Thread-based microfluidics: Flow patterns in homogeneous and heterogeneous microfiber bundles.

Thread-based microfluidics has recently seen considerable developments in the domain of portable diagnostic systems, smart bandages and tissue engineering. Similarly to paper-based microfluidics, thread-based microfluidics uses the wicking of fibers to move fluids. It has the advantage of confining and guiding the fluid along the yarns in a one, two or three dimensional space. A global approach to the motion of fluids in yarns and fiber bundles has already been reported in the literature based on the Lucas-Washburn-Rideal law. However no detailed investigation of the flow pattern inside the bundle has been conducted, depending on the internal structure of the bundle. Especially when the bundle possesses heterogeneous wetting properties, such as two different wetting regions interior and exterior, different flow patterns may exist. In this work, we perform a theoretical and numerical analysis of the different flow regimes for homogenous and heterogeneous fiber bundles. It is demonstrated that a limited number of fibers is sufficient for thread-based capillary flows, and that a caging of the flow can be achieved by realizing a lyophobic envelope.

On the halt of spontaneous capillary flows in diverging open channels.

Due to their compactness and independence of exterior energy sources, capillary microsystems are increasingly used in many different scientific domains, from biotechnology to medicine and biology, chemistry, energy and space. Obtaining a capillary flow depends on channel geometry and contact angle. A general condition for the establishment of a spontaneous capillary flow in a uniform cross section channel has already been derived from Gibbs free energy. In this work, we consider spontaneous capillary flows (SCF) in diverging open rectangular channels and suspended channels, and we show that they do not flow indefinitely but stop at some location in the channel. In the case of linearly diverging open channels, we derive the expression that determines the location where the flow stops. The theoretical approach is verified by using the Surface Evolver numerical program and is checked by experiments. The approach is extended to sudden enlargements, and it is shown that the enlargements can act as stop and trigger valves.

On the pinning of interfaces on micropillar edges.

Microsystems for biotechnology often make use of pillars to perform the targeted microfluidic functions. In many cases the role of the pillars is to block or maintain fixed an interface between two immiscible fluids. This phenomenon is usually called pinning. The pining principle is used for capillary valves, liquid-liquid extraction devices, etc. It is common to estimate the pinning efficiency by considering mathematically perfect edges. In reality, microfabricated edges always show some smoothness that can be modeled by a small curvature radius. In this work, we investigate the pinning on square, circular, triangular, and diamond-shaped pillars, and analyze the anchoring on the upstream edges (first pinning conditions) and possibly on the downstream edges (second pinning conditions). It is shown that pinning efficiency decreases very quickly with the curvature radius of the pillar edge. It is concluded that the quality of the microfabrication is essential. Especially oxidation of the silicon reduces considerably the pinning efficiency. Moreover, it is shown that square pillars pin better an interface than triangular pillars. For triangular pillars, a pillar angle--angle between two facets--optimal for pinning has been determined that depends on the quality of microfabrication.

Invasive aspergillosis and allogeneic hematopoietic stem cell transplantation in children: a 15-year experience.

Despite progress in diagnosis and treatment, invasive aspergillosis (IA) remains a principal cause of mortality due to infection after allogeneic hematopoietic stem cell transplantation (AHSCT). In order to clarify the course of IA among children receiving an AHSCT before the advent of new drugs such as voriconazole or caspofungin, we retrospectively reviewed the medical records of all proven and probable IA between January 1986 and December 2000. 1) Ten children developed IA after AHSCT, mostly long after transplantation. Overall incidence was 2.7%. Seven of those children experienced 1 or more complications after AHSCT and before IA. Mortality was 90% with a median survival of 23 days (2-90). 2) Five children underwent AHSCT after a previous episode of IA. All patients were treated with systemic antifungal therapy combined with surgery. Median time between IA and AHSCT was 110 days (73-370). Two children were diagnosed with IA relapse after transplantation. One child was cured while the other died of IA and AHSCT complications. AHSCT could be considered even in the setting of previous IA, but established strategies implementing newer less toxic antifungal agents as treatment or prophylaxis in high-risk patients are needed.

A model for the determination of the dimensions of dents for jagged electrodes in electrowetting on dielectric microsystems.

The motion of a droplet from one electrode to the next in electrowetting on dielectric microsystems is not straightforward. Microfabrication imposes a gap separating the electrodes. This hydrophobic gap has the effect of pinning the triple contact line, preventing the motion of the microdrop. To avoid such a drawback, jagged electrodes, i.e., electrodes with crenellated side boundaries have been designed. In this work, an analytical model for dimensioning the size of the dents of the electrodes is derived based on the contact line elasticity theory. This model determines a lower limit for the nondimensional ratio of the length of a dent to its width. The designs of jagged electrodes in the literature have been verified to satisfy the condition, but with very different safety margins.

Shape, size and multiplicity of main-belt asteroids I. Keck Adaptive Optics survey.

This paper presents results from a high spatial resolution survey of 33 main-belt asteroids with diameters >40 km using the Keck II Adaptive Optics (AO) facility. Five of these (45 Eugenia, 87 Sylvia, 107 Camilla, 121 Hermione, 130 Elektra) were confirmed to have satellite. Assuming the same albedo as the primary, these moonlets are relatively small (∼5% of the primary size) suggesting that they are fragments captured after a disruptive collision of a parent body or captured ejecta due to an impact. For each asteroid, we have estimated the minimum size of a moonlet that can positively detected within the Hill sphere of the system by estimating and modeling a 2-σ detection profile: in average on the data set, a moonlet located at 2/100 × R(Hill) (1/4 × R(Hill)) with a diameter larger than 6 km (4 km) would have been unambiguously seen. The apparent size and shape of each asteroid was estimated after deconvolution using a new algorithm called AIDA. The mean diameter for the majority of asteroids is in good agreement with IRAS radiometric measurements, though for asteroids with a D < 200 km, it is underestimated on average by 6-8%. Most asteroids had a size ratio that was very close to those determined by lightcurve measurements. One observation of 104 Klymene suggests it has a bifurcated shape. The bi-lobed shape of 121 Hermione described in Marchis et al. [Marchis, F., Hestroffer, D., Descamps, P., Berthier, J., Laver, C., de Pater, I., 2005c. Icarus 178, 450-464] was confirmed after deconvolution. The ratio of contact binaries in our survey, which is limited to asteroids larger than 40 km, is surprisingly high (∼6%), suggesting that a non-single configuration is common in the main-belt. Several asteroids have been analyzed with lightcurve inversions. We compared lightcurve inversion models for plane-of-sky predictions with the observed images (9 Metis, 52 Europa, 87 Sylvia, 130 Elektra, 192 Nausikaa, and 423 Diotima, 511 Davida). The AO images allowed us to determine a unique photometric mirror pole solution, which is normally ambiguous for asteroids moving close to the plane of the ecliptic (e.g., 192 Nausikaa and 52 Europa). The photometric inversion models agree well with the AO images, thus confirming the validity of both the lightcurve inversion method and the AO image reduction technique.

Rat bite fever caused by Streptobacillus moniliformis in a child: human infection and rat carriage diagnosed by PCR.

A child owning pet rats developed an eruptive fever with blisters, polyarthritis, and spectacular desquamation of the hands. Streptobacillus moniliformis was identified after culture of the child's blister fluid and was detected in rat samples by molecular methods. Such detection in the pet of a human victim of rat bite fever has not been reported previously.

Antileukemic and long-term effects of two regimens with or without TBI in allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia.

Between September 1986 and June 1997, 24 children with high-risk ALL in CR1 were allografted after TAM (fractionated TBI, high-dose Ara-C, and melphalan; n = 10) or BAM protocol (busulfan, high-dose Ara-C, and melphalan; n = 14). The EFS for transplants from sibling donors was 33% with TAM and 62% with BAM (P = 0.148). The probability of acute GvHD was 70% with TAM and 15% with BAM (P = 0.003). Four of 17 evaluable patients relapsed: one after TAM and three after BAM. In all, 46 other children transplanted in CR beyond CR1 were studied for sequelae. Long-term side effects were more frequent in TAM vs BAM. In children with ALL, busulfan may be a good alternative to TBI to improve the quality of life.

In vivo transfection microsystems.

Transfection is currently used to insert molecules into cells. In vivo transfection is mainly performed via viral or chemical transfection. However, electrical transfection is known to be a more efficient way to insert drugs into cells without side effects. In spite of this advantage, not too many devices allow to perform electrotransfection in vivo because of their invasiveness. Here we present a new microfluidic microdevice which is small enough to be inserted into deep region with a minimum of drawbacks. Therapeutic molecules, genes or drugs can be injected into targeted tissues. High voltage electric impulsions can be applied. This device offers the advantage to be a stand alone device with a 500 mum square section. This generic tool can be used for drug delivery, electrotransfection as well as electrostimulation.

Molecular and phylogenetic analyses of 16 novel simian T cell leukemia virus type 1 from Africa: close relationship of STLV-1 from Allenopithecus nigroviridis to HTLV-1 subtype B strains.

A serological survey searching for antibodies reacting with human T-cell leukemia virus type 1 (HTLV-1) antigens was performed on a series of 263 sera/plasma obtained from 34 monkey species or subspecies, originating from different parts of Africa. Among them, 34 samples exhibited a typical HTLV-1 Western blot pattern. Polymerase chain reaction was performed with three primer sets specific either to HTLV-1/STLV-1 or HTLV-2 and encompassing gag, pol, and tax sequences, on genomic DNA from peripheral blood mononuclear cells of 31 animals. The presence of HTLV-1/simian T-cell leukemia virus type 1 (STLV-1) related viruses was determined in the 21 HTLV-1 seropositive animals tested but not in the 10 HTLV-1 seronegative individuals. Proviral DNA sequences from the complete LTR (750 bp) and a portion of the env gene (522 bp) were determined for 16 new STLV-1 strains; some of them originating from species for which no STLV-1 molecular data were available as Allenopithecus nigroviridis and Cercopithecus nictitans. Comparative and phylogenetic analyses revealed that these 16 new sequences belong to five different molecular groups. The A. nigroviridis STLV-1 strains exhibited a very strong nucleotide similarity with HTLV-1 of the subtype B. Furthermore, four novel STLV-1, found in Cercocebus torquatus, C. m. mona, C. nictitans, and Chlorocebus aethipos, were identical to each other and to a previously described Papio anubis STLV-1 strain (PAN 503) originating from the same primate center in Cameroon. Our data extend the range of the African primates who could be permissive and/or harbor naturally STLV-1 and provide new evidences of cross-transmission of African STLV-1 between different monkey species living in the same environment and also of STLV-1 transmissions from some monkeys to humans in Central Africa.

Synthetic peptide strategy for the detection of and discrimination among highly divergent primate lentiviruses.

We developed a simple, rapid, inexpensive, and highly sensitive and specific strategy for the detection and lineage differentiation of primate lentiviruses (PIV-ELISA). It is based on the use of two indirect ELISA methods using synthetic peptides mapping the gp41/36 region (detection component) and the V3 region (differentiation component) of four lentivirus lineages, namely SIVcpz/HIV-1 (groups M, O, N, and SIVcpz-gab), SIVmnd, SIVagm, and SIVsm/SIVmac/HIV-2. This strategy was evaluated with panels of sera originating from both humans and nonhuman primates. The human reference panel consisted of 144 HIV Western blot (WB)-positive sera in which the corresponding virus had been genotyped (HIV-1: 72 group M, 28 group O, and 6 group N; HIV-2: 21 subtype A and 10 subtype B; and 7 HIV-1+2) and 105 HIV WB-negative samples. The nonhuman primate reference panel consisted of 24 sera from monkeys infected by viruses belonging to the four lineages included in the PIV-ELISA strategy (5 chimpanzees, 5 macaques, 8 mandrills, and 6 vervets) and 42 samples from seronegative animals. Additional field evaluation panels consisted of 815 human sera from Gabon, Cameroon, and France and 537 samples from 25 nonhuman primate species. All the samples from the two reference panels were correctly detected and discriminated by PIV-ELISA. In the human field evaluation panel, the gp41/36 component correctly identified all the test samples, with 98% specificity. The V3 component discriminated 206 HIV-1 group M, 98 group O, 12 group M+O, and 128 HIV-2 sera. In the primate field evaluation panel, both gp41/36 and V3 detected and discriminated all the WB-positive samples originating from monkeys infected with SIVcpz, SIVagm-ver, SIVmnd-1, SIVmnd-2, SIVdrl, or SIVsun. These results were confirmed by genotyping in every case. Four SIV-infected red-capped mangabeys (confirmed by PCR) were correctly identified by gp41/36, but only two reacted with the V3 peptides in the absence of a specific SIVrcm V3 peptide. Addition of a V3 SIVrcm peptide discriminated all the SIVrcm-positive samples. Fourteen Papio papio samples were positive for SIVsm gp 36 and by WB, but negative by PCR, whereas three Papio cynocephalus samples were positive by gp41/36 but indeterminate by WB and negative by PCR. This combined ELISA system is thus highly sensitive and specific for antibodies directed against HIV and SIV. In addition, the V3-based serotyping results always agreed with genotyping results. This method should prove useful for studies of lentivirus prevalence and diversity in human and nonhuman primates, and may also have the potential to detect previously undescribed SIVs.

Assessment of acyclovir intraindividual pharmacokinetic variability during continuous hemofiltration, continuous hemodiafiltration, and continuous hemodialysis.

The use of intravenous acyclovir can be particularly complicated in pediatric patients with evolving renal impairment, because of intraindividual pharmacokinetic variability linked to the patient's clinical condition. The objective of this study was to use therapeutic drug monitoring data to assess acyclovir intraindividual pharmacokinetic variability during several types of renal replacement therapy. Bayesian adaptive control of acyclovir dosage regimen was performed in a pediatric patient with bone marrow transplant who developed severe renal impairment. Acyclovir pharmacokinetic parameter values corresponding to the different techniques and periods of renal replacement therapy were estimated using USCPACK PC Clinical Programs and therapeutic drug monitoring data. Results showed a wide intraindividual pharmacokinetic variability during CAVH, CAVHDF, and CVVHD, reflecting not only the performance of each dialysis technique but also the difficulty in making use of each one. The acyclovir elimination rate constant was higher during CVVHD compared to CAVH or CAVHDF. Bayesian method appears to be valuable in assessing intraindividual pharmacokinetic variability, as it allows the clinician to deal with sparse routine patient data.

Fat in the heart. A feature unique to the human species? Observational reflections on an unsolved problem.

Fat that is well demarcated from underlying muscle is found on the right ventricular free wall and around epicardial coronary vessels. Fat is not present in the left ventricle in normal subjects. In right ventricular dysplasia, fat and fibrosis may massively displace right ventricular myocardial tissue. It is frequently associated with some clusters of fat and fibrosis in the left ventricle. Adipocytes may be also found within fibrous tissue. In this situation it may be associated with inflammatory cellular infiltrates in both ventricles and this is called metaplastic fat. All these findings may be seen and sometimes are associated to a variable degree in the same myocardial specimen. However, fat may be interspersed with right ventricular myocardial fibres but without fibrosis or signs of inflammation. This situation is observed in more than half of the normal hearts and represents an over-looked pathologic condition only observed in the human species. The term "fat dissociation syndrome" is proposed to identify this condition. This new understanding of right ventricular myocardial structure which may be investigated by MRI may have important clinical consequences.

Simian immunodeficiency virus replicates to high levels in sooty mangabeys without inducing disease.

A serologic survey of primates living in a French zoo allowed identification of three cases of infection with simian immunodeficiency virus in sooty mangabeys (Cercocebus atys) (SIVsm). Viral isolates, which were designated SIVsmFr66, SIVsmFr74, and SIVsmFr85, were obtained after short-term culture of mangabey lymphoid cells. Phylogenetic analysis of gag and env sequences amplified directly from mangabey tissues showed that the three SIVsmFr were genetically close and that they constituted a new subtype within the diverse SIVsm-SIVmac-human immunodeficiency virus type 2 (HIV-2) group. We could reconstruct the transmission events that likely occurred in 1986 between the three animals and evaluate the divergence of SIVsmFr sequences since transmission. The estimated rate of mutation fixation was 6 x 10(-3) substitutions per site per year, which was as high as the rate found for SIVmac infection in macaques. These data indicated that SIVsmFr replicated at a high rate in mangabeys, despite the nonpathogenic character of infection in this host. The viral load evaluated by competitive PCR reached 20,000 viral DNA copies per 10(6) lymph node cells. In addition, productively infected cells were readily detected in mangabey lymphoid tissues by in situ hybridization. The amounts of viral RNA in plasma ranged from 10(5) to 10(7) copies per ml. The cell-associated and plasma viral loads were as high as those seen in susceptible hosts (humans or macaques) during the asymptomatic stage of HIV or SIVmac infections. Thus, the lack of pathogenicity of SIVsm for its natural host cannot be explained by limited viral replication or by tight containment of viral production.

Sequence conservation of microsatellites between Bos taurus (cattle), Capra hircus (goat) and related species. Examples of use in parentage testing and phylogeny analysis.

A panel of 70 bovine microsatellites was tested for amplification from goat DNA. Forty-three could be successfully amplified by PCR, 20 of which were tested for polymorphism. Three were applied for parentage testing in goat families and their exclusion probability evaluated. Fourteen were cloned and sequenced from goat DNA, and goat and bovine sequences were compared to evaluate interspecific conservation. Correlation between the structure of the dinucleotide repeat and the number of alleles was studied and indicated that interruption(s) in the repeat could explain the difference in the levels of polymorphism between the two species. This study provides a valuable in vivo clue to the mechanism generating polymorphism in microsatellites. Sequence conservation was also observed for several microsatellites with two wild species of Bovidae, Nilgaï (Boselaphus tragocamelus) and Himalayan Tur (Capra cylindricornis), and with one species of Cervidae, the fallow deer (Cervus dama). This study showed that an estimated 40 per cent of the microsatellites isolated from cattle will prove useful to study the caprine genome and to characterize economically important genetic loci in this species. Moreover, bovine microsatellites were shown to constitute very useful tools for the study of genetic diversity of the Artiodactyla.

[Tetraparesis in an infant after prolonged administration of pancuronium]. / Tétraparésie chez un nourrisson après administration prolongée de pancuronium.

Long-term administration of pancuronium for ventilatory support of adults with ARDS may result in severe tetraparesis, with areflexia and atrophy of distal muscles. This adverse effect occurs rarely in paediatric intensive care units. We describe a case of tetraparesis after prolonged pancuronium infusion in a 9-month-old girl who experienced a severe bronchopneumonia caused by para-influenza virus, requiring endotracheal intubation and mechanical ventilation. To decrease chest wall rigidity, pancuronium was administered over 11 days, with a total dose of approximately 120 mg of pancuronium bromide. The day after discontinuation of the muscle relaxant she had a severe tetraplegia with areflexia, but normal head movements. Electromyography showed a normal neuromuscular transmission. She recovered from tetraplegia three months later. Other causes of peripheral neuropathy were eliminated. Electroencephalograms and head CT-scans were normal. The recovery pattern observed in our patient corresponded to the process of regeneration seen after axonal degeneration. It is suggested that these neuromuscular complications were caused by prolonged high-dosage pancuronium treatment, associated with corticosteroid and aminoglycoside administration.

[A rare cause of hyponatremia during introductory treatment of acute lymphoblastic leukemia in an infant: inappropriate secretion of atrial natriuretic factor?]. / Une cause rare d'hyponatrémie lors du traitement d'induction d'une leucémie aiguë lymphoblastique chez un nourrisson: la sécrétion inappropriée de facteur atrial natriurétique?

BACKGROUND: --Hyponatremia is frequently seen during the treatment of acute lymphoblastic leukemia: its causes are numerous. This work aims to present a case in whom hyponatremia was possibly due to an increased secretion of atrial natriuretic factor. CASE REPORT: --A 3 week-old baby was admitted because of malignant hemopathy. A diagnosis of acute lymphoblastic leukemia was rapidly made and the patient was firstly given alkaline diuresis, urate-oxidase and corticosteroids. Vincristine and daunorubicin were associated one week later. Insertion of a central intravenous line in the right subclavicular artery failed so that this catheter was finally inserted into the left jugular vein. Natremia was 126 mmol/l at that time and dramatically decreased within 24 hours to 109 mmol/l without net changes in water and electrolytic input. At that time, sodium urinary excretion was 6 mmol/kg/day (diuresis: 420 mlF/day). There was no hemodynamic changes, nor digestive or cardiac manifestations. Ultrasonography showed that the left superior cava vein drained into the right cardiac atrium. The catheter was withdrawn and the patient was given sodium supplementation permitting complete and definitive cure of hyponatremia within 2 days. CONCLUSIONS: --All usual causes of hyponatremia having been ruled out in this patient, we postulate that hyponatremia was due to direct stimulation of atrial natriuretic peptide through an increase in atrial pressure secondary to the catheter insertion near the cardiac atrium.