Prenatal diagnosis of trisomy 13 on fetal cells obtained from maternal blood after minor enrichment

In a pilot study to establish fetal nucleated red blood cell (NRBC) detection in maternal blood, trisomy 13 was diagnosed by FISH analysis at 11 weeks' gestation. The NRBCs were detected after a single-step ficoll density gradient enrichment. In blood samples taken both before and after CVS, 52 and 80 NRBCs, respectively, were found to be positive for fetal haemoglobin. In 47 per cent of these cells, FISH analysis for X and Y chromosomes confirmed the fetal sex. Moreover, 48 per cent of these NRBCs showed three fluorescent signals for a chromosome 13 probe, which confirmed the diagnosis of trisomy 13, previously detected at CVS karyotyping. This is the first report of non-invasive prenatal diagnosis of trisomy 13, i.e., pre-CVS, in the first trimester. The high number of fetal NRBCs detected indicates a connection with aneuploidy, probably due to early impairment of the feto-maternal barrier.     

The Human Genome Project and the role of genetics in health care

The Human Genome Project, the mapping of our 100,000 genes and the sequencing of all of our DNA, will have major impact on biomedical research and the therapeutic and preventive health care. The tracing of genetic diseases to their molecular causes is rapidly expanding diagnostic and preventive options, while the increased insights into molecular pathways open tremendous perspectives for pharmacological and genetic therapies. The design of animal model systems for the functional study of disease and development of bioinformatics and biostatistics to improve our pattern recognition abilities are greatly accelerating progress. However, the optimal value from the current explosion of 'data mining' possibilities will only be gained when the basic data are made and kept publicly accessible, at the same time preventing the jeopardisation of the protection of intellectual property, arising from downstream inventions. This is one of the goals of HUGO, the international Human Genome Organisation, established 9 years ago to assist coordinating data acquisition and exchange and societal implementation of the genome project. Additional points of major importance in this historic endeavour are the safeguarding of a worldwide balance in the contribution and benefits to countries and population, the prevention of stigmatisation and discrimination of individuals and groups and the maintenance of respect for the priceless diversity of our world's cultures and traditions.     

Internal balloon compression: a method to achieve hemostasis when removing an inadvertently placed pacemaker lead from the subclavian artery

One of the possible complications of subclavian vein puncture is entry into the subclavian artery. If this is not recognized, a pacemaker lead may be placed arterially. Since this may lead to systemic emboli, the pacemaker lead must be removed. This case report describes a patient in whom an atrial lead was inadvertently placed in the ascending aorta, where it had good sensing values but poor atrial capture threshold values. This lead was subsequently removed and hemostasis was achieved with intraarterial balloon compression via the brachial artery.     

Optimal placement of probes for dynamic pressure measurements in large-scale fluidized beds

Pressure data sampled at sufficiently high frequency (typically 20 Hz or higher) can yield much information about the hydrodynamic state of a fluidized bed. Since part of the pressure waves travelling through large (industrial) fluidized beds is only detectable in a limited area of the bed, pressure measurements need to be performed at several positions to cover the whole bed. We examine these local pressure waves (caused by, e.g., passing bubbles or coalescing bubbles) in a 0.80 m i.d. bubbling fluidized bed of Geldart B particles. Experiments and simulations are performed to determine the intensity decrease as local pressure waves propagate from their origin. A new spectral method is applied to determine the degree of coherence for pressure signals measured at two different positions in a fluidized bed. For a superficial gas velocity of 5u_mf, local pressure waves can be detected up to a radial distance of about 0.5 m from their origin; this distance is somewhat lower for lower gas velocities. This means that the radial spacing of pressure probes should not exceed 1 m. For large diameter beds with a bed height below 1.5 m, a set of probes at a single level and at several radial positions is sufficient to observe or monitor the dynamic state of the complete bed; the probes should preferably be placed at a height of 30% to 40% of the total bed height.     

The oxidative coupling of methane and the oxidative dehydrogenation of ethane over a niobium promoted lithium doped magnesium oxide catalyst

The promoting effect of niobium in a Li/MgO catalyst for the oxidative coupling of methane (OCM) and for the oxidative dehydrogenation of ethane (ODHE) has been studied in some detail. It has been found that a Li/Nb/MgO catalyst with 16 wt % niobium showed the highest activity for the C₂ production in the OCM reaction; the activity at 600 °C was ten times that of the Li/MgO catalyst at the same temperature. The Li/Nb/MgO catalyst was also slightly more active for the ODHE reaction than was the Li/MgO catalyst. However, the Li/Nb/MgO catalyst produced considerably more carbon dioxide in the both reactions. Structural investigation of the catalyst showed that the addition of niobium to the Li/MgO catalyst increased the surface area and gave an increase in the lithium content of the calcined catalysts. Two niobium phases, LiNbO₃ and Li₃NbO₄, were formed; it is shown that the first of these probably causes the increased activity. Ageing experiments showed that the activity of the catalyst was lost if the catalyst was used above 720 °C, the melting point of the lithium carbonate phase. The catalyst showed a decrease of surface area after ageing and a sharp decrease of the amount of the two niobium phases. The addition of carbon dioxide to the feed could not prevent the deactivation of the Li/Nb/MgO catalyst.     

Species-specific cutaneous biotransformation of the pesticide propoxur during percutaneous absorption in vitro

Propoxur (2-isopropoxyphenyl N-methylcarbamate) is a pesticide with a wide spectrum of applications, including use in agriculture and greenhouses. Percutaneous absorption and concurrent cutaneous metabolism of propoxur were studied in a two-compartment organ culture model. Nontoxic concentrations of [14C]propoxur were applied topically to skin discs from human, rabbit, and porcine origin. Permeation rates were comparable in human and rabbit skin, while pig skin was found to be twice as permeable. Furthermore, it was demonstrated that skin tissue of all three species had the capacity to metabolize propoxur. Hydrolysis of propoxur yielded 2-isopropoxyphenol (IPP), followed by phase II conjugation reactions. Interestingly, the type of IPP conjugation appeared to be species specific. In porcine skin cultures, glucuronides and sulfates were detected in equal amounts, whereas in human skin only sulfate conjugation was observed. For rabbit skin, glucuronidation was the major route of conjugation, with minor amounts of the sulfate conjugate and an unidentified metabolite. The percentage of propoxur metabolism in rabbit skin was not influenced by the dose in the range of 25-200 micrograms/cm2; in contrast, human skin metabolism was virtually saturated at 100 micrograms/cm2.     

Gas phase hydroformylation of ethylene using organometalic Rh-complexes as heterogeneous catalysts

The heterogeneously catalysed gas phase hydroformylation of ethylene to propionaldehyde was studied over solid RhCl(PPh₃)₃ and RhCl(CO)(PPh₃)₂. At 3 bar and 185 °C, an active phase formed from RhCl(PPh₃)₃ which was different from RhCl(CO)(PPh₃)₂ under the reaction conditions studied. The selectivity of RhCl(PPh₃)₃ to propanal was much better than that of supported Rh-metal. Thus, solid metal-complexes operated in gas phase reactions clearly hold promise as a new class of heterogeneous catalysts.     

Confirmation of clinical diagnosis in requests for prenatal prediction of SMA type I

Fourteen cases of alveolar echinococcosis were examined by computed tomographic (CT) scanning of the liver, including 3 cases before treatment and 11 cases 2.0-7.5 years after long-term continuous albendazole therapy. In 7 cases the hepatic lesions were almost completely calcified and cured, while in 3 cases incomplete calcification of the peripheral margin of the hepatic lesions was observed. CT scanning of the one uncured case and the 3 cases before treatment showed active lesions with heterogeneous hypodense areas in the liver without calcification on the peripheral margin. Long-term continuous albendazole therapy can result in parasitological cure with death of the parasite.     

Large-scale human metabolomics studies: a strategy for data (pre-) processing and validation

A large metabolomics study was performed on 600 plasma samples taken at four time points before and after a single intake of a high fat test meal by obese and lean subjects. All samples were analyzed by a liquid chromatography-mass spectrometry (LC-MS) lipidomic method for metabolic profiling. A pragmatic approach combining several well-established statistical methods was developed for processing this large data set in order to detect small differences in metabolic profiles in combination with a large biological variation. Such metabolomics studies require a careful analytical and statistical protocol. The strategy included data preprocessing, data analysis, and validation of statistical models. After several data preprocessing steps, partial least-squares discriminant analysis (PLS-DA) was used for finding biomarkers. To validate the found biomarkers statistically, the PLS-DA models were validated by means of a permutation test, biomarker models, and noninformative models. Univariate plots of potential biomarkers were used to obtain insight in up- or downregulation. The strategy proposed proved to be applicable for dealing with large-scale human metabolomics studies.