Low second-trimester maternal serum human chorionic gonadotrophin in a trisomy 9 pregnancy.
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Biomedical subjects
Publications and source records attributed to M H Tang.
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Homozygous alpha-thalassaemia-1 is the commonest cause of hydrops fetalis in South-East Asia. Ultrasonographic features of hydrops fetalis were said to be evident only after 20 weeks of gestation. We studied 111 pregnancies at risk of homozygous alpha-thalassaemia-1 at 12-14 gestational weeks and 101 pregnancies at 17-18 weeks by abdominal ultrasound examination. Ultrasonographic features of hydrops fetalis were seen in 3 out of 44 pregnancies affected by homozygous alpha-thalassaemia-1 at 12-14 weeks [7 per cent; 95 per cent confidence interval (CI) 1-19 per cent] and in 7 out of 21 affected pregnancies at 17-18 weeks (33 per cent; 95 per cent CI 15-57 per cent). In conclusion, homozygous alpha-thalassaemia-1 can cause hydrops fetalis in the early second trimester. It should constitute one of the differential diagnoses in the work-up of second-trimester hydrops fetalis.
Couples with alpha-thalassaemia-1 face a 25 per cent risk of having fetuses with haemoglobin (Hb) Bart's disease. Prenatal diagnosis is conventionally performed by DNA studies of chorionic villi or amniocytes obtained from chorionic villus biopsy or amniocentesis. DNA studies are expensive and time-consuming. We identified 11 affected pregnancies on abdominal ultrasound examination at 12-14 weeks when the placental thickness exceeded the mean plus 2 SD measurement for the gestational week and the cardiothoraic ratio was more than 0.5. Cordocentesis was then performed with a free hand technique. The procedures were successful in ten cases using a 26-gauge spinal needle with a 20-gauge introducer. Hb Bart's disease was confirmed in all cases by Hb electrophoresis. The procedure was unsuccessful in one case when a 22-gauge spinal needle was used. Hb study of fetal blood collected at abortion also confirmed Hb Bart's disease. In conclusion, ultrasound findings of concomitant placentomegaly and cardiomegaly at 12-14 weeks is highly specific of disease in pregnancies at risk of Hb Bart's disease. Cordocentesis and Hb study in pregnancies with these sonographic manifestations may be an alternative prenatal diagnostic approach. This diagnostic approach is of particular value in areas where resources for molecular studies are limited.
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Homozygous alpha-thalassaemia-1 is conventionally diagnosed by invasive testing on all at-risk pregnancies. We evaluated the diagnostic efficacy of non-invasive abdominal ultrasonographic cardiothoracic ratio measurement in 62 pregnancies at 13-14 weeks and 75 pregnancies at 17-18 weeks. This performed better than placental thickness measurement. Using a cardiothoracic ratio cut-off level of > or = 0.5, 75 per cent of affected pregnancies were detected at 13-14 weeks and all cases were detected at 17-18 weeks. False-positive rates were 7 and 8 per cent, respectively. There was no false-positive diagnosis if the cardiothoracic ratio was > or = 0.53. With this approach, invasive procedures can be selectively performed and fewer pregnancies will be lost unnecessarily. The reduction in medical expenses is likely to be substantial.
Couples in whom one is heterozygous for alpha-thalassaemia-1 and the other is heterozygous for beta-thalassaemia are assumed not to be at risk of having offspring with homozygous alpha-thalassaemia-1 or homozygous beta-thalassaemia. We retrospectively reviewed the genetic outcome of 189 pregnancies of 178 couples in whom the partners were diagnosed to be discordant heterozygotes of alpha-thalassaemia and beta-thalassaemia on haematological tests. Zeta gene mapping was performed on 158 beta-thalassaemia carriers to diagnose the presence of co-existing alpha-thalassaemia-1. Eleven patients (7 per cent) were found to be compound alpha- and beta-thalassaemia heterozygotes. They accounted for 16 pregnancies, of which five were diagnosed to be affected by homozygous alpha-thalassaemia-1. Our results show that couples presumed to be discordant heterozygotes of alpha- and beta-thalassaemia on haematological testing are at risk of having offspring with homozygous alpha-thalassaemia-1 if the zeta gene mapping of the heterozygous beta-thalassaemia partner shows co-inheritance of alpha-thalassaemia-1. Prenatal diagnosis of homozygous alpha-thalassaemia-1 should be performed on these at-risk pregnancies.
Maternal urinary gonadotrophin peptide (UGP) was recently found to be elevated in second-trimester Down syndrome pregnancies. There is controversy about its screening efficacy. Data in the Asian population are scanty. We measured the UGP levels in 29 Down syndrome pregnancies and 297 controls and expressed them as a ratio of the urine creatinine concentration. Median UGP MOM was elevated to 3.44 (95 per cent confidence interval 1.99-5.13) in cases, compared with controls. UGP values were widely scattered in cases and controls with extensive overlap such that only 35 per cent of Down syndrome cases were expected to be detected at a 5 per cent false-positive rate. The data of the present study and previous reports show that there is a wide variability of gestation-specific UGP median values. UGP alone does not appear to be an effective screening marker for fetal Down syndrome.
Limb reduction defect is a rare event. Its exact pathogenesis is unknown. We retrospectively reviewed the outcome of 130 fetuses affected by homozygous alpha-thalassaemia-1 and found that 11 of them (8 per cent; 95 per cent confidence interval: 4-13 per cent) had terminal transverse limb reduction defects. Chromosome study was available in ten fetuses with limb defects and the results were normal. We postulate that the strong association between homozygous alpha-thalassaemia-1 and limb reduction is related to the hypoxic insult in early gestation. This may be the final common pathway in the pathogenesis of other forms of limb reduction defects.
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Homozygous alpha-thalassaemia-1, a common cause of hydrops fetalis, is usually diagnosed invasively. We measured placental thickness by ultrasound at 10-21 weeks' gestation in 231 at-risk pregnancies. 60 were affected (by DNA analysis). The sensitivity and specificity in detecting affected pregnancies at cut-off of mean placental thickness plus 2 SD before 12 weeks' gestation were 0.72 (95% CI 0.52-0.93) and 0.97 (0.9-1.0). After 12 weeks sensitivity increased to 0.95 (0.89-1.0) and by 18 weeks reached 1.0 (0.60-0.99) without change in specificity. Selection of pregnancies at risk by measurement of placental thickness will reduce the number of invasive diagnostic procedures.
We have established an IL-2 independent malignant lymphoma line (CM-1) from peripheral T lymphocytes donated by a female patient with nervous system disease, the biological characteristics of CM-1 cells was studied in this paper. Another T lymphocytes, such as peripheral T lymphocytes donated by a male patient with multiple sclerosis, could be transformed into a malignant lymphoma line by using filtered supernatant of the CM-1 cultured medium, thus the CM-2 cell line was established. The CM-1 and CM-2 cells were transplanted by subcutaneous inoculation into nude mice, and could cause the occurrence of typical malignant lymphoma. The observation of electron micrographs suggested the existence of virions in the CM-1 and CM-2 cells, and these virions were similar to retrovirus in the ultra-structure characteristics. It was found that this virus possesses reverse transcriptase activity. Results obtained from serological assay, molecular hybridization and PCR excluded the existence of other human viruses, which were commonly used in our laboratory. The unknown virus possesses strong transformation activity, and probably is a new retrovirus. Meanwhile, the work on the clone and sequence analysis of this virus are being carried out.
Between January 1987 and December 1990, 60 fetuses were found to have renal abnormalities on antenatal ultrasonography. Six fetuses were aborted because of major renal abnormalities with or without associated chromosomal aberrations. Twelve babies with major renal abnormalities died in the immediate neonatal period. Forty-two babies were studied after birth and followed up. Babies who were found to have mild dilation of the renal pelvis of 6 to 10 mm during fetal life revealed either normal renal findings in the postnatal period or complete resolution of the abnormalities within the first year. Significant pelvic dilation of more than 10 mm occurred in 32 babies. A significant proportion (34%) had transitional hydronephrosis that resolved spontaneously during the follow-up period (mean, 2 1/2 years; range, 1 1/2 to 4 1/2 years). Extrarenal pelvis, another benign condition, accounted for 15.6%. Most babies with pelviureteral junction obstruction (15%) and vesicoureteral junction obstruction (6.2%) required early neonatal surgery. The technetium-99m diethylenetriamine renal scan with the diuretic renogram half-time was found to be a very useful tool to distinguish between obstructive and nonobstructive hydronephrosis. With early diagnosis and intervention, the prognosis for many of these renal abnormalities is much more favorable and such information is invaluable for antenatal counseling.
The immunologic phenotypes of 68 cases of acute nonlymphoblastic leukemia (ANLL) were analysed with a panel of monoclonal antibodies. The results showed that the frequencies of myeloid antigens expressed on ANLL cells are CD15 > CD33 > CD13 > CD14 and there were few cases expressing lymphoid antigens. The expression of myeloid antigen on leukemia cells is not only the evidence for diagnosis ANLL, but also is valuable predicting prognosis. In cases with the ratio of CD33/CD13 < 1, the complete remission (CR) rate was higher than those with CD33/CD13 > 1 (P < 0.05). Patients with expression of CD15 antigen on their leukemia cells appeared to be associated with long survival.
Congenital chylothorax is an uncommon but well-described condition. Recurrent congenital chylothorax is extremely rare. Yancy and Spock (1967) reviewed 31 reported cases of spontaneous chylothorax which occurred in the first 2 months of life and noted that male infants were affected twice as commonly as females. Two other cases of recurrent congenital chylothorax in male offspring (Defoort and Thiery, 1978; Reece et al., 1987) led to the suggestion of possible X-linked recessive inheritance. We describe a case of recurrent congenital chylothorax in which two consecutive female infants in a sibship were affected. The underlying cause of this disorder remains unknown. Inheritance as an X-linked recessive is not possible and this case is suggestive of autosomal recessive inheritance. The case also serves to emphasize the need for caution in counselling for recurrence risks when the underlying aetiology of the disorder is unknown.
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The reactivity of a new Pan-B monoclonal antibody, MA6, against 69 cases of ALL, three plasmacytoma, 10 AML and five CML was evaluated. The antibody reacted positively against five of the 11 cases of U-ALL, 15 of the 26 C-ALL and all the cases of Pre B-ALL (one), B-ALL (one), B-CLL (12) and HCL (two). The MA6 did not react against the 16 cases of T-ALL, three plasmacytoma, 10 AML and five CML. The antibody has a broader spectrum of B-cell reactivity than CD9 and CD20 but is similar to the Pan-B antibody, CD19. MA6 appears to react against some of the very immature B cells and is therefore potentially useful, in conjunction with other antibodies such as CD9 and CD19, to confirm the B-lineage of some cases of U-ALL. The difference in the spectrum of reactivity against B-cell malignancies between MA6 and the other CDw40 antibody, G28-5, confirms their difference in antigenic specificity.
Cell surface markers of 18 patients with non-T, non-B acute lymphoblastic leukemia (ALL) were analysed with a panel of monoclonal antibodies (McAbs) by indirect immunofluorescence. The results showed that the cells of 13/18 patients originated from immature B cell or B progenitors. The cells of 12/18 patients expressed B cell antigens (CD 19+ or CDw 40+). It was suggested that antibodies directed to these two surface markers could help each other in the diagnosis of ALL of B cell origin. Diagnosis might be further improved if anti-CD19 and CDw 40 McAb be used at the same time. CD 9 antigen was expressed on immature B cell surface. 13/14 patients with B-CLL did not react with anti-CD 9, but 14/18 with non-T, non-B ALL were positive. Cells of 7/18 patients expressed CALLA (CD 10), HLA-DR and CD 19/CDw 40, but did not express T cell associated antigens (CD1, CD2, CD3, CD7), so CALLA(+)-ALL also belongs to B cell lineage.
Twenty-six pregnant Chinese women who were at risk of giving birth to a fetus affected with homozygous alpha-thalassaemia-1 were examined serially by ultrasound. Six of these 26 pregnancies were affected. In one third of the affected pregnancies progressive fetal ascites appeared before 24 weeks gestation and these pregnancies were terminated. In the remaining two thirds abnormal estimated fetal weight-placental volume (EFW-PV) ratio and fetal growth retardation as evidenced by a falling biparietal diameter (BPD), femur length (FL) but a normal abdominal circumference (AC) was apparent by 28 weeks gestation. Increased transverse cardiac (TC) diameter was another consistent finding but appeared late. All these features appeared before the onset of fetal ascites. A normal EFW-PV ratio and fetal growth until 28 weeks gestation was a reassuring sign of normality. Abnormal EFW-PV ratio was the earliest sign to appear in affected pregnancies and a normal ratio until 28 weeks gestation had a 100 per cent predictive value.