Biomedical subjects

T M Ko

Publications and source records attributed to T M Ko.

At least 73 records · Page 4Linked to original sources

PubMed1990

DNA polymorphism and globin chain analysis in the prenatal diagnosis of beta-thalassaemia major in Taiwan.

Thirty-six pregnancies in 25 families at risk of beta-thalassaemia major received prenatal diagnosis. Chorionic villus sampling or amniocentesis was done in 35 pregnancies to obtain fetal cells for DNA linkage study, for which Southern blotting and DNA hybridization were used to detect seven restriction fragment length polymorphisms (RFLPs) within the beta-globin gene cluster: epsilon-HincII, G gamma-HindIII, A gamma-HindIII, phi beta-HincII, 3' phi beta-HincII, beta-AvaII, and 3' beta-BamHI. beta-Thalassaemia major was diagnosed in seven and excluded in 22 pregnancies. In the remaining six cases, beta-thalassaemia major could not be excluded. In these six pregnancies and another one with late booking, ultrasound-guided cordocentesis was performed at the 22nd to 27th week of gestation. Globin chain composition was determined with urea-acetic acid-Triton X-100-12 per cent polyacrylamide gel electrophoresis. beta-Thalassaemia major was diagnosed in two fetuses and excluded in the other five. Eleven fetuses (in which beta-thalassaemia major was excluded) have been delivered and are healthy at more than 5 months old. DNA linkage analysis coupled with globin chain electrophoresis provides an effective way for prenatal diagnosis of beta-thalassaemia major, although these methods are being replaced by more direct detection techniques using oligonucleotide probes.

Chorionic Villi Sampling↗

PubMed1990

The significance of abnormally high and low maternal serum alpha-fetoprotein levels between 14 and 25 weeks of gestation.

A total of 6,160 gravidas with gestational ages from 14 to 25 weeks were collected to quantify maternal serum alpha-fetoprotein (MSAFP) using an enzyme immunoassay kit. A level over 2.5 MoM (multiples of the median) was defined as high and a level below 0.4 MoM as low. Ninety-eight women (1.59%) had an initially high MSAFP and 88 (1.42%) a low MSAFP. In the low MSAFP group, 80% returned for a further checkup. Among them, 46% had an over-estimation of gestational age based on their last menstrual period (LMP), 28% had a normal MSAFP and 9% still had a low MSAFP level on a repeat test. Pathologic conditions in other pregnancies included a hydatidiform mole, miscarriage and pseudocyesis. One nonresponder had an ectopic pregnancy. After delivery, no major fetal abnormalities, including trisomy syndromes, were noted in pregnancies carried to term. In the high MSAFP group, 84% returned for check-up. Among them, 15% had an under-estimation of gestational age based on LMP, 16% had twin pregnancies, 46% had a normal MSAFP and 12% still had a high MSAFP on a repeat test. Pathologic conditions in the other pregnancies included one anencephaly, one hydrocephaly and 6 miscarriages. Wrong dating by LMP and false positivity were the most frequent causes of abnormal levels of MSAFP. Two gravidas had artificial abortions because of undue anxiety. MSAFP screening in Taiwan for open neural tube defects does not seem appropriate and using 0.4 MoM as a fixed low cut-off point is inadequate for trisomy syndrome screening. Maternal anxiety should be seriously considered and proper genetic counseling implemented in a screening procedure.

Anencephaly↗

PubMed1990

Prenatal diagnosis of hemophilia A by DNA analysis of chorionic villi.

Hemophilia A is an X-linked recessive single gene disease. If a female is a carrier, her sons have a 50% risk of being affected. Five gravidas, each with a positive family history of hemophilia A, were collected for prenatal diagnosis using DNA analysis on chorionic villi. We used two closely linked extragenic DNA markers, St14 and DX13, and three restriction enzymes, TaqI, MspI, and BglII, to study four restriction fragment length polymorphisms in the Xq28 region. From family analysis, haplotypes were constructed to track the inheritance of X-chromosomes. In family 1, the male fetus inherited the X-chromosome from his normal grandfather, thus his probability of being affected was predicted to be less than 5%. In families 2 and 3, the gravidas inherited the maternal X-chromosome with a different haplotype from that of the affected brother or nephew, thus they both have a low probability (less than 5%) of being carriers. In family 4, the gravida and her male fetus inherited the same X-chromosome as her affected brother. With coagulation assay also showing a high probability of the gravida being a carrier, the fetus was at high risk for the disease. On pregnancy termination, fetal plasma analysis confirmed the diagnosis. In family 5, the gravida's mother had homozygous haplotypes, making the distinction between two X-chromosomes impossible. Coagulation assay classified the gravida as a probable carrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Villi Sampling↗

PubMed1990

Alpha-thalassemia minor and neonatal hyperbilirubinemia.

Infants on this island are known to have higher incidences of neonatal hyperbilirubinemia and alpha-thalassemia minor than Caucasians. In order to investigate the correlation between these two conditions, we collected a total of 110 newborns with alpha-thalassemia minor delivered at the National Taiwan University Hospital during the period from January 1985 through February 1988 for this retrospective study. The infants in the study group were ascertained to have the condition by the presence of Hb Bart's with a concentration from 3% to 13%, in the cord blood. None of them had glucose-6-phosphate dehydrogenase (G6PD) deficiency. For each study infant, two control infants were selected. Criteria for enrollment in the control group were: (1) same sex; (2) absence of G6PD deficiency; and (3) birth time as close as possible to that of the study infant, with the 1st control born before the study infant and the 2nd control after. The timing of bilirubin quantitation was based on clinical judgement of jaundice by the pediatricians and phototherapy was started as indicated. Gestational age, birth weight, and rates of preterm delivery, low birth weight infants and low Apgar scores were comparable between the study and control groups. On day 3 after birth, the incidence of hyperbilirubinemia (bilirubin level over 10 mg/dl) was significantly lower in the study group than in the control group (0.9% vs 9.5%, Fisher's exact probability = 0.0012). However, the difference was not significant later. The incidence of phototherapy was also significantly lower in the study group (20%) than in the control group (31%).(ABSTRACT TRUNCATED AT 250 WORDS)

ABO Blood-Group System↗

PubMed1990

Molecular analysis of 25 Chinese families with Duchenne/Becker muscular dystrophy.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic X-linked progressive neuromuscular diseases. We have collected 25 Chinese families each with at least one DMD/BMD patient for DNA analysis in the Xp21 region. Eight genomic probes, 6 within and 2 flanking the DMD gene, and 7 restriction enzymes were used to detect 9 restriction fragment length polymorphisms (RFLPs): C7-EcoRV, J-Bir-BamHI, pERT87-30-BglII, pERT87-15-BamHI, pERT87-15-XmnI, pERT87-1-XmnI, XJ1.1-TaqI, XJ5.1-SphI, and 754-PstI. From analysis of unrelated subjects, we found that the 4 most informative RFLPs in the linkage study were pERT87-15-XmnI, pERT87-1-XmnI, XJ5.1-SphI and J-Bir-BamHI. Two flanking markers, C7 and 754, were noninformative in most families. Three families (12%) had gene deletion: family M-25 at pERT87-1 to 87-30; M-105 at XJ 5.1, 1.1, pERT87-1, and 87-15; and M-110 at XJ5.1, 1.1, and pERT87-1 to 87-30. Two recombinations were detected: M-10 between C7 and pERT87-15; and M-39 between J-Bir and pERT87-15. In the 25 mothers with affected sons, 2 had gene deletion, 1 was homozygous at all 9 polymorphic loci and the other 22 were heterozygous at more than one locus. Twenty-four at-risk female siblings were studied for carriership. Nine were classified as at high risk of carriership, 13 at low risk of carriership by haplotyping, and the remaining two were uncertain, with one due to recombination and the other to maternal homozygous haplotypes. Gene deletion and RFLP analysis are very useful in genetic counseling of Chinese DMD/BMD.

Chromosome Deletion↗

PubMed1989

Prenatal diagnosis of Chinese homozygous alpha-thalassaemia 1 and haemoglobin H disease by analysis of alpha- and phi zeta-globin genes in chorionic villi and amniocytes.

Eighty-eight high-risk pregnancies, 81 for homozygous alpha-thalassaemia 1 and 7 for haemoglobin (Hb) H disease, were collected in this study. Chorionic villus sampling (CVS) was done in 63 cases and amniocentesis in 25 cases to obtain fetal cells. Southern blotting and DNA hybridization with alpha- and phi zeta-globin gene probes were used to determine the alpha-globin gene status. In two non-informative families with non-deletional mutations, DNA analysis failed to rule out the affected condition, and fetal blood sampling (FBS) and Hb electrophoresis were used for the final diagnosis. In the 81 fetuses at risk for homozygous alpha-thalassaemia 1, 17 (13 by CVS and 4 by amniocentesis) were affected, 30 were alpha-thalassaemia 1 heterozygotes, 19 were normal, and the remaining 15 were either normal or heterozygous. In the seven fetuses at risk for Hb H disease, one was normal, three were alpha-thalassaemia 1 heterozygotes, two were alpha-thalassaemia 2 heterozygotes, and one was affected with Hb H disease and developed hydrops fetalis. DNA analysis on fetal cells enabled us to diagnose prenatally severe alpha-thalassaemias, to prevent the birth of infants with Hb H disease, and to minimize maternal obstetrical complications from harbouring a fetus with Hb Bart's hydrops fetalis.

Amniocentesis↗

PubMed1989

DNA polymorphism haplotype analysis of beta-thalassemia genes in Taiwan.

Twenty unrelated families of homozygous beta-thalassemia were collected for restriction polymorphism haplotype study of the beta-thalassemia (beta T) genes. DNA was extracted from WBC of the family members. With Southern blotting and DNA hybridization, restriction fragment length polymorphisms (RFLPs) were studied at 7 sites within the beta-globin gene cluster, including 5' epsilon-HincII, G gamma-HindIII, A gamma-HindIII, psi beta-HincII,3' psi beta-HincII, beta-AvaII,3' beta-BamHI. From RFLPs of the family members, restriction polymorphism haplotypes of the 40 beta T chromosomes and the 40 normal beta-globin gene (beta A)-bearing chromosomes were constructed. In beta T chromosomes. 26 (65%) belonged to haplotype I (+----++), 12 (30%) to haplotype II (+-----+), 1 (2.5%) to haplotype III (-++-+-+) and 1 (2.5%) to haplotype IV (++---++) which has not been reported in Chinese before. In beta A chromosomes, 12 different haplotypes were found. Seven (17.5%) belonged to haplotype I, 13 (32.5%) to haplotype II, and 6 (15%) to haplotype V (+----+-). The implications of RFLP and haplotyping of beta T genes in terms of molecular defects and prenatal diagnosis are discussed.

Asian People↗

PubMed1989

Percutaneous ultrasound-guided fetal blood sampling: experience in the first 100 cases.

Percutaneous ultrasound-guided fetal blood sampling was performed on 100 pregnancies with various fetal problems. Our technique involved the use of a 45 degree needle guide attached to a sector probe. Their gestational ages ranged from 17-38 weeks, mostly over 20-35 weeks. Seventy percent of cases were successful at the first sampling and 33% of cases had bleeding from the punctured cord. In 43 cases, a positive diagnosis was established after ultrasound-guided fetal blood sampling, including 25 Hemoglobin Bart's hydrops fetalis, 2 beta-thalassemia major, 1 hemophilia, 1 rubella infection, 1 syphilis and 13 chromosome aberrations. There were 33 survivors in this series. Seven anomalous fetuses ended in intrauterine deaths. Sixty cases resulted in neonatal deaths after spontaneous or induced labors. No fetal loss occurred in 25 normal fetuses. One fetal loss was probably related to the procedure (fetal loss rate 1/100). No immediate fetal death after sampling procedure was noted. In conclusion, ultrasound-guided fetal blood sampling had reasonable safety and technical feasibility. More common use of this technique in fetal investigations is justified and expected.

Blood Specimen Collection↗

PubMed1989

Intrauterine diagnosis of short-limbed dwarfism.

Ten short-limbed fetuses caused by skeletal dysplasia were diagnosed prenatally from September 1984 through July 1988. The final diagnosis was thanatophoric dwarfism in 7 cases and osteogenesis imperfecta congenita in 3 cases. The diagnosis was based on sonographic findings in all cases and postnatal radiography was performed in 3 cases for further confirmation. Sonographic examinations revealed markedly shortened limbs and other associated abnormalities, including abnormal skull appearance, pear-shaped chest with protuberant abdomen, polyhydramnios and hydrops in fetuses with thanatophoric dwarfism. Fetuses with osteogenesis imperfecta congenita were characterized by fractures of the long bones. These findings were helpful in making the specific diagnosis of short-limbed dwarfism. According to our experience, sonographic examination is effective in the prenatal diagnosis of short-limbed dwarfism.

Adult↗

PubMed1989

Incidence study of heterozygous beta-thalassemia in northern Taiwan.

Determined with automated cell counters, mean corpuscular volume (MCV) of erythrocytes was screened in 4,100 consecutive gravidas who delivered at the National Taiwan University Hospital during the period from July 1986 through August 1988. In total, 248 (6%) women had MCV less than 80 fl and were recruited for further study, including Hb A2 quantitation using microcolumn chromatography, cord blood Hb electrophoresis on cellulose acetate membrane, and alpha-globin gene mapping in some cases. In the first control group of 51 cases of obligate carriers of heterozygous beta-thalassemia, the mean MCV +/- standard deviation (SD) was 67 +/- 4.5fl (range 59 to 76fl) and the mean Hb A2 +/- SD was 6.53 +/- 1.31% (range 4.3 to 8.0%). In the second control group of 40 cases of obligate carriers of heterozygous alpha-thalassemia 1, the mean MCV +/- SD was 70 +/- 3.7fl (range 63 to 78fl) and the mean Hb A2 +/- SD was 2.28 +/- 0.54% (range 1.5 to 3.8). Forty-five microcytic women (1.1%) had Hb A2 over 4%, a cut-off level for heterozygous beta-thalassemia in our laboratory. In this study group, the mean MCV +/- SD was 68 +/- 5.4 and the mean Hb A2 +/- SD was 6.03 +/- 1.41. None of the newborns delivered by these women had Hb Bart's in cord blood. alpha-Globin gene mapping using DNA hybridization was done in 14 women, and the results were all compatible with the exclusion of deletional alpha-thalassemia. It is concluded that approximately 1% of people in northern Taiwan are beta-thalassemia heterozygotes.

Erythrocyte Indices↗

PubMed1989

The antenatal blood gas and acid-base status of normal fetuses and hydropic fetuses with Bart hemoglobinopathy.

Funipuncture offers direct access to the fetal circulation. The blood gas and acid-base status of the fetus can be studied, and fetal hypoxia and acidosis can be diagnosed directly. To establish normal ranges of fetal blood gas and acid-base status, we analyzed umbilical venous blood samples obtained by funipuncture from 62 normal fetuses (20-35 weeks). These fetuses were studied because of suspected fetal diseases and were subsequently proved to be normal by the fetal blood examinations. Umbilical vein pH and pO2 decreased whereas pCO2 and bicarbonate increased with gestational age. The umbilical vein base excess did not correlate with gestational duration, but oxygen saturation tended to decrease with gestational age. Twenty hydropic fetuses with Bart hemoglobinopathy were also studied; they were found to be more acidotic, hypoxic, and hypercarbic than normal fetuses.

Acid-Base Equilibrium↗

PubMed1988

Umbilical artery flow velocity waveforms in fetuses dying with congenital anomalies.

Absent or reversed diastolic component in umbilical artery (UA) flow velocity waveform was observed in eight fetuses with major malformations. Because of the uncorrectable fetal conditions or the parents' reluctance to terminate the pregnancy, no interventions were undertaken and eventually all eight fetuses died in utero. The interval between the abnormal waveform recording and fetal death was between 1 and 7 days (mean 3.6 days). In two fetuses with abnormal diastolic flow, analysis of umbilical vein blood obtained by ultrasound-guided sampling revealed moderately severe acidosis and hypoxia (pH 7.228 and 7.241, PCO2 47.5 and 46.9 mmHg; PO2 14.6 and 14.7 mmHg, respectively). Our observation suggests that once the diastolic component of UA flow velocity waveforms becomes absent or reversed, the fetus is in a state of hypoxia and acidosis and fetal death is impending. This limited experience may help in formulating clinical management when using UA flow velocity waveforms in the monitoring of high-risk fetuses.

Blood Flow Velocity↗

PubMed1988

Rapid karyotyping in fetuses with abnormal sonogram.

Prenatal karyotyping of fetuses having an abnormal sonogram was undertaken in 27 pregnancies between 17 and 39 weeks, using fetal blood obtained by percutaneous umbilical cord blood sampling under ultrasound guidance. Eight chromosomal abnormalities (29.7%) were detected, including 45, X (2 cases), trisomy 21(1 case), 46, XY,-13,+t(13,13) (1 case), 47, XX,+18(3 cases), 47, XXY (1 case). Nineteen fetuses had a normal karyotype (46,XX:9 cases, 46,XY:10 cases). The fetal karyotype was available within 72 h and fetal management was planned accordingly. We concluded that in fetuses with an abnormal sonogram, rapid karyotyping using fetal blood obtained under ultrasound guidance had important implications in obstetric and neonatal management and would facilitate genetic counselling.

Adult↗

PubMed1988

Umbilical vein blood flow measurement in nonimmune hydrops fetalis.

Twenty-five measurements of fetal umbilical vein blood flow were performed in 22 cases of nonimmune hydrops fetalis using real-time and pulsed Doppler duplex ultrasound. The umbilical vein diameter, blood velocity, and blood flow in fetuses with hemoglobin Bart's hydrops fetalis were usually higher than those in fetuses with hydrops fetalis from other causes. Umbilical vein blood flow measurement appears to be an effective technique for differentiating hemoglobin Bart's from non-Bart's hydrops in this series. This hemodynamic characteristic of umbilical vein blood flow may be helpful in determining the etiology of nonimmune hydrops fetalis.

Adult↗

PubMed1988