Phase II study with the combination of gemcitabine and DTIC in patients with advanced soft tissue sarcomas.

PURPOSE: Based on the promising results of a Phase I study with a combination of gemcitabine and DTIC performed in advanced soft tissue sarcoma (ASTS) patients, and due to the limited efficacy of second or third line therapies in those patients, we designed a Phase II study to determine the activity of this new regimen. METHODS: Patients with ASTS, measurable disease, pretreated with chemotherapy, received gemcitabine 1,800 mg/m2 infused over 180 min followed by DTIC 500 mg/m2 (one cycle), every 2 weeks. The pharmacokinetics (PK) of gemcitabine and 2',2'-difluorodeoxyuridine (dFdU), and the accumulation of gemcitabine triphosphate (dFdCTP) by peripheral blood mononuclear cells were studied. The influence of the sequence of administration on those parameters was examined to exclude potential drug interactions. RESULTS: Twenty-six patients received a total of 158 cycles (mean four cycles, range 1-18). Grade 3-4 anemia (23% of patients), granulocytopenia (46%) or thrombocytopenia (12%), and grade 3 increase in AST (18%), ALT (21%), or gamma-glutamyl-transferase (9%) were noted. Response rate in 23 patients was 4% (95% CI: 0-24%), and in 8 of 11 patients stable disease lasted > 6 months. Progression-free rate (PFR) at 3 and 6 months was, respectively, 48 and 28%, and median overall survival 37 weeks. Pooled data from the Phase I and Phase II studies showed clinical benefit in patients with leiomyosarcomas (LMS) (57%) and malignant fibrous histiocytomas (MFH) (33%). The sequence of administration did not influence PK of gemcitabine or dFdU. There was a trend (P = 0.11) toward a lower accumulation of dFdCTP when DTIC preceded gemcitabine. CONCLUSIONS: Although the remission rate was low, PFR figures indicate that this regimen has activity in patients with ASTS. It should be compared with DTIC, or other gemcitabine-containing combinations, in patients with LMS or MFH, to determine whether this combination offers advantages in PFR or in overall activity.

Presencia familiar durante maniobras de reanimación: Estudio en el ámbito extrahospitalario en la Comunidad Autónoma Vasca / Presence of relatives during resuscitation manoeuvres: a study in the extrahospitalary environment in the Basque Autonomous Community

Objetivos: Los objetivos de este estudio son conocer las opiniones y actitudes de los profesionales de los Equipos de Emergencias (EE) de la Comunidad Autónoma Vasca (CAV) con relación a la presencia familiar durante maniobras de reanimación cardiopulmonar (RCP) en ámbito domiciliario, recoger información a través de los mismos de la actitud de la familia y analizar posibles diferencias de opinión según la categoría profesional. Métodos: Encuesta de opinión anónima e individual dirigida a 112 profesionales de Emergencias de la CAV. Resultados: La participación fue del 76,79%. El 60,47% de los encuestados no impiden que la familia presencie la reanimación de su pariente. Los médicos ven más ventajas que inconvenientes a la presencia familiar. Opinan que la familia siente que acompaña a su ser querido (45,46%), que asumen mejor la muerte de su familiar (60,61%) lo que facilita la notificación del fallecimiento (81,82%) y considera que puede haber menos reclamaciones legales (54,55%). El 71,43% del personal de enfermería, piensa que se debe ofertar a los familiares la oportunidad de estar presentes en la RCP de su familiar. El 52% de los técnicos no impiden que la familia presencie la reanimación; y el 44% de estos opinan que impedir o facilitar la presencia familiar no entra dentro de sus funciones. Cuando el familiar es sanitario actúa por lo general, de forma diferente presentándose y manifestando su deseo de presenciar la reanimación y colaborar. Conclusiones: Los profesionales de los EE piensan que los familiares tienen derecho a estar presentes durante las maniobras de RCP, que esa presencia beneficia tanto a la familia como al equipo reanimador; y que, en general la familia no interfiere en su labor. El objetivo inicial de los EE es el paciente a reanimar, pero no podemos descuidar la atención al resto de la familia, permitiendo su presencia, si así lo solicitan, y brindándoles la información precisa, de forma que puedan tomar conciencia y elaborar el duelo de la forma menos traumática posible (AU)

Aim: To assess the opinions and attitudes of the Emergency Team professionals in the Basque Autonomous Community (BAC) regarding (ET) the presence of relatives during at-home cardiopulmonary resuscitation manoeuvres (CPR), to gather from the same sources information about the relatives’ attitude and to analyse possible differences in opinion according to professional category. Methods: Anonymous and individual opinion survey performed on 112 ET professionals in the BAC. Results: The participation rate was 76.79%. Among those professionals completing the survey, 60.47% do not prevent relatives from being present during CPR. Physicians consider that there are more advantages than disadvantages to the presence of relatives. They hold that the family considers they are accompanying and supporting their veloved one (45.46%), that they cope better with their relative’s demise (60.61%) –which renders the notification of death easier (81.82%)–, and that less legal reclamations arise (54.55%). Among the nursing personnel, 71.43% believe the family members should be offered the opportunity to be present during CPR of their relative. As regards the technicians, 52% do not prevent relatives from being present during resuscitation, and 44% consider that preventing or facilitating the presence of relatives is not one of their functions. When the relative is sanitary him(her)self as such and expresses a desire to be present and to help. Conclusiones: The ET professionals consider that relatives have a righg to be present during CPR manoeuvres, that their presence benefits both the family and the resuscitation team, and that generally the relatives do not interfere in their task. The initial target of the ET is the patient to be resuscitated, but we should never put aside the attention to the family, allowing their presence if so requested and provinding the required information (AU)

Hiperhomocisteinemia y lesión vascular / Homocystenemia and vascular lesion

La homocisteína es un metabolismo intermedio de la vía biosintética que convierte la metionina en cisteína, la metionina es un aminoácido esencial aportado de las proteínas de la dieta. Se ha propuesto que niveles plasmáticos elevados de homocisteína se asocian con el desarrollo de lesión vascular, considerándose actualmente a la homocisteinuria como un factor de riesgo independiente para enfermedad arterial coronaria, enfermedad vascular periférica, enfermedad cerebro-vascular y trombosis venosa. Estudios epidemiológicos han mostrado una correlación negativa entre homocisteína y Vit B12 plasmática y una correlación positiva fuerte con la edad, sexo masculino, hábitos tabáquicos, hipertensión arterial, hipercolesterolemia y sedentarismo. Con relación a los mecanismos fisiopatológicos, estos no estan muy claros, sin embargo se cree que la homocisteína induciría el desarrollo de enfermedad a través de la alteración de mecanismos antitrombóticos, caracterizándose por acumulación plaquetaria sustancial y formación de trombos ricos en plaquetas en áreas de injuria endotelial. La hiperhomicisteinemia puede corregirse con la combinación de ácido fólico(5 mg) Vit B6(25mg) y Vit B12(250mcgr). Como conclusión se ha encontrado que las concentraciones elevadas de homocisteína en plasma es un factor de riesgo independiente para enfermedad vascular, no obstante no se conoce si es un efecto directo, por un metabolito, o si funge como cofactor, razón por la cual, estudios prospectivos serán necesarios para explicar el metabolismo de acción

Birefringence measurement in double-clad fiber lasers with large cross section.

We report on birefringence measurements in double-clad fibers with large cross section, doped with neodymium and ytterbium. The experimental results for rectangular double-clad fibers are compared with those for single-clad circular neodymium-doped fibers, taking into account existing models of stress- and geometry-induced birefringence. We demonstrated that the ellipticity of an outer silica cladding has no effect on birefringence in large-area double-clad fibers. The stress-induced birefringence is shown to depend on the ratio between the diameter of an internal silica support and the linear dimensions of the rectangular outer cladding. The stress-distribution pattern is derived to prove the experimental results.