A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer: a randomized trial.

BACKGROUND: The dose intensity of chemotherapy can be increased to the highest possible level by early administration of multiple and sequential high-dose cycles supported by transfusion with peripheral blood progenitor cells (PBPCs). A randomized trial was performed to test the impact of such dose intensification on the long-term survival of patients with small cell lung cancer (SCLC). METHODS: Patients who had limited or extensive SCLC with no more than two metastatic sites were randomly assigned to high-dose (High, n = 69) or standard-dose (Std, n = 71) chemotherapy with ifosfamide, carboplatin, and etoposide (ICE). High-ICE cycles were supported by transfusion with PBPCs that were collected after two cycles of treatment with epidoxorubicin at 150 mg/m(2), paclitaxel at 175 mg/m(2), and filgrastim. The primary outcome was 3-year survival. Comparisons between response rates and toxic effects within subgroups (limited or extensive disease, liver metastases or no liver metastases, Eastern Cooperative Oncology Group performance status of 0 or 1, normal or abnormal lactate dehydrogenase levels) were also performed. RESULTS: Median relative dose intensity in the High-ICE arm was 293% (range = 174%-392%) of that in the Std-ICE arm. The 3-year survival rates were 18% (95% confidence interval [CI] = 10% to 29%) and 19% (95% CI = 11% to 30%) in the High-ICE and Std-ICE arms, respectively. No differences were observed between the High-ICE and Std-ICE arms in overall response (n = 54 [78%, 95% CI = 67% to 87%] and n = 48 [68%, 95% CI = 55% to 78%], respectively) or complete response (n = 27 [39%, 95% CI = 28% to 52%] and n = 24 [34%, 95% CI = 23% to 46%], respectively). Subgroup analyses showed no benefit for any outcome from High-ICE treatment. Hematologic toxicity was substantial in the Std-ICE arm (grade > or = 3 neutropenia, n = 49 [70%]; anemia, n = 17 [25%]; thrombopenia, n = 17 [25%]), and three patients (4%) died from toxicity. High-ICE treatment was predictably associated with severe myelosuppression, and five patients (8%) died from toxicity. CONCLUSIONS: The long-term outcome of SCLC was not improved by raising the dose intensity of ICE chemotherapy by threefold.

Renal failure after high-dose methotrexate in a child homozygous for MTHFR C677T polymorphism

We report the case of an 11-year-old female treated for mediastinal T-cell lymphoma who presented renal failure following the second cycle of high-dose methotrexate (HDMTX). Because of life threatening plasma methotrexate (MTX) levels, carboxypeptidase G2 (CPDG2) was administered resulting in a dramatic decrease within 1 hr. The patient recovered from renal failure and no other side effects were observed. Homozygosity for the methylentetrahydrofolate reductase (MTHFR) C677T polymorphism diagnosed by molecular genetic analysis was the only explanation for this toxicity.

Dose optimization approach to fast X-ray microtomography of the lung alveoli.

A basic prerequisite for in vivo X-ray imaging of the lung is the exact determination of radiation dose. Achieving resolutions of the order of micrometres may become particularly challenging owing to increased dose, which in the worst case can be lethal for the imaged animal model. A framework for linking image quality to radiation dose in order to optimize experimental parameters with respect to dose reduction is presented. The approach may find application for current and future in vivo studies to facilitate proper experiment planning and radiation risk assessment on the one hand and exploit imaging capabilities on the other.

Status of eye lens radiation dose monitoring in European hospitals.

A questionnaire was developed by the members of WG12 of EURADOS in order to establish an overview of the current status of eye lens radiation dose monitoring in hospitals. The questionnaire was sent to medical physicists and radiation protection officers in hospitals across Europe. Specific topics were addressed in the questionnaire such as: knowledge of the proposed eye lens dose limit; monitoring and dosimetry issues; training and radiation protection measures. The results of the survey highlighted that the new eye lens dose limit can be exceeded in interventional radiology procedures and that eye lens protection is crucial. Personnel should be properly trained in how to use protective equipment in order to keep eye lens doses as low as reasonably achievable. Finally, the results also highlighted the need to improve the design of eye dosemeters in order to ensure satisfactory use by workers.

Randomized controlled trial of olanzapine or chlorpromazine as addition to lithium in the treatment of a first manic episode with psychotic features: an 8-week, flexible dose, single-blind trial

Background: Association of mood stabiliser and antipsychotic medication is indicated in psychotic mania, but specific guidelines for the treatment of a first episode of psychotic mania are needed. Aims: To compare safety and efficacy profiles of chlorpromazine and olanzapine augmentation of lithium treatment in a first episode of psychotic mania. Methods: A total of 83 patients were randomised to either lithium + chlorpromazine or lithium + olanzapine in an 8-week trial. Data was collected on side effects, vital signs and weight modifications, as well as on clinical variables. Results: There were no differences in the safety profiles of both medications, but patients in the olanzapine group were significantly more likely to have reached mania remission criteria after 8 weeks. Mixed effects models repeated measures analysis of variance showed that patients in the olanzapine group reached mania remission significantly earlier than those in the chlorpromazine group. Conclusions: These results suggest that while olanzapine and chlorpromazine have a similar safety profile in a cohort of patients with first episode of psychotic mania, the former has a greater efficacy on manic symptoms. On this basis, it may be a better choice for such conditions.

Efficacy of clarithromycin versus that of clindamycin for single-dose prophylaxis of experimental streptococcal endocarditis.

Clarithromycin is compared with clindamycin for single-dose prophylaxis of streptococcal endocarditis in rats. Human-like kinetics of the two antibiotics prevented endocarditis in animals challenged with both small and large amounts of bacterial inocula. Clarithromycin was marginally superior to clindamycin against small amounts of inocula. Clarithromycin may be considered for endocarditis chemoprophylaxis in human.

La crítica de la verdad en Nietzsche

El objeto del presente trabajo es el analizar la crítica de Nietzsche al concepto de verdad, tratando de identificar aquellos elementos filosóficos fundamentales que le hacen adoptar una de las actitudes más radicales e influyentes del pensamiento contemporáneo.De este modo he elegido los núcleos de su filosofía que ponen en cuestión prácticamente toda la tradición de pensamiento de ccidente.

La lectura crítica en ELE: análisis de la comprensión crítica de los discursos virtuales

Gran parte de la lectura que se realiza en una lengua extranjera es a través de Internet y desde contextos muy distintos a los que han dado origen a los textos. Este trabajo se basa en la convicción de que el éxito en el aprendizaje de una lengua distinta a la materna radica en comprender el sentido que tiene el uso de la lengua en una sociedad determinada, es decir, en poder interpretar el significado –o los significados- que los discursos adquieren en sus contextos. Internet es un nuevo ámbito para la lectura, que multiplica las posibilidades (los textos, los contextos, los autores, etc.) y que introduce también nuevas incógnitas (menos control de calidad de lo publicado, ubicuidad de los discursos, reducción de los índices de contextualización, etc.). Conocer en profundidad las características de la comprensión en la lectura en línea es un reto para todo el que pretenda contribuir a mejorar el aprendizaje de una lengua extranjera.Por ello, este estudio pretende investigar en qué medida algunos estudiantes de ELE -con un conocimiento avanzado de la lengua y que acostumbran a leer en Internet- son capaces de leer de forma crítica en Internet, entendiendo la ideología que subyace a los discursos. Se estudian los procesos de comprensión, y se evalúa y analiza la comprensión de los textos, con el objetivo de obtener datos que puedan contribuir, en un futuro, a mejorar la metodología de enseñanza de la lectura crítica a través de Internet.

La Lectura crítica en los libros de educación secundaria : concepción y tratamiento metodológico

La presente investigación propone comparar y analizar la concepción y la forma cómo abordan la lectura crítica los libros de texto del Ministerio de Educación y las editoriales privadas de educación secundaria en el Perú. El estudio se desarrolla desde la perspectiva de los Nuevos Estudios de Literacidad y la Literacidad crítica, que conciben la lectura como una práctica social situada. La metodología es descriptiva y explorativa; se sustenta en el análisis cuantitativo y cualitativo. El corpus de análisis lo constituyen los textos de lectura y las actividades de comprensión crítica de 4 manuales del Ministerio de Educación y 3 de las editoriales Norma y Santillana. Los resultados demuestran que tanto los objetivos como el tratamiento de los textos de lectura se desarrollan desde la perspectiva psicolingüística y lingüística de la lectura. Leer críticamente significa opinar sobre el texto y la práctica de la literacidad crítica es aún incipiente, porque las actividades siguen concentradas en la comprensión literal del texto y, generalmente, se callan las ideologías y las relaciones de poder. En conclusión, no existen diferencias significativas entre los dos tipos de manuales.

A las dos orillas del barco. Sobre la obra crítica y cinematográfica de Jacques Rivette

El presente trabajo analiza la relación entre crítica y obra cinematográfica enJacques Rivette en base a los postulados románticos recogidos por Walter Benjamin en su ensayo Le concepte de critique esthétique dans le romantisme allemand. Estudia algunas de las ideas y conceptos de su crítica: la noción de puesta en escena, la figura del autor, la responsabilidad moral y la singularidad de la obra fílmica. Analiza su obra cinematográfica, que se sitúa, insistentemente, entre dos esferas; el uso de los géneros como vehículo para reflexionar sobre el cine; y el estrecho vínculo que establece entre obra y crítica. Su cine resulta así un cine que se piensa a sí mismo.

Optimisation des doses en tomographie computérisée pédiatrique [Patient dose optimization in pediatric computerized tomography]

The development of CT applications might become a public health problem if no effort is made on the justification and the optimisation of the examinations. This paper presents some hints to assure that the risk-benefit compromise remains in favour of the patient, especially when one deals with the examinations of young patients. In this context a particular attention has to be made on the justification of the examination. When performing the acquisition one needs to optimise the extension of the volume investigated together with the number of acquisition sequences used. Finally, the use of automatic exposure systems, now available on all the units, and the use of the Diagnostic Reference Levels (DRL) should allow help radiologists to control the exposure of their patients.

Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice.

In vitro studies suggested that sub-millisecond pulses of radiation elicit less genomic instability than continuous, protracted irradiation at the same total dose. To determine the potential of ultrahigh dose-rate irradiation in radiotherapy, we investigated lung fibrogenesis in C57BL/6J mice exposed either to short pulses (≤ 500 ms) of radiation delivered at ultrahigh dose rate (≥ 40 Gy/s, FLASH) or to conventional dose-rate irradiation (≤ 0.03 Gy/s, CONV) in single doses. The growth of human HBCx-12A and HEp-2 tumor xenografts in nude mice and syngeneic TC-1 Luc(+) orthotopic lung tumors in C57BL/6J mice was monitored under similar radiation conditions. CONV (15 Gy) triggered lung fibrosis associated with activation of the TGF-β (transforming growth factor-β) cascade, whereas no complications developed after doses of FLASH below 20 Gy for more than 36 weeks after irradiation. FLASH irradiation also spared normal smooth muscle and epithelial cells from acute radiation-induced apoptosis, which could be reinduced by administration of systemic TNF-α (tumor necrosis factor-α) before irradiation. In contrast, FLASH was as efficient as CONV in the repression of tumor growth. Together, these results suggest that FLASH radiotherapy might allow complete eradication of lung tumors and reduce the occurrence and severity of early and late complications affecting normal tissue.