192
relation. The embryological association between the omentum and spleen is certainly curious, but to attribute a functional link between the two organs on the basis of a common venous drainage seems unconvincing and irrelevant. When considering the role of the omentum, a property that should not be forgotten is its angiogenic capacity. Omental capillaries provide a source of new blood vessels that may be important in repair and ischaemia within the abdominal cavity.’7 Whether this in turn owes anything to an activation of cells within milky spots is questionable. R. J. L. WILLIAMS Chase Farm Hospital, A. J. S. DAVIES Enfield EN2 8JL, UK
HEIGHTS AND HEIGHT DEFICITS IN TWO SURVEYS IN BRAZIL
spleen6-a systemic
RHJ, Fluitsma DM, Hoefsmit ECM. The cellular composition of omentum milky spots and the ultrastructure of milky spot macrophages and reticulum cells. J Reticuloendoth Soc 1980; 28: 585-99. 2. de Souza GEP, Ferreira SH Blockade of antimacrophage serum of the migration of PMN neutrophils into the inflamed pentoneal cavity. Agents Actions 1985; 17: 1. Beelen
97-103. 3. Matsuno K, Schaffner T, Gerber HA, Ruchti C, Hess MW, Cottier H. Uptake by enterocytes and subsequent translocation to internal organs, eg thymus, of Percoll microspheres administered per os to suckling mice. J Reticuloendoth Soc 1983; 33: 263-73. 4. Dux J, Rouse RV, Kyewski B. Composition of the lymphoid cell populations from omental milky spots during the immune response in C57BL/Ka mice. Eur J
Immunol 1986; 16: 1029-32. 5 Cottier H, Hees MW, Keller H-U Structural basis for lymphoid tissue functions: established and disputable sites of antigen-cell and cell to cell interactions in vivo. Monogr Allergy 1980; 60: 50-71. 6. Williams RJL, Brittle M. The influence of splenectomy on local immunity in the peritoneal cavity. Eur Surg Res 1989; 21 (suppl 2). 16. 7. Williams RJL. Angiogenesis and the greater omentum. In: Goldsmith HS, ed. The omentum. research and clinical applications. New York: Springer Verlag, 1990: 45-61.
for males and + 3-3 cm for females) could be approximated from the 1989 survey by subtracting the height deficits found in age groups 22 and 7 (7-8-4-5 =3-3 cm for males, 7-0-3-5=3-5 cm for females). Similar results were found using adjacent age groups (6 and 21 or 8 and 23). In other words, the single survey approach works, at least for Brazilian data. The lower values (0-8 cm for boys, 1. 1 cm for girls) obtained by subtracting height deficits in age groups 22 and 7 in the 1974 survey could indicate a recent acceleration in the trends, consistent with the patterns observed in other indicators, such as the infant mortality .*’ rates If our findings are confirmed in other studies, a very practical alternative for assessing trends in child growth would be immediately available. For example, household anthropometric surveys could include a sample of young adults, or parents’ height could be measured in surveillance systems of school-aged children. School of Public Health, University of Sao Paulo, Sao Paulo, Brazil
Delegacion
Trends in child
growth
from
a
single
cross-sectional survey SIR,-Growth in children is a good indicator of the health and wellbeing of a population and trends in child growth reflect the impact of social and economic changes and specific public health interventions. However, information on national trends is rarely available because few countries have two or more comparable anthropometric surveys.1 We propose a simpler alternative. The natural history of stunting in developing countries is quite well known: linear growth begins to fall off in the second 3 months of life and remains at about 80% of reference values until the second or third year; from then up to 5 years growth increments are not substantially different from those in developed countries.2 Four studies in developing countries have monitored growth from childhood, through adolescence, to adulthood,3-6 and all point to the same general fmding-namely, that total height gain from 5 years of age to adulthood is remarkably similar to reference values obtained in healthy and well-nourished populations. A relation has been postulated between the degree of stunting before puberty and the duration of the adolescent growth spurt-the more severe the stunting, the longer the growth spurts-and that would provide an efficient compensatory mechanism against further deterioration in growth after childhood. If this mechanism operates universally, a cohort of individuals, in any population, will tend to present similar height deficits at the end of childhood and as adults. Therefore, one cross-sectional survey on 5-year-old children and young adults (20-25 years) could provide useful information on trends in child
growth over a 15-20-year period. Two national surveys, done in 1974 and 1989 in Brazil’ and
entirely comparable with respect to sampling and data collection, provide a unique opportunity to test the "single survey" approach. Since mortality is very low among older children and young adults and the effect of migration in and out of the country is negligible, we will assume that adults of X years of age in 1989 represent the same cohort as children (X-15) years of age in 1974. The table shows median heights (and SE) for children aged 7 and adults aged 22 in the two surveys, and differences between median heights and the reference heights.8 The height deficits at adult ages were already present at age 7 (7-4 cm out of a total deficit of 7.8 cm for males, 6-8 out of 7-0 cm for females). On this basis, the 15-year trends between the two cross-sectional surveys (+2-9 cm
CARLOS A. MONTEIRO*
Provincial de Salud,
ALBERTO M. TORRES
Jaen, Andalucia, Spain *
Present address: Nutrition Unit, World Health Switzerland.
Organisation, CH-1211 Geneva 27,
ACC/SCN. Update report on the nutrition situation: recent trends in nutrition m 33 countries. Geneva: ACC/SCN, 1989. 2. Waterlow JC. Observations on the natural history of stunting. In: Waterlow J, ed Linear growth retardation in less developed countries. Nestlé Nutr Workshop Ser 1.
1988, no 14. 3.
Hauspie RC, Das SR, Preece MA, Tanner JM. A longitudinal study of the growth in height of boys and girls in West Bengal (India) aged six months to 20 years. Ann
Hum Biol 1980; 7: 429-41. WZ, McGregor IA. A birth-to-maturity longitudinal study of heights and weights in two West African (Gambian) villages, 1951-1975. Ann Hum Biol 1982, 9: 309-20. 5. Satyanarayana K, Radhaiah G, Murali Mohan B, et al. The adolescent growth spurt of height among rural Indian boys in relation to childhood nutritional background. a 18 year longitudinal study. Ann Hum Biol 1989; 16: 289-300. 6. Martorell R, Rivera J, Kaplowitz H. Consequences of stunting in early childhood for adult body size in rural Guatemala. Ann Nestlé 1990; 48: 85-92. 7. Monteiro CA, Benicio MHD’A, Gouveia NC. Growth and nutritional status of Brazilian children findings from the 1989 national health and nutritional survey (NUT/ANTREF/1/91). Geneva: WHO, 1991. 8. Dibley MJ, Goldsby JB, Staehling NW, et al Development of normalized curves for the international growth reference: historical and technical considerations. AmJ Clin Nutr 1987; 46: 749-62. 9. FIBGE/UNICEF. Perfil estatistico de criancas e maes no Brasil. Mortalidade infantil e saude na decada de 80. Rio de Janeiro: IBGE, 1989.
4. Billewicz
Pseudomembranous colitis
complicating
chemotherapy SIR,-A 43-year-old premenopausal woman with early-stage, node-positive breast cancer was treated with adjuvant CMF (oral cyclophosphamide 100 mg once daily for 14 days, fluorouracil 1 g intravenously on days 1 and 8, and methotrexate 50 mg intravenously on days 1 and 8). She tolerated the first three courses of chemotherapy well, her only complaint being increased bowel frequency (four times daily) for about 3 days after treatment. 3 days after her fourth course of chemotherapy diarrhoea developed (up to six times daily) which continued for 10 days, when she was admitted for further investigations. On admission she complained of anorexia, stabbing abdominal pains, and diarrhoea. She was mildly dehydrated and had diffuse abdominal tenderness but no evidence of peritonitis. Plain radiography of the abdomen showed slight distension of the small intestine with fluid, and sigmoidoscoPY revealed grade 1 colitis, but no pseudomembranes were seen. She
193
neutropenic (haemoglobin 10-7 g/dl, white blood cells 74 x 109/1, platelets 188 x 109/1). Stool specimens were cultured and intravenous fluids were started. Diarrhoea continued for a further 4 days, when Clostridium difficile toxin was detected in stool. She was therefore started on oral vancomycin 125 mg four times daily and diarrhoea stopped within 48 hours. Pseudomembranous colitis is an acute colonic infection caused by C difficile that usually occurs as a complication of antibiotic therapy and rarely develops spontaneously in healthy individuals. C difficile colitis has been reported in patients undergoing intensive chemotherapy usually for acute leukaemia, and in whom antibiotics had been given.’ There is only one previous report of pseudomembranous colitis after chemotherapy without previous antibiotic administration.2 was not
50% of patients on CMF report diarrhoea although only 7% have severe diarrhoea;’ however, it is rarely longlasting. Our findings emphasise the importance of investigating the aetiology of longlasting diarrhoea in patients receiving chemotherapy since they may have an increased susceptibility to pseudomembranous colitis. Department of Medicine,
Royal Marsden Hospital,
T. J. IVESON
London SW3 6JJ, UK
A. CHAN
GM, Luna M, Valdivieso M, et al Necrotizing colitis in patients with cancer. Am J Med 1979; 67: 646-55. 2. Fainstein V, Bodey GP, Fekety R. Relapsing pseudomembranous colitis associated with cancer chemotherapy J Infect Dis 1981; 143: 865. 3. Jodrell DI, Smith IE, Mansi JL, et al A randomised comparative trial of mitozantrone/methotrexate/mitomycin C (MMM) and cyclophosphamide/ methotrexate/5FU (CMF) in the treatment of advanced breast cancer. Br J Cancer 1991, 63: 794-98 1. Dosik
Fetal
haemorrhagic lesions after chorionic villous sampling
SIR,-A causal relation between chorionic villous sampling
(CVS) and limb reduction anomalies is controversial (ref 1 and subsequent correspondence, Lancet 1991; 337: 1091-92, 1422-24). Haemodynamic insult at a critical time in gestation has been proposed as a mechanism for these anomalies, but no direct evidence for this proposal exists. We have seen with embryoscopy fetal ecchymotic lesions after transvaginal CVS before termination of pregnancy at 9-5 menstrual weeks. Lesions were located on the calvarium, face (philtrum), thorax, and distal segments of the limbs (figure). The lesions became larger during 10 minutes of observation. Ultrasonography during CVS showed the development of a subchorionic haematoma. There was no family history of a haemorrhagic disorder. This fmding suggested that the trauma associated with CVS may lead to haemorrhagic fetal lesions.
Endoscopic demonstration of vessels of the fetal forehead Fetal eye is
on
left
two
haemorrhagic
(arrows).
lesions
along
To test this hypothesis we did embryoscopy before and after CVS in patients scheduled to have elective pregnancy termination between 8 and 12 weeks’. Human investigation committee approval and informed consent were obtained for all these studies. Embryoscopy was done with a ’Storz’ 27 mm 30° angle endoscope.2 CVS was done with a standard 1 5mm ’Portex’ cannula. No lesions were seen before or after CVS. We then proceeded to induce partial placental detachment and subchorionic haematoma formation with a blunt instrument (uterine sound or cervical dilator). No changes in fetal heart rate were seen during this procedure. After placental trauma, six of seven fetuses showed ecchymotic lesions on the head, face, and thorax. In one of these six, lesions were also seen along the tract of the vitelline vessels and on the yolk sac. These observations provide direct evidence that placental trauma in early pregnancy may lead to demonstrable fetal lesions. The clinical significance of these lesions and the mechanism by which they occur are unknown. Although some lesions may be unimportant, others may be the pathological basis for limb reduction anomalies and oromandibular hypogenesis reported in fetuses after CVS procedures, especially if placental trauma is extensive. Our observations probably represent the extreme of a spectrum of lesions after placental trauma. We do not believe that these lesions are the result of embryoscopy since they have not been noted in over 200 embryoscopies done in our institution during the past three years. The frequency with which these lesions occur after routine CVS is unknown. Gestational age, technique of CVS, and degree of placental trauma, as shown, for example, by the appearance of sub-chorionic haemorrhage, may be implicated. Embryoscopy affords the opportunity to study these factors under controlled conditions. RUBEN A. QUINTERO ROBERTO ROMERO MAURICE J. MAHONEY MARILYN VECCHIO Department of Obstetrics and Gynecology, HOLDEN JOANN Yale University School of Medicine, New Haven, Connecticut 06510, USA JOHN C. HOBBINS 1. Firth HV, Boyd PA, Chamberlain P, MacKenzie IZ, Lindenbaum RH, Huson SM. Severe limb abnormalities after chonon villus sampling at 56-66 days’ gestation. Lancet 1991; 337: 782-83. 2. Cullen MT, Reece EA, Whetham J, Hobbins JC Embryoscopy. description and utility of a new technique Am JObstet Gynecol 1990; 162: 82-86.
Interaction
of thyrotropin and thyroid-stimulating antibodies with recombinant extracellular region of human TSH receptor SIR,-The human thyrotropin (TSH) receptor (hTSHr) is one of the commonest targets of autoimmune disease, but its structure was unknown until its cDNA was cloned. The predicted aminoacid sequence suggests a large extracellular region, seven transmembrane regions, and a cytoplasmic tail; TSH is presumed to bind to the extracellular region. Autoantibodies to hTSHr are very heterogeneous. 2 years after the receptor was cloned, the hTSHr domains that are important in interacting with these antibodies remain uncertain. Several groups have investigated the effect of synthetic peptides corresponding to the predicted sequence of various regions, and of antibodies raised against these peptides, on autoantibody and TSH binding and on functional stimulation of thyroid cells, but, unfortunately, no clear and consistent answers have been obtained (eg, refs 1 and 2). Indeed, Libert and colleagues3 have produced compelling evidence that linear sequences (up to 70 aminoacids) are not sufficient for autoantibody binding. Thus, it is clear that the difficulties in developing useful assays for the detection and measurement of hTSHr autoantibodies will not be solved by use of a few synthetic peptides. We therefore sought to produce substantial quantities of a recombinant protein consisting of the entire extracellular region; to facilitate correct glycosylation and other post-translational processing, we used a eukaryotic system. A stop codon was introduced into hTSHr cDNA just before the first predicted transmembrane region (residue 417) and this was expressed in Chinese hamster ovary (CHO) cells with the novel amplifiable
relation. The embryological association between the omentum and spleen is certainly curious, but to attribute a functional link between the two organs on the basis of a common venous drainage seems unconvincing and irrelevant. When considering the role of the omentum, a property that should not be forgotten is its angiogenic capacity. Omental capillaries provide a source of new blood vessels that may be important in repair and ischaemia within the abdominal cavity.’7 Whether this in turn owes anything to an activation of cells within milky spots is questionable. R. J. L. WILLIAMS Chase Farm Hospital, A. J. S. DAVIES Enfield EN2 8JL, UK
HEIGHTS AND HEIGHT DEFICITS IN TWO SURVEYS IN BRAZIL
spleen6-a systemic
RHJ, Fluitsma DM, Hoefsmit ECM. The cellular composition of omentum milky spots and the ultrastructure of milky spot macrophages and reticulum cells. J Reticuloendoth Soc 1980; 28: 585-99. 2. de Souza GEP, Ferreira SH Blockade of antimacrophage serum of the migration of PMN neutrophils into the inflamed pentoneal cavity. Agents Actions 1985; 17: 1. Beelen
97-103. 3. Matsuno K, Schaffner T, Gerber HA, Ruchti C, Hess MW, Cottier H. Uptake by enterocytes and subsequent translocation to internal organs, eg thymus, of Percoll microspheres administered per os to suckling mice. J Reticuloendoth Soc 1983; 33: 263-73. 4. Dux J, Rouse RV, Kyewski B. Composition of the lymphoid cell populations from omental milky spots during the immune response in C57BL/Ka mice. Eur J
Immunol 1986; 16: 1029-32. 5 Cottier H, Hees MW, Keller H-U Structural basis for lymphoid tissue functions: established and disputable sites of antigen-cell and cell to cell interactions in vivo. Monogr Allergy 1980; 60: 50-71. 6. Williams RJL, Brittle M. The influence of splenectomy on local immunity in the peritoneal cavity. Eur Surg Res 1989; 21 (suppl 2). 16. 7. Williams RJL. Angiogenesis and the greater omentum. In: Goldsmith HS, ed. The omentum. research and clinical applications. New York: Springer Verlag, 1990: 45-61.
for males and + 3-3 cm for females) could be approximated from the 1989 survey by subtracting the height deficits found in age groups 22 and 7 (7-8-4-5 =3-3 cm for males, 7-0-3-5=3-5 cm for females). Similar results were found using adjacent age groups (6 and 21 or 8 and 23). In other words, the single survey approach works, at least for Brazilian data. The lower values (0-8 cm for boys, 1. 1 cm for girls) obtained by subtracting height deficits in age groups 22 and 7 in the 1974 survey could indicate a recent acceleration in the trends, consistent with the patterns observed in other indicators, such as the infant mortality .*’ rates If our findings are confirmed in other studies, a very practical alternative for assessing trends in child growth would be immediately available. For example, household anthropometric surveys could include a sample of young adults, or parents’ height could be measured in surveillance systems of school-aged children. School of Public Health, University of Sao Paulo, Sao Paulo, Brazil
Delegacion
Trends in child
growth
from
a
single
cross-sectional survey SIR,-Growth in children is a good indicator of the health and wellbeing of a population and trends in child growth reflect the impact of social and economic changes and specific public health interventions. However, information on national trends is rarely available because few countries have two or more comparable anthropometric surveys.1 We propose a simpler alternative. The natural history of stunting in developing countries is quite well known: linear growth begins to fall off in the second 3 months of life and remains at about 80% of reference values until the second or third year; from then up to 5 years growth increments are not substantially different from those in developed countries.2 Four studies in developing countries have monitored growth from childhood, through adolescence, to adulthood,3-6 and all point to the same general fmding-namely, that total height gain from 5 years of age to adulthood is remarkably similar to reference values obtained in healthy and well-nourished populations. A relation has been postulated between the degree of stunting before puberty and the duration of the adolescent growth spurt-the more severe the stunting, the longer the growth spurts-and that would provide an efficient compensatory mechanism against further deterioration in growth after childhood. If this mechanism operates universally, a cohort of individuals, in any population, will tend to present similar height deficits at the end of childhood and as adults. Therefore, one cross-sectional survey on 5-year-old children and young adults (20-25 years) could provide useful information on trends in child
growth over a 15-20-year period. Two national surveys, done in 1974 and 1989 in Brazil’ and
entirely comparable with respect to sampling and data collection, provide a unique opportunity to test the "single survey" approach. Since mortality is very low among older children and young adults and the effect of migration in and out of the country is negligible, we will assume that adults of X years of age in 1989 represent the same cohort as children (X-15) years of age in 1974. The table shows median heights (and SE) for children aged 7 and adults aged 22 in the two surveys, and differences between median heights and the reference heights.8 The height deficits at adult ages were already present at age 7 (7-4 cm out of a total deficit of 7.8 cm for males, 6-8 out of 7-0 cm for females). On this basis, the 15-year trends between the two cross-sectional surveys (+2-9 cm
CARLOS A. MONTEIRO*
Provincial de Salud,
ALBERTO M. TORRES
Jaen, Andalucia, Spain *
Present address: Nutrition Unit, World Health Switzerland.
Organisation, CH-1211 Geneva 27,
ACC/SCN. Update report on the nutrition situation: recent trends in nutrition m 33 countries. Geneva: ACC/SCN, 1989. 2. Waterlow JC. Observations on the natural history of stunting. In: Waterlow J, ed Linear growth retardation in less developed countries. Nestlé Nutr Workshop Ser 1.
1988, no 14. 3.
Hauspie RC, Das SR, Preece MA, Tanner JM. A longitudinal study of the growth in height of boys and girls in West Bengal (India) aged six months to 20 years. Ann
Hum Biol 1980; 7: 429-41. WZ, McGregor IA. A birth-to-maturity longitudinal study of heights and weights in two West African (Gambian) villages, 1951-1975. Ann Hum Biol 1982, 9: 309-20. 5. Satyanarayana K, Radhaiah G, Murali Mohan B, et al. The adolescent growth spurt of height among rural Indian boys in relation to childhood nutritional background. a 18 year longitudinal study. Ann Hum Biol 1989; 16: 289-300. 6. Martorell R, Rivera J, Kaplowitz H. Consequences of stunting in early childhood for adult body size in rural Guatemala. Ann Nestlé 1990; 48: 85-92. 7. Monteiro CA, Benicio MHD’A, Gouveia NC. Growth and nutritional status of Brazilian children findings from the 1989 national health and nutritional survey (NUT/ANTREF/1/91). Geneva: WHO, 1991. 8. Dibley MJ, Goldsby JB, Staehling NW, et al Development of normalized curves for the international growth reference: historical and technical considerations. AmJ Clin Nutr 1987; 46: 749-62. 9. FIBGE/UNICEF. Perfil estatistico de criancas e maes no Brasil. Mortalidade infantil e saude na decada de 80. Rio de Janeiro: IBGE, 1989.
4. Billewicz
Pseudomembranous colitis
complicating
chemotherapy SIR,-A 43-year-old premenopausal woman with early-stage, node-positive breast cancer was treated with adjuvant CMF (oral cyclophosphamide 100 mg once daily for 14 days, fluorouracil 1 g intravenously on days 1 and 8, and methotrexate 50 mg intravenously on days 1 and 8). She tolerated the first three courses of chemotherapy well, her only complaint being increased bowel frequency (four times daily) for about 3 days after treatment. 3 days after her fourth course of chemotherapy diarrhoea developed (up to six times daily) which continued for 10 days, when she was admitted for further investigations. On admission she complained of anorexia, stabbing abdominal pains, and diarrhoea. She was mildly dehydrated and had diffuse abdominal tenderness but no evidence of peritonitis. Plain radiography of the abdomen showed slight distension of the small intestine with fluid, and sigmoidoscoPY revealed grade 1 colitis, but no pseudomembranes were seen. She
193
neutropenic (haemoglobin 10-7 g/dl, white blood cells 74 x 109/1, platelets 188 x 109/1). Stool specimens were cultured and intravenous fluids were started. Diarrhoea continued for a further 4 days, when Clostridium difficile toxin was detected in stool. She was therefore started on oral vancomycin 125 mg four times daily and diarrhoea stopped within 48 hours. Pseudomembranous colitis is an acute colonic infection caused by C difficile that usually occurs as a complication of antibiotic therapy and rarely develops spontaneously in healthy individuals. C difficile colitis has been reported in patients undergoing intensive chemotherapy usually for acute leukaemia, and in whom antibiotics had been given.’ There is only one previous report of pseudomembranous colitis after chemotherapy without previous antibiotic administration.2 was not
50% of patients on CMF report diarrhoea although only 7% have severe diarrhoea;’ however, it is rarely longlasting. Our findings emphasise the importance of investigating the aetiology of longlasting diarrhoea in patients receiving chemotherapy since they may have an increased susceptibility to pseudomembranous colitis. Department of Medicine,
Royal Marsden Hospital,
T. J. IVESON
London SW3 6JJ, UK
A. CHAN
GM, Luna M, Valdivieso M, et al Necrotizing colitis in patients with cancer. Am J Med 1979; 67: 646-55. 2. Fainstein V, Bodey GP, Fekety R. Relapsing pseudomembranous colitis associated with cancer chemotherapy J Infect Dis 1981; 143: 865. 3. Jodrell DI, Smith IE, Mansi JL, et al A randomised comparative trial of mitozantrone/methotrexate/mitomycin C (MMM) and cyclophosphamide/ methotrexate/5FU (CMF) in the treatment of advanced breast cancer. Br J Cancer 1991, 63: 794-98 1. Dosik
Fetal
haemorrhagic lesions after chorionic villous sampling
SIR,-A causal relation between chorionic villous sampling
(CVS) and limb reduction anomalies is controversial (ref 1 and subsequent correspondence, Lancet 1991; 337: 1091-92, 1422-24). Haemodynamic insult at a critical time in gestation has been proposed as a mechanism for these anomalies, but no direct evidence for this proposal exists. We have seen with embryoscopy fetal ecchymotic lesions after transvaginal CVS before termination of pregnancy at 9-5 menstrual weeks. Lesions were located on the calvarium, face (philtrum), thorax, and distal segments of the limbs (figure). The lesions became larger during 10 minutes of observation. Ultrasonography during CVS showed the development of a subchorionic haematoma. There was no family history of a haemorrhagic disorder. This fmding suggested that the trauma associated with CVS may lead to haemorrhagic fetal lesions.
Endoscopic demonstration of vessels of the fetal forehead Fetal eye is
on
left
two
haemorrhagic
(arrows).
lesions
along
To test this hypothesis we did embryoscopy before and after CVS in patients scheduled to have elective pregnancy termination between 8 and 12 weeks’. Human investigation committee approval and informed consent were obtained for all these studies. Embryoscopy was done with a ’Storz’ 27 mm 30° angle endoscope.2 CVS was done with a standard 1 5mm ’Portex’ cannula. No lesions were seen before or after CVS. We then proceeded to induce partial placental detachment and subchorionic haematoma formation with a blunt instrument (uterine sound or cervical dilator). No changes in fetal heart rate were seen during this procedure. After placental trauma, six of seven fetuses showed ecchymotic lesions on the head, face, and thorax. In one of these six, lesions were also seen along the tract of the vitelline vessels and on the yolk sac. These observations provide direct evidence that placental trauma in early pregnancy may lead to demonstrable fetal lesions. The clinical significance of these lesions and the mechanism by which they occur are unknown. Although some lesions may be unimportant, others may be the pathological basis for limb reduction anomalies and oromandibular hypogenesis reported in fetuses after CVS procedures, especially if placental trauma is extensive. Our observations probably represent the extreme of a spectrum of lesions after placental trauma. We do not believe that these lesions are the result of embryoscopy since they have not been noted in over 200 embryoscopies done in our institution during the past three years. The frequency with which these lesions occur after routine CVS is unknown. Gestational age, technique of CVS, and degree of placental trauma, as shown, for example, by the appearance of sub-chorionic haemorrhage, may be implicated. Embryoscopy affords the opportunity to study these factors under controlled conditions. RUBEN A. QUINTERO ROBERTO ROMERO MAURICE J. MAHONEY MARILYN VECCHIO Department of Obstetrics and Gynecology, HOLDEN JOANN Yale University School of Medicine, New Haven, Connecticut 06510, USA JOHN C. HOBBINS 1. Firth HV, Boyd PA, Chamberlain P, MacKenzie IZ, Lindenbaum RH, Huson SM. Severe limb abnormalities after chonon villus sampling at 56-66 days’ gestation. Lancet 1991; 337: 782-83. 2. Cullen MT, Reece EA, Whetham J, Hobbins JC Embryoscopy. description and utility of a new technique Am JObstet Gynecol 1990; 162: 82-86.
Interaction
of thyrotropin and thyroid-stimulating antibodies with recombinant extracellular region of human TSH receptor SIR,-The human thyrotropin (TSH) receptor (hTSHr) is one of the commonest targets of autoimmune disease, but its structure was unknown until its cDNA was cloned. The predicted aminoacid sequence suggests a large extracellular region, seven transmembrane regions, and a cytoplasmic tail; TSH is presumed to bind to the extracellular region. Autoantibodies to hTSHr are very heterogeneous. 2 years after the receptor was cloned, the hTSHr domains that are important in interacting with these antibodies remain uncertain. Several groups have investigated the effect of synthetic peptides corresponding to the predicted sequence of various regions, and of antibodies raised against these peptides, on autoantibody and TSH binding and on functional stimulation of thyroid cells, but, unfortunately, no clear and consistent answers have been obtained (eg, refs 1 and 2). Indeed, Libert and colleagues3 have produced compelling evidence that linear sequences (up to 70 aminoacids) are not sufficient for autoantibody binding. Thus, it is clear that the difficulties in developing useful assays for the detection and measurement of hTSHr autoantibodies will not be solved by use of a few synthetic peptides. We therefore sought to produce substantial quantities of a recombinant protein consisting of the entire extracellular region; to facilitate correct glycosylation and other post-translational processing, we used a eukaryotic system. A stop codon was introduced into hTSHr cDNA just before the first predicted transmembrane region (residue 417) and this was expressed in Chinese hamster ovary (CHO) cells with the novel amplifiable
