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Biomedical subjects

F Y Chan

Publications and source records attributed to F Y Chan.

At least 37 records · Page 2Linked to original sources

Clinical value of real-time tertiary fetal ultrasound consultation by telemedicine: preliminary evaluation.

Congenital fetal abnormalities are major causes of perinatal mortality and morbidity. The performance of ultrasound in the diagnosis and assessment of fetal anomalies varies enormously between tertiary referral centers and general units. Telemedicine offers a chance for tertiary realtime ultrasound consultations using standard telephone lines for remote sites. Preliminary investigations by our group have shown that real-time transmission of fetal ultrasound images over long distances via telephone (integrated systems digital network [ISDN]) lines is technically feasible. A live link of up to 2 Mb/s was established between Mater Mothers Hospital in Brisbane and Kirwan Hospital for Women in Townsville, which are 1,500 km apart. The objective of the current study was to evaluate the clinical value of a tertiary teleultrasound consultation service. Patients requiring tertiary ultrasound consultations were recruited from North Queensland. Clinicians from the referral site established an initial diagnosis and management plan. Using standard ISDN lines, the real-time ultrasound images were transmitted to the maternal fetal medicine subspecialists in Brisbane. The ultrasound examination was completed under the direction of the subspecialist. The subspecialist explained the findings to the patient at the end of the session, and discussed the diagnosis and management plans with the clinicians involved. Any diagnosis and management variations were classified into minor and major upon agreement by the two teams of clinicians involved. The clinicians and patients in Townsville rated the value of the consultation, and the subspecialists rated the confidence of their diagnoses on five-point scales. Pregnancy outcomes were obtained and the data analyzed. Over a 3-month period, 24 teleultrasound consultations were carried out. The indications for referral were: assessment of growth restriction/fetal wellbeing in the third trimester (6); detailed assessment for high-risk patients (5); evaluation of markers for anomalies (5); isolated fetal anomalies (1); and complex fetal problems such as twin/twin transfusion, multiple anomalies, etc. (7). Overall, the consultations resulted in some modifications to the clinical diagnosis in 45.8% of the cases, and modifications to the management plan in 33.3% of the cases (about half of which were minor variations). The clinicians rated the teleconsultations highly (mean rating 4.7, SD 0.44). The patients also rated the consultations highly, and were comfortable that their privacy and confidentiality were maintained during the consultation. The subspecialists were confident in making their diagnoses by telemedicine (mean score for confidence 4.2, SD 0.43). All the pregnancies have now been completed, with all antenatal diagnoses confirmed to be correct postnatally. Tertiary real-time ultrasound consultation by telemedicine is not only technically feasible, it is welcomed by the clinicians and patients involved. It also contributes to diagnostic and management differences. Larger scale clinical trials are needed to evaluate the true benefits and costs involved. The social benefits in bridging the healthcare gap between the country and the city, and in enabling patients in remote areas to stay close to their family under times of stress is well recognized by all involved.

Congenital Abnormalities↗

Long term outcome of twin-twin transfusion syndrome.

AIMS: To compare the perinatal mortality and morbidity of infants with twin-twin transfusion syndrome (TTTS) with those of gestation matched twin controls and to assess the neurodevelopmental outcome of surviving twins with TTTS. METHODS: A cohort of 17 consecutive pregnancies with TTTS was enrolled over three years together with gestation matched twin pregnancies unaffected by TTTS. Serial amnioreduction for the TTTS pregnancies was performed as appropriate. Perinatal death and neonatal morbidities were recorded for both the TTTS cohort and controls. The TTTS survivors had neurodevelopmental follow up to at least 2 years of age. RESULTS: In 12 of the pregnancies, serial amniocenteses were performed, but, in five, the infants were born before intervention. The mean gestational age at delivery was 29.1 weeks (range 23-36). There were five intrauterine deaths in the TTTS cohort and six neonatal deaths (survival 68%). In the control group, there was one intrauterine death and five neonatal deaths (survival 82%). Infants in the TTTS group had a greater requirement for inotropes (p = 0.04) and a higher incidence of renal failure (p = 0.005). Periventricular leucomalacia and cerebral atrophy were seen in 17% of the TTTS group, but none of the controls (p = 0.03). The 23 surviving TTTS infants were all followed up, with 22% having significant neurological morbidity: cerebral palsy and global developmental delay. CONCLUSIONS: Twins with TTTS have high perinatal mortality and neonatal morbidity, and long term neurodevelopmental morbidity in survivors is high. Further investigation into the pathogenesis and management of TTTS is required.

Acute Kidney Injury↗

Placental growth hormone (GH), GH-binding protein, and insulin-like growth factor axis in normal, growth-retarded, and diabetic pregnancies: correlations with fetal growth.

We previously described significant changes in GH-binding protein (GHBP) in pathological human pregnancy. There was a substantial elevation of GHBP in cases ofnoninsulin-dependent diabetes mellitus and a reduction in insulin-dependent diabetes mellitus. GHBP has the potential to modulate the proportion of free placental GH (PGH) and hence the impact on the maternal GH/insulin-like growth factor I (IGF-I) axis, fetal growth, and maternal glycemic status. The present study was undertaken to investigate the relationship among glycemia, GHBP, and PGH during pregnancy and to assess the impact of GHBP on the concentration of free PGH. We have extended the analysis of specimens to include measurements of GHBP, PGH, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 and have related these to maternal characteristics, fetal growth, and glycemia. The simultaneous measurement of GHBP and PGH has for the first time allowed calculation of the free component of PGH and correlation of the free component to indexes of fetal growth and other endocrine markers. PGH, free PGH, IGF-I, and IGF-II were substantially decreased in IUGR at 28-30 weeks gestation (K28) and 36-38 weeks gestation (K36). The mean concentration (+/-SEM) of total PGH increased significantly from K28 to K36 (30.0 +/- 2.2 to 50.7 +/- 6.2 ng/mL; n = 40), as did the concentration of free PGH (23.4 +/- 2.3 to 43.7 +/- 6.0 ng/mL; n = 38). The mean percentage of free PGH was significantly less in IUGR than in normal subjects (67% vs. 79%; P < 0.01). Macrosomia was associated with an increase in these parameters that did not reach statistical significance. Multiple regression analysis revealed that PGH/IGF-I and IGFBP-3 account for 40% of the variance in birth weight. IGFBP-3 showed a significant correlation with IGF-I, IGF-II, and free and total PGH at K28 and K36. Noninsulin-dependent diabetes mellitus patients had a lower mean percentage of free PGH (65%; P < 0.01), and insulin-dependent diabetics had a higher mean percentage of free PGH (87%; P < 0.01) than normal subjects. Mean postprandial glucose at K28 correlated positively with PGH and free PGH (consistent with the hyperglycemic action of GH). GHBP correlated negatively with both postprandial and fasting glucose. Although GHBP correlated negatively with PGH (r = -0.52; P < .001), free PGH and total PGH correlated very closely (r = 0.98). The results are consistent with an inhibitory function for GHBP in vivo and support a critical role for placental GH and IGF-I in driving normal fetal growth.

Adult↗

A study of correlation between NPM-translocation and apoptosis in cells induced by daunomycin.

Human leukemia K562 and HeLa cells were treated with daunomycin (DA) for 1-4 hr. With the indirect immunofluorescence technique, we observed that the nucleolar protein nucleophosmin/B23 (NPM) shifted its location from the nucleolus to the nucleoplasm (NPM-translocation). The degree of NPM-translocation was determined by the relative immunofluorescent intensity in the nucleoli vs the nucleoplasm (defined as localization index, LI). We found that NPM-translocation, as determined by the decrease of LI, correlates with cytotoxicity. The degrees of NPM-translocation, chromatin condensation, and DNA fragmentation in HeLa cells were determined after treatment with 0.1, 0.5 and 1 microg/mL DA for 1 hr. We found that NPM-translocation (LI < 2.5) was observed in cells during the treatment with 0.5 and 1 but not with 0.1 microg/mL DA. Also, cells treated with 1 microg/mL remained in an NPM-translocated state for a longer time (5-6 hr) than those cells treated with 0.5 microg/mL (1-2 hr). Cells treated with 0.5 and 1 microg/mL DA showed increased levels of chromatin condensation beginning at 5 hr after the drug treatment. The number of cells with condensed chromatin increased with both time and drug concentration. No cells with condensed chromatin were observed in samples treated with 0.1 microg/mL DA, which also showed no significant NPM-translocation. Similar results were observed for induction of DNA fragmentation. We found that the drug concentration required for induction of DNA fragmentation and chromatin condensation coincided with the drug concentration required for NPM-translocation. Taken together, these results indicate that NPM-translocation correlates with apoptosis induced by daunomycin.

Antibiotics, Antineoplastic↗

Minimum requirements for remote realtime fetal tele-ultrasound consultation.

We studied the transmission bandwidth required for accurate diagnoses when performing realtime fetal tele-ultrasound consultations. The study was divided into three phases. In phase I, three experienced clinicians evaluated the quality of ultrasound images transmitted at various bandwidths (internally looped back within Brisbane) using eight commercially available codecs at random. The two codecs that performed best proceeded to phase 2, in which a realtime video-link of up to 2 Mbit/s was set up between Brisbane and Townsville (1,500 km apart). Testing with a standard video-tape was performed at seven different bandwidths selected at random, with four clinicians (who were blinded to the equipment and bandwidths used). The optimum line rates for transmission were determined, and testing was then performed using these line rates for fetuses with various anomalies (phase 3). The results showed significant differences in performance according to bandwidths used, but not according to observers. Bandwidths were grouped into three levels. At level I (256 kbit/s) the performance was significantly worse than at level II (384, 512 or 768 kbit/s), which was in turn worse than that at level III (1, 1.5 or 2 Mbit/s). However, within each level, performance at one bandwidth was not significantly different from that at the others. The most cost-effective transmission rates therefore appeared to be 384 kbit/s and 1 Mbit/s. Further testing with fetuses affected by various anomalies confirmed that the majority could be diagnosed using a 384 kbit/s link, with slight improvement in evaluation when the bandwidth was increased to 1 Mbit/s.

Analysis of Variance↗

Intrapartum fetal oxygen saturation monitoring in congenital fetal heart block.

Conventional intrapartum electronic fetal heart rate monitoring is not informative in certain fetal conditions because the electronically-monitored fetal heart rate pattern is uninterpretable in terms of reflecting fetal normoxia. Such fetal conditions include various cardiac dysrrhythmias and some central nervous system abnormalities. Difficulties with intrapartum fetal welfare surveillance in such conditions often lead to operative delivery as a precautionary measure. We report 2 cases of intrapartum fetal oxygen saturation monitoring in the presence of congenital complete heart block (CCHB), using the Nellcor N400/FS14 oxygen saturation monitoring system. Mean intrapartum fetal oxygen saturation (FSpO2) was 32% (SEM +/- 1%) in the first case and 48% (SEM +/- 0.3%) in the second case. In both cases, vaginal delivery of otherwise healthy infants was achieved. Fetal pulse oximetry is a promising new technique which directly measures fetal oxygenation without reference to fetal heart rate patterns. It may assist in the intrapartum fetal welfare assessment in conditions such as complete heart block, thereby helping to avoid otherwise unnecessary operative delivery.

Adult↗

Assessment of the clinical usefulness of the 'Queenan' chart versus the 'Liley' chart in predicting severity of rhesus iso-immunization.

In 1961 Liley developed a chart of changing amniotic fluid bilirubin levels (delta OD450) and gestation, with three zones delineating the severity of rhesus disease. This chart ranged from 27 to 40 weeks and was found to be clinically useful. Extrapolating the use of the Liley chart to earlier gestations however, was unsuccessful. Currently, cordocentesis is the only reliable means of assessing the fetal condition accurately prior to 27 weeks. In 1993, Queenan proposed a chart of delta OD450 from 14 to 40 weeks, with four zones to guide management. The aim of the current study is to assess the clinical usefulness of the 'Queenan' chart vs. the 'Liley' chart. There were 35 pregnancies affected by rhesus disease between 1990 and 1997 at the Mater Mothers' Hospital, Brisbane. The quantitative anti-D and delta OD450 levels obtained before intra-uterine transfusions were recorded. Each sample was labelled with the fetal condition at the time the sample was taken. Of the 72 delta OD450 samples, 36 (50 per cent) were performed before 27 weeks, and these included all four of the severely affected samples and 11 of the 13 moderately affected samples. The sensitivity of the Queenan chart in predicting the severely affected pregnancies was 100 per cent, with specificity of 79.4 per cent, positive predictive value of 22.2 per cent and negative predictive value of 100 per cent. For prediction of moderate/severely affected pregnancies, the sensitivity was 83.3 per cent, with specificity of 94.4 per cent, positive predictive value of 83.3 per cent and negative predictive value of 96.3 per cent. In conclusion, an delta OD450 chart which includes gestations less than 27 weeks is necessary with our changing caseload of rhesus iso-immunized patients, where severely affected pregnancies seemed to occur early and intervention even in moderately affected pregnancies seemed appropriate. We found that the Queenan chart is a suitable alternative to the Liley chart.

Amniocentesis↗

Isolation and characterization of the human nucleophosmin/B23 (NPM) gene: identification of the YY1 binding site at the 5' enhancer region.

NPM (nucleophosmin/B23) is a major nucleolar protein which is 20 times more abundant in tumor or proliferating cells than in normal resting cells. Recently, it was found that NPM gene is located at the breakpoints of the t(2:5), t(3:5) and t(5:17) chromosome translocation. To understand the human NPM gene's structure and regulation, four genomic clones were isolated from the human chromosome 5 library and their DNA sequences analyzed. The human NPM gene has 12 exons of sizes ranging from 58 to 358 bp. The chromosome breakpoint for t(2:5) and t(5:17) translocation is within intron 4 and the breakpoint for t(3:5) translocation is within intron 6. The initiation site is located 96 bp upstream from the ATG site. A typical TATA box (at -25 nt) and a GC box (at -65 nt) were identified in the promoter region. We identified two gel-shift bands (A and B) with DNA fragment E (-741/-250 nt) by EMSA. A DNA footprint was observed at (-371/-344 nt) with the nuclear extract. A double stranded DNA with the footprint sequence (-371/-344 nt) competed the formation of gel-shift bands A and B in EMSA suggesting that proteins A and B bind to the footprint region. We confirmed that protein A is transcription factor YY1. These results suggest that YY1 may play a role in NPM gene expression. This is the first report on human NPM gene structure and sequence.

Animals↗

Characterization of adult alpha- and beta-globin genes in the zebrafish.

Developmental switching of hemoglobins (Hbs) occurs in most vertebrates, yet the cellular and molecular basis for this process remains elusive. The zebrafish is a new genetic and developmental system that can be used to study embryogenesis, and mutants with a variety of defects in hematopoiesis have recently been derived. To initiate our studies on Hb switching in this organism, we have characterized the globins expressed in the adult. Reversed-phase high performance liquid chromatography and mass spectrometric analyses of adult peripheral blood hemolysates showed that there are three major alpha globins and two beta globins in circulating erythroid cells. In addition, we have isolated and characterized zebrafish adult alpha- and beta-globin cDNA clones that encode some of these globins. High levels of alpha- and beta-globin gene expression were detected in adult erythroid cells, whereas embryonic erythroid cells expressed little, if any, of these RNAs. We have also shown that the alpha- and beta-globin genes are tightly linked on the same chromosome and are arrayed in a 3'-5' to 5'-3' configuration, respectively. The characterization of these genes and regulatory elements in this globin locus will provide insight into the process of globin gene transcription. With these reagents, future studies of Hb switching in zebrafish mutants with defective hematopoiesis will be possible.

Amino Acid Sequence↗

Antecedents to and outcomes of Rh(D) isoimmunization: Mater Mothers Hospital, Brisbane, 1988-1995.

We analyzed the antecedents and outcomes of Rh(D) isoimmunization in a local population. Forty-two Rh(D) isoimmunized women attending Mater Mothers Hospital for antenatal care were identified through the Mater Hospital Blood Bank database; their records were reviewed for variables including sensitizing events, obstetric interventions and pregnancy outcomes. In this group, 74% of women became sensitized despite receiving anti-D immune globulin, 17% did not receive anti-D appropriately and the other failed to attend for treatment of bleeding in pregnancy. Antenatal sensitization was implicated in 6 women (14%) and potentially responsible for isoimmunization in another 18. Over half of the 80 viable pregnancies in this study group required some form of obstetric intervention. Thirty pregnancies required amniocentesis and 1 in 3 babies underwent either intrauterine or exchange transfusion. Three fetal deaths occurred as a result of severe disease. This study offers information highlighting circumstances in which immunoprophylaxis guidelines have failed to impart protection against Rh(D) sensitization and the consequences of such failures.

Female↗

Growth hormone-binding protein in normal and pathologic gestation: correlations with maternal diabetes and fetal growth.

To date, measurements of GH-binding protein (GHBP) during human pregnancy have been carried out using assays susceptible to interference by the elevated levels of human placental GH typical of late gestation. We recruited a large cohort of pregnant women (n = 140) for serial measurements of GHBP and used the ligand immunofunctional assay for GHBP. For normal gravidas, GHBP levels fell throughout gestation. Mean levels were 1.07 nmol/L (SE = 0.18) in the first trimester, 0.90 nmol/L (SE = 0.08) at 18-20 weeks, 0.73 nmol/L (SE = 0.05) at 28-30 weeks, and 0.62 nmol/L (SE = 0.06) at 36-38 weeks. GHBP levels in the first trimester correlated significantly with maternal body mass index (r = 0.58; P < 0.01). GHBP levels in pregnancies complicated by noninsulin-dependent diabetes mellitus (NIDDM) were substantially elevated at all gestational ages. The mean value in the first quarter (2.29 nmol/L) was more than double the normal mean (P < 0.01). In contrast, patients with insulin-dependent diabetes mellitus (IDDM) showed reduced GHBP concentrations at 36-38 weeks. The correlation between body mass index and GHBP is consistent with a metabolic role for GHBP during pregnancy, as is the dramatic elevation in GHBP observed in cases of NIDDM. At 36 weeks gestation, GHBP was significantly elevated (P < 0.01) in those women whose neonates had low birth weight (< 10th percentile). In early gestation (< 14 weeks), GHBP tended to be higher in women whose fetuses were designated to be at risk of intrauterine growth retardation (1.39 nmol/L; n = 4; compared with 1.07 nmol/L in normals), but this did not reach statistical significance. Although both NIDDM and IDDM pregnancies are at risk of fetal macrosomia, their GHBP concentrations are markedly divergent. This paradox and the roles of glucose and insulin in the regulation of GHBP during gestation warrant further investigation.

Carrier Proteins↗

A third Ig light chain gene isotype in Xenopus laevis consists of six distinct VL families and is related to mammalian lambda genes.

Xenopus laevis is a unique model for studying the ontogenetic development of immune functions. A short primer PCR amplification method was employed to amplify fragments from Xenopus genomic DNA that are related to Ig light chains and TCR. One fragment was identified that appeared to represent a novel type of light chain and was used as a probe to recover the corresponding cDNA from a spleen cDNA library. We designate these light chains type III. Using an iterative screening procedure, six families of VL genes, two distinct JL and two distinct CL sequences, were identified. In a comparison of phylogenetically diverse light chains, the type III genes align with higher vertebrate lambda genes. Southern blot hybridization analyses with genomic DNA from different animals showed the VL and CL sequences to be both diverse and polymorphic. Intrafamily sequence comparisons of VL genes revealed additional diversity. Collectively, these studies confirm the existence of a third type of light chain gene in Xenopus, establish a high degree of genetic variation in the sequences encoding the light chain V regions, and provide the most significant evidence to date for the presence of a lambda-like light chain gene at the phylogenetic level of the amphibians.

Amino Acid Sequence↗

Fetal cerebral Doppler studies as a predictor of perinatal outcome and subsequent neurologic handicap.

OBJECTIVE: To study the use of middle cerebral arterial Doppler findings in a group of high-risk fetuses as a predictor of adverse perinatal outcome, including subsequent neurologic handicap. METHODS: A group of very high-risk fetuses was recruited over a 2-year period for study. Weekly fetal biometries and Doppler studies of the umbilical artery and middle cerebral arteries were carried out until delivery. Main outcome indices analyzed included birth weight ratio (ratio of observed birth weight to mean birth weight for gestation), days of ventilator requirement, neonatal intracranial hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and follow-up data on major neurologic handicap and death. RESULTS: Seventy-four patients were recruited. One hundred thirty-four sets of examinations were made and prospective follow-up data were available for up to 2 years. The ratio of the umbilical and middle cerebral arterial resistance index was found to be inversely proportional to the birth weight ratio. Fetuses who had a high prenatal umbilical-cerebral Doppler ratio had significantly lower birth weight ratios than those with normal findings (0.72 versus 0.92; P < .001). The ratio was a more sensitive marker for growth restriction (sensitivity 78%) than conventional fetal biometry and umbilical arterial systolic-diastolic ratio. However, fetuses with high ratios did not have higher incidences of perinatal complications or subsequent neurologic handicap. CONCLUSION: Prenatal cerebral vasodilation is a sensitive marker for growth restriction and it seems to be a physiologic response to hypoxia. Fetuses with intrauterine cerebral vasodilation do not have increased risk for subsequent gross neurologic damage.

Adult↗

The role of Doppler sonography in assessment of malignant trophoblastic disease.

An observational study on the role of Doppler sonography in the assessment of patients with malignant trophoblastic disease was performed in an Oncology Unit of a University teaching hospital. A total of 32 consecutive patients referred for chemotherapy were recruited. Twenty-three non-pregnant and 18 women in the first trimester of pregnancy acted as controls. The patients were prospectively followed-up for 2 years. It was found that the uterine arterial resistance index and pulsatility index in patients who required chemotherapy were significantly lower when compared with the non-pregnant and pregnant controls; (Student t-test; P < 0.001 and P < 0.01, respectively). Stepwise regression analysis of beta-hCG titres on uterine artery resistance index showed significant correlation, after controlling for uterine volume (adjusted multiple R = 0.71, P < 0.00001). There were, however, no significant independent associations between the initial uterine artery resistance index and the need for chemotherapy, number of courses of chemotherapy required, duration required for the beta-hCG titre to return to normal, presence of metastatic disease, or the subsequent development of drug resistance or relapse. It was concluded that uterine arterial Doppler indices are significantly correlated with trophoblastic activity (beta-hCG titres) in malignant trophoblastic disease. However, their role in the prediction of subsequent tumour behaviour need to be assessed in larger series.

Chorionic Gonadotropin, beta Subunit, Human↗

Intraembryonic hematopoietic cell migration during vertebrate development.

Vertebrate hematopoietic stem cells are derived from vental mesoderm, which is postulated to migrate to both extra- and intraembryonic positions during gastrula and neurula stages. Extraembryonic migration has previously been documented, but the origin and migration of intraembryonic hematopoietic cells have not been visualized. The zebrafish and most other teleosts do not form yolk sac blood islands during early embryogenesis, but instead hematopoiesis occurs solely in a dorsal location known as the intermediate cell mass (IM) or Oellacher. In this report, we have isolated cDNAs encoding zebrafish homologs of the hematopoietic transcription factors GATA-1 and GATA-2 and have used these markers to determine that the IM is formed from mesodermal cells in a posterior-lateral position on the yolk syncytial layer of the gastrula yolk sac. Surprisingly, cells of the IM then migrate anteriorly through most of the body length prior to the onset of active circulation and exit onto the yolk sac. These findings support a hypothesis in which the hematopoietic program of vertebrates is established by variations in homologous migration pathways of extra- and intraembryonic progenitors.

Amino Acid Sequence↗

Cloning and chromosomal localization of a mouse cDNA with homology to the Saccharomyces cerevisiae gene zuotin.

The eukaryotic DnaJ homologs form a family of proteins with diverse functions. One member of the family, the Saccharomyces cerevisiae gene zuotin, was isolated for its ability to bind Z-DNA. Here, we have isolated a mouse cDNA called ZRF1 (for zuotin-related factor1) with significant homology to zuotin. The DnaJ domain and candidate phosphorylation sites of zuotin and ZRF1 are highly conserved. ZRF1 gene is localized on chromosome 5. The structural similarity of zuotin and ZRF1 suggests conservation of function of this DnaJ subfamily.

Amino Acid Sequence↗