agonist and Antagonist Actions of Narcotic Analgesic Drugs (edited by H. W. Kosterlitz, H. O. J. Collier, and J. E. Villareal); p 110. New Vork, 1973. 7. Levine, J. D., Gordon, N. C., Fields, H. L. Lancet, 1978, ii, 654. 8. Mayer, D. J., Price, D. D., Rafli, A. Brain Res. 1977, 121, 360. 9. Levine, J. D., and others. Nature, 1978, 272, 826. 3. 4.
multiple pregnancy. Amniocentesis (on 0.63% of the total) would yield 68 cases of N.T.D. and 9 of congenital nephrosis, assuming that
minal intracardial puncture of twin 1 was done in the 24th week of pregnancy. A 0-8x80 mm needle was used. After two attempts the fetal heart stopped. Twin 2 did not seem to be affected. Serial ultrasound scans showed that the biparietal diameter of twin 2 increased, whereas that of twin 1 got smaller (fig. 2). Examination of amniotic cells of twin 1 obtained at cardiac puncture ("2nd amniocentesis") confirmed the diagnosis of Hurler’s disease (fig. lB, table). Labour contractions started in the 33rd week of pregnancy. An attempt to inhibit contractions by p-mimetic drugs was unsuccessful. The remnants of the dead fetus were delivered vaginally. The living fetus, however, was delivered by a caaarean section due to a transverse position. This was done without
or
N.T.D. would be open, and 84% of open defects would have a maternal serum-A.F.p. over 2.5 times the normal medianFetal losses due to amniocentesis (1%) might number 6. If the amniotic-fluid-A.F.P. cut-off were set at 5 S.D. above the normal mean the N.T.D. yield might be 61, while that for congenital nephrosis would be 9. In the first 212 samples from 125 pregnancies there were 4 pregnancies in which the maternal serum-A.F.P. was above 2.5
90% of
times the normal median. Repeat assay confirmed this increase in 3; 2 were multiple pregnancies (ultrasonography). Amniocentesis was done in the remaining case where the maternal serum-A.F.P. had been 259 ng/ml at 17 weeks, or 9-6 times the normal median. The amniotic-fluid A.F.P. was 227 ug/ml, which is 51 S.D. above the normal mean for 18 weeks. This pregnancy was terminated, and congenital nephrosis was verified by light and electron miscroscopy of the fetal kidneys.4 The previous pregnancy of this woman had ended in stillbirth. Since our previous report5 our accumulated experience now includes 27 pregnancies of women who were considered to be at 25% risk of having another child with congenital nephrosis. 7 had maternal serum-A.F.p.s over the normal 97-5 percentile, and in 9 cases the amniotic-fluid A.F.P. level was 12-137 s.D. above the normal mean. The 9 cases with raised amniotic-fluid A.F.P.S were terminated, and congenital nephrosis was identified in all. A healthy child was born in all those cases where the amniotic-fluid A.F.P. was normal.4 The early experience from our screening programme is encouraging. Although rare, congential nephrosis has been encountered in most parts of the world, and this condition should be borne in mind whenever a pregnancy is terminated on the basis of raised A.F.P. values and the fetus shows no overt malformation.
any complications. After the delivery of twin 2, a girl, an analysis of cultured fibroblasts showed a normal mucopolysaccharide metabolism (fig. lc) and an oc-L-iduronidase activity of 64% of normal (table), thus confirming the prenatal tests. In view of the large variation of a-L-iduronidase activity in normal fibroblast cultures we cannot say whether twin 2 is a Hurler heterozygote. However, as Hurler’s disease is an autosomal recessive trait, this question is of no consequence to the child’s health. The girl, now 8 months old, shows normal psychomotor development.
Under certain favourable conditions it may be possible to avoid abortion of an unaffected twin when prenatal diagnosis has revealed one normal fetus, the other being affected with a serious disease. The procedure is technically simple, and should carry no risk for the healthy co-twin. When one twin fetus dies spontaneously it is gradually resorbed, and at delivery a fetus papyraceus or even no remnants may be found. In a monozygous twin pair there may be a risk of brain damage in the co-twin due to disseminated intravascular coagulation.5 In dizygous twins, however, there are no data, to our knowledge, suggesting that the living twin may be harmed by the dead co-twin. Mother and child are in perfect health.
Department of Obstetrics and Gynæcology, University Central Hospital, 70100 Kuopio 10, Finland
The expert technical assistance of Dr Dan Erik Wicklund, Mrs Christa Becker, Mrs Renate Hellmann, and Miss HelgardMesser is gratefully acknowledged. Part of this work was supported by a grant from the Deutsche Forschungsgemeinschaft.
Department of Obstetrics and Gynæcology, University Hospital, Lund
Department of Clinical Genetics, University Hospital,
ANDERS
Department of Pædiatrics, University of Mainz, Mainz, West Germany
Hospital,
University
of Helsinki
J. RAPOLA
Department of Obstetrics and Gynæcology, and Laboratory of Prenatal Genetics University of Helsinki
ÅBERG
P. AULA M. SEPPÄLÄ
REVERSAL OF HYPNOSIS-INDUCED ANALGESIA BY NALOXONE
FELIX MITELMAN
S-221 85 Lund, Sweden
Children’s
M. RYYNÄNEN O. CASTREN
SiR,—The neurological basis of hypnosis is obscure. This letter describes a preliminary investigation into the mechanism of hypnotic pain relief. Naloxone is a pure opiate antagonist6 with no pain-enhancing properties in moderate doses.7 These
MICHAEL CANTZ
JÜRGEN GEHLER
properties
make it ideal to detect those situations
in
whicn
implicated in endogenous opioid peptides (endorphins) pain suppression. By this means the analgesia induced by acupuncture8 or placeb07.9 have been shown to be endorphin mediated. I gave naloxone single-blind within a series of saline injections and found that, after a short latency, hypnosisinduced analgesia seemed to be reversed. A 53 kg healthy young adult consented to the study. This volunteer was known to be able to sustain a deep hypnotic trance with eyes open ("somnambulistic state"). The pain stiare
PRENATAL SCREENING FOR CONGENITAL NEPHROSIS
SIR,-We wish to report the first prenatal diagnosis of congenital nephrosis based on maternal serum-A.F.p. (alpha-fetoprotein) screening. In June, 1978, we started a screening programme for congenital nephrosis and other A.F.p.-related fetal disorders in an area of Finland where the incidence of congenital nephrosis is high. We expected that such a programme, when applied to 100 000 pregnancies at 16-18 weeks, would allow the prenatal diagnosis of 9 cases with congenital nephrosis and 61 ’
cases
.
mulus was hand. The
a sharp sterile needle pressed onto the back of the pain-rating scale was a 10 cm horizontal line on a
of neural-tube defect.
This estimate is based on the assumed incidence of 0-12 per 1000 for congenital nephrosis and 0.90 per 1000 for neural-tube defects in the whole of Finland.’2 These 100 000 pregnancies might be expected to yield 3377 with a maternal serum-A.F.p. more than 2.5 the normal median. Of these, 2747 would not come to amniocentesis because a repeat A.F.P. measurement was normal or because of an error in dates
1. Huttunen, N.-P. Archs Dis. Childh. 2. Saxén, L., Klemetti, A., Härö, A. S.
1976, 51, 344.
Am. J. Epidem. 1974, 100, 297.
Report of U. K. Collaborative Study. Lancet, 1977, i, 1323. Aula, P., Rapola, J., Karjalainen, O., Lindgren, J., Hartikainen, A.-L., Seppälä, M. Am. J. Dis. Child. (in the press). 5. Seppälä, M., Aula, P., Rapola, J., Karjalainen, O., Huttunen, N.-P., Ruoslahti, E. Lancet, 1976, ii, 123. 6. Blumberg, H., Dayton, H. B. in Agonist and Antagonist Actions of Narcotic Analgesic Drugs (edited by H. W. Kosterlitz, H. O. J. Collier, and J. E. Villareal); p 110. New Vork, 1973. 7. Levine, J. D., Gordon, N. C., Fields, H. L. Lancet, 1978, ii, 654. 8. Mayer, D. J., Price, D. D., Rafli, A. Brain Res. 1977, 121, 360. 9. Levine, J. D., and others. Nature, 1978, 272, 826. 3. 4.