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See detailDosages réalisables pour le diagnostic de gestation
Melo de Sousa, Noelita ULg; El Amiri, B.; Sulon, J. et al

in Journées Européennes de la Société Française de Buiatrie 2002 (2002)

Lorsque les signaux embryonnaires de la gestation induisent une modification du côté maternel, une possibilité nouvelle s’ouvre aux chercheurs attentifs au développement de tests pour le diagnostic ou le ... [more ▼]

Lorsque les signaux embryonnaires de la gestation induisent une modification du côté maternel, une possibilité nouvelle s’ouvre aux chercheurs attentifs au développement de tests pour le diagnostic ou le suivi de la gestation. Dans ce chapitre, nous essayerons de passer en revue les différentes molécules dont le dosage ou la mise en évidence a fait l’objet de publications scientifiques en relation avec le diagnostic de la gestation. Dans la mesure du possible, nous envisagerons les différents marqueurs en suivant la chronologie de leur apparition au cours de la gestation, mais ce critère ne prendra pas un caractère absolu car souvent plusieurs molécules se recouvrent, ou encore leur apparition au niveau de placenta précède largement le moment où elles apparaissent dans le sang maternel en quantités mesurables. Nous essayerons également, de connecter chaque molécule avec l’application que son dosage permet dans la clinique vétérinaire. Pour terminer, nous ferons une description rétrospective de quelques cas cliniques bien documentés qui montrent l’importance de l’association du dosage de protéines associées à la gestation et de la progestérone pour arriver à une meilleure compréhension des échecs observés dans le déroulement de la gestation. [less ▲]

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See detailA dose adjustment in patients with rheumatoid arthritis not optimally responding to a standard dose of infliximab of 3 mg/kg every 8 weeks can be effective: a Belgian prospective study
Durez, P.; Van den Bosch, F.; Corluy, L. et al

in Rheumatology (2005), 44(4), 465-468

Objectives. To analyse the effect of a dose increase in patients with severe rheumatoid arthritis (RA) with insufficient clinical response to 3 mg/kg infliximab every 8 weeks. Methods. Patients suffering ... [more ▼]

Objectives. To analyse the effect of a dose increase in patients with severe rheumatoid arthritis (RA) with insufficient clinical response to 3 mg/kg infliximab every 8 weeks. Methods. Patients suffering from active refractory RA despite methotrexate, were treated with i.v. infusions of infliximab (3 mg/kg) on week 0, 2, 6 and every 8 weeks thereafter. Based on the clinical judgement at week 22, patients received a dose increase of 100 mg from week 30 on. The American College of Rheumatology (ACR) core set for disease activity measures was regularly assessed. Results. Five hundred and eleven RA patients were included. At week 22, 61.4, 34 and 14.1% of all patients met ACR 20, ACR 50 and ACR 70 criteria, respectively, and 6.1% of patients were in remission. A low swollen joint count at baseline was correlated with improvement at week 22 for ACR 20 (P < 0.06), ACR 50 (P < 0.06) and ACR 70 (P < 0.005). The change in HAQ score between weeks 0 and 22 was predictive for response at week 54 (P < 0.01). The dose of infliximab was increased by 100 mg in 22% of the patients. Most baseline values of patients requiring dose increase were higher (P <= 0.001) than the baseline values of the remaining patients. Increasing the dose of infliximab by one vial from week 30 on could circumvent the partial loss of response in these patients. Conclusion. Infliximab use in this large out-patient cohort resulted in a significant clinical improvement. A subgroup that partially lost response during the first 22 weeks could regain response by adding 100 mg of infliximab to the subsequent doses. Due to the current study design, however, a regression to the mean like effect could not be ruled out. [less ▲]

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See detailDose-dependent caffeine-induced conditioned locomotion in mice
Pirona, Alexandre; Ferrara, André Onofrio; Tirelli, Ezio ULg

in Behavioural Pharmacology (2001), 12

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See detailDose-dependent effect of experimental Schmallenberg virus infection in sheep
Poskin, A; Martinelle, Ludovic ULg; Mostin, L et al

in Veterinary Journal (in press)

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See detailDose-dependent modulation of choroidal neovascularization by plasminogen activator inhibitor type 1: Implications for clinical trials
Lambert, Vincent ULg; Munaut, Carine ULg; Carmeliet, Peter et al

in Investigative Ophthalmology & Visual Science (2003), 44(6), 2791-2797

PURPOSE. To explain the conflicting reports about the influence of plasminogen activator inhibitor type (PAI-1) on pathologic angiogenesis, such as occurs during the exudative form of age-related macular ... [more ▼]

PURPOSE. To explain the conflicting reports about the influence of plasminogen activator inhibitor type (PAI-1) on pathologic angiogenesis, such as occurs during the exudative form of age-related macular degeneration. METHODS. The expression of PAI-1 mRNA was analyzed in human and murine choroidal neovascularization (CNV) by RTPCR. The influences of increasing doses of recombinant PAI-1 were evaluated by daily intraperitoneal injections in PAI-1-1-and wild-type animals with a model of laser-induced CNV. The double mechanism of action of PAI-1 (proteolytic activity inhibition versus vitronectin binding) was explored by immunohistochemical localization of fibrinogen/fibrin and by injection of recombinant PAI-1 protein defective for vitronectin binding or with adenoviral vectors bearing a mutated binding-deficient PAI-1 gene. RESULTS. PAI-1 expression was present in human CNV and strongly induced in the course of experimental subretinal neovascularization. Daily injections of recombinant PAI-1 proteins in control and PAI-1(-/-) animals demonstrated that PAI-1 could exhibit both pro- and antiangiogenic effects, dependent on the dose. PAI-1 mutants defective for vitronectin binding were used to show that PAI-1 promotes choroidal pathologic angiogenesis merely through its antiproteolytic activity. CONCLUSIONS. These observations may help to reconcile reports with opposite results regarding the effects of PAI-1 on angiogenesis and certainly warn against uncontrolled use of PAL I modulating drugs in clinical trials. [less ▲]

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See detailDose-dependent RNAi-mediated geminivirus resistance in the tropical root crop cassava.
Vanderschuren, Hervé ULg; Alder, Adrian; Zhang, Peng et al

in Plant molecular biology (2009), 70(3), 265-72

Cassava mosaic disease is a major constraint for cassava production in Africa, resulting in significant economic losses. We have engineered transgenic cassava with resistance to African cassava mosaic ... [more ▼]

Cassava mosaic disease is a major constraint for cassava production in Africa, resulting in significant economic losses. We have engineered transgenic cassava with resistance to African cassava mosaic virus (ACMV), by expressing ACMV AC1-homologous hairpin double-strand RNAs. Transgenic cassava lines with high levels of AC1-homologous small RNAs have ACMV immunity with increasing viral load and different inoculation methods. We report a correlation between the expression of the AC1-homologous small RNAs and the ACMV resistance of the transgenic cassava lines. Characterization of the small RNAs revealed that only some of the hairpin-derived small RNAs fall into currently known small interfering RNA classes in plants. The method is scalable to stacking by targeting multiple virus isolates with additional hairpins. [less ▲]

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See detailA Dose-Effect Relationship For Deltaretrovirus-Dependent Leukemogenesis In Sheep
Pomier, Carole; Alcaraz, Maria Teresa Sanchez; Debacq, Christo^phe et al

in Retrovirology (2009), 6

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See detailDose-related bone effects of strontium ranelate in postmenopausal women
Meunier, P. J.; Reginster, Jean-Yves ULg

in Osteoporosis International (2002), 13(S1), 153

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See detailDose-Response and Pharmacokinetic Study with Almitrine Bismesylate after Single Oral Administrations in Copd Patients
Bury, Thierry ULg; Jeannot, J. P.; Ansquer, J. C. et al

in European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology (1989), 2(1), 49-55

To better define the dose-effect relationship and the pharmacokinetics of almitrine, sixteen stable hypoxaemic COPD patients received random single oral administrations of almitrine bismesylate 50, 100 ... [more ▼]

To better define the dose-effect relationship and the pharmacokinetics of almitrine, sixteen stable hypoxaemic COPD patients received random single oral administrations of almitrine bismesylate 50, 100 and 150 mg or placebo at two-week intervals in a double-blind manner. Resting ventilation, arterial blood gases and plasma almitrine levels were measured. No significant changes were seen after placebo administration. Almitrine 50 and 100 mg caused a significant dose-related improvement in arterial oxygen tension (PaO2) in thirteen of the sixteen patients. Almitrine 150 mg caused little if any additional PaO2 increment. PaO2 returned to near basal values after 24 h. Two patients responded to almitrine 100 and 150 mg only, whereas one patient did not respond at all. Mean PaO2 increases in the sixteen patients were 0.9 kPa (7 mmHg), 1.5 kPa (11 mmHg) and 1.6 kPa (12 mmHg) 3 h after 50, 100 and 150 mg, respectively. A significant mean 0.9 kPa (7 mmHg) decrease in arterial carbon dioxide tension (PaCO2) and a l.min-1 increase in ventilation were observed after almitrine 150 mg. Mean maximum almitrine plasma concentration and area under the curve correlated linearly with dose. The relationship between mean PaO2 improvement and mean almitrine plasma level was curvilinear with a flattening of the curve over plasma levels of 150 ng.ml-1. Almitrine plasma half-life was found to be 116-140 h. [less ▲]

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See detailDose-response curve for torasemide in healthy volunteers.
Scheen, André ULg

in Arzneimittel Forschung (1988), 38(1A), 156-9

The safety and diuretic activity of torasemide (1-isopropyl-3- ([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea) were investigated in a phase I single-blind clinical study. After a pretreatment control ... [more ▼]

The safety and diuretic activity of torasemide (1-isopropyl-3- ([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea) were investigated in a phase I single-blind clinical study. After a pretreatment control day on placebo, a single dose of torasemide was administered orally according to an escalating dosage of 2.5, 5, 10 and 20 mg, respectively, in 4 groups of 3 healthy young male volunteers, after an overnight fast and 1 h before breakfast. The peak stimulatory effect on urinary volume was observed within 1 to 2 h and was followed by a gradual decline at the 3rd or 4th h back to or even slightly below the corresponding control values. Thus, the duration of action averaged 3-4 h and only moderate rebound effects were detected. This time-related diuretic activity perfectly fitted with the pharmacokinetics data since torasemide plasma levels peaked at the 1st h after drug administration and thereafter rapidly fell to less than 10% of the maximal plasma concentrations after the 4th h. While 2.5 mg torasemide showed only minor diuretic action, urinary volume and urinary excretion of sodium, chloride and calcium increased linearly with the logarithm of the dose during the first 4 h as well as during the whole 24 h period with 5, 10 and 20 mg torasemide. Conversely, the urinary density and osmolality fell progressively as the dose of torasemide increased. There was a trend towards a moderate decrease in urinary excretion of uric acid which seemed independent of the dose given. Finally, only minimal potassium urinary losses were observed without clear tendency towards an increase with increasing drug doses.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]

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See detailDose-response relationship between plasma oxytocin and ACTH concentrations during oxytocin infusion in normal men
Legros, Jean-Jacques ULg; Chiodera, Paolo; Geenen, Vincent ULg et al

in Journal of Clinical Endocrinology and Metabolism (1984), 58

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See detailA dosimetric selectivity intercomparison of HDR brachytherapy, IMRT and helical tomotherapy in prostate cancer radiotherapy
Hermesse, Johanne ULg; Biver, Sylvie; JANSEN, Nicolas ULg et al

in Strahlentherapie und Onkologie (2009), 185(11), 736-742

Background and Purpose: Dose escalation in order to improve the biochemical control in prostate cancer requires the application of irradiation techniques with high conformality. The dosimetric selectivity ... [more ▼]

Background and Purpose: Dose escalation in order to improve the biochemical control in prostate cancer requires the application of irradiation techniques with high conformality. The dosimetric selectivity of three radiation modalities is compared: high-dose-rate brachytherapy (HDR-BT), intensity-modulated radiation radiotherapy (IMRT), and helical tomotherapy (HT). <br />Patients and Methods: Ten patients with prostate adenocarcinoma treated by a 10-Gy HDR-BT boost after external-beam radiotherapy were investigated. For each patient, HDR-BT, IMRT and HT theoretical treatment plans were realized using common contour sets. A 10-Gy dose was prescribed to the planning target volume (PTV). The PTVs and critical organs’ dose-volume histograms obtained were compared using Student’s t-test. <br />Results: HDR-BT delivers spontaneously higher mean doses to the PTV with smaller cold spots compared to IMRT and HT. 33% of the rectal volume received a mean HDR-BT dose of 3.86 ± 0.3 Gy in comparison with a mean IMRT dose of 6.57 ± 0.68 Gy and a mean HT dose of 5.58 ± 0.71 Gy (p < 0.0001). HDR-BT also enables to better spare the bladder. The hot spots inside the urethra are greater with HDR-BT. The volume of healthy tissue receiving 10% of the prescribed dose is reduced at least by a factor of 8 with HDR-BT (p < 0.0001). <br />Conclusion: HDR-BT offers better conformality in comparison with HT and IMRT and reduces the volume of healthy tissue receiving a low dose. [less ▲]

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See detailA dosimetric study comparing breast radiotherapy planned in the prone versus supine positions and via conformal 3D versus IMRT techniques
Coucke, Philippe ULg

in Belgian Journal of Medical Oncology [=BJMO] (2009), 3(3), 117

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See detailLa dosimétrie vocale : quantification de l’usage vocal chez des enseignants
Remacle, Angélique ULg; Morsomme, Dominique ULg; Simon, Marie ULg et al

Conference (2011, October 17)

La dosimétrie ou accumulation vocale permet d’objectiver le comportement vocal en situation écologique. Différents types d’accumulateurs vocaux existent actuellement sur le marché. Il s’agit d’appareils ... [more ▼]

La dosimétrie ou accumulation vocale permet d’objectiver le comportement vocal en situation écologique. Différents types d’accumulateurs vocaux existent actuellement sur le marché. Il s’agit d’appareils portables qui mesurent la durée de phonation, l’intensité et la fréquence fondamentale moyenne de la voix. Ces données sont extraites plusieurs fois par seconde à l’aide d’un accéléromètre fixé sur le larynx, et relié à un microprocesseur stockant les données recueillies tout au long de la journée. Les données sont ensuite téléchargées sur un ordinateur et analysées à l’aide d’un logiciel prévu à cet effet. Cette étude tente de quantifier la charge vocale au sein d’une population d’enseignants, reconnue comme étant des professionnels de la voix. L’accumulateur utilisé est l’Ambulatory Phonation Monitor, Model 3200 (KayPENTAX, Lincoln Park, NJ). La récolte de données durant 1 semaine de travail chez 23 enseignants nous a permis d’objectiver l’utilisation vocale propre à cette population. [less ▲]

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See detailDosimétrie vocale chez des enseignantes des niveaux maternel et primaire
Remacle, Angélique ULg; Morsomme, Dominique ULg; FINCK, Camille ULg

in Cahiers de l'ASELF (2013), 10(4), 14-29

Objectifs - Cette étude quantifie l’usage vocal professionnel et extra-professionnel chez des enseignantes en différenciant deux niveaux scolaires : le maternel et le primaire. L’objectif est d’identifier ... [more ▼]

Objectifs - Cette étude quantifie l’usage vocal professionnel et extra-professionnel chez des enseignantes en différenciant deux niveaux scolaires : le maternel et le primaire. L’objectif est d’identifier le contexte (professionnel versus extra- professionnel) ainsi que le niveau scolaire (maternel versus primaire) requérant la charge vocale la plus importante. Méthodologie - Le comportement vocal de 21 enseignantes du maternel et de 20 enseignantes du primaire a été accumulé à l’aide d’un dosimètre pendant une semaine de travail (5 jours). Les paramètres analysés sont les suivants : l’intensité vocale, la fréquence fondamentale, la durée de phonation, le nombre de vibrations et la distance parcourue par les plis vocaux. Résultats - Comme attendu, le contexte professionnel est associé à des valeurs significativement plus élevées que le contexte extra-professionnel pour tous les paramètres mesurés. Par ailleurs, la comparaison entre les deux groupes montre des valeurs significativement plus élevées chez les enseignantes du maternel pour le nombre de vibrations et la distance parcourue par les plis vocaux. Conclusions - Le risque de développer des pathologies liées à la charge vocale est principalement associé à l’usage vocal professionnel des enseignantes, et il semble davantage présent chez les institutrices du niveau maternel que chez celles du primaire. [less ▲]

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See detailDosimetry for 6-[18F]Fluoro-L-DOPA in Humans Based on Biodistribution in Mice
Bretin, Florian ULg; Warnock, Geoffrey ULg; Bahri, Mohamed Ali ULg et al

Poster (2012, October)

Aim. The objective of this work was to estimate human dosimetry for 6-[18F]Fluoro-L-DOPA (F-DOPA) from biodistribution in mice, obtained from organ harvesting at different time points and from a hybrid ... [more ▼]

Aim. The objective of this work was to estimate human dosimetry for 6-[18F]Fluoro-L-DOPA (F-DOPA) from biodistribution in mice, obtained from organ harvesting at different time points and from a hybrid method combining dynamic PET followed by organ harvesting. Materials and methods. The tissue distribution of F-DOPA over time was determined in isoflurane-anaesthetized mice. Radioassay was performed on harvested organs at 2, 5, 10, 30, 60 and 120 minutes post administration (n = 5 at each time point). Dynamic PET images were acquired in list-mode with a Siemens FOCUS 120 microPET for 120 minutes after injection and followed by radioassay of harvested organs (n = 4). List-mode data were histogrammed in 6*5s, 6*10s, 3*20s, 5*30s, 5*60s, 8*150s, 6*300s, 6*600s 3D sinograms. Final images were obtained using filtered backprojection with correction for all physical effects except for scatter. Attenuation correction resulted from a pre-injection transmission scan with a cobalt-57 point source. Organs were manually delineated. The organ time-activity-curves (TACs) from both methods were extrapolated from a simulated 35 g standard mouse to a 70 kg standard male human using a technique based on organ to bodyweight ratios. A bladder voiding scenario was used to simulate excretion every 2 h. The absorbed doses in major human organs were calculated using the extrapolated TACs with the commercially available software OLINDA/EXM (Version 1.1). Results. The extrapolated organ activity curves obtained using the harvesting and imaging methods showed a high correlation (r = 0.94 ± 0.05, p < 0.001). However, TACs from PET alone under- or overestimated the activity in individual organs in contrast to TACs obtained using the cross-calibration of the PET data with the activity in post-scan dissected organs. Those organs in the excretion pathways, comprising bladder wall, kidneys and liver, received the highest organ doses. The total body absorbed dose was 0.0118 mGy/MBq for both the imaging based and harvesting based methods. The effective dose was 0.0193 mSv/MBq for the hybrid imaging-harvesting technique and 0.0189 mSv/MBq for the pure harvesting technique. Conclusion. The doses obtained agreed well with the few results available in the literature. The hybrid technique combining dynamic PET scanning followed by organ harvesting appeared to be a good alternative to the gold standard ex vivo radioassay method. It is much faster and minimizes the effect of some weakness of the pure imaging technique, such as partial volume effect. [less ▲]

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See detailDosimetry for 6-[18F]Fluoro-L-DOPA in humans based on in vivo microPET scans and ex vivo tissue distribution in mice
Bretin, Florian ULg; Warnock, Geoffrey ULg; Bahri, Mohamed Ali ULg et al

Poster (2012, September)

Radiation dosimetry of new radiopharmaceuticals generally starts with studies in small animals such as mice and rats. The traditional technique has long been ex vivo measurement of the biodistribution ... [more ▼]

Radiation dosimetry of new radiopharmaceuticals generally starts with studies in small animals such as mice and rats. The traditional technique has long been ex vivo measurement of the biodistribution over time using harvested organs at different times post administration of the radiopharmaceutical. Since this approach requires a significant amount of animals, dynamic microPET studies, where the biodistribution of the tracer over time can be determined in vivo in a single scan, are an invaluable alternative. Due to known imaging artifacts and limitations, such as partial volume effect, a hybrid technique combining harvesting organs (post-scan) and dynamic imaging was introduced to achieve a cross-calibration to account for these limitations. Since 6-[18F]Fluoro-L-DOPA is a widely used PET tracer to study the dopaminergic system in neurology and oncology and there is no sound published dosimetry data, absorbed doses for major organs in humans were estimated using the traditional ex vivo technique and by dynamic microPET imaging in mice, allowing direct comparison of the results from the two techniques. The tissue distribution over time of 6-[18F]Fluoro-L-DOPA was determined by radioassay of harvested organs at 2, 5, 10, 30, 60, 120 minutes post administration (n=5 at each time point) in isoflurane-anaesthetized mice. Dynamic PET images were acquired with a FOCUS 120 microPET for 120 minutes after injection of 6-[18F]Fluoro-L-DOPA followed by radioassay of harvested organs (n=4). A bladder voiding scenario was used to simulate excretion every 2 h. The organ time-activity-curves (TACs) from both methods were extrapolated from a simulated 35 g standard mouse to a 70 kg standard male human using a technique based on organ to bodyweight ratios. The absorbed doses in major human organs were calculated with the commercially available human dosimetry software OLINDA/EXM (Version 1.1) using the extrapolated TACs. The extrapolated organ TACs obtained using the two methods showed a high correlation (average r = 0.94 ± 0.05, p < 0.001). However, TACs from PET alone under- or overestimated the activity in individual organs in contrast to TACs obtained using the cross-calibration of the PET data with the activity in post-scan dissected organs. Those organs in the excretion pathways, comprising bladder wall, kidneys and liver, received the highest organ doses. The total body absorbed dose was 0.0118 mGy/MBq for both the imaging based and harvesting based methods. The effective dose was 0.0193 mSv/MBq for the hybrid imaging-harvesting technique and 0.0189 mSv/MBq for the pure harvesting technique. Scaling errors in the PET TACs are likely caused by quantification errors such as partial volume effects and image artifacts. The use of a hybrid imaging technique to cross-calibrate the TACs improved the accuracy of the imaging-based dosimetry estimates. Therefore the hybrid technique combining dynamic imaging and harvesting organs (post-scan) is a suitable alternative to the gold standard ex vivo radioassay method. It yields comparable results yet reduces significantly the amount of animals needed in the study and can accelerate data acquisition. [less ▲]

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