Morphometric Analysis of McCoy Cells Inoculated with Cerebrospinal Fluid from Patients with Rabies

To demonstrate the potential of McCoy cells for the isolation of rabies virus from the cerebrospinal (CSF) fluid of a patient with a diagnosis of rabies, McCoy cells were inoculated with CSF from a patient with a clinical diagnosis of rabies and investigated in terms of morphometric aspect using the JAVA analysis system for the quantification of the increased size of infected cells compared to noninfected cells. The cells were also examined in terms of specific staining for the diagnosis of rabies by the method of Sellers for the observation of intracytoplasmic inclusions and by specific immunofluorescence staining for rabies virus. Infected cells showed changes in cell permeability and morphologic modifications which differed significantly compared to normal cells (P<0.001) when analyzed by the Mann-Whitney and Kruskal-Wallis tests. Intense activity of the endoplasmic reticulum was also observed, as indicated by the presence of intracytoplasmic inclusions visualized by specific staining. The present study demonstrated the isolation of rabies virus from the CSF of a patient with rabies, showing that McCoy cells can be used for the laboratory diagnosis of patients suspected to have rabies.

An approximate solution method for boundary layer flow of a power law fluid over a flat plate

The work in this paper deals with the development of momentum and thermal boundary layers when a power law fluid flows over a flat plate. At the plate we impose either constant temperature, constant flux or a Newton cooling condition. The problem is analysed using similarity solutions, integral momentum and energy equations and an approximation technique which is a form of the Heat Balance Integral Method. The fluid properties are assumed to be independent of temperature, hence the momentum equation uncouples from the thermal problem. We first derive the similarity equations for the velocity and present exact solutions for the case where the power law index n = 2. The similarity solutions are used to validate the new approximation method. This new technique is then applied to the thermal boundary layer, where a similarity solution can only be obtained for the case n = 1.

The borehole-fluid effect in electrical resistivity imaging

Fluid that fills boreholes in crosswell electrical resistivity investigations provides the necessary electrical contact between the electrodes and the rock formation but it is also the source of image artifacts in standard inversions that do not account for the effects of the boreholes. The image distortions can be severe for large resistivity contrasts between the rock formation and borehole fluid and for large borehole diameters. We have carried out 3D finite-element modeling using an unstructured-grid approach to quantify the magnitude of borehole effects for different resistivity contrasts, borehole diameters, and electrode configurations. Relatively common resistivity contrasts of 100:1 and borehole diameters of 10 and 20 cm yielded, for a bipole length of 5 m, apparent resistivity underestimates of approximately 12% and 32% when using AB-MN configurations and apparent resistivity overestimates of approximately 24% and 95% when using AM-BN configurations. Effects are generally more severe at shorter bipole spacings. We report the results obtained by either including or ignoring the boreholes in inversions of 3D field data from a test site in Switzerland, where approximately 10,000 crosswell resistivity-tomography measurements were made across six acquisition planes among four boreholes. Inversions of raw data that ignored the boreholes filled with low-resistivity fluid paradoxically produced high-resistivity artifacts around the boreholes. Including correction factors based on the modeling results fora ID model with and without the boreholes did not markedly improve the images. The only satisfactory approach was to use a 3D inversion code that explicitly incorporated the boreholes in the actual inversion. This new approach yielded an electrical resistivity image that was devoid of artifacts around the boreholes and that correlated well with coincident crosswell radar images.

No Role for Cerebrospinal Fluid Myelin Basic Protein Levels in Patients Treated for Childhood Acute Lymphoblastic Leukemia.

INTRODUCTION: Central nervous system prophylaxis of childhood acute lymphoblastic leukemia has dropped rates of relapses but has been associated with neurotoxicity and imaging abnormalities. Predictors of neurotoxicity are lacking, because of inconsistency between clinical symptoms and imaging. Some have suggested that cerebrospinal fluid myelin basic protein (MBP) levels to be of potential interest. A retrospective analysis of MBP levels in correlation with clinical and radiologic data is presented. MATERIALS AND METHODS: MBP levels obtained at the time of intrathecals, charts, and neuroradiology reports were retrospectively analyzed. Academic achievement data were obtained from phone contacts with patients and families. RESULTS: We retrieved 1248 dosages of MBP in 83 patients, 381 neurologic examinations in 34 patients and 69 neuroradiologic investigations in 27 patients. Fifty-two patients had abnormal MBP levels. Radiologic anomalies were present in 47% of those investigated, 14% of them having school difficulties. Proportions of patients with school difficulties in the groups with abnormal MBP levels but no radiologic anomalies or with no radiologic investigations were 0% and 3%, respectively, which was lower than in the group of patients with normal MBP levels (100%, 22%, and 5%, respectively). DISCUSSION: Notwithstanding the retrospective character of our study, we conclude that there is limited usefulness of systematic dosage of MBP as indicator of treatment-induced neurotoxicity in acute lymphoblastic leukemia patients.

Oligo-Miocene extensional tectonics and fluid flow across the Northern Snake Range detachment system, Nevada

The Northern Snake Range (Nevada) represents a spectacular example of a metamorphic core complex and exposes a complete section from the mylonitic footwall into the hanging wall of a fossil detachment system. Paired geochronological and stable isotopic data of mylonitic quartzite within the detachment footwall reveal that ductile deformation and infiltration of meteoric fluids occurred between 27 and 23 Ma. Ar-40/Ar-39 ages display complex recrystallization-cooling relationships but decrease systematically from 26.9 +/- 0.2 Ma at the top to 21.3 +/- 0.2 Ma at the bottom of footwall mylonite. Hydrogen isotope (delta D) values in white mica are very low (-150 to -145 %) within the top 80-90 m of detachment footwall, in contrast to values obtained from the deeper part of the section where values range from -77 to -64 %, suggesting that time-integrated interaction between rock and meteoric fluid was restricted to the uppermost part of the mylonitic footwall. Pervasive mica-water hydrogen isotope exchange is difficult to reconcile with models of Ar-40 loss during mylonitization solely by volume diffusion. Rather, we interpret the Ar-40/Ar-39 ages of white mica with low-delta D values to date syn-mylonitic hydrogen and argon isotope exchange, and we conclude that the hydrothermal system of the Northern Snake Range was active during late Oligocene (27-23 Ma) and has been exhumed by the combined effects of ductile strain, extensional detachment faulting, and erosion.

Low-pressure, water-assisted anatexis of basic dykes in a contact metamorphic aureole, Fuerteventura (Canary Islands): oxygen isotope evidence for a meteoric fluid origin

Migmatites produced by low-pressure anatexis of basic dykes are found in a contact metamorphic aureole around a pyroxenite-gabbro intrusion (PX2), on Fuerteventura. Dykes outside and inside the aureole record interaction with meteoric water, with low or negative delta O-18 whole-rock values (+0.2 to -3.4 parts per thousand), decreasing towards the contact. Recrystallised plagioclase, diopside, biotite and oxides, from within the aureole, show a similar evolution with lowest delta O-18 values (-2.8, -4.2, - 4.4 and -7.6 parts per thousand, respectively) in the migmatite zone, close to the intrusion. Relict clinopyroxene phenocrysts preserved in all dykes, retain typically magmatic delta O-18 values up to the anatectic zone, where the values are lower and more heterogeneous. Low delta O-18 values, decreasing towards the intrusion, can be ascribed to the advection of meteoric water during magma emplacement, with increasing fluid/rock ratios (higher dyke intensities towards the intrusion acting as fluid-pathways) and higher temperatures promoting increasing exchange during recrystallisation.

Amniotic fluid insulin-like growth factor binding protein 3 concentration as early indicator of fetal growth restriction.

OBJECTIVE: Insulin-like growth factor-I (IGF-I) is an important regulator of fetal growth and its bioavailability depends on insulin-like growth factor binding proteins (IGFBPs). Genes coding for IGF-I and IGFBP3 are polymorphic. We hypothesized that either amniotic fluid protein concentration at the beginning of the second trimester or genotype of one of these two genes could be predictive of abnormal fetal growth. STUDY DESIGN: Amniotic fluid samples (14-18 weeks of pregnancy) from 123 patients with appropriate for gestational age (AGA) fetuses, 39 patients with small for gestational age (SGA) fetuses and 34 patients with large for gestational age (LGA) were analyzed. Protein concentrations were evaluated by ELISA and gene polymorphisms by PCR. RESULTS: Amniotic fluid IGFBP3 concentrations were significantly higher in SGA compared to AGA group (P=0.030), and this was even more significant when adjusted to gestational age at the time of amniocentesis and other covariates (ANCOVA analysis: P=0.009). Genotypic distribution of IGF-I variable number of tandem repeats (VNTR) polymorphism was significantly different in SGA compared to AGA group (P=0.029). 19CA/20CA genotype frequency was threefold decreased in SGA compared to AGA group and the risk of SGA occurrence of this genotype was decreased accordingly: OR=0.289, 95%CI=0.1-0.9, P=0.032. Genotype distribution of IGFBP3(A-202C) polymorphism was similar in all three groups. CONCLUSIONS: High IGFBP3 concentrations in amniotic fluid at the beginning of the second trimester are associated with increased risks of SGA while 19CA/20CA genotype at IGF-I VNTR polymorphism is associated with reduced risks of SGA. Neither IGFBP3 concentrations, nor IGF-I/IGFBP3 polymorphisms are associated with modified risks of LGA.

Registration & Inspection Units 2003 (pdf 620 kb)

Summary of Statistical Results

Prenatally engineered autologous amniotic fluid stem cell-based heart valves in the fetal circulation.

Prenatal heart valve interventions aiming at the early and systematic correction of congenital cardiac malformations represent a promising treatment option in maternal-fetal care. However, definite fetal valve replacements require growing implants adaptive to fetal and postnatal development. The presented study investigates the fetal implantation of prenatally engineered living autologous cell-based heart valves. Autologous amniotic fluid cells (AFCs) were isolated from pregnant sheep between 122 and 128 days of gestation via transuterine sonographic sampling. Stented trileaflet heart valves were fabricated from biodegradable PGA-P4HB composite matrices (n = 9) and seeded with AFCs in vitro. Within the same intervention, tissue engineered heart valves (TEHVs) and unseeded controls were implanted orthotopically into the pulmonary position using an in-utero closed-heart hybrid approach. The transapical valve deployments were successful in all animals with acute survival of 77.8% of fetuses. TEHV in-vivo functionality was assessed using echocardiography as well as angiography. Fetuses were harvested up to 1 week after implantation representing a birth-relevant gestational age. TEHVs showed in vivo functionality with intact valvular integrity and absence of thrombus formation. The presented approach may serve as an experimental basis for future human prenatal cardiac interventions using fully biodegradable autologous cell-based living materials.

Registration & Inspection Units 2002 (pdf 308 kb)

Summary of Statistical Results

Registration & Inspection Units 2001 (pdf 332 kb)

Summary of Statistical Results

Registration & Inspection Units 2000 (pdf 428 kb)

Summary of Statistical Results