- Email: [email protected]
HAEMODILUTION IN ACUTE STROKE
825 EFFECT OF CHRONICALLY ADMINISTERED DILTIAZEM ON
ABNORMAL INVOLUNTARY MOVEMENTS
Fig 1—Cerebetlar uptake of radioactivity during Wada test. was
14.5
14
(maximum possible 28) and his tardive dystonia score was (maximum possible 40). After giving informed consent, the
Black
=
left and hatched
right cerebellum.
=
patient took 30 mg diltiazem and was reassessed at 30-min intervals for 2 h. Over the next 10 weeks he was treated with up to 60 mg diltiazem, four times a day. No clinically significant improvement was observed for the 2 h after the first dose. However, objective and subjective improvement subsequently occurred, especially at a dose of 150 mg a day (table). In addition, the patient reported much less time spent in bed (8 h), could read a whole book within a couple of days, and was able to do household chores he had not done for years. No clinically significant effects on vital signs were observed. There was no complaint of side-effects, and no evidence of cardiac toxicity, which has been reported with lithium combined with verapamil, another calciumchannel blocker.4 The patient requested he remain on diltiazem as he felt it assisted his overall functioning better than previous trials of other drugs. Objective and subjective benefit was observed in the mid-dose range; the higher dose of 240 mg was associated with worsening of symptoms. However, when contacted by phone 25 weeks after starting diltiazem, the patient reported that, in the past month, the severity of his movement disorder had reverted to baseline. We did not see a beneficial response to a single dose, which may have been due to the lower dose we used compared with Ley et al.3 The objective and subjective benefit observed over the first 3 months may have been due to a placebo response. If the response was "real" we could explain the later worsening by tolerance to diltiazem’s beneficial effect or to the natural course of this patient’s TD. However, the final assessment was negative. Had we not followed the patient up at 25 weeks, our report would have been
inappropriately encouraging. Arbour and Mass General Hospitals, and Harvard Medical School, Boston, Massachusetts 02130, USA
WILLIAM E. FALK
JOANNE D. WOJICK ALAN J. GELENBERG
N, Childs A. An anti-tardive dyskinesia effect of verapamil. Am J Psychiatry 1986, 143: 1485 2 Ross JL, Mackenzie TB, Hanson DR, Charles CR. Diltiazem for tardive dyskinesia Lancet 1987; i: 268 3. Leys D, Vermersch P, Danel T, et al Diltiazem for tardive dyskinesia Lancet 1988; i: 1. Barrow
250-51. 4 Pnce WA, Giannini AJ. Neurotoxicity caused by lithium-verapamil synergism. J Clin Pharmacol 1986, 26: 717-19.
Fig 2-SPECT images of brain (upper) and cerebellum (lower) during Wada test showing reversible crossed cerebellar diaschisis.
Left = left-sided middle normal.
and
right= right-sided
hemispheric
anaesthesia;
=
Single photon emission computerised tomographic (SPECT) images were obtained with a rotating gamma-camera within 3 h after the intravenous injection of 555 MBq technetium-99m labelled hexamethylpropyleneamine oxime (HMPAO, ’Ceretec’, Amersham) (fig 2). During the left-sided Wada test, activity in the left cerebral hemisphere and the contralateral right cerebellar hemisphere was decreased. During the right-sided Wada test a similar decrease of activity (right cerebral hemisphere and left cerebellar hemisphere) was seen. Under normal conditions there brain or cerebellar asymmetry. These studies suggest that reversible cerebellar diaschisis is not due to the interruption of cortico-ponto-cerebellar pathways but to decreased or increased spino-cerebellar neuronal activity. was no
Institute for Clinical and Experimental Nuclear Medicine, and Division of Clinical Electro-Physiology,
Department of Neurosurgery, University of Bonn, D 5300 Bonn-1, West Germany
H. J. BIERSACK F. GRÜNWALD D. B. LINKE
TRANSIENT CEREBELLAR DIASCHISIS
SIR,-Dr Duncan and colleagues (Sept 12, p 625) report on reversible cerebellar diaschisis in focal epilepsy. We had previously reported results in patients with cerebrovascular disease and hemiplegia. We found that crossed cerebellar diaschisis was frequent in patients with hemiplegia but not in patients with stroke and no paralysis in the limbs. We speculated that this is due to decreased neuronal spino-cerebellar input in hemiplegia, which is supported by Kennedy et al,2 who reported increased glucose metabolism in the ipsilateral cerebellar hemisphere on movement of the limbs. In our opinion Duncan and colleagues’ finding can be explained by the same mechanism, namely increased neuronal input from the seizure-induced hyperactivity of the contralateral limbs. We observed the opposite during a Wada test.3 Anaesthesia of one hemisphere during this test caused a decrease in blood flow to the contralateral cerebellar hemisphere of 15% (fig 1). Decreased neuronal spino-cerebellar input from the contralateral (temporary) paralysed limbs might be responsible for this finding.
1 Biersack HJ, Hartmann A, Friedrich G, et al. Zur Ursache der gekreuzten cerebellaren
Diaschisis bei zerebrovaskularer Erkrankung Nucl Med 1984, 23: 227-31. Suda S, et al. Local metabolic responses in brain accompanying motor activity. Ann Neurol 1980, 8: 90-95. 3. Biersack HJ, Linke D, Brassel F, et al. Technetium-99m HM-PAO brain SPECT in epileptic patients before and during unilateral hemispheric anesthesia (Wada test): Report of three cases. J Nucl Med 1987; 28: 1763-67. 2
Kennedy C, Miyaoka M,
HAEMODILUTION IN ACUTE STROKE
SiR,—I would modify the conclusion of the Italian Acute Stroke Study Group (Feb 13, p 318) that "moderate haemodilution does not improve the outcome in acute stroke patients". Staedt et al’ showed in a smaller controlled trial that the clinical outcome after 10 days is better with 10 % hydroxyethyl starch 200/0-5 than with 10 % ’Dextran 40’. Similarly in animals starch induces more favourable rheological effects than dextran, thus leading to an increase of cerebral blood flow, which decreases after dextran.1 Furthermore
826 haemodilution may be effective only under certain haemodynamic work in patients with peripheral vascular disease.3 Thus the conclusion of the study group should be that their form of haemodilution was ineffective in patients meeting their criteria. There is evidence that haemodilution with starch is effective in certain other patients. Future research should determine the most suitable plasma expander, the optimum treatment schedule, and likely responders.
conditions,
as
suggested by
our
Haemorheology Research Laboratory, Department of Physical Medicine, University of Munich, 8000 Munich 2, West Germany
E. ERNST
et al. Hypervolemic hemodilution with 10% HES and 10% Dextran 40 in patients with ischemic stroke. In: Hartman A, Kuschinsky W, eds. Cerebral ischemia and hemorheology. Berlin: Springer, 1987: 429-35. 2. Tsuda Y, Hartmann A, Weiland J, Solymosi L. Effect of hydroxyethyl starch and low molecular weight dextran on cerebral blood flow and hemorheology in normal baboons. In: Hartmann A, Kuschinsky W, eds. Cerebral ischemia and hemorheology. Berlin. Springer, 1987. 398-407. 3. Ernst E, Matrai A, Kollar L. Placebo-controlled, double-blind study of haemodilution in peripheral arterial disease. Lancet 1987; ii: 1449-51.
1. Staedt
U, Schlierf G, Oster P,
200/0·5
PRENATAL EXCLUSION OF HEREDITARY RETINOBLASTOMA
SIR,-Retinoblastoma is the commonest ophthalmic malignancy of childhood and there is a family history in 25 % of cases.’The cloning of a candidate gene for the locus predisposing to retinoblastoma2 and the isolation of highly polymorphic DNA probes from within this locus3 perniit accurate tracking of predisposition to this tumour in affected families and prenatal prediction for individuals at high risk. We report here the first use of intragenic polymorphic probes in conjunction with chorionic villus sampling4 to provide early prenatal exclusion of inheritance of predisposition to retinoblastoma. A 22-year-old woman was seen in the ninth week of pregnancy. She had had bilateral retinoblastoma diagnosed in childhood, her father and her sister both had retinoblastoma, as did her son (see figure). The family was uninformative for the esterase D protein polymorphism5 and karyotyping and esterase D measurement revealed no detectable deletion of chromosome 13, an anomaly present in 3-4% of cases.6 The family were, however, informative for the DNA probe p68RS2.0, which detects a DNA sequence lying within the putative retinoblastoma locus.3 The linkage is close (lod score 12 at 6= zero) and no recombinations were observed by Wiggs et al ;3 nor have we observed any (unpublished). 60 mg chorionic villi was collected in the 9th to 10th week of pregnancy and high-molecular weight DNA was prepared for analysis in parallel with DNA from peripheral blood leucocytes of both parents and the sibling. The affected sibling is homozygous for the 1 ’7 kb allele (figure); the mother carries the 1 ’75 and 1.7kb alleles; and the father has 17
and 1kb alleles. Thus the predisposition segregates with the matemal 1-7 kb allele, a finding confirmed by data from the mother’s family (not shown). The fetus has inherited the 18 kb allele from its father and the 1 75 kb allele from its mother so we predict that this child will be unaffected by retinoblastoma. Confirmation of this prediction will require several years of assessment by an ophthalmologist. The prediction in this case is not limited by the possibility of genetic recombination;’ nor are there the difficulties associated with demonstration of gene dosage.8 The combination of chorionic villus sampling and the highly polymorphic probes now available means that prenatal testing for retinoblastoma will be available to a large proportion of affected families at an early stage of pregnancy. We thank Dr F. A. Beresford, Dr M. S. Erram, Dr C. W. Frith, and Dr S. Sahay for collecting specimens, Dr Maurice Super for help and advice, Dr Ted Dryja for the probes, and Dr Jon Pritchard for comments. ICRF Molecular Oncology Laboratory, Institute of Child Health, London WC1N 1EH; Harris Birthright Research Centre, for Fetal Medicine, King’s College School of Medicine and Dentistry, London SE5; Departments of Paediatrics and Ophthalmology, St Bartholomews Hospital, London EC1; and Department of Clinical Ophthalmology, Moorfields Eye Hospital, London EC1
CHRISTOPHER MITCHELL KYPROS NICOLAIDES JUDITH KINGSTON JOHN HUNGERFORD
MARCELLE JAY JOHN COWELL
Jay M, Cowell JK, Hungerford J. Register of retinoblastoma: Preliminary results. Eye (in press). 2. Friend SH, Bernards R, Rogelj S, et al. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 1986; 323: 1.
643-46.
3.
4.
5.
6. 7.
8.
Yandell D, et al Prediction of the risk of hereditary retinoblastoma using DNA polymorphisms within the retinoblastoma gene N Engl J Med 1988; 318: 151-57. Rodeck CH, Nicolaides RH, Morsmann JM, McKenzie C, Gosden CM, Gosden JR A single operator technique for first trimester chorion biopsy. Lancet 1983; ii: 1340. Cowell JK, Kay M, Rutland P, Hungerford J. An assessment of the usefulness of the esterase-D protein polymorphism in the antenatal prediction of retinoblastoma in the United Kingdom. Br J Cancer 1987; 55: 661-64. Cowell JK, Rutland P, Jay M, Hungerford J. Deletions of the esterase-D locus from a survey of 200 retinoblastoma patients. Hum Genet 1986; 72: 164-67. Cavenee WK, Murphree AL, Schull MM, Benedict WF, Sparkes RS, Kock E, Nordenskjold M. Prediction of familial predisposition to retinoblastoma. N Engl J Med 1986; 314: 1201-07. Horsthemke B, Barnert HJ, Greger V, Passarge E, Hopping W. Early diagnosis in hereditary retinoblastoma by detection of molecular deletions at gene locus. Lancet 1987; i: 511.
Wiggs J, Nordenskjeld M,
FIRST TRIMESTER ALPHA-FETOPROTEIN LEVELS AND FETAL CHROMOSOMAL ANEUPLOIDIES
SiR,—There have been several reports demonstrating a during the second trimester in maternal serum alphafetoprotein (MSAFP) in pregnancies affected by chromosomal abnormalities. 1-3 There have now been two studies demonstrating reduction
that
MSAFP is also reduced in the first trimester. Brambati et al4
reported on eight cases of trisomy 21, three cases of trisomy 18, and various other trisomies, and Barkai et a15 reported two cases of trisomy 21 and one of combined trisomy 21 and 14. These observations have led to the suggestion that a reduction of MSAFP in the first trimester could be used as a screen for fetal trisomy and that collaborative studies should be started to examine the value of MSAFP screening in the first trimester of pregnancy. We question whether low MSAFP levels in the first trimester will be able to differentiate sufficiently between pregnancies affected by fetal trisomy 21 and normal pregnancies. We have studied MSAFP in the first trimester (8-10 weeks) and the ranges in a non-pregnant
Autoradiograph
of Southern
blots from
family affected by
retinoblastoma. DNA digested with Rsal (Bethesda Research Laboratories), subjected to electrophoresis through 12 ’Agarose’, and transferred to nitrocellulose membrane. p68RS2.0 was labelled to high specific activity by oligoprimer extension using 32P-CTP. After hybridisation filter was washed at high stringency and exposed to Kodak XAR-5 autoradiographic film with an intensifying screen at - 70°C for 24 h.
population. We have developed a highly sensitive AFP assay by modifying the method of Stevenson et al6 for the measurement of AFP in serum. The assay is sensitive to 0.2 ag/1, with between-batch coefficients of variation at 1 ’4 and 53 pg/l of 4%, and at 178 pg/1 of 6-3%. For zero calibration we used horse serum but identical values were obtained with ovine or bovine serum. The results of our study are shown in the table.
ABNORMAL INVOLUNTARY MOVEMENTS
Fig 1—Cerebetlar uptake of radioactivity during Wada test. was
14.5
14
(maximum possible 28) and his tardive dystonia score was (maximum possible 40). After giving informed consent, the
Black
=
left and hatched
right cerebellum.
=
patient took 30 mg diltiazem and was reassessed at 30-min intervals for 2 h. Over the next 10 weeks he was treated with up to 60 mg diltiazem, four times a day. No clinically significant improvement was observed for the 2 h after the first dose. However, objective and subjective improvement subsequently occurred, especially at a dose of 150 mg a day (table). In addition, the patient reported much less time spent in bed (8 h), could read a whole book within a couple of days, and was able to do household chores he had not done for years. No clinically significant effects on vital signs were observed. There was no complaint of side-effects, and no evidence of cardiac toxicity, which has been reported with lithium combined with verapamil, another calciumchannel blocker.4 The patient requested he remain on diltiazem as he felt it assisted his overall functioning better than previous trials of other drugs. Objective and subjective benefit was observed in the mid-dose range; the higher dose of 240 mg was associated with worsening of symptoms. However, when contacted by phone 25 weeks after starting diltiazem, the patient reported that, in the past month, the severity of his movement disorder had reverted to baseline. We did not see a beneficial response to a single dose, which may have been due to the lower dose we used compared with Ley et al.3 The objective and subjective benefit observed over the first 3 months may have been due to a placebo response. If the response was "real" we could explain the later worsening by tolerance to diltiazem’s beneficial effect or to the natural course of this patient’s TD. However, the final assessment was negative. Had we not followed the patient up at 25 weeks, our report would have been
inappropriately encouraging. Arbour and Mass General Hospitals, and Harvard Medical School, Boston, Massachusetts 02130, USA
WILLIAM E. FALK
JOANNE D. WOJICK ALAN J. GELENBERG
N, Childs A. An anti-tardive dyskinesia effect of verapamil. Am J Psychiatry 1986, 143: 1485 2 Ross JL, Mackenzie TB, Hanson DR, Charles CR. Diltiazem for tardive dyskinesia Lancet 1987; i: 268 3. Leys D, Vermersch P, Danel T, et al Diltiazem for tardive dyskinesia Lancet 1988; i: 1. Barrow
250-51. 4 Pnce WA, Giannini AJ. Neurotoxicity caused by lithium-verapamil synergism. J Clin Pharmacol 1986, 26: 717-19.
Fig 2-SPECT images of brain (upper) and cerebellum (lower) during Wada test showing reversible crossed cerebellar diaschisis.
Left = left-sided middle normal.
and
right= right-sided
hemispheric
anaesthesia;
=
Single photon emission computerised tomographic (SPECT) images were obtained with a rotating gamma-camera within 3 h after the intravenous injection of 555 MBq technetium-99m labelled hexamethylpropyleneamine oxime (HMPAO, ’Ceretec’, Amersham) (fig 2). During the left-sided Wada test, activity in the left cerebral hemisphere and the contralateral right cerebellar hemisphere was decreased. During the right-sided Wada test a similar decrease of activity (right cerebral hemisphere and left cerebellar hemisphere) was seen. Under normal conditions there brain or cerebellar asymmetry. These studies suggest that reversible cerebellar diaschisis is not due to the interruption of cortico-ponto-cerebellar pathways but to decreased or increased spino-cerebellar neuronal activity. was no
Institute for Clinical and Experimental Nuclear Medicine, and Division of Clinical Electro-Physiology,
Department of Neurosurgery, University of Bonn, D 5300 Bonn-1, West Germany
H. J. BIERSACK F. GRÜNWALD D. B. LINKE
TRANSIENT CEREBELLAR DIASCHISIS
SIR,-Dr Duncan and colleagues (Sept 12, p 625) report on reversible cerebellar diaschisis in focal epilepsy. We had previously reported results in patients with cerebrovascular disease and hemiplegia. We found that crossed cerebellar diaschisis was frequent in patients with hemiplegia but not in patients with stroke and no paralysis in the limbs. We speculated that this is due to decreased neuronal spino-cerebellar input in hemiplegia, which is supported by Kennedy et al,2 who reported increased glucose metabolism in the ipsilateral cerebellar hemisphere on movement of the limbs. In our opinion Duncan and colleagues’ finding can be explained by the same mechanism, namely increased neuronal input from the seizure-induced hyperactivity of the contralateral limbs. We observed the opposite during a Wada test.3 Anaesthesia of one hemisphere during this test caused a decrease in blood flow to the contralateral cerebellar hemisphere of 15% (fig 1). Decreased neuronal spino-cerebellar input from the contralateral (temporary) paralysed limbs might be responsible for this finding.
1 Biersack HJ, Hartmann A, Friedrich G, et al. Zur Ursache der gekreuzten cerebellaren
Diaschisis bei zerebrovaskularer Erkrankung Nucl Med 1984, 23: 227-31. Suda S, et al. Local metabolic responses in brain accompanying motor activity. Ann Neurol 1980, 8: 90-95. 3. Biersack HJ, Linke D, Brassel F, et al. Technetium-99m HM-PAO brain SPECT in epileptic patients before and during unilateral hemispheric anesthesia (Wada test): Report of three cases. J Nucl Med 1987; 28: 1763-67. 2
Kennedy C, Miyaoka M,
HAEMODILUTION IN ACUTE STROKE
SiR,—I would modify the conclusion of the Italian Acute Stroke Study Group (Feb 13, p 318) that "moderate haemodilution does not improve the outcome in acute stroke patients". Staedt et al’ showed in a smaller controlled trial that the clinical outcome after 10 days is better with 10 % hydroxyethyl starch 200/0-5 than with 10 % ’Dextran 40’. Similarly in animals starch induces more favourable rheological effects than dextran, thus leading to an increase of cerebral blood flow, which decreases after dextran.1 Furthermore
826 haemodilution may be effective only under certain haemodynamic work in patients with peripheral vascular disease.3 Thus the conclusion of the study group should be that their form of haemodilution was ineffective in patients meeting their criteria. There is evidence that haemodilution with starch is effective in certain other patients. Future research should determine the most suitable plasma expander, the optimum treatment schedule, and likely responders.
conditions,
as
suggested by
our
Haemorheology Research Laboratory, Department of Physical Medicine, University of Munich, 8000 Munich 2, West Germany
E. ERNST
et al. Hypervolemic hemodilution with 10% HES and 10% Dextran 40 in patients with ischemic stroke. In: Hartman A, Kuschinsky W, eds. Cerebral ischemia and hemorheology. Berlin: Springer, 1987: 429-35. 2. Tsuda Y, Hartmann A, Weiland J, Solymosi L. Effect of hydroxyethyl starch and low molecular weight dextran on cerebral blood flow and hemorheology in normal baboons. In: Hartmann A, Kuschinsky W, eds. Cerebral ischemia and hemorheology. Berlin. Springer, 1987. 398-407. 3. Ernst E, Matrai A, Kollar L. Placebo-controlled, double-blind study of haemodilution in peripheral arterial disease. Lancet 1987; ii: 1449-51.
1. Staedt
U, Schlierf G, Oster P,
200/0·5
PRENATAL EXCLUSION OF HEREDITARY RETINOBLASTOMA
SIR,-Retinoblastoma is the commonest ophthalmic malignancy of childhood and there is a family history in 25 % of cases.’The cloning of a candidate gene for the locus predisposing to retinoblastoma2 and the isolation of highly polymorphic DNA probes from within this locus3 perniit accurate tracking of predisposition to this tumour in affected families and prenatal prediction for individuals at high risk. We report here the first use of intragenic polymorphic probes in conjunction with chorionic villus sampling4 to provide early prenatal exclusion of inheritance of predisposition to retinoblastoma. A 22-year-old woman was seen in the ninth week of pregnancy. She had had bilateral retinoblastoma diagnosed in childhood, her father and her sister both had retinoblastoma, as did her son (see figure). The family was uninformative for the esterase D protein polymorphism5 and karyotyping and esterase D measurement revealed no detectable deletion of chromosome 13, an anomaly present in 3-4% of cases.6 The family were, however, informative for the DNA probe p68RS2.0, which detects a DNA sequence lying within the putative retinoblastoma locus.3 The linkage is close (lod score 12 at 6= zero) and no recombinations were observed by Wiggs et al ;3 nor have we observed any (unpublished). 60 mg chorionic villi was collected in the 9th to 10th week of pregnancy and high-molecular weight DNA was prepared for analysis in parallel with DNA from peripheral blood leucocytes of both parents and the sibling. The affected sibling is homozygous for the 1 ’7 kb allele (figure); the mother carries the 1 ’75 and 1.7kb alleles; and the father has 17
and 1kb alleles. Thus the predisposition segregates with the matemal 1-7 kb allele, a finding confirmed by data from the mother’s family (not shown). The fetus has inherited the 18 kb allele from its father and the 1 75 kb allele from its mother so we predict that this child will be unaffected by retinoblastoma. Confirmation of this prediction will require several years of assessment by an ophthalmologist. The prediction in this case is not limited by the possibility of genetic recombination;’ nor are there the difficulties associated with demonstration of gene dosage.8 The combination of chorionic villus sampling and the highly polymorphic probes now available means that prenatal testing for retinoblastoma will be available to a large proportion of affected families at an early stage of pregnancy. We thank Dr F. A. Beresford, Dr M. S. Erram, Dr C. W. Frith, and Dr S. Sahay for collecting specimens, Dr Maurice Super for help and advice, Dr Ted Dryja for the probes, and Dr Jon Pritchard for comments. ICRF Molecular Oncology Laboratory, Institute of Child Health, London WC1N 1EH; Harris Birthright Research Centre, for Fetal Medicine, King’s College School of Medicine and Dentistry, London SE5; Departments of Paediatrics and Ophthalmology, St Bartholomews Hospital, London EC1; and Department of Clinical Ophthalmology, Moorfields Eye Hospital, London EC1
CHRISTOPHER MITCHELL KYPROS NICOLAIDES JUDITH KINGSTON JOHN HUNGERFORD
MARCELLE JAY JOHN COWELL
Jay M, Cowell JK, Hungerford J. Register of retinoblastoma: Preliminary results. Eye (in press). 2. Friend SH, Bernards R, Rogelj S, et al. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 1986; 323: 1.
643-46.
3.
4.
5.
6. 7.
8.
Yandell D, et al Prediction of the risk of hereditary retinoblastoma using DNA polymorphisms within the retinoblastoma gene N Engl J Med 1988; 318: 151-57. Rodeck CH, Nicolaides RH, Morsmann JM, McKenzie C, Gosden CM, Gosden JR A single operator technique for first trimester chorion biopsy. Lancet 1983; ii: 1340. Cowell JK, Kay M, Rutland P, Hungerford J. An assessment of the usefulness of the esterase-D protein polymorphism in the antenatal prediction of retinoblastoma in the United Kingdom. Br J Cancer 1987; 55: 661-64. Cowell JK, Rutland P, Jay M, Hungerford J. Deletions of the esterase-D locus from a survey of 200 retinoblastoma patients. Hum Genet 1986; 72: 164-67. Cavenee WK, Murphree AL, Schull MM, Benedict WF, Sparkes RS, Kock E, Nordenskjold M. Prediction of familial predisposition to retinoblastoma. N Engl J Med 1986; 314: 1201-07. Horsthemke B, Barnert HJ, Greger V, Passarge E, Hopping W. Early diagnosis in hereditary retinoblastoma by detection of molecular deletions at gene locus. Lancet 1987; i: 511.
Wiggs J, Nordenskjeld M,
FIRST TRIMESTER ALPHA-FETOPROTEIN LEVELS AND FETAL CHROMOSOMAL ANEUPLOIDIES
SiR,—There have been several reports demonstrating a during the second trimester in maternal serum alphafetoprotein (MSAFP) in pregnancies affected by chromosomal abnormalities. 1-3 There have now been two studies demonstrating reduction
that
MSAFP is also reduced in the first trimester. Brambati et al4
reported on eight cases of trisomy 21, three cases of trisomy 18, and various other trisomies, and Barkai et a15 reported two cases of trisomy 21 and one of combined trisomy 21 and 14. These observations have led to the suggestion that a reduction of MSAFP in the first trimester could be used as a screen for fetal trisomy and that collaborative studies should be started to examine the value of MSAFP screening in the first trimester of pregnancy. We question whether low MSAFP levels in the first trimester will be able to differentiate sufficiently between pregnancies affected by fetal trisomy 21 and normal pregnancies. We have studied MSAFP in the first trimester (8-10 weeks) and the ranges in a non-pregnant
Autoradiograph
of Southern
blots from
family affected by
retinoblastoma. DNA digested with Rsal (Bethesda Research Laboratories), subjected to electrophoresis through 12 ’Agarose’, and transferred to nitrocellulose membrane. p68RS2.0 was labelled to high specific activity by oligoprimer extension using 32P-CTP. After hybridisation filter was washed at high stringency and exposed to Kodak XAR-5 autoradiographic film with an intensifying screen at - 70°C for 24 h.
population. We have developed a highly sensitive AFP assay by modifying the method of Stevenson et al6 for the measurement of AFP in serum. The assay is sensitive to 0.2 ag/1, with between-batch coefficients of variation at 1 ’4 and 53 pg/l of 4%, and at 178 pg/1 of 6-3%. For zero calibration we used horse serum but identical values were obtained with ovine or bovine serum. The results of our study are shown in the table.