Reduced fetal growth velocity precedes antepartum fetal death.

OBJECTIVES: To determine whether decreased fetal growth velocity precedes antepartum fetal death and to evaluate whether fetal growth velocity is a better predictor of antepartum fetal death compared to a single fetal biometric measurement at the last available ultrasound scan prior to diagnosis of demise. METHODS: This was a retrospective, longitudinal study of 4285 singleton pregnancies in African-American women who underwent at least two fetal ultrasound examinations between 14 and 32 weeks of gestation and delivered a liveborn neonate (controls; n = 4262) or experienced antepartum fetal death (cases; n = 23). Fetal death was defined as death diagnosed at ≥ 20 weeks of gestation and confirmed by ultrasound examination. Exclusion criteria included congenital anomaly, birth at < 20 weeks of gestation, multiple gestation and intrapartum fetal death. The ultrasound examination performed at the time of fetal demise was not included in the analysis. Percentiles for estimated fetal weight (EFW) and individual biometric parameters were determined according to the Hadlock and Perinatology Research Branch/Eunice Kennedy Shriver National Institute of Child Health and Human Development (PRB/NICHD) fetal growth standards. Fetal growth velocity was defined as the slope of the regression line of the measurement percentiles as a function of gestational age based on two or more measurements in each pregnancy. RESULTS: Cases had significantly lower growth velocities of EFW (P < 0.001) and of fetal head circumference, biparietal diameter, abdominal circumference and femur length (all P < 0.05) compared to controls, according to the PRB/NICHD and Hadlock growth standards. Fetuses with EFW growth velocity < 10th percentile of the controls had a 9.4-fold and an 11.2-fold increased risk of antepartum death, based on the Hadlock and customized PRB/NICHD standards, respectively. At a 10% false-positive rate, the sensitivity of EFW growth velocity for predicting antepartum fetal death was 56.5%, compared to 26.1% for a single EFW percentile evaluation at the last available ultrasound examination, according to the customized PRB/NICHD standard. CONCLUSIONS: Given that 74% of antepartum fetal death cases were not diagnosed as small-for-gestational age (EFW < 10th percentile) at the last ultrasound examination when the fetuses were alive, alternative approaches are needed to improve detection of fetuses at risk of fetal death. Longitudinal sonographic evaluation to determine growth velocity doubles the sensitivity for prediction of antepartum fetal death compared to a single EFW measurement at the last available ultrasound examination, yet the performance is still suboptimal. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Erysipelothrix Septicaemia and Hepatitis in a Colony of Humboldt Penguins (Spheniscus humboldti).

This report describes an outbreak of erysipelas in a colony of captive Humboldt penguins (Spheniscus humboldti). The only previously reported case in a related species was of an individual little blue penguin (Eudyptula minor). Five Humboldt penguins in a mixed colony displayed non-specific signs of illness, including lethargy, inappetence and regurgitation after movement for exhibit upgrading. There was no improvement after 5 days of treatment with oral enrofloxacin (10 mg/kg q24h). Four Humboldt penguins, including two that were not part of the original five displaying signs of illness, died during this outbreak and Erysipelothrix rhusiopathiae was cultured from organ samples collected post mortem. Oral clavulanic acid/amoxycillin (125 mg/kg q12h) was added to the treatment of the sick Humboldt penguins, as well as itraconazole (8.5 mg/kg q12h) and silymarin (10 mg/kg q24h) for 10 days (both per os), which resolved their clinical signs. The likely source of E. rhusiopathiae was the fish they were fed, but this could not be confirmed. Another contributing factor to the growth of E. rhusiopathiae in the exhibit pool was the increase in water temperature due to a fault in the water circulating system. The temperature of the pool water had increased to 29°C, which was rectified, and the water temperature decreased to 13°C. However, there was one further Humboldt penguin death after the decrease in water temperature. This episode suggests that E. rhusiopathiae infection should be high on the differential list of piscivorous avian species with non-specific clinical signs. A liver biopsy for bacterial culture and sensitivity may be required for definitive diagnosis.

Epigenetic silencing of the dual-role signal mediator, ANGPTL4 in tumor tissues and its overexpression in the urothelial carcinoma microenvironment.

Urothelial carcinoma (UC) carcinogenesis has been hypothesized to occur through epigenetic repression of tumor-suppressor genes (TSGs). By quantitative real-time polymerase chain reaction array, we found that one potential TSG, angiopoietin-like 4 (ANGPTL4), was expressed at very low levels in all bladder cancer cell lines we examined. Previous studies had demonstrated that ANGPTL4 is highly expressed in some cancers, but downregulated, by DNA methylation, in others. Consequently, owing to these seemingly conflicting functions in distinct cancers, the precise role of ANGPTL4 in the etiology of UC remains unclear. In this study, using methylation-specific PCR and bisulfite pyrosequencing, we show that ANGPTL4 is transcriptionally repressed by DNA methylation in UC cell lines and primary tumor samples, as compared with adjacent noncancerous bladder epithelium. Functional studies further demonstrated that ectopic expression of ANGPTL4 potently suppressed UC cell proliferation, monolayer colony formation in vitro, and invasion, migration, and xenograft formation in vivo. Surprisingly, circulating ANGPTL4 was significantly higher in plasma samples from UC patients than normal control, suggesting it might be secreted from other cell types. Interestingly, our data also indicated that exogenous cANGPTL4 could promote cell proliferation and cell migration via activation of signaling through the Erk/focal adhesion kinase axis. We further confirmed that mouse xenograft tumor growth could be promoted by administration of exogenous cANGPTL4. Finally, immunohistochemistry demonstrated that ANGPTL4 was downregulated in tumor cells but overexpressed in tumor adjacent stromal tissues of muscle-invasive UC tissue samples. In conclusion, our data support dual roles for ANGPTL4 in UC progression, either as a tumor suppressor or oncogene, in response to microenvironmental context.

Multi-organ Metastasis of Fibrolamellar Hepatocellular Carcinoma in a Malayan Gharial (Tomistoma schlegelii).

A 38-year-old Malayan gharial (Tomistoma schlegelii) with a 2-week history of anorexia was found dead and presented for post-mortem examination. Numerous white firm nodules of various sizes were found on the surface of the liver, both left and right kidneys, the spleen and the serosa of the intestinal tract. All masses had similar microscopical appearance and were diagnosed as metastasizing fibrolamellar hepatocellular carcinoma. Immunohistochemically, the tumour cells did not react with antibodies specific for pan-cytokeratin, vimentin or HepPar-1. The anti-HepPar-1 and anti-pan-cytokeratin antibodies also did not react with normal hepatocytes or exocrine pancreatic cells. This is the first description of fibrolamellar hepatocellular carcinoma with metastases in a crocodilian.

PP079. Evidence of placental and vascular endothelial apotosis and dysfunction by elevated serum human chorionic gonadotropin, soluble selectin and soluble Fas in HELLP syndrome.

INTRODUCTION: The etiology of Hemolysis, Elevated Liver enzyme, and Low Platelets (HELLP) syndrome remains unknown. We hypothesized that placental and vascular endothelial apoptosis and dysfunction might be the pathogenesis of HELLP syndrome. OBJECTIVES: To determine maternal serum levels and association among human chorionic gonadotropin (hCG), soluble Fas (sFas), and E-selectin (sE-selectin) in HELLP syndrome. METHODS: Forty-two singleton pregnant women were studied. Fourteen patients were with HELLP syndrome and 28 patients were healthy gravidas. The serum levels of total beta-hCG, sFas, and sE-selectin were measured by enzyme-linked immunoassays. Mann-Whitney test and Spearman rank correlation were used for statistical analyses. Data were expressed as median and ranges. P value less than 0.05 is considered statistically significant. RESULTS: There were no significant differences in maternal age, gestational age, parity or race in patients with and without HELLP syndrome. The median levels of serum total beta-hCG, sFas, and sE-selectin were significantly higher in women with HELLP syndrome than in healthy gravidas {total beta-hCG: 52,168 (14,936-213,445)mIU/mL vs. 17,942 (966-176,600)mIU/mL, p=0.016; sFas: 8.20 (3.0-22.6)U/ml vs. 5.8 (1.2-18.5)U/ml, p=0.001; sE-selectin: 107.7 (26.2-194.7)ng/mL vs. 23.0 (11.1-107.7)ng/mL, p<0.0001}. Moreover, serum total beta-hCG levels were significantly correlated with serum sFas (r=0.32, p=0.039) and sE-selectin levels (r=0.32, p=0.038). Serum sFas levels were also significantly correlated with serum sE-slectin (r=0.47, p=0.003) CONCLUSION: Our data suggest that placental and vascular endothelial apoptosis in preeclampsia may further lead to placental and endothelial dysfunction as the possible pathogenesis in HELLP syndrome.

PP126. Are placental fas and fas ligand gene polymorphisms associated with preeclampsia?

INTRODUCTION: Increased placental trophoblastic apoptosis has been reported in pregnancies complicated by preeclampsia. Fas-Fas ligand is one of the major signal transduction pathways of apoptosis. OBJECTIVES: To determine if placental Fas and Fas ligand gene polymorphisms differ between patients with and without preeclampsia. METHODS: Forty-five singleton placentas were studied. Twenty-three placentas were from preeclamptic pregnancies and 22 were from normotensive controls. The study was approved by IRB. Genotyping was performed for Fas-1377, Fas-691, Fas-670, Fas ligand-844, Fas ligand-1174, Fas ligand-2777. Chi-square and Fisher's exact tests were used for statistical analysis. RESULTS: There were no significant differences in maternal age, parity or race between the two groups. There were no significant differences in genotypes or allele frequencies for the placental Fas-1377, Fas-691, Fas-670, Fas ligand-844, Fas ligand-1174 and Fas ligand-2777. CONCLUSION: Immune intolerance of maternal and placental interaction plays an important role in the pathogenesis of preeclampsia. Our findings do not support the role of placental Fas and Fas ligand gene polymorphisms in the pathogenesis of preeclampsia. The heterogeneous and complex etiology of preeclampsia makes it unrealistic to expect a single nucleotide polymorphism to explain the pathogenesis of this pregnancy complication. This relatively understudied area warrants further investigation.

PP128. Placental Caspase-3 gene polymorphisms is associated with preeclampsia.

INTRODUCTION: Increased placental trophoblastic apoptosis (programmed cell death) was previously reported in pregnancies complicated by preeclampsia. Caspase-3 is one of the key executioners of apoptosis. Caspase are expressed in many tissues including human placental trophoblast and other tissues. Variations in the promoter area of the Caspase genes may modulate apoptotic signaling, contributing to an increased risk of preeclampsia OBJECTIVES: To determine if gene polymorphisms of Caspase 3 proteins differ between patient with and without preeclampsia. METHODS: Forty-three singleton placentas were studied. Twenty-two placentas were with preeclampsia and 21 were normotensive controls. DNA was extracted from placentas using QIAAmp DNA Minikit. Genotyping of Caspase 3 +567 was determined by real-time PCR using the Applied Biosystems Prism 7900 HT SDS machine. Chi-square and Fisher's exact tests were used for statistical analysis. RESULTS: There were no significant differences in maternal age, parity or race between the two groups. Preeclamptic placentas had higher frequency of wild type TT of Caspase-3 SNP (+567) as compared with normotensive controls (59% versus 28.5%). Preeclamptic placentas expressed significantly more genotype of TT of Caspase-3 SNP (+567) than normotensive patients when compared to CC (p=0.02). The alle frequencies of the Caspase SNP (+567) in preeclampstic placentas were 0.77 and 0.23 for T and C, respectively, as compared to 0.52 and 0.48, respectively, in placentas from normotensive pregnancies. CONCLUSION: Immune intolerance of maternal and placental interaction plays an important role in the pathogenesis of preeclampsia. Increased of placental apoptosis was reported in pregnancy complicated with preeclamsia. Our findings indicate placental Caspase 3 (+567) gene polymorphisms is associated with preeclampsia. Altered placental alle frequencies and caspase-3 SNP (+567) in preeclampsia further suggests preeclampsia is a trophoblastic disorder.

Probing the validity of average Hamiltonian theory for spin I=1, 3/2 and 5/2 nuclei by analyzing a simple two-pulse sequence.

In this work, we investigate the accuracy of controlling spin I=1, 3/2 and 5/2 spin systems by average Hamiltonian theory. By way of example, we consider a simple two-pulse echo sequence and compare this perturbation scheme to a numerical solution of the Von Neumann equation. For the different values of I, we examine this precision as a function of the quadrupolar coupling as well as various experimental parameters such as the pulse spacing and pulse width. Experiments and simulations on I=3/2 and I=5/2 spin systems are presented that highlight a spectral artifact introduced due to finite pulse widths as predicted by average Hamiltonian theory. The control of these spin systems by this perturbation scheme is considered by investigating a phase cycling scheme that suppresses these artifacts to zeroth-order of the Magnus expansion.

The role of hyperglycosylated hCG in trophoblast invasion and the prediction of subsequent pre-eclampsia.

OBJECTIVE: Hyperglycosylated hCG (HhCG) is the predominant form of chorionic gonadotrophin in states characterized by aggressive trophoblast invasion such as early pregnancy or choriocarcinoma. Pre-eclampsia may be the result of failed or inadequate trophoblast invasion. We investigated whether low levels of maternal urine HhCG levels would predict subsequent pre-eclampsia. STUDY DESIGN: Mid-trimester urine (14-21 weeks) was collected and frozen from non-hypertensive women undergoing genetic amniocentesis. Inclusion criteria were: normal singleton pregnancies without a prior history of pre-eclampsia, hypertension, diabetes or other vascular disorders. The specimens were subsequently thawed, and HhCG levels standardized to urine creatinine were measured. Maternal charts were reviewed after delivery to determine the development of pre-eclampsia. There were a total of 568 study subjects. RESULTS: Pre-eclampsia developed in 26 (4.6%) women. There was a significant correlation between low urine HhCG and subsequent pre-eclampsia (Mantel-Haenszel test of linear association: Chi-square 10.52, p=0.001). The mean HhCG level (ng/mg creatinine) was significantly greater in normals than in those destined to develop pre-eclampsia: 42.7 versus 20.3, p=0.002 (Mann-Whitney U-test). There was a progressive increase in the risk of subsequent pre-eclampsia as HhCG levels fell: HhCG < or =0.9 MoM RR (95% CI)=1.51 (1.15-1.98) compared with < or =0.1 MoM 10.42 (2.0-54.3). CONCLUSION: Low maternal mid-trimester urine HhCG predicted subsequent pre-eclampsia. This appears to support the view that pre-eclampsia results at least in part from poor trophoblast invasion. Thus, HhCG may play a role in trophoblast invasion and measurement of this in urine identifies women at high risk for developing pre-eclampsia.

No association of vitamin D receptor gene BsmI polymorphisms with calcium oxalate stone formation.

BACKGROUND AND PURPOSE: The formation of urinary stones is reported to be associated with the vitamin D receptor (VDR). As the most frequently seen polymorphism within the VDR gene is BsmI, it has been used as a genetic marker in searching for the cause of urolithiasis. We aimed to evaluate the association between calcium stone disease and the BsmI polymorphisms. MATERIALS AND METHODS: A control group of 90 healthy people and a group of 124 patients with calcium oxalate stones were examined. The polymorphism was detected using polymerase chain reaction (PCR)-based restriction analysis. A PCR product length was determined to be 580 bp (BB) whereas two fragments of 405 bp and 175 bp were determined to be excisable (bb) by BsmI endonuclease. Associations between calcium stone disease and BsmI polymorphisms were evaluated. RESULTS AND CONCLUSIONS: The results revealed no significant difference between normal individuals and stone patients (P = 0.891). The allelic distribution of B and b were similar within both the normal group and the stone patients. Therefore, the BsmI polymorphism of the VDR gene at intron 8 is not a suitable genetic marker for urinary stone disease.

Relation of the estrogen receptor alpha gene microsatellite polymorphism to bone mineral density and the susceptibility to osteoporosis in postmenopausal Chinese women in Taiwan.

OBJECTIVE: Osteoporosis is a common disorder with a strong genetic component. Our aim was to investigate the correlation of the estrogen receptor alpha gene microsatellite polymorphism (TA dinucleotide repeat polymorphism 5' upstream of exon 1) with bone mineral density and their relationship to osteoporosis. METHODS: We determined the estrogen receptor alpha gene microsatellite polymorphism using polymerase chain reaction-based microsatellite analysis in postmenopausal Chinese women in Taiwan. Bone mineral density of the lumbar spine and proximal femur were measured using dual-energy X-ray absorptiometry. RESULTS: The ERalpha genotype was classified into '12' through '27' according to the number of TA dinucleotide repeats they contained, as a 'signpost'. After adjustment for potential confounding factors including age, height, and weight, subjects with genotype 18+ (n=4) had lower bone mineral density values and a 54.5 times greater risk for osteoporosis when compared with subjects with genotype 18- (n=170) at the lumbar spine. This should be interpreted with caution because of the small number of subjects with the unfavorable genotype 18+. According to mean number of TA dinucleotide repeats, women with a high number of repeats (TA > or =20) (n=38) had the lowest bone mineral density and a 6.1 times greater risk for osteoporosis than women with a low number of repeats (TA < or =15) (n=61) at the femoral neck, after adjustment for potential confounding factors such as age, height, and weight. CONCLUSION: The present study suggests that the estrogen receptor alpha gene microsatellite polymorphism may be a candidate genetic marker for risk of osteoporosis in postmenopausal Chinese women in Taiwan.

Amniotic fluid matrix metalloproteinase-8 indicates intra-amniotic infection.

OBJECTIVE: This study was undertaken to determine whether matrix metalloproteinase-8, which is produced by neutrophils, is a useful marker for the detection of intra-amniotic infection. STUDY DESIGN: We performed a case-control study using enzyme-linked immunosorbent assays to detect matrix metalloproteinase-8 in 77 amniotic fluid specimens that were obtained by amniocentesis from women with preterm contractions or preterm labor and intact fetal membranes (n = 66) and from women with preterm premature rupture of membranes (n = 11). RESULTS: Thirty women had culture-proven intra-amniotic infection (cases), 21 of whom had intact membranes. After constructing receiver operating characteristic curves to establish the optimal threshold concentration of matrix metalloproteinase-8 for a positive test result, we detected matrix metalloproteinase-8 in 27 of 30 women with intra-amniotic infection; only 10 of 47 control specimens contained matrix metalloproteinase-8 (P <.001; odds ratio, 33.3; 95% CI, 8.4, 132.7). Matrix metalloproteinase-8 was present in 20 of 21 women with intact membranes and intra-amniotic infection and in only 10 of 45 control subjects (P <.001; odds ratio, 70.0; 95% CI, 8.3, 587.6). Among women with intact membranes, the sensitivity of the assay was 0.95 and the specificity was 0.78. CONCLUSION: Our results indicate that matrix metalloproteinase-8 is highly correlated with intra-amniotic infection and that enzyme-linked immunosorbent assay for matrix metalloproteinase-8 may be a clinically useful test for the diagnosis of intra-amniotic infection in women with preterm contractions and preterm labor.

The association of androgen- and oestrogen-receptor gene polymorphisms with urolithiasis in men.

OBJECTIVE: To evaluate the association of urolithiasis with polymorphic microsatellite (encoding cytosine, adenine, and guanine, CAG) repeats in the exon 1 region of the androgen receptor (AR) gene and thymine/adenine (TA) repeats in the oestrogen receptor (ER). PATIENTS AND METHODS: Patients with urolithiasis (149) and a group of normal controls (102) were examined and compared. The CAG repeats of the AR gene and TA repeats of the ER gene were detected by polymerase chain reaction. The CAG repeats ranged from 171 bp (10 CAG repeats with 141 bp of amplified flanking sequences) to 270 bp (43 CAG repeats). The TA repeats ranged from 160 bp to 194 bp. Associations between calcium oxalate stone disease and the CAG repeats in AR gene and TA repeats in ER gene were then evaluated. The results were classified according to sex and peaks in allelic frequency distribution. RESULTS: There was a significant difference between the male stone patients and the normal controls in the distribution of CAG repeats in the AR gene. Both groups showed a high percentage of 21-repeats in the allelic distribution, at 17 (16%) and 20 (37%) in stone patients and normal controls, respectively. The results indicate that 21-CAG repeats might be related to a lower risk of stone formation in men (P < 0.05). In the ER gene, the peak allelic distribution of TA repeats was 14, showing a significant difference between male stone patients and the normal control subjects (P < 0.01). There were no statistical differences between female stone patients and the control subjects in either the AR or the ER gene. CONCLUSION: Urolithiasis among men appears to be associated with AR gene CAG repeat and ER gene TA repeat polymorphisms, whereas there was no significant association among female stone patients. These sex hormone receptors seem to be related to the higher incidence of stone formation among men.

Serum soluble Fas in the syndrome of hemolysis, elevated liver enzymes, and low platelets.

OBJECTIVE: To assess whether serum levels of soluble Fas and soluble Fas ligand are altered in the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). METHODS: Serum samples from 22 pregnant women diagnosed with HELLP syndrome were compared with sera from 37 healthy women with noncomplicated singleton pregnancies. Serum levels of soluble Fas and soluble Fas ligands were determined by enzyme immunoassay. Student t, chi(2), Pearson's correlation coefficient, and multiple regression tests were used for statistical analyses. RESULTS: Both soluble Fas and soluble Fas ligand were detected in the sera of normal pregnancies as well as in those with HELLP syndrome. The mean serum level of soluble Fas was significantly higher in women with HELLP syndrome than in healthy gravidas (10.75 +/- 0.93 versus 5.81 +/- 0.37 U/mL, P <.001). However, there was no significant difference in mean serum soluble Fas ligand levels of the two groups (0.60 +/- 0.06 compared with 0.50 +/- 0.22 ng/mL, P =.23). In women with HELLP syndrome, there were no significant correlations between serum levels of soluble Fas or soluble Fas ligand with liver transaminases (aspartate and alanine aminotransferase) and platelet count. CONCLUSION: Serum levels of soluble Fas, but not soluble Fas ligand, are significantly higher in women with HELLP syndrome than healthy gravidas. The source of elevated serum levels of soluble Fas in HELLP syndrome remains to be determined.

Monoamniotic twins in a triplet gestation with favorable outcome.

BACKGROUND: Monoamniotic twins in a triplet gestation is a rare combination. Each condition is separately associated with significant perinatal morbidity and mortality. There are no data about the outcome and management of such gestations. CASE: We report a case of monoamniotic twins in a spontaneous dichorionic triplet gestation with a favorable outcome. Transvaginal ultrasound examination at nine weeks confirmed the diagnosis. Close follow-up was established that included continuous fetal monitoring after 30 weeks. At 35 weeks and after confirming fetal lung maturity, elective cesarean delivery was performed resulting in three liveborn female infants. CONCLUSION: Favorable outcome of such a rare coexistence of monoamniotic twins in a triplet gestation is possible. Vigilant fetal monitoring and timed delivery remain the mainstays of management.

Arginine form of p21 gene codon 31 is less prominent in patients with calcium oxalate stone.

The formation of urinary stones is associated with cell death in response to various injuries. P21 (WAF1/CIP1) is a downstream protein of P53 and can arrest the cell cycle at G1/S with resulting cell death. We aimed to investigate the polymorphism of p2 gene codon 31 as the genetic marker in searching for the association of urolithiasis. One hundred and nineteen healthy controls and 95 patients with calcium oxalate stone were examined in this study. The polymorphism was seen from the result of polymerase chain reaction-based restriction analysis. The result revealed significant differences between normal individuals and stone patients (P < 0.05) and the distribution of arginine homozygote in the control group (31.9%) was higher than in the patient group (16.8%). It is concluded that polymorphisms of p21 codon 31 can be a genetic marker for urinary stone disease. Individuals possessing arginine form of p21 codon 31 have less risk of developing calcium stone disease.

Ratio of nuchal thickness to humerus length for Down syndrome detection.

OBJECTIVE: Ultrasonographic biometry markers are now being used clinically to adjust Down syndrome risk. The limitations are that the definitions of "abnormal" measurements used are arbitrary, thus reducing screening performance, and also that patient-specific Down syndrome risks cannot be calculated. We report a new ultrasonographic algorithm that is sensitive for Down syndrome detection and that estimates individual risk. STUDY DESIGN: Overall in fetal populations with Down syndrome the humerus length is decreased, whereas the nuchal thickness is increased relative to that of a normal population. The nuchal thickness/humerus length ratio therefore shows an even greater increase and magnifies the separation between Down syndrome and healthy groups. Prospective data were collected in midtrimester amniocentesis cases. A regression equation for the median nuchal thickness/humerus length ratio based on biparietal partial diameter was generated. The Down syndrome likelihood ratio, or the odds on the basis of the nuchal thickness/humerus length ratio (multiples of the median), was multiplied by the age-related risk to give the posterior Down syndrome risk. Charts for rapid estimation of individual Down syndrome risk on the basis of maternal age and the nuchal thickness/humerus length ratio were constructed. RESULTS: There were 94 cases of Down syndrome and 4700 cases in which the karyotype was normal. The mean (+/-SD) gestational age of the study population was 16.1 +/- 1.6 weeks. Thirty-three fetuses with Down syndrome and 68 karyotypically normal fetuses had gross anomalies. The equation for the expected median nuchal thickness/humerus length ratio was as follows: 10e(1.7163 - 0.0292) x BPD + 0.0003 x BPD2, where BPD is the biparietal diameter. In the overall study population the nuchal thickness/humerus length ratio and maternal age had a 79.8% detection rate at a 22.1% false-positive rate, compared with maternal age plus humerus length (sensitivity, 55.1%) or maternal age plus nuchal thickness (sensitivity, 66.7%) at the same false-positive rate. For women > or =35 years old the values were 80% and 22.0%, respectively. CONCLUSIONS: We report an ultrasonographic biometry algorithm that, in combination with maternal age, detects 79.6% of Down syndrome cases in a high-risk group. Individual Down syndrome risk can be quickly calculated at the bedside and made available to women who desire this information before making a decision on amniocentesis. On the basis of published standards, ultrasonographic biometry as described would be a cost-effective alternative to amniocentesis in this high-risk group.

Serum soluble Fas levels in preeclampsia.

OBJECTIVE: To determine if serum soluble Fas levels are altered in women with preeclampsia. METHODS: Thirty-four pregnant women with preeclampsia and 34 normotensive pregnant women were studied. Subjects were matched as much as possible for demographics. Preeclampsia was defined as proteinuric hypertension. Serum soluble Fas levels were measured by enzyme-linked immunoassay. Two-tailed Student t test, chi(2) test, Pearson correlation coefficients, and analysis of variance with post hoc test were used for statistical analyses. RESULTS: Mean serum soluble Fas levels were significantly higher in preeclamptic than normotensive women (10.59 +/- 0.68 U/mL versus 5.65 +/- 0.35 U/mL, P <.001). CONCLUSION: Elevated serum soluble Fas is associated with preeclampsia. Such elevation might indicate protection of maternal T-lymphocyte apoptosis and consequently lead to the maternal immune intolerance noted in preeclampsia.

Association of the vitamin D receptor gene start codon Fok I polymorphism with calcium oxalate stone disease.

OBJECTIVE: To assess the use of Fok I polymorphism (the most frequent polymorphism, at the start codon of the vitamin D receptor gene, VDR) as a convenient genetic marker in identifying the cause of urolithiasis. PATIENTS, SUBJECTS AND METHODS: A normal control group of 90 healthy subjects and 146 patients with calcium oxalate stones were examined. Using polymerase chain reaction (PCR)-based restriction analysis, the relationship between Fok I polymorphism and urolithiasis was evaluated. An unexcisable length of 265 bp was identified (allele CC) and two fragments (169 bp and 96 bp) identified as excisable lengths (allele TT). RESULTS: There was a statistically significant difference between the groups (chi-square test, P < 0.05) for the genotype of the VDR Fok I start codon polymorphism. The odds ratio (95% confidence interval) for the C allele in those at risk of stone disease was 1.672 (1.149-2.432). CONCLUSIONS: These results suggest that the VDR Fok I start codon polymorphism may be a good candidate for a genetic marker in calcium oxalate stone disease.

Lack of evidence for the association of tumor necrosis factor-alpha gene promoter polymorphism with calcium oxalate stone and bladder cancer patients.

Urinary stone disease and bladder cancer are two of the most commonly seen urologic diseases in Taiwan. Tumor necrosis factor-alpha (TNF-alpha) is one of the cytokines secreted by macrophages and is related to a sequence of events in response to inflammation and cancer formation. We investigated the polymorphism of the TNF-alpha gene promoter -308 as a genetic marker in searching for the association between these two commonly seen urologic diseases. One hundred and fourteen patients with transitional cell carcinoma of the urinary bladder and 103 patients with calcium oxalate stone were compared with 150 healthy controls. The polymorphism was detected by polymerase chain reaction-based restriction analysis (Nco I endonuclease). The results revealed no significant differences between normal individuals and the patients with the two commonly seen urologic diseases (P > 0.05). We concluded that the polymorphism of the TNF-alpha promoter -308 is not a valid genetic marker for these two urologic diseases.