Biomedical subjects
Publications and source records attributed to T K Lau.
The discovery of cell-free nucleic acids in plasma has opened up new possibilities for noninvasive clinical diagnosis. We demonstrate the presence of cell-free fetal RNA in maternal plasma, indicating that plasma fetal RNA might be used as a marker for noninvasive prenatal diagnosis.
OBJECTIVE: To assess the timing and risk factors of preterm delivery in pregnancies complicated by antepartum hemorrhage of unknown origin (APHUO) before 34 weeks of gestation, and to formulate a clinical management protocol. METHODS: A retrospective study involving singleton pregnancies with APHUO occurring before the 34th week of gestation was performed over a 4-year period at a university teaching hospital. RESULTS: Seventy-five cases were identified. Fifty-nine (78.7%) did not have any associated uterine contractions, 74.7 and 90.7% of the cases were classified as having mild bleeding according to history and physical examination, respectively. The number of cases delivering before 37 weeks of gestation and before 34 weeks were 28 (37.3%) and 22 (29.3%), respectively. Eighteen cases (24%) delivered within the first week of APHUO, and 4 (5.3%) within the first day. The number of cases delivering within the first week was significantly higher when there were uterine contractions (62.5 vs. 13.6%, p < 0.001). The severity of bleeding was not shown to be related to the time of delivery. CONCLUSION: APHUO that occurs before 34 weeks is associated with a high risk of preterm delivery before 34 weeks (29.3%). The chance of delivery within the first week is 62.5% when there are coexisting uterine contractions. Even if contractions are absent, the risk is still high (13.6%) and persists beyond the first week. We suggest that this group of patients should be managed with a course of steroid injection and hospitalization for 4 days.
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Cerivastatin is the new 3rd-generation of the synthetic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, the 1st drugs of choice for treating hypercholesterolemia. A potent inhibitor of HMG-CoA reductase, it possesses a high affinity for liver tissue and decreases plasma low-density lipoprotein cholesterol at microgram doses. Cerivastatin produces reductions in low-density lipoprotein cholesterol of 31.3% and 36.1% at doses of 0.3 and 0.4 mg/day, respectively It is an uncomplicated agent with regard to its pharmacokinetic profile, low potential for interaction with other drugs, and suitability for use in those with impaired renal function. Most other statins have been implicated in causing rhabdomyolysis, either as monotherapy or in combination with other agents. We report what to our knowledge is the most profound case yet in the literature of rhabdomyolysis in association with cerivastatin-gemfibrozil combination therapy, in regard both to the extreme elevation in serum creatinine kinase and to the patient's near-paralytic weakness.
BACKGROUND: Recently, apoptotic cells have been found in plasma obtained by centrifugation of blood from pregnant women, raising the question of what constitutes plasma and whether plasma is truly cell free. We compared the effects of different blood-processing protocols on the quantification, DNA composition, and day-to-day fluctuation of fetal and total DNA in maternal plasma. METHODS: Blood samples were collected from healthy pregnant women. The blood sample from each individual was simultaneously processed by different means, including the following: Percoll separation, centrifugation, microcentrifugation, and filtration. The resulting plasma aliquots were subjected to real-time quantitative amplification of the beta-globin (for total DNA) and SRY (for fetal DNA) genes. The differences in the beta-globin and SRY DNA concentrations and the degree of variation between the various plasma aliquots were assessed statistically. RESULTS: Different protocols of blood processing significantly affected the quantification and the day-to-day fluctuation of total (P <0.001), but not fetal (quantification, P = 0.336; fluctuation, P = 0.206), DNA in maternal plasma. The quantitative difference could be attributed to the fact that efficacies of different protocols for generating cell-free plasma vary. Processing blood samples by centrifugation followed by filtration or microcentrifugation is effective in producing cell-free plasma. CONCLUSIONS: Standardization in plasma-processing protocols is needed for maternal plasma DNA analysis, especially for quantification of total DNA in maternal plasma. Such preanalytic factors may also affect other applications of plasma DNA analysis.
OBJECTIVE: To evaluate the clinical outcomes of pyometra. STUDY DESIGN: Retrospective study conducted between 1993 and 1999 in two regional hospitals. RESULTS: Pyometra represented 0.038% of gynecologic admissions. Of the 27 women with pyometra, 6 (22.2%) cases were associated with malignancy, 1 (3.7%) was associated with genital tract abnormality, and 20 (74.1%) were idiopathic. Patients with idiopathic pyometra tended to be older and had a higher incidence of concurrent medical conditions. Five (18.5%) women experienced spontaneous perforation of pyometra. A preoperative diagnosis was correctly made in 17 of 22 (77.3%) patients without spontaneous perforation. Most women were treated with dilatation of the cervix and drainage. Nine women (33.3%) had persistent or recurrent pyometra; three of them were asymptomatic. CONCLUSION: Pyometra is an uncommon condition, but the incidence of associated malignancy is considerable, and the risk of spontaneous perforation is higher than previously thought. Dilatation and drainage is the treatment of choice, and regular monitoring after initial treatment is warranted to detect persistent and recurrent disease.
Subendocardial ischemia as indicated by electrocardiography during exercise, in association with severe systolic anterior motion of the anterior mitral valve leaflet without left ventricular hypertrophy, has not been well described. We report the case of a 42-year-old man who presented with symptoms of exertional angina and 2-mm ST depression on treadmill electrocardiography but had a normal perfusion scan and coronary angiogram. Initially the negative angiographic results caused us to regard the treadmill results as false-positive. Subsequently, low-dose dobutamine echocardiography showed severe systolic anterior motion of the anterior mitral valve leaflet with a >144-mmHg left ventricular outflow tract gradient; we then recognized the original treadmill results to be pseudo-false-positive. Electrocardiographic changes in association with the above-described motion of the anterior mitral valve leaflet and increased left ventricular outflow tract gradient were verified by use of treadmill and supine bicycle stress echocardiography.
Fetal DNA is present in maternal plasma, and a proportion of such DNA is seen in intact fetal cells. We investigated the use of fluorescence in-situ hybridisation (FISH) techniques on maternal plasma samples. In plasma samples obtained from three women carrying fetuses affected by trisomy 21 (Down's syndrome), we identified fetal cells with three chromosome-21 signals. These results show the feasibility of non-invasive detection of fetal chromosomal aneuploidy by maternal plasma analysis.
OBJECTIVE: To characterize the distribution of maternal weight gain in Chinese women living in a well-nourished community, to recommend target weight gains from quartile values derived from women with good pregnancy outcomes, and to quantify the risk for adverse pregnancy outcomes encountered among subjects with weight gain outside these recommendations. DESIGN: A retrospective study on maternal anthropometry and pregnancy outcomes was conducted among Chinese women who delivered a singleton pregnancy in a university hospital in Hong Kong. SUBJECTS: Nine hundred eight women who delivered during the study period were identified. Among them, 754 (83%) had complete anthropometry data. The normative distribution of maternal weight gain was derived from 504 women who had a good pregnancy outcome. STATISTICS: Analysis of variance was used to compare total weight gain among women of different prepregnancy weight. Fisher exact test was used in the univariate analysis of the association between risk factors and corresponding adverse pregnancy outcomes. Adjusted odds ratios for adverse outcomes were determined by multiple logistic regression models controlling for the following factors: maternal age, duration of gestation, prepregnancy body mass index (BMI), height, parity, and smoking. RESULTS: A maternal weight-gain chart and recommendations for total weight gains in Chinese women were derived from the distribution of weight gain in subjects with good pregnancy outcomes. The recommended total weight gain was 13 to 16.7 kg, 11 to 16.4 kg, and 7.1 to 14.4 kg respectively for women of low (BMI < 19), moderate (BMI: 19 to 23.5), and high (BMI > 23.5) prepregnancy BMI. Women who did not achieve the lower quartile value had more than twice the risk of having low-birth-weight infants. Those with excessive weight gain were at risk for needing assisted delivery. APPLICATIONS: As maternal anthropometry differs across ethnic groups, different recommendations should be made for specific populations.
We present the radiographic, computed tomographic (CT), and magnetic resonance (MR) findings in a woman with constrictive pericarditis due to an embolized hypodermic needle. The chest films revealed pleural effusions but no foreign body. The CT showed pericardial thickening and a linear foreign body of metallic attenuation in the right ventricular apex, and MR imaging revealed a signal void with magnetic susceptibility artifact. This case illustrates the capabilities and limitations of CT and MR imaging in hypodermic needle-induced constrictive pericarditis.
OBJECTIVE: To compare the accuracy of intrapartum ultrasound with and without color Doppler for identification of nuchal cord displacement during labor. METHODS: 180 normal pregnant women, admitted in labor, or for induction to labor, were examined independently by two researchers, using either conventional real-time gray-scale imaging or color Doppler imaging. A repeat examination was performed by the other researcher using the other ultrasound modality. Nuchal cord displacement was classified as either negative, definite or suspicious. Nuchal cord at birth was classified as either tight or loose. RESULTS: Sixty-two (34%) cases examined using the two ultrasound imaging modalities presented with nuchal cord at delivery. The sensitivity of color Doppler was 96.8%. The accuracy of color Doppler in detecting nuchal cord during labor was significantly better (P < 0.05) than gray-scale imaging alone. The results of a restricted sequential t-test analysis of 53 un-tied pairs showed an overall preference in favor of color Doppler assessment: statistical significance (P < 0.01) was reached after 41 un-tied pairs. CONCLUSIONS: The tight and loose nuchal cord could not be distinguished by ultrasound. Color Doppler imaging can provide useful additional information to gray-scale imaging in the detection of nuchal cord displacement during labor.
OBJECTIVE: We sought to investigate the subclinical effect of external cephalic version on fetal circulation. STUDY DESIGN: A prospective observational study was conducted on 136 subjects who had external cephalic version at or beyond 36 weeks of gestation without clinical complication. Doppler ultrasonographic studies of the umbilical and middle cerebral circulations were performed before and after the external cephalic version. The following Doppler indexes were measured: (1) the pulsatility index of the umbilical artery, which represents disturbance of placental circulation, and (2) the pulsatility index of the fetal middle cerebral artery, which represents fetal response. The Wilcoxon signed rank test was used for all statistical analyses. RESULTS: There was no significant difference in pulsatility index of the umbilical artery before and after external cephalic version (P =.674). There was a statistically significant reduction in the pulsatility index of the middle cerebral artery after external cephalic version (P =.043), and this difference existed only among multiparous women (P =.029), among those in whom the external cephalic version was considered to be difficult (P =.038), and when the placenta was posteriorly located (P =.028). The reduction in pulsatility index was not related to whether the external cephalic version was successful. In all cases the Doppler indexes remained within the normal ranges, and there were no associated fetal complications. CONCLUSION: External cephalic version was not associated with any significant disturbance of placental resistance to blood flow. Conversely, external cephalic version was associated with a significant reduction in the pulsatility index of the middle cerebral circulation, especially among the multiparous women, after a difficult procedure or in those with a posterior placenta. This probably represents a normal fetal physiologic response to manipulation of the fetal head.
OBJECTIVE: Our aim was to investigate whether external cephalic version performed near term increases the concentration of cell-free fetal deoxyribonucleic acid in maternal plasma. STUDY DESIGN: Forty-five patients who had singleton male fetuses and were undergoing external cephalic version at or beyond 36 weeks of gestation were recruited during a 20-month period. Maternal venous blood samples were taken before and within 10 minutes after external cephalic version. Deoxyribonucleic acid was extracted from the plasma samples. The amount of fetal deoxyribonucleic acid was quantified by means of the SRY gene on the Y chromosome as a fetal marker. The change in SRY gene concentration before and after external cephalic version was compared by paired sample t test. RESULTS: There was a significant increase in the concentration of fetal deoxyribonucleic acid in maternal serum after external cephalic version (before, 296 +/- 209 copies per milliliter; after, 369 +/- 228 copies per milliliter; P =.014). This increase in the concentration of deoxyribonucleic acid was most profound among the nulliparous patients after a successful version and in the presence of a posterior placenta. The location of the placenta was found to be the most significant factor accounting for the change in the deoxyribonucleic acid concentration. CONCLUSIONS: External cephalic version near term imposed a significant disturbance to the maternalplacental interface. Fetal deoxyribonucleic acid is a sensitive marker that is useful in the assessment of subclinical fetal-maternal hemorrhage.
Diclofenac is a commonly used non-steroidal anti-inflammatory drug in women of reproductive age. It has teratogenic effects in animals. The aim of this study was to investigate the placental transfer of diclofenac in the first trimester of human pregnancy. Thirty patients undergoing surgical termination of pregnancy between 8 and 12 weeks gestation were given two doses of diclofenac before the procedure. Corresponding samples of maternal serum, amniotic fluid, coelomic fluid and fetal tissue were analysed by high-performance liquid chromatography. Diclofenac was detectable in all fetal tissue samples, with a concentration similar to that found in maternal venous samples. However, diclofenac was detectable in only 56.7 and 23.3% of the coelomic and amniotic fluid samples respectively, and the highest concentration attained was 80 and 5% of the maternal concentration respectively. In summary, we confirmed that diclofenac crosses the human placenta readily during the first trimester. Further studies are required to investigate the potential teratogenic effect of diclofenac in human embryos.
UNLABELLED: We performed a randomized, double-blinded dose-finding study of IV ephedrine for prophylaxis for hypotension in 80 women who received an IV crystalloid preload and spinal anesthesia for elective cesarean delivery. One minute after the intrathecal injection, patients were given saline control or ephedrine 10, 20, or 30 mg IV for 30 s. Systolic arterial pressure (SAP) in the first 12 min after the spinal injection was greater in the 30-mg group compared with other groups (P < 0.05). Hypotension occurred in 7 patients (35%) in the 30-mg group compared with 19 (95%), 17 (85%), and 16 (80%) patients in the control and 10- and 20-mg groups, respectively (P < 0.0001). Maximum decrease in SAP was smaller in the 30-mg group (mean lowest SAP 87% of baseline, range 58%-105%) compared with other groups (P < 0.01). Reactive hypertension occurred in 9 patients (45%) in the 30-mg group (mean highest SAP 120% of baseline, range 104%-143%) compared with 2 (10%), 1 (5%), and 5 (25%) patients in the other groups (P = 0.009). Heart rate changes, total ephedrine requirement, incidence of nausea and vomiting, and neonatal outcome were similar among groups. The proportion of patients with umbilical arterial pH < 7.2 was 10.5%, 25%, 42%, and 22% in the control, 10-, 20-, and 30-mg groups, respectively (P = 0. 12). We conclude that the smallest effective dose of ephedrine to reduce the incidence of hypotension was 30 mg. However, this dose did not completely eliminate hypotension, nausea and vomiting, and fetal acidosis, and it caused reactive hypertension in some patients. IMPLICATIONS: We investigated different doses of IV ephedrine as prophylaxis for hypotension during spinal anesthesia for cesarean delivery and found that the smallest effective dose was 30 mg. However, this dose did not completely eliminate hypotension, caused reactive hypertension in some patients, and did not improve neonatal outcome.
OBJECTIVES: To investigate factors associated with the occurrence of transient fetal bradycardia after external cephalic version, and labour outcome after isolated transient fetal bradycardia. DESIGN: Cohort study. SETTING: Teaching hospital with a policy of offering external cephalic version for breech presentation at or beyond 36 weeks of gestation. POPULATION: Four hundred and twenty-nine external cephalic versions performed over a 5-year period. METHODS: Between group differences were compared with the unpaired t test or the chi2 test. Logistic regression analysis was performed to exclude confounding effects. MAIN OUTCOME MEASURES: Incidence of caesarean section for fetal distress. RESULTS: Transient fetal bradycardia occurred in 8.4% of external cephalic versions, and was associated with a successful version (OR 16.45, P < 0.001), a difficult procedure (OR 3.70, P = 0.001), and nulliparity (OR 2.83, P = 0.007). The incidence of intrapartum caesarean section for fetal distress was 16.7% in pregnancies with transient fetal bradycardia, compared with 7.9% in those without (OR 2.34, 95% CI 0.81, 6.71). CONCLUSIONS: Transient fetal bradycardia after external cephalic version may be associated with a higher risk of intrapartum caesarean section for fetal distress.