Prenatal detection of free sialic acid storage disease: genetic and biochemical studies in nine families

Sialic acid storage disorders, Salla disease (SD) and a severe infantile form of disease (ISSD), are recessively inherited allelic lysosomal storage disorders due to impaired egress of free sialic acid from lysosomes. Fourteen pregnancies at risk of adult-type free sialic acid storage disease, SD, were monitored by sialic acid assays, genetic linkage or mutation detection analyses using chorionic villus samples. Three affected and 12 unaffected fetuses were identified. The first studies were based on the sialic acid assays alone, but the location of the gene enabled the use of genetic linkage analysis and, more recently, the identification of the SLC17A5 gene and disease-causing mutations added yet another possibility for prenatal studies. A missense mutation 115C→T (R39C) is present in 95% of all Finnish SD alleles, providing an easy and reliable means of diagnostic studies. Both molecular and biochemical (sialic acid assay) studies can be used for prenatal diagnosis of free sialic acid storage diseases. Copyright © 2001 John Wiley & Sons, Ltd.     

Potential Approaches to Assess the Infectivity of Hepatitis E Virus in Pork Products: A Review

The zoonotic transmission of hepatitis E, caused by the hepatitis E virus (HEV), is an emerging issue. HEV appears common in pigs (although infected pigs do not show clinical signs), and evidence suggests that a number of hepatitis E cases have been associated with the consumption of undercooked pork meat and products. Little information is available on whether cooking can eliminate HEV, since there is currently no robust method for measuring its infectivity. HEV infectivity can be clearly demonstrated by monitoring for signs of infection (e.g., shedding of virus) in an animal model. However, this approach has several disadvantages, such as lack of reproducibility and unsuitability for performing large numbers of tests, high costs, and not least ethical considerations. Growth in cell culture can unambiguously show that a virus is infectious and has the potential for replication, without the disadvantages of using animals. Large numbers of tests can also be performed, which can make the results more amenable to statistical interpretation. However, no HEV cell culture system has been shown to be applicable to all HEV strains, none has been standardized, and few studies have demonstrated their use for measurement of HEV infectivity in food samples. Nonetheless, cell culture remains the most promising approach, and the main recommendation of this review is that there should be an extensive research effort to develop and validate a cell culture-based method for assessing HEV infectivity in pork products. Systems comprising promising cell lines and HEV strains which can grow well in cell culture should be tested to select an assay for effective and reliable measurement of HEV infectivity over a wide range of virus concentrations. The assay should then be harnessed to a procedure which can extract HEV from pork products, to produce a method suitable for further use. The method can then be used to determine the effect of heat or other elimination processes on HEV in pork meat and products, or to assess whether HEV detected in any surveyed foodstuffs is infectious and therefore poses a risk to public health.     

Antenatal manifestation of congenital pancreatoblastoma in a fetus with Beckwith–Wiedemann syndrome

An Erratum has been published for this article in Prenatal Diagnosis 23(9) 2003, 771 Antenatal detection of an isolated abdominal cyst was found to be a pancreatoblastoma in a female fetus with Beckwith–Wiedemann syndrome. Prenatal and post-natal features and management of this very rare tumour are discussed. Molecular investigation disclosed a mosaic paternal 11p15 uniparental disomy in the tumoral cells. The prognosis of a congenital pancreatoblastoma is good if complete surgical excision is achieved. However, the association with Beckwith–Wiedemann syndrome requires a prolonged follow-up because of the increased risk of developing malignant tumours. Copyright © 2003 John Wiley & Sons, Ltd.     

Can gestational dates routinely derived from very early ultrasound be used to interpret maternal serum alpha-fetoprotein measurements?

This study assesses the reliability of estimating gestational age via crown-rump or gestational sac measurements obtained at 8 weeks' gestation or earlier as part of routine physician office practice. To accomplish this, we studied 88 pregnancies managed at 45 different sites in which both an early first-trimester ultrasonically-derived gestational age estimate and a second-trimester biparietal diameter (BPD) estimate were available. The first-and second-trimester determinations were highly correlated, but the first-trimester determinations were, on average, 0.43 weeks earlier than the second. The first-trimester estimates were satisfactory for use in interpreting maternal serum alpha-fetoprotein (MSAFP) screening measurements, but second-trimester BPD measurements obtained prior to MSAFP screening should be the method of choice for interpreting MSAFP values, due to the increased sensitivity for detecting open spina bifida.     

The psychological effects of false-positive results in prenatal screening for fetal abnormality: A prospective study

The purpose of the study was to describe the impact of false-positive results from initial maternal serum alpha-fetoprotein (MS-AFP) screening. The analyses compared two groups of women, those receiving a negative result (n = 346) and those receiving an initial positive result (n = 26), over four time points—prior to testing, immediately after testing, later in pregnancy, and in the post-partum period. Receiving an abnormal result was associated with high levels of anxiety which were reflected in increased worry about the baby's health and a more negative attitude towards the pregnancy and the baby. Women who had an initial abnormal result were offered a variety of further tests. Those women who went on to have amniocentesis were less worried about their baby's health in the third trimester and also less anxious post-partum than those who did not have amniocentesis. In view of the increasing number of screening tests available, it is necessary to establish whether and how these levels of distress can best be reduced.     

Pseudomosaicism,true mosaicism,and maternal cell contamination in amniotic fluid processed with in situ culture and robotic harvesting

This study was designed to test the usefulness of the common definitions for maternal cell contamination, true mosaicism, and pseudomosaicism for amniotic fluid specimens processed by in situ culture and robotic harvesting. We prospectively studied 4309 consecutive amniotic fluid specimens processed with these methods and found that 0.84 per cent had maternal cell contamination, 0.28 per cent had true mosaicism, and 5.4 per cent had pseudomosaicism. Although the frequencies of maternal cell contamination and true mosaicism were comparable to those in similar published studies, the frequency of pseudomosaicism was more than twice as high as that in previous reports. This finding is most likely not due to the method, but rather to a more accurate estimate of the actual frequency of pseudomosaicism in amniotic fluid cultures than reported heretofore. Follow-up clinical information was available on 72 per cent of the cases. In three cases of true mosaicism involving structural anomalies, the results of cytogenetic follow-up studies on the neonates were normal. None of the pseudomosaic cases involving trisomy 8, 13, 18, or 21; triple X; or monosomy X were associated with newborns who had birth defects.     

Chromosomal abnormalities associated with a single umbilical artery

A single umbilical artery was seen in 10 out of 117 cytogenetically abnormal pregnancies. The abnormal karyotypes found to be associated with a single umbilical artery were trisomy 18 (n = 5), monosomy X (n = 2), triploidy (n = 1), sex chromosome (47,XYY; n = 1) and translocation (46t(X,5)(q13p15); n = 1). With the exception of the translocation case, all cases with a single umbilical artery had anatomical defects which were detectable ultrasonographically. This suggests that a single umbilical artery alone is not an indication for prenatal fetal karyotyping.     

Source identification of personal exposure to fine particulate matter using organic tracers

Personal exposure to fine particulate matter (PM2.5) is due to both indoor and outdoor sources. Contributions of sources to personal exposure can be quite different from those observed at ambient sampling locations. The primary goal of this study was to investigate the effectiveness of using trace organic speciation data to help identify sources influencing PM2.5 exposure concentrations. Sixty-four 24-h PM2.5 samples were obtained on seven different subjects in and around Boulder, CO. The exposure samples were analyzed for PM2.5 mass, elemental and organic carbon, organic tracer compounds, water-soluble metals, ammonia, and nitrate. This study is the first to measure a broad distribution of organic tracer compounds in PM2.5 personal samples. PM2.5 mass exposure concentrations averaged 8.4 μg m^?3. Organic carbon was the dominant constituent of the PM2.5 mass. Forty-four organic species and 19 water-soluble metals were quantifiable in more than half of the samples. Fifty-four organic species and 16 water-soluble metals had measurement signal-to-noise ratios larger than two after blank subtraction.The dataset was analyzed by Principal Component Analysis (PCA) to determine the factors that account for the greatest variance. Eight significant factors were identified; each factor was matched to its likely source based primarily on the marker species that loaded the factor. The results were consistent with the expectation that multiple marker species for the same source loaded the same factor. Meat cooking was an important source of variability. The factor that represents meat cooking was highly correlated with organic carbon concentrations (r = 0.84). The correlation between ambient PM2.5 and PM2.5 exposure was relatively weak (r = 0.15). Time participants spent performing various activities was generally not well correlated with PCA factor scores, likely because activity duration does not measure emissions intensity. The PCA results demonstrate that organic tracers can aid in identifying factors that influence personal exposures to PM2.5.     

A Comparison of Bayesian Methods for Uncertainty Analysis in Hydraulic and Hydrodynamic Modeling

We evaluate and compare the performance of Bayesian Monte Carlo (BMC), Markov chain Monte Carlo (MCMC), and the Generalized Likelihood Uncertainty Estimation (GLUE) for uncertainty analysis in hydraulic and hydrodynamic modeling (HHM) studies. The methods are evaluated in a synthetic 1D wave routing exercise based on the diffusion wave model, and in a multidimensional hydrodynamic study based on the Environmental Fluid Dynamics Code to simulate estuarine circulation processes in Weeks Bay, Alabama. Results show that BMC and MCMC provide similar estimates of uncertainty. The posterior parameter densities computed by both methods are highly consistent, as well as the calibrated parameter estimates and uncertainty bounds. Although some studies suggest that MCMC is more efficient than BMC, our results did not show a clear difference between the performance of the two methods. This seems to be due to the low number of model parameters typically involved in HHM studies, and the use of the same likelihood function. In fact, for these studies, the implementation of BMC results simpler and provides similar results to MCMC. The results of GLUE are, on the other hand, less consistent to the results of BMC and MCMC in both applications. The posterior probability densities tend to be flat and similar to the uniform priors, which can result in calibrated parameter estimates centered in the parametric space.