1132
normally appear in the substantia nigra dopamine neurons until 18 months of age.’ The "premature" appearance of neuromelanin in the implanted fetal cells may be indicative of metabolic overactivity and premature ageing.4 Alternatively, its presence may reflect cellular damage by quinones and oxygen radicals generated by
Experiments were done with enriched extracts of D pteronyssinus spent growth medium (20 mg/ml) and with purified Der pI (0-3 mg/ml). Both agents were added to the apical side of the epithelium. The proteinase activities of the two preparations were first assayed by ’Azocoll’ degradation and then matched for use in the chamber
auto-oxidation of dopamine,’ although the significance of neuromelanin in dopamine cells as either a pathological marker of Parkinson’s disease or a possible cause of Parkinson’s disease is dubious.6 Redmond’s report reinforces the worrying possibility that the grafts may have been subjected to similar process(es) to those that caused parkinsonism in the first place. The effect of the degree of severity of the disease is important. The patient had end-stage parkinsonism. Did any of the fetal dopamine cells in the grafts or in the host substantia nigra described by Redmond et al contain anything resembling Lewy bodies?7
studies. Incubations were also done in the presence of 1-5 mmol/l dithiothreitol to render the cysteine proteinase catalytically competent. The results demonstrate that Der pI can increase bronchial permeability to serum albumin (and presumably other macromolecules). Further experiments are required to investigate the time and concentration-dependency of these effects and whether inert Der pI can be activated by reducing agents in the airways.’ However, these preliminary results reinforce the hypothesis that allergens may enhance airways disease by means other than their antigenic activity.
Parkinson’s Disease Society Research Laboratories,
Immunopharmacology Group, Pharmacology and Medicine 1, Southampton General Hospital, Southampton SOB 4XY, UK
C. A. HERBERT S. T. HOLGATE C. ROBINSON
University Department of Medicine, Queen Elizabeth II Medical Centre, and Western Australian Institute of Child Health, Perth, Western Australia
P. J. THOMPSON G. A. STEWART
Clinical
Pharmacology Group, Biomedical Sciences Division, King’s College, London SW3 6LX, UK
S.B.BLUNT
1. Javoy Agid F, Hirsch EC, Dumas S, Duyckaerts C, Mallet J, Agid Y Decreased tyrosine hydrolase messenger RNA in the survival dopamine neurons of the substantia nigra in Parkinson’s disease: an in situ hybridization study. Neuroscience
1990; 38: 245-53. 2. Pasinetti GM, Lemer SP, Johnson SA, Morgan DG, Telford NA, Finch CE. Chronic lesions differentially decrease tyrosine hydroxylase messenger RNA in dopaminergic neurons of the substantia nigra. Mol Brain Res 1989; 5: 203-09. 3. Hornykiewicz O, Kish SJ. Biochemical pathophysiology of Parkinson’s disease. Adv Neurol 1986; 45: 19-34. 4. Mann DM, Yates PO. Lipoprotein pigments—their relationship to ageing in the human nervous system II: the melanin content of pigmented nerve cells. Brain
1974; 97: 489-98. 5. Cohen G. Monoamine oxidase, hydrogen peroxide and Parkinson’s disease Adv Neurol 1986; 45: 119-25. 6 Marsden CD. Neuromelanin and Parkinson’s disease. J Neural Transm 1983; 19 (suppl): 121-41 7. Forno LS. Pathology of Parkinson’s disease. In. Marsden CD, Fahn S, eds. Movement disorders. London: Butterworths, 1982.
1. Chua
KY, Stewart GA, Thomas WR, Simpson RJ, Dilworth RJ, Plozza TM. Sequence analysis of cDNA coding for a major house dust mite allergen, Der pi, homology with cysteine proteases. J Exp Med 1988; 167: 175-82. 2. Stewart GA, Thompson PJ, Simpson RJ Protease antigens from house dust mite Lancet 1989; ii: 154-55. 3. Stewart GA, Lake FR, Thompson PJ. Faecally-derived hydrolytic enzymes from the house dust mite: characterization of potential allergens. J Allergy Clin Immunol
(in press) CA, Summers JA, Robinson C. In vitro techniques for the study of transepithelial protein flux in the airways and its modulation by inflammatory cells and mediators. Br J Pharmacol 1990; 100: 477P. 5. Herbert CA, Edwards D, Boot JR, Robinson C. Modulation of eosinophil-induced enhancement of bronchial epithelial permeability. Br J Pharmacol 1990; 100: 373P. 6. Heffner JE, Repine JE. Pulmonary strategies of antioxidant defense. Am Rev Respir 4. Herbert
Dis 1989; 140: 531-54
Effect of mite allergen on permeability of bronchial mucosa SIR,-The allergen Der pI from the house dust mite Dermatophagoides pteronyssinus is a cysteine proteinase in which the antigenic epitopes are distinct from the catalytic site. 1-3 As a development of our studies suggesting that proteinases disrupt the bronchial epithelium to augment transmucosal macromolecule movement we postulated that the enzymatic activity of Der pI might enhance the access of antigens to immunocompetent cells in the asthmatic airway by a similar mechanism. We have tested this hypothesis with an in vitro model in which sheets of bovine mounted between two heated halfpermit defined 02 cmz areas of tissue to be exposed to bathing solutions on either side. The apical sides of the tissues were exposed for 3 h to the various treatments (table). The net apical-basolateral flux of 12sI-Iabelled bovine serum albumin was then measured after replacement of the medium with fresh proteinase-free buffer.
bronchial mucosa chambers4 which
are
EFFECT OF SPENT GROWTH MEDIUM AND DER pl ON APICAL-BASOLATERAL FLUX OF ALBUMIN IN BOVINE BRONCHIAL MUCOSA
*In fmol cm - 2 mln - 1, as mean (SEM), p values refer to appropriate controls tUnlts/ml with azocoll substrate
SGM =spent growth
medium DTT=drthiothrertol
Extracorporeal membrane oxygenation SIR,-Dr Greenough and Dr Emery (Sept 22, p 760) suggest that at King’s College Hospital there would be a likely requirement for extracorporeal membrane oxygenation (ECMO) in 1/5000 births if predicted mortality rates of 80% were applied. They go on to say that of the 5 infants who seemed to be suitable, 3 survived without problems and the remaining 2 died following rapid collapse. Bartlett et all in Michigan estimated 1 infant per 1000 livebirths would be saved by ECMO each year according to these same criteria. With colleagues I wished to validate a projected figure of 20 infants a year in South Australia, having studied ECMO use. The medical records of infants between 34 weeks’ gestation and 12 months of age and between 2 and 10 kg in weight who died in Adelaide paediatric intensive care units between July, 1981, and June, 1986, were reviewed to see how many might have been considered for ECMO had it been available as a clinical service. Criteria for such consideration included reversible disease, artificial ventilation for less than seven days, and no intracranial haemorrhage. An additional criterion was that 90 min could have elapsed for an ECMO circuit to be established. In this five years there were 126 deaths of which 40 might have been considered for ECMO had it been available. Deaths were classified according to the system affected and whether the disease was acquired or congenital. In the largest group (acquired pulmonary disease), 25 of 33 would certainly have been considered for ECMO whereas in only 1 of 15 congenital pulmonary deaths might this have been beneficial. Nearly all these deaths were due to pulmonary hypoplasia. All 4 infants dying from acquired cardiac disease could have benefited from the use of ECMO whereas in only 3 of 21 infants dying from congenital heart disease would ECMO have been considered. There were no ECMO appropriate deaths involving other systems; and most (75%) were in the neonatal
period.
1133
There are on average 8 infant deaths a year in South Australia that might be avoided by ECMO-ie,1/3000 births, which is lower than Bardett and co-workers’ prediction, mainly because of the lower incidence of meconium aspiration syndrome. Nevertheless, such an incidence would support the introduction of ECMO as a clinical service. Redhill Hospital, Redhill, Surrey RH1 6LA, UK
1. Bartlett RH,
I. G. LEWIS
Gazzaniga AB, Toomasian JM. Extracorporeal membrane oxygenation respiratory failure: 100 cases. Ann Surg 1986; 204: 23.
m neonatal
Tolerance and the fetal
graft
Characteristic nuchal oedema with trisomy 21.
(arrow)
at 11.2 weeks in a fetus
.
SiR,—Your Sept 1 editorial discusses the paradox of the fetal allograft and in particular the possible role of the HLA-G antigen on the cytotrophoblast. You conclude that a special nonimmunogenic form of the major histocompatibility complex (MHC) class I molecule expressed at the fetomaternal interface prevented the baby being rejected as foreign by his mother. We question that such a molecule does not elicit a maternal immune response. Many workers have shown that antibodies to paternal antigens can be detected during pregnancy.1-3 We have demonstrated a non-cytotoxic IgG antibody response to paternal lymphocytes in sera from first trimester primigravidae4 and in placental eluates from these women at term.s The antibodies were directed to HLA-linked antigens but not to recognised class I (HLA-A, HLA-B, and HLA-C) or class II (HLA-DR) specificitiesAlthough the target for these antibodies has not been further defined, our data suggested that it may be an antigen similar to the special MHC molecule considered by you. Therefore such a molecule might be responsible for eliciting the antibody response we described. These antibodies are non-cytotoxic and might not be harmful to the survival of the fetal allograft.
Department of Renal Medicine, City Hospital, Nottingham NG5 1PB, UK
ANDREW INNES
Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen
DAVID POWER GRAEME CATTO
CHARLES CUNNINGHAM
H, Perry WM, Rocklin RE. Suppression of maternal responsiveness to paternal antigens by material plasma J Immunol 1975; 114: 525-28. 2. Rocklin RE, Kitzmiller JL, Garovoy MR. Maternal-fetal relation: II, further characterisation of an immunological blocking factor that develops during pregnancy, Clin Immunol Immunopathol 1982, 22: 305-15 3 Power DA, Catto GRD, Mason RJ, MacLeod AM, Stewart GM, Shewan WG. The fetus as an allograft: evidence for protective antibodies to HLA-linked paternal antigens. Lancet 1983; ii: 701-04. 4. Innes A, Cunningham C, Power DA, Catto GRD. Fetus and an allograft: non-cytotoxic maternal antibodies to HLA-linked paternal antigens. Am J Reprod 1. Pence
Immunol 1989; 19: 146-50. A, Stewart GM, Thomson MAR, Cunningham C, Catto GRD. Human placenta an antibody sponge? Am J Reprod Immunol 1988; 17: 57-60.
5 Innes
Nuchal fluid accumulation in trisomy-21 detected by vaginosonography in first trimester SIR,-Fetal anatomy in the first trimester can be seen with a high degree of accuracy by vaginosonography.1,2 During the past three years we have examined with sonography 7 fetuses with trisomy 21 diagnosed by karyotyping in our first-trimester chorionic villus sampling programme. In all 7 fetuses we demonstrated accumulation of subcutaneous fluid in various amounts in the nuchal region (figure). However, of 105 control fetuses with normal karyotype matched for gestational age (11 and 12 weeks) excessive nuchal fluid was detected in only 1. In the fetuses with normal karyotype the nuchal thickness was less than 2-5 mm, whereas in the affected fetuses this measured between 3 and 7 mm. Redundant nuchal folds are among the characteristic features of second-trimester fetuses with trisomy 21; however, this sign alone is
Sagittal plane. of little value in screening for Down syndrome. Spontaneous resolution of first-trimester nuchal oedema later in pregnancy has also been described/3 and greater attention should be paid to this sign in the first trimester. Aneuploidy cannot be assumed to be present in every fetus with this appearance but it is highly probable that fetal nuchal oedema detectable by vaginosonography in the first trimester is a manifestation of trisomy 211,2 or other aneuploid syndromesand could be an indication for chromosomal studies. Vaginosonography between weeks 9 and 12 of gestation might result in a higher pick-up rate of abnormalities than other methods, and this could be a promising approach in screening for trisomy 21 in patients at risk and in young pregnant women, since the procedure is non-invasive and therefore less risky than other methods. Department of Obstetrics and Gynaecology, Medical University A Szent-Gyorgyi, 6701 Szeged, Hungary
J. SZABÓ J. GELLEN
1. Rottem
S, Bronshtem M, Thaler I, Brandes JM. First trimester transvaginal sonographic diagnosis of fetal anomalies. Lancet 1989; i: 444-45. 2. Bronshtein M, Rotten S, Yoffe N, Blumenfeld Z. First-trimester and early second trimester diagnosis of nuchal cystic hygroma by transvaginal sonography: diverse prognosis of septated from nonseptated lesion. Am J Obstet Gynecol 1989; 161: 78-82. 3. Rodis JF, Vintziloes AM,
Campbell WA, Nochimson DJ. Spontaneous resolution of fetal cystic hygroma m Down’s syndrome. Obstet Gynecol 1988; 71: 976-77. 4. Szabó J, Gellén J, Szemere G. Nonimmune hydrops in trisomy 18: diagnosis by chorionic villus sampling and vaginosonography in the first trimester. Br J Obstet Gynaecol (in press).
Bone density screening for osteoporosis SiR,—We are afraid that Dr van Hemert’s reply (Sept 29, p 818) to views (Aug 25, p 502) will add further confusion to what should straightforward approach to bone density screening for osteoporosis. Osteoporosis is a condition that is identified by the presence of a low bone mineral density (BMD), a consequence of the decline in bone mass per unit volume. Whether that disease expresses itself as a fracture in the future depends on several other factors such as a continuing adverse lifestyle and absence of sex hormone replacement therapy (contributing to further bone loss), a fall, or a lack of muscle and fat which may protect against the consequences of a fall. Van Hemert confuses the diagnosis of the disease by BMD scanning with risk evaluation for osteoporosis. We are agreed that clinical risk factors have poor diagnostic value but to use, as he does, metacarpal cortical bone loss measured by a magnifying glass from X-ray films of the hands as a predictive test is mistaken.1,2 Trabecular bone loss is the major feature of postmenopausal osteoporosis due to oestrogen deficiency and is the main reason for the greatly increased prevalence in women. Dual photon bone densitometry screening identifies this trabecular loss in the spine or hip, the critical areas of fracture. His work did not test this predictive performance. The important epidemiological question is not the overlap in BMD between fracture and non-fracture groups but
our
be
a
normally appear in the substantia nigra dopamine neurons until 18 months of age.’ The "premature" appearance of neuromelanin in the implanted fetal cells may be indicative of metabolic overactivity and premature ageing.4 Alternatively, its presence may reflect cellular damage by quinones and oxygen radicals generated by
Experiments were done with enriched extracts of D pteronyssinus spent growth medium (20 mg/ml) and with purified Der pI (0-3 mg/ml). Both agents were added to the apical side of the epithelium. The proteinase activities of the two preparations were first assayed by ’Azocoll’ degradation and then matched for use in the chamber
auto-oxidation of dopamine,’ although the significance of neuromelanin in dopamine cells as either a pathological marker of Parkinson’s disease or a possible cause of Parkinson’s disease is dubious.6 Redmond’s report reinforces the worrying possibility that the grafts may have been subjected to similar process(es) to those that caused parkinsonism in the first place. The effect of the degree of severity of the disease is important. The patient had end-stage parkinsonism. Did any of the fetal dopamine cells in the grafts or in the host substantia nigra described by Redmond et al contain anything resembling Lewy bodies?7
studies. Incubations were also done in the presence of 1-5 mmol/l dithiothreitol to render the cysteine proteinase catalytically competent. The results demonstrate that Der pI can increase bronchial permeability to serum albumin (and presumably other macromolecules). Further experiments are required to investigate the time and concentration-dependency of these effects and whether inert Der pI can be activated by reducing agents in the airways.’ However, these preliminary results reinforce the hypothesis that allergens may enhance airways disease by means other than their antigenic activity.
Parkinson’s Disease Society Research Laboratories,
Immunopharmacology Group, Pharmacology and Medicine 1, Southampton General Hospital, Southampton SOB 4XY, UK
C. A. HERBERT S. T. HOLGATE C. ROBINSON
University Department of Medicine, Queen Elizabeth II Medical Centre, and Western Australian Institute of Child Health, Perth, Western Australia
P. J. THOMPSON G. A. STEWART
Clinical
Pharmacology Group, Biomedical Sciences Division, King’s College, London SW3 6LX, UK
S.B.BLUNT
1. Javoy Agid F, Hirsch EC, Dumas S, Duyckaerts C, Mallet J, Agid Y Decreased tyrosine hydrolase messenger RNA in the survival dopamine neurons of the substantia nigra in Parkinson’s disease: an in situ hybridization study. Neuroscience
1990; 38: 245-53. 2. Pasinetti GM, Lemer SP, Johnson SA, Morgan DG, Telford NA, Finch CE. Chronic lesions differentially decrease tyrosine hydroxylase messenger RNA in dopaminergic neurons of the substantia nigra. Mol Brain Res 1989; 5: 203-09. 3. Hornykiewicz O, Kish SJ. Biochemical pathophysiology of Parkinson’s disease. Adv Neurol 1986; 45: 19-34. 4. Mann DM, Yates PO. Lipoprotein pigments—their relationship to ageing in the human nervous system II: the melanin content of pigmented nerve cells. Brain
1974; 97: 489-98. 5. Cohen G. Monoamine oxidase, hydrogen peroxide and Parkinson’s disease Adv Neurol 1986; 45: 119-25. 6 Marsden CD. Neuromelanin and Parkinson’s disease. J Neural Transm 1983; 19 (suppl): 121-41 7. Forno LS. Pathology of Parkinson’s disease. In. Marsden CD, Fahn S, eds. Movement disorders. London: Butterworths, 1982.
1. Chua
KY, Stewart GA, Thomas WR, Simpson RJ, Dilworth RJ, Plozza TM. Sequence analysis of cDNA coding for a major house dust mite allergen, Der pi, homology with cysteine proteases. J Exp Med 1988; 167: 175-82. 2. Stewart GA, Thompson PJ, Simpson RJ Protease antigens from house dust mite Lancet 1989; ii: 154-55. 3. Stewart GA, Lake FR, Thompson PJ. Faecally-derived hydrolytic enzymes from the house dust mite: characterization of potential allergens. J Allergy Clin Immunol
(in press) CA, Summers JA, Robinson C. In vitro techniques for the study of transepithelial protein flux in the airways and its modulation by inflammatory cells and mediators. Br J Pharmacol 1990; 100: 477P. 5. Herbert CA, Edwards D, Boot JR, Robinson C. Modulation of eosinophil-induced enhancement of bronchial epithelial permeability. Br J Pharmacol 1990; 100: 373P. 6. Heffner JE, Repine JE. Pulmonary strategies of antioxidant defense. Am Rev Respir 4. Herbert
Dis 1989; 140: 531-54
Effect of mite allergen on permeability of bronchial mucosa SIR,-The allergen Der pI from the house dust mite Dermatophagoides pteronyssinus is a cysteine proteinase in which the antigenic epitopes are distinct from the catalytic site. 1-3 As a development of our studies suggesting that proteinases disrupt the bronchial epithelium to augment transmucosal macromolecule movement we postulated that the enzymatic activity of Der pI might enhance the access of antigens to immunocompetent cells in the asthmatic airway by a similar mechanism. We have tested this hypothesis with an in vitro model in which sheets of bovine mounted between two heated halfpermit defined 02 cmz areas of tissue to be exposed to bathing solutions on either side. The apical sides of the tissues were exposed for 3 h to the various treatments (table). The net apical-basolateral flux of 12sI-Iabelled bovine serum albumin was then measured after replacement of the medium with fresh proteinase-free buffer.
bronchial mucosa chambers4 which
are
EFFECT OF SPENT GROWTH MEDIUM AND DER pl ON APICAL-BASOLATERAL FLUX OF ALBUMIN IN BOVINE BRONCHIAL MUCOSA
*In fmol cm - 2 mln - 1, as mean (SEM), p values refer to appropriate controls tUnlts/ml with azocoll substrate
SGM =spent growth
medium DTT=drthiothrertol
Extracorporeal membrane oxygenation SIR,-Dr Greenough and Dr Emery (Sept 22, p 760) suggest that at King’s College Hospital there would be a likely requirement for extracorporeal membrane oxygenation (ECMO) in 1/5000 births if predicted mortality rates of 80% were applied. They go on to say that of the 5 infants who seemed to be suitable, 3 survived without problems and the remaining 2 died following rapid collapse. Bartlett et all in Michigan estimated 1 infant per 1000 livebirths would be saved by ECMO each year according to these same criteria. With colleagues I wished to validate a projected figure of 20 infants a year in South Australia, having studied ECMO use. The medical records of infants between 34 weeks’ gestation and 12 months of age and between 2 and 10 kg in weight who died in Adelaide paediatric intensive care units between July, 1981, and June, 1986, were reviewed to see how many might have been considered for ECMO had it been available as a clinical service. Criteria for such consideration included reversible disease, artificial ventilation for less than seven days, and no intracranial haemorrhage. An additional criterion was that 90 min could have elapsed for an ECMO circuit to be established. In this five years there were 126 deaths of which 40 might have been considered for ECMO had it been available. Deaths were classified according to the system affected and whether the disease was acquired or congenital. In the largest group (acquired pulmonary disease), 25 of 33 would certainly have been considered for ECMO whereas in only 1 of 15 congenital pulmonary deaths might this have been beneficial. Nearly all these deaths were due to pulmonary hypoplasia. All 4 infants dying from acquired cardiac disease could have benefited from the use of ECMO whereas in only 3 of 21 infants dying from congenital heart disease would ECMO have been considered. There were no ECMO appropriate deaths involving other systems; and most (75%) were in the neonatal
period.
1133
There are on average 8 infant deaths a year in South Australia that might be avoided by ECMO-ie,1/3000 births, which is lower than Bardett and co-workers’ prediction, mainly because of the lower incidence of meconium aspiration syndrome. Nevertheless, such an incidence would support the introduction of ECMO as a clinical service. Redhill Hospital, Redhill, Surrey RH1 6LA, UK
1. Bartlett RH,
I. G. LEWIS
Gazzaniga AB, Toomasian JM. Extracorporeal membrane oxygenation respiratory failure: 100 cases. Ann Surg 1986; 204: 23.
m neonatal
Tolerance and the fetal
graft
Characteristic nuchal oedema with trisomy 21.
(arrow)
at 11.2 weeks in a fetus
.
SiR,—Your Sept 1 editorial discusses the paradox of the fetal allograft and in particular the possible role of the HLA-G antigen on the cytotrophoblast. You conclude that a special nonimmunogenic form of the major histocompatibility complex (MHC) class I molecule expressed at the fetomaternal interface prevented the baby being rejected as foreign by his mother. We question that such a molecule does not elicit a maternal immune response. Many workers have shown that antibodies to paternal antigens can be detected during pregnancy.1-3 We have demonstrated a non-cytotoxic IgG antibody response to paternal lymphocytes in sera from first trimester primigravidae4 and in placental eluates from these women at term.s The antibodies were directed to HLA-linked antigens but not to recognised class I (HLA-A, HLA-B, and HLA-C) or class II (HLA-DR) specificitiesAlthough the target for these antibodies has not been further defined, our data suggested that it may be an antigen similar to the special MHC molecule considered by you. Therefore such a molecule might be responsible for eliciting the antibody response we described. These antibodies are non-cytotoxic and might not be harmful to the survival of the fetal allograft.
Department of Renal Medicine, City Hospital, Nottingham NG5 1PB, UK
ANDREW INNES
Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen
DAVID POWER GRAEME CATTO
CHARLES CUNNINGHAM
H, Perry WM, Rocklin RE. Suppression of maternal responsiveness to paternal antigens by material plasma J Immunol 1975; 114: 525-28. 2. Rocklin RE, Kitzmiller JL, Garovoy MR. Maternal-fetal relation: II, further characterisation of an immunological blocking factor that develops during pregnancy, Clin Immunol Immunopathol 1982, 22: 305-15 3 Power DA, Catto GRD, Mason RJ, MacLeod AM, Stewart GM, Shewan WG. The fetus as an allograft: evidence for protective antibodies to HLA-linked paternal antigens. Lancet 1983; ii: 701-04. 4. Innes A, Cunningham C, Power DA, Catto GRD. Fetus and an allograft: non-cytotoxic maternal antibodies to HLA-linked paternal antigens. Am J Reprod 1. Pence
Immunol 1989; 19: 146-50. A, Stewart GM, Thomson MAR, Cunningham C, Catto GRD. Human placenta an antibody sponge? Am J Reprod Immunol 1988; 17: 57-60.
5 Innes
Nuchal fluid accumulation in trisomy-21 detected by vaginosonography in first trimester SIR,-Fetal anatomy in the first trimester can be seen with a high degree of accuracy by vaginosonography.1,2 During the past three years we have examined with sonography 7 fetuses with trisomy 21 diagnosed by karyotyping in our first-trimester chorionic villus sampling programme. In all 7 fetuses we demonstrated accumulation of subcutaneous fluid in various amounts in the nuchal region (figure). However, of 105 control fetuses with normal karyotype matched for gestational age (11 and 12 weeks) excessive nuchal fluid was detected in only 1. In the fetuses with normal karyotype the nuchal thickness was less than 2-5 mm, whereas in the affected fetuses this measured between 3 and 7 mm. Redundant nuchal folds are among the characteristic features of second-trimester fetuses with trisomy 21; however, this sign alone is
Sagittal plane. of little value in screening for Down syndrome. Spontaneous resolution of first-trimester nuchal oedema later in pregnancy has also been described/3 and greater attention should be paid to this sign in the first trimester. Aneuploidy cannot be assumed to be present in every fetus with this appearance but it is highly probable that fetal nuchal oedema detectable by vaginosonography in the first trimester is a manifestation of trisomy 211,2 or other aneuploid syndromesand could be an indication for chromosomal studies. Vaginosonography between weeks 9 and 12 of gestation might result in a higher pick-up rate of abnormalities than other methods, and this could be a promising approach in screening for trisomy 21 in patients at risk and in young pregnant women, since the procedure is non-invasive and therefore less risky than other methods. Department of Obstetrics and Gynaecology, Medical University A Szent-Gyorgyi, 6701 Szeged, Hungary
J. SZABÓ J. GELLEN
1. Rottem
S, Bronshtem M, Thaler I, Brandes JM. First trimester transvaginal sonographic diagnosis of fetal anomalies. Lancet 1989; i: 444-45. 2. Bronshtein M, Rotten S, Yoffe N, Blumenfeld Z. First-trimester and early second trimester diagnosis of nuchal cystic hygroma by transvaginal sonography: diverse prognosis of septated from nonseptated lesion. Am J Obstet Gynecol 1989; 161: 78-82. 3. Rodis JF, Vintziloes AM,
Campbell WA, Nochimson DJ. Spontaneous resolution of fetal cystic hygroma m Down’s syndrome. Obstet Gynecol 1988; 71: 976-77. 4. Szabó J, Gellén J, Szemere G. Nonimmune hydrops in trisomy 18: diagnosis by chorionic villus sampling and vaginosonography in the first trimester. Br J Obstet Gynaecol (in press).
Bone density screening for osteoporosis SiR,—We are afraid that Dr van Hemert’s reply (Sept 29, p 818) to views (Aug 25, p 502) will add further confusion to what should straightforward approach to bone density screening for osteoporosis. Osteoporosis is a condition that is identified by the presence of a low bone mineral density (BMD), a consequence of the decline in bone mass per unit volume. Whether that disease expresses itself as a fracture in the future depends on several other factors such as a continuing adverse lifestyle and absence of sex hormone replacement therapy (contributing to further bone loss), a fall, or a lack of muscle and fat which may protect against the consequences of a fall. Van Hemert confuses the diagnosis of the disease by BMD scanning with risk evaluation for osteoporosis. We are agreed that clinical risk factors have poor diagnostic value but to use, as he does, metacarpal cortical bone loss measured by a magnifying glass from X-ray films of the hands as a predictive test is mistaken.1,2 Trabecular bone loss is the major feature of postmenopausal osteoporosis due to oestrogen deficiency and is the main reason for the greatly increased prevalence in women. Dual photon bone densitometry screening identifies this trabecular loss in the spine or hip, the critical areas of fracture. His work did not test this predictive performance. The important epidemiological question is not the overlap in BMD between fracture and non-fracture groups but
our
be
a
