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1.
Rev Med Liege ; 77(3): 153-160, 2022 Mar.
Artículo en Francés | MEDLINE | ID: mdl-35258863

RESUMEN

Medulloblastoma is a cerebellar grade IV tumour according to the WHO classification, mainly seen in children under the age of 15. This cancer can nevertheless occur in adults. We report the case of a 22-year-old patient with a medulloblastoma disseminated in the spine. The patient had a type 1 Arnold-Chiari malformation causing hydrocephalus treated by ventriculoperitoneal shunt. The current condition began with perineal and lower limb hypoesthesia, ataxic gait, erectile dysfunction and urinary incontinence. Subsequently, a predominant paraparesis of the right lower limb appeared. The patient was treated according to the PNET HR+5 protocol combining two courses of conventional chemotherapy followed by two courses of high-dose chemotherapy with autograft recovery. Given the excellent response, a proton therapy was then delivered to the whole cerebrospinal axis with boosts to the primary tumour sites. The case of this young adult patient shows on the one hand an atypical presentation, and on the other hand underlines, in the absence of a specific therapeutic strategy established for adults, the importance of collaboration between the adult and pediatric oncology departments, with management integrating innovations such as proton therapy and molecular typing.


Le médulloblastome est une tumeur cérébelleuse de grade IV selon l'Organisation Mondiale de la Santé, principalement observée chez les enfants de moins de 15 ans. Ce cancer peut néanmoins survenir chez l'adulte. Nous rapportons le cas d'un patient de 22 ans présentant un médulloblastome disséminé au niveau du rachis. Le patient est porteur d'une malformation d'Arnold-Chiari de type 1 provoquant une hydrocéphalie traitée par dérivation ventriculo-péritonéale. L'affection actuelle a débuté par une hypoesthésie du périnée et des membres inférieurs, une démarche ataxique, un trouble érectile et des troubles vésico-sphinctériens. Par la suite est apparue une paraparésie prédominant au membre inférieur droit. Le patient a été traité selon le protocole pédiatrique PNET HR+5 combinant deux cures de chimiothérapie conventionnelle suivies de deux cures de chimiothérapie à haute dose avec rattrapage par autogreffe. Vu l'excellente réponse, une protonthérapie a été administrée sur l'axe cérébrospinal avec surdosages sur les sites primaires de la tumeur. Le cas de ce jeune adulte illustre, d'une part, une présentation atypique et d'autre part, souligne, en l'absence de stratégie thérapeutique spécifique établie pour l'adulte, l'importance de la collaboration entre les services d'Oncologie adulte et pédiatrique, la prise en charge intégrant les innovations telles que la protonthérapie et le typage moléculaire.


Asunto(s)
Neoplasias Cerebelosas , Meduloblastoma , Adulto , Neoplasias Cerebelosas/tratamiento farmacológico , Neoplasias Cerebelosas/patología , Neoplasias Cerebelosas/cirugía , Niño , Humanos , Masculino , Meduloblastoma/tratamiento farmacológico , Meduloblastoma/terapia , Adulto Joven
2.
Front Pharmacol ; 12: 755826, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34658895

RESUMEN

Inhibitory potassium channels of the TREK1/TRAAK family are integrators of multiple stimuli, including temperature, membrane stretch, polyunsaturated fatty acids and pH. How these signals affect the gating of these channels is the subject of intense research. We have previously identified a cytoplasmic domain, pCt, which plays a major role in controlling channel activity. Here, we use pharmacology to show that the effects of pCt, arachidonic acid, and extracellular pH converge to the same gate within the channel. Using a state-dependent inhibitor, fluoxetine, as well as natural and synthetic openers, we provide further evidence that the "up" and "down" conformations identified by crystallography do not correspond to open and closed states of these channels.

3.
J Med Vasc ; 42(3): 133-140, 2017 May.
Artículo en Francés | MEDLINE | ID: mdl-28705401

RESUMEN

OBJECTIVE: Determine how familiar general practitioners (GPs) working in Paris and surrounding areas are with prescriptions for direct oral anticoagulants (DOACs). MATERIAL AND METHOD: A questionnaire sent to 189 GP working in Paris and surrounding areas yielded 100 responses. Data collected included a brief summary of sociodemographic items, comparative knowledge about DOACs and vitamin K antagonists (VKAs), and responses to two clinical situations for DOAC prescriptions (renewal of a first prescription). RESULTS: The majority (65%) of the responding GPs were over 50. The GPs were knowledgeable about data in the literature concerning the following items: patient quality of life (72% considered it improved); adherence (55% suggested it was improved); rules for DOAC prescription (88% knew the set doses; 81% knew biological monitoring does not exist; 38% were aware of potential interactions). They were not knowledgeable about the following points: main sites for bleeding risks are the gut and the brain; 44% thought risk was lowered for gastrointestinal bleeding and concerning brain hemorrhages 26% thought there was a lesser risk while 40% had no opinion; cost (20% thought it was lower). For prescription modalities, 90% of the GPs renewed the DOAC previously prescribed for non-valvular atrial fibrillation while 76% preferred a LMWH-VKA scheme for the first prescription for deep vein thrombosis. CONCLUSION: Without being reticent about DOACs, the GPs questioned in this study recognized the usefulness of these medications for their patients' quality of life but were hesitant to use DOACs as the first intention anticoagulant, undeniably due to lack of experience and knowledge about the lower risk of bleeding. Initial training and continuing education should be strengthened on this point with dedicated workshops.


Asunto(s)
Anticoagulantes/administración & dosificación , Actitud del Personal de Salud , Medicina General , Conocimientos, Actitudes y Práctica en Salud , Pautas de la Práctica en Medicina , Administración Oral , Prescripciones de Medicamentos , Femenino , Encuestas de Atención de la Salud , Humanos , Masculino , Paris
4.
Br J Dermatol ; 177(1): 206-211, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27992062

RESUMEN

BACKGROUND: Leg ulcers (LUs) are a chronic and severe complication of sickle cell disease (SCD). A prospective study in patients with SCD to identify factors associated with complete healing and recurrence of LUs is lacking. OBJECTIVES: To determine clinical and biological factors associated with SCD-LU complete healing and recurrence. METHODS: This prospective, observational cohort study was conducted at two adult SCD referral-centre sites (2009-2015) and included 98 consecutive patients with at least one LU lasting ≥ 2 weeks. The primary end points compared patients with healed vs. nonhealed LUs at week 24, and patients with vs. without recurrence during follow-up. RESULTS: The median (interquartile range) LU area, duration and follow-up were, respectively, 6·2 cm2 (3-12·8), 9 weeks (4-26) and 65·8 weeks (23·8-122·1). At week 24, LUs were healed in 47% of patients, while 49% of LUs recurred. Univariate analyses identified inclusion LU area < 8 cm2 (82% vs. 35%; P < 0·001), inclusion LU duration < 9 weeks (65% vs. 35%; P = 0·0013) and high median fetal haemoglobin level (P = 0·008) as being significantly associated with complete healing at week 24, and low lactate dehydrogenase level (P = 0·038) as being associated with recurrence. Multivariate analyses retained LU area < 8 cm2 (odds ratio 6·73, 95% confidence interval 2·35-19. 31; P < 0·001) and < 9 weeks' duration (OR 3·19, 95% confidence interval 1·16-8·76; P = 0·024) as being independently associated with healing at week 24. Factors independently associated with recurrence could not be identified. CONCLUSIONS: SCD-LU complete healing is independently associated with the clinical characteristics of LUs rather than the clinical or biological characteristics of SCD.


Asunto(s)
Anemia de Células Falciformes/fisiopatología , Úlcera de la Pierna/fisiopatología , Cicatrización de Heridas/fisiología , Adulto , Anemia de Células Falciformes/complicaciones , Vendajes de Compresión , Femenino , Humanos , Úlcera de la Pierna/complicaciones , Úlcera de la Pierna/terapia , Masculino , Pronóstico , Estudios Prospectivos , Recurrencia
5.
Acta Clin Belg ; 70(2): 105-11, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25380026

RESUMEN

OBJECTIVE: To date, only a small number of epidemiological studies on myelofibrosis have been performed. The current study aimed to characterize the myelofibrosis patient population in Belgium according to pre-defined disease parameters (diagnosis, risk categories, hemoglobin <10 g/dl, spleen size, constitutional symptoms, platelet count, myeloblast count), with a view to obtaining a deeper understanding of the proportion of patients that may benefit from the novel myelofibrosis therapeutic strategies. METHODS: A survey was used to collect data on prevalence and disease parameters on all myelofibrosis patients seen at each of 18 participating hematologic centers in 2011. Aggregated data from all centers were used for analysis. Analyses were descriptive and quantitative. RESULTS: A total of 250 patients with myelofibrosis were captured; of these, 136 (54%) were male and 153 (61%) were over 65 years old. One hundred sixty-five (66%) of myelofibrosis patients had primary myelofibrosis and 85 (34%) had secondary myelofibrosis. One hundred ninety-three myelofibrosis patients (77%) had a palpable spleen. About a third of patients (34%) suffered from constitutional symptoms. Two hundred twenty-two (89%) myelofibrosis patients had platelet count ≧50 000/µl and 201 (80%) had platelet count ≧100 000/µl. Of 250 patients, 85 (34%) had a myeloblast count ≧1%. Six (2%) patients had undergone a splenectomy. Thirteen (5·2%) patients had undergone radiotherapy for splenomegaly. CONCLUSIONS: The results of this survey provide insight into the characteristics of the Belgian myelofibrosis population. They also suggest that a large proportion of these patients could stand to benefit from the therapies currently under development.


Asunto(s)
Mielofibrosis Primaria/diagnóstico , Anciano , Bélgica/epidemiología , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Prevalencia , Mielofibrosis Primaria/sangre , Mielofibrosis Primaria/epidemiología
6.
Med Phys ; 41(12): 121711, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25471958

RESUMEN

PURPOSE: A beamlet based direct aperture optimization (DAO) for modulated electron radiotherapy (MERT) using photon multileaf collimator (pMLC) shaped electron fields is developed and investigated. METHODS: The Swiss Monte Carlo Plan (SMCP) allows the calculation of dose distributions for pMLC shaped electron beams. SMCP is interfaced with the Eclipse TPS (Varian Medical Systems, Palo Alto, CA) which can thus be included into the inverse treatment planning process for MERT. This process starts with the import of a CT-scan into Eclipse, the contouring of the target and the organs at risk (OARs), and the choice of the initial electron beam directions. For each electron beam, the number of apertures, their energy, and initial shape are defined. Furthermore, the DAO requires dose-volume constraints for the structures contoured. In order to carry out the DAO efficiently, the initial electron beams are divided into a grid of beamlets. For each of those, the dose distribution is precalculated using a modified electron beam model, resulting in a dose list for each beamlet and energy. Then the DAO is carried out, leading to a set of optimal apertures and corresponding weights. These optimal apertures are now converted into pMLC shaped segments and the dose calculation for each segment is performed. For these dose distributions, a weight optimization process is launched in order to minimize the differences between the dose distribution using the optimal apertures and the pMLC segments. Finally, a deliverable dose distribution for the MERT plan is obtained and loaded back into Eclipse for evaluation. For an idealized water phantom geometry, a MERT treatment plan is created and compared to the plan obtained using a previously developed forward planning strategy. Further, MERT treatment plans for three clinical situations (breast, chest wall, and parotid metastasis of a squamous cell skin carcinoma) are created using the developed inverse planning strategy. The MERT plans are compared to clinical standard treatment plans using photon beams and the differences between the optimal and the deliverable dose distributions are determined. RESULTS: For the idealized water phantom geometry, the inversely optimized MERT plan is able to obtain the same PTV coverage, but with an improved OAR sparing compared to the forwardly optimized plan. Regarding the right-sided breast case, the MERT plan is able to reduce the lung volume receiving more than 30% of the prescribed dose and the mean lung dose compared to the standard plan. However, the standard plan leads to a better homogeneity within the CTV. The results for the left-sided thorax wall are similar but also the dose to the heart is reduced comparing MERT to the standard treatment plan. For the parotid case, MERT leads to lower doses for almost all OARs but to a less homogeneous dose distribution for the PTV when compared to a standard plan. For all cases, the weight optimization successfully minimized the differences between the optimal and the deliverable dose distribution. CONCLUSIONS: A beamlet based DAO using multiple beam angles is implemented and successfully tested for an idealized water phantom geometry and clinical situations.


Asunto(s)
Neoplasias/radioterapia , Radioterapia de Intensidad Modulada/métodos , Fenómenos Biofísicos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/radioterapia , Femenino , Humanos , Método de Montecarlo , Neoplasias/diagnóstico por imagen , Órganos en Riesgo , Neoplasias de la Parótida/diagnóstico por imagen , Neoplasias de la Parótida/radioterapia , Neoplasias de la Parótida/secundario , Fantasmas de Imagen , Fotones/uso terapéutico , Radiografía , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/estadística & datos numéricos , Radioterapia de Alta Energía , Radioterapia de Intensidad Modulada/estadística & datos numéricos , Neoplasias Torácicas/diagnóstico por imagen , Neoplasias Torácicas/radioterapia
7.
J Mal Vasc ; 39(3): 169-77, 2014 May.
Artículo en Francés | MEDLINE | ID: mdl-24679962

RESUMEN

The benefits of anti-vitamin K (AVK) drugs have been acknowledged in several indications. Such indications increasing with increasing age, AVK prescriptions also increases with age. At the same time, conditions involving significant bleeding are common in this elderly population. It is thus essential to recognize the determining factors. This study included all patients taking AVK drugs aged 75 years and older who sought emergency care at the Cochin Hospital from January to December 2011 for significant bleeding. These patients were compared with a cohort of patients aged 75 years or older who were taking AVK drugs and who were admitted to the same unit during the same time period for other reasons. The case-control comparison included demographic data, comorbidity factors, multiple medications, emergency measured INR, and CHA2DS2VASC level. The hemorrhagic risk was evaluated by HEMORR2HAGES and HAS-BLED. A total of 34 patients were studied and compared with 70 case-controls. The Charlson comorbidity index was higher in patients than case-controls (P<0.05), with a much higher hemorrhagic risk for scores ≥ 9 (OR=2.5; P<0.05). Multiple medication was also more predominant in patients (P<0.05). The risk of serious hemorrhage was also higher when the hemorrhagic scores were high, especially for HEMORR2HAGES (P<0.0001) and HAS-BLED (P<0.001). The risk of serious hemorrhage in elderly outpatients taking AVK drugs is related to their higher comorbidity and hemorrhagic levels which need to be evaluated before starting or stopping AVK treatment.


Asunto(s)
Anticoagulantes/efectos adversos , Hemorragia/inducido químicamente , Pacientes Ambulatorios/estadística & datos numéricos , Vitamina K/antagonistas & inhibidores , Warfarina/efectos adversos , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Estudios de Casos y Controles , Comorbilidad , Femenino , Hemorragia/epidemiología , Humanos , Relación Normalizada Internacional , Masculino , Polifarmacia , Factores de Riesgo , Trombofilia/tratamiento farmacológico , Trombofilia/etiología , Warfarina/uso terapéutico
8.
Med Phys ; 41(2): 021714, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24506605

RESUMEN

PURPOSE: Modulated electron radiotherapy (MERT) promises sparing of organs at risk for certain tumor sites. Any implementation of MERT treatment planning requires an accurate beam model. The aim of this work is the development of a beam model which reconstructs electron fields shaped using the Millennium photon multileaf collimator (MLC) (Varian Medical Systems, Inc., Palo Alto, CA) for a Varian linear accelerator (linac). METHODS: This beam model is divided into an analytical part (two photon and two electron sources) and a Monte Carlo (MC) transport through the MLC. For dose calculation purposes the beam model has been coupled with a macro MC dose calculation algorithm. The commissioning process requires a set of measurements and precalculated MC input. The beam model has been commissioned at a source to surface distance of 70 cm for a Clinac 23EX (Varian Medical Systems, Inc., Palo Alto, CA) and a TrueBeam linac (Varian Medical Systems, Inc., Palo Alto, CA). For validation purposes, measured and calculated depth dose curves and dose profiles are compared for four different MLC shaped electron fields and all available energies. Furthermore, a measured two-dimensional dose distribution for patched segments consisting of three 18 MeV segments, three 12 MeV segments, and a 9 MeV segment is compared with corresponding dose calculations. Finally, measured and calculated two-dimensional dose distributions are compared for a circular segment encompassed with a C-shaped segment. RESULTS: For 15 × 34, 5 × 5, and 2 × 2 cm(2) fields differences between water phantom measurements and calculations using the beam model coupled with the macro MC dose calculation algorithm are generally within 2% of the maximal dose value or 2 mm distance to agreement (DTA) for all electron beam energies. For a more complex MLC pattern, differences between measurements and calculations are generally within 3% of the maximal dose value or 3 mm DTA for all electron beam energies. For the two-dimensional dose comparisons, the differences between calculations and measurements are generally within 2% of the maximal dose value or 2 mm DTA. CONCLUSIONS: The results of the dose comparisons suggest that the developed beam model is suitable to accurately reconstruct photon MLC shaped electron beams for a Clinac 23EX and a TrueBeam linac. Hence, in future work the beam model will be utilized to investigate the possibilities of MERT using the photon MLC to shape electron beams.


Asunto(s)
Electrones/uso terapéutico , Modelos Biológicos , Método de Montecarlo , Fotones/uso terapéutico , Algoritmos , Estudios de Factibilidad , Órganos en Riesgo/efectos de la radiación , Dosificación Radioterapéutica , Reproducibilidad de los Resultados
9.
Thromb Res ; 133(6): 1068-73, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24360929

RESUMEN

BACKGROUND: Early diagnosis of immune heparin-induced thrombocytopenia (HIT) is essential to improve clinical outcome but remains challenging. The release of platelet microparticles (PMPs) is considered of major pathophysiological significance. OBJECTIVES: The aim of this study was to evaluate performances of PMP generation assay (PMPGA) compared to clinical outcome to diagnose HIT. The second objective was to compare PMPGA with performances of (14)C-serotonin release assay (SRA) on the same series of patients. METHODS: Sera of 53 HIT-suspected patients were retrospectively incubated with citrated-whole blood from healthy donors with 1IU and 500IU/ml of unfractionated heparin (UH). PMPGA was performed using FACSAria® flow cytometer. The clinical diagnosis was established by two blinded independent investigators analysing in a standardized manner the patient's medical records. Performances of PMPGA and SRA (n=53) were evaluated using ROC curve analysis with clinical outcome as reference. RESULTS: In positive HIT patients, PMPs expressing phosphatidylserine are generated with low UH concentration whereas PMP rate decreases significantly in presence of high UH concentration. Using clinical outcome as reference, sensitivity and specificity of PMPGA reached 88.9% (95% CI: 50.7-99.4) and 100.0% (95% CI: 90.0-100.0). Sensitivity and specificity of (14)C-SRA were 88.9% (95% CI: 50.7-99.4) and 95.5% (95% CI: 83.3-99.2). CONCLUSIONS: PMPGA is a rapid and reliable assay for HIT diagnosis. PMPGA showed good correlation with (14)C-SRA performances and predominately with clinical outcome.


Asunto(s)
Anticoagulantes/efectos adversos , Plaquetas/ultraestructura , Micropartículas Derivadas de Células/metabolismo , Heparina/efectos adversos , Trombocitopenia/sangre , Adulto , Anciano , Anciano de 80 o más Años , Plaquetas/patología , Micropartículas Derivadas de Células/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Heparina/inmunología , Humanos , Masculino , Persona de Mediana Edad , Trombocitopenia/inducido químicamente , Trombocitopenia/inmunología , Adulto Joven
10.
Thromb Res ; 132(3): 352-9, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23803389

RESUMEN

BACKGROUND: Early diagnosis of immune heparin-induced thrombocytopenia (HIT) is challenging. HemosIL® AcuStar HIT and heparin-induced multiple electrode aggregometry (HIMEA) were recently proposed as rapid diagnostic methods. OBJECTIVES: We conducted a study to assess performances of AcuStar HIT-IgG (PF4-H) and AcuStar HIT-Ab (PF4-H). The secondary objective was to compare the performances of the combination of Acustar HIT and HIMEA with standardised clinical diagnosis. METHODS: Sera of 104 suspected HIT patients were retrospectively tested with AcuStar HIT. HIMEA was performed on available sera (n=81). The clinical diagnosis was established by analysing in a standardized manner the patient's medical records. These tests were also compared with PF4-Enhanced®, LTA, and SRA in subsets of patients. Thresholds were determined using ROC curve analysis with clinical outcome as reference. RESULTS: Using the recommended thresholds (1.00AU), the negative predictive value (NPV) of HIT-IgG and HIT-Ab were 100.0% (95% CI: 95.9%-100.0% and 95.7%-100.0%). The positive predictive value (PPV) were 64.3% (95% CI: 35.1%-87.2.2%) and 45.0% (95% CI: 23.2%-68.6%), respectively. Using our thresholds (HIT-IgG: 2.89AU, HIT-Ab: 9.41AU), NPV of HIT-IgG and HIT-Ab were 100.0% (95% CI: 96.0%-100.0% and 96.1%-100.0%). PPV were 75.0% (95% CI: 42.7%-94.5%) and 81.8% (95% CI: 48.3%-97.7%), respectively. Of the 79 patients with a medium-high pretest probability score, 67 were negative using HIT-IgG (PF4-H) test at our thresholds. HIMEA was performed on HIT-IgG positive patients. Using this combination, only one patient on 79 was incorrectly diagnosed. CONCLUSION: Acustar HIT showed good performances to exclude the diagnosis of HIT. Combination with HIMEA improves PPV.


Asunto(s)
Heparina/efectos adversos , Mediciones Luminiscentes/métodos , Agregación Plaquetaria/efectos de los fármacos , Pruebas de Función Plaquetaria/métodos , Trombocitopenia/inducido químicamente , Trombocitopenia/diagnóstico , Adulto , Anciano , Automatización , Estudios de Casos y Controles , Electrodos , Ensayo de Inmunoadsorción Enzimática , Femenino , Heparina/inmunología , Humanos , Mediciones Luminiscentes/instrumentación , Masculino , Persona de Mediana Edad , Agregación Plaquetaria/fisiología , Estudios Retrospectivos , Trombocitopenia/sangre , Trombocitopenia/inmunología
12.
Pharmacogn Mag ; 8(30): 175-80, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22701294

RESUMEN

AIM AND BACKGROUND: A botanical study is conducted to provide a standard diagnostic tool. In order to improve the quality assurance of the secondary tuberized roots of Harpagophytum procumbens, derived extract and phytomedicine, a simple, rapid, and accurate high-performance liquid chromatography (HPLC) method was developed to assess the harpagoside. MATERIAL AND MEHODS: This HPLC assay was performed on a reversedphase C18 column with methanol and water (50/50-V/V) as the mobile phase with a flow rate of 1.5 mL/min and using a monitoring wavelength at 278 nm. RESULTS AND CONCLUSION: This method was successfully applied to quantify these bioactive iridoid in an aqueous extract of H. procumbens and in its related phytomedicine "harpagophyton". The result demonstrated that the quantification of harpagoside, indicating that the quality control of the bioactive ingredient in H. procumbens, derived extract and phytomedicine, is critical to ensure its clinical benefits.

13.
J Pharm Belg ; (1): 8-17, 2012 Mar.
Artículo en Francés | MEDLINE | ID: mdl-22536678

RESUMEN

Atrial fibrillation (AF) is the most frequent cardiac arrhythmia, especially in older people. This condition is associated with an increased risk of stroke, and long-term anticoagulation treatment is therefore needed. Vitamin K antagonists are effective in reducing the risk of stroke but optimal use of these drugs remains difficult. The development of new oral anticoagulant drugs is therefore highly relevant. Dabigatran is an oral direct thrombin inhibitor. Its prodrug, dabigatran etexilate, is marketed under the name of Pradaxa and was initially approved for the prevention of thromboembolic events in major orthopedic surgery. It has been recently approved for stroke prevention in patients with AF. The purpose of this paper is to review--in light of current knowledge--the interests and limits of using dabigatran etexilate in AF. Briefly, dabigatran etexilate is not inferior to warfarin in AF. However many questions remain unanswered, including questions related to the concomitant use of dabigatran etexilate and acetylsalicylic acid, the possible increased risk of myocardial infarction and the need for drug monitoring.


Asunto(s)
Antiarrítmicos/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Bencimidazoles/uso terapéutico , beta-Alanina/análogos & derivados , Anciano , Anticoagulantes/uso terapéutico , Antídotos/uso terapéutico , Ensayos Clínicos como Asunto , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Dabigatrán , Femenino , Humanos , Masculino , Monitoreo Fisiológico , Agregación Plaquetaria/efectos de los fármacos , Accidente Cerebrovascular/prevención & control , Tromboembolia/prevención & control , Warfarina/uso terapéutico , beta-Alanina/uso terapéutico
15.
Phys Rev Lett ; 106(14): 148101, 2011 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-21561223

RESUMEN

Recent tumor growth models are often based on the multiphase mixture framework. Using bifurcation theory techniques, we show that such models can give contour instabilities. Restricting to a simplified but realistic version of such models, with an elastic cell-to-cell interaction and a growth rate dependent on diffusing nutrients, we prove that the tumor cell concentration at the border acts as a control parameter inducing a bifurcation with loss of the circular symmetry. We show that the finite wavelength at threshold has the size of the proliferating peritumoral zone. We apply our predictions to melanoma growth since contour instabilities are crucial for early diagnosis. Given the generality of the equations, other relevant applications can be envisaged for solving problems of tissue growth and remodeling.


Asunto(s)
Modelos Biológicos , Neoplasias/patología , Comunicación Celular , Proliferación Celular , Humanos
16.
Forensic Sci Int ; 160(2-3): 168-72, 2006 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-16229982

RESUMEN

A collaborative study was conducted in France in order to determine the prevalence of cannabinoids, opiates, cocaine metabolites and amphetamines in blood samples from drivers killed in road accidents in 2003 and 2004 and to compare these values with those of a previous study performed during the period 2000-2001 involving 900 drivers. Blood samples were provided from 2003 under 30-year-old drivers, killed in a traffic accident. Drugs of abuse were determined by gas chromatography-mass spectrometry using the same analytical procedures in all the 12 laboratories. The most frequently observed compounds were by far cannabinoids, that tested positive in 39.6% of the total number of samples. Delta9 tetrahydrocannabinol (THC), the most active of the principle constituents in marijuana (cannabis sativa), was detected in the blood of 28.9% drivers and was the single drug of abuse in 80.2% of the positive cases. It was associated with amphetamines in 7.4% and with opiates and cocaine in 1.9 and 4.8%, respectively. Amphetamines were present in 3.1% of the total number of samples, cocaine metabolites in 3.0% and opiates in 3.5%. When comparing these results with those of a previous study performed 3 years before, a significant increase is observed for THC (28.9% versus 16.9%), cocaine metabolites (3.0% versus 0.2%) and amphetamines (3.1% versus 1.4%). This study demonstrates the critical necessity of implementing in France as soon as possible systematical roadside testing for drugs of abuse.


Asunto(s)
Accidentes de Tránsito/mortalidad , Trastornos Relacionados con Sustancias/sangre , Adolescente , Adulto , Anfetaminas/sangre , Cannabinoides/sangre , Cocaína/sangre , Inhibidores de Captación de Dopamina/sangre , Dronabinol/sangre , Femenino , Medicina Legal , Francia/epidemiología , Cromatografía de Gases y Espectrometría de Masas , Alucinógenos/sangre , Humanos , Masculino , Morfina/sangre , Narcóticos/sangre , Detección de Abuso de Sustancias
18.
Urology ; 58(6): 882-6, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11744451

RESUMEN

OBJECTIVES: To evaluate the anatomic and functional results of transperitoneal-transvesical repair of simple and complex vesicovaginal fistulas (VVFs). METHODS: Between 1978 and 1995, 30 VVFs in 28 patients (mean age 44.6 years, range 21 to 80) were treated by way of a transperitoneal-transvesical approach. VVFs were secondary to hysterectomy in 67.8% of cases; 46.7% of VVFs were considered complex fistulas. Fifty percent of the VVFs were retrotrigonal and 40% were trigonal. A flap was interposed in 70% of cases. The vaginal fistula orifice was left open in 66% of cases, and 33% of VVFs required ureteral reimplantation. The mean duration of bladder drainage was 15.8 days (range 6 to 42), and the mean follow-up was 30 months (range 23 days to 14.6 years). The anatomic and functional results were evaluated by physical examination, cystoscopy, and a self-assessment questionnaire. Success was defined as the disappearance of the fistula. RESULTS: The overall success rate was 85% (24 of 28). The success rate was 87.5% for simple VVFs, 71% for complex VVFs, 93% for retrotrigonal VVFs, 66% for cervicotrigonal VVFs, and 80% for fistulas requiring ureteral reimplantation. Postoperative voiding disorders were reported in 38% of patients. CONCLUSIONS: Transperitoneal-transvesical repair of simple and complex VVFs remains the reference treatment for a disease that has become rare in countries with a well-developed healthcare system, but that is disabling and poorly tolerated by patients after the treatment of another disease.


Asunto(s)
Complicaciones Posoperatorias/cirugía , Fístula Vesicovaginal/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Histerectomía/efectos adversos , Persona de Mediana Edad , Peritoneo/cirugía , Vejiga Urinaria/cirugía , Fístula Vesicovaginal/etiología
19.
Phys Rev E Stat Nonlin Soft Matter Phys ; 64(3 Pt 2): 036120, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11580407

RESUMEN

We study by extensive Monte Carlo simulations the effect of random bond dilution on the phase transition of the three-dimensional four-state Potts model that is known to exhibit a strong first-order transition in the pure case. The phase diagram in the dilution-temperature plane is determined from the peaks of the susceptibility for sufficiently large system sizes. In the strongly disordered regime, numerical evidence for softening to a second-order transition induced by randomness is given. Here a large-scale finite-size scaling analysis, made difficult due to strong crossover effects presumably caused by the percolation fixed point, is performed.

20.
Phys Rev Lett ; 86(17): 3883-6, 2001 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-11329348

RESUMEN

In ferromagnetic thin films, the Curie temperature variation with the thickness is always considered as continuous when the thickness is varied from n to n+1 atomic planes. We show that it is not the case for Fe in Fe/Ir superlattices. For an integer number of atomic planes, a unique magnetic transition is observed by susceptibility measurements, whereas two magnetic transitions are observed for fractional numbers of planes. This behavior is attributed to successive transitions of areas with n and n+1 atomic planes, for which the T(c)'s are not the same. Indeed, the magnetic correlation length is presumably shorter than the average size of the terraces. Monte Carlo simulations are performed to support this explanation.

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