Helical tomotherapy for the treatment of anal canal cancer: a dosimetric comparison with 3D conformal radiotherapy.

AIMS AND BACKGROUND: The standard treatment of anal canal cancer (ACC) is combined chemotherapy and radiation therapy (RT), which is complex because of the shape of the target volumes and the need to minimize the irradiation of normal pelvic structures. In this study we compared the dosimetric results of helical tomotherapy (HT) plans with traditional 3D conformal RT (3DRT) plans for the treatment of ACC. METHODS AND STUDY DESIGN: Twelve patients (median age 57 years, range 38-83; F/M 8/4) treated with HT and concurrent chemotherapy for locally advanced ACC were selected. All had histologically confirmed squamous-cell carcinoma. A clinical target volume including the tumor and pelvic and inguinal lymph nodes was treated with HT to a total dose of 36 Gy in 1.8-Gy daily fractions. Then a sequential boost of 23.4 Gy in 1.8-Gy daily fractions (total dose 59.4 Gy) was delivered to the tumor and involved nodes. For all 12 patients, 3DRT plans were generated for comparison. Treatment plans were evaluated by means of standard dose-volume histograms. Dose coverage of the planning target volumes (PTVs), homogeneity index (HI), and mean doses to organs at risk (OARs) were compared. RESULTS: The coverage of PTV was comparable between the two treatment plans. HI was better in the HT vs. 3DRT plans (1.25 and 3.57, respectively; p<0.0001). HT plans resulted in better sparing of OARs (p<0.0001). CONCLUSIONS: HT showed superior target dose conformality and significant sparing of pelvic structures compared with 3DRT. Further investigation should determine if these dosimetric improvements will improve clinical outcomes regarding locoregional control, survival, and treatment-related acute and late morbidity.

Image quality in CT: From physical measurements to model observers.

Evaluation of image quality (IQ) in Computed Tomography (CT) is important to ensure that diagnostic questions are correctly answered, whilst keeping radiation dose to the patient as low as is reasonably possible. The assessment of individual aspects of IQ is already a key component of routine quality control of medical x-ray devices. These values together with standard dose indicators can be used to give rise to 'figures of merit' (FOM) to characterise the dose efficiency of the CT scanners operating in certain modes. The demand for clinically relevant IQ characterisation has naturally increased with the development of CT technology (detectors efficiency, image reconstruction and processing), resulting in the adaptation and evolution of assessment methods. The purpose of this review is to present the spectrum of various methods that have been used to characterise image quality in CT: from objective measurements of physical parameters to clinically task-based approaches (i.e. model observer (MO) approach) including pure human observer approach. When combined together with a dose indicator, a generalised dose efficiency index can be explored in a framework of system and patient dose optimisation. We will focus on the IQ methodologies that are required for dealing with standard reconstruction, but also for iterative reconstruction algorithms. With this concept the previously used FOM will be presented with a proposal to update them in order to make them relevant and up to date with technological progress. The MO that objectively assesses IQ for clinically relevant tasks represents the most promising method in terms of radiologist sensitivity performance and therefore of most relevance in the clinical environment.

Objective assessment of low contrast detectability in computed tomography with Channelized Hotelling Observer.

PURPOSE: Iterative algorithms introduce new challenges in the field of image quality assessment. The purpose of this study is to use a mathematical model to evaluate objectively the low contrast detectability in CT. MATERIALS AND METHODS: A QRM 401 phantom containing 5 and 8 mm diameter spheres with a contrast level of 10 and 20 HU was used. The images were acquired at 120 kV with CTDIvol equal to 5, 10, 15, 20 mGy and reconstructed using the filtered back-projection (FBP), adaptive statistical iterative reconstruction 50% (ASIR 50%) and model-based iterative reconstruction (MBIR) algorithms. The model observer used is the Channelized Hotelling Observer (CHO). The channels are dense difference of Gaussian channels (D-DOG). The CHO performances were compared to the outcomes of six human observers having performed four alternative forced choice (4-AFC) tests. RESULTS: For the same CTDIvol level and according to CHO model, the MBIR algorithm gives the higher detectability index. The outcomes of human observers and results of CHO are highly correlated whatever the dose levels, the signals considered and the algorithms used when some noise is added to the CHO model. The Pearson coefficient between the human observers and the CHO is 0.93 for FBP and 0.98 for MBIR. CONCLUSION: The human observers' performances can be predicted by the CHO model. This opens the way for proposing, in parallel to the standard dose report, the level of low contrast detectability expected. The introduction of iterative reconstruction requires such an approach to ensure that dose reduction does not impair diagnostics.

Fosfomycin plus β-Lactams as Synergistic Bactericidal Combinations for Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus aureus.

The urgent need of effective therapies for methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) is a cause of concern. We aimed to ascertain the in vitro and in vivo activity of the older antibiotic fosfomycin combined with different beta-lactams against MRSA and glycopeptide-intermediate-resistant S. aureus (GISA) strains. Time-kill tests with 10 isolates showed that fosfomycin plus imipenem (FOF+IPM) was the most active evaluated combination. In an aortic valve IE model with two strains (MRSA-277H and GISA-ATCC 700788), the following intravenous regimens were compared: fosfomycin (2 g every 8 h [q8h]) plus imipenem (1 g q6h) or ceftriaxone (2 g q12h) (FOF+CRO) and vancomycin at a standard dose (VAN-SD) (1 g q12h) and a high dose (VAN-HD) (1 g q6h). Whereas a significant reduction of MRSA-227H load in the vegetations (veg) was observed with FOF+IPM compared with VAN-SD (0 [interquartile range [IQR], 0 to 1] versus 2 [IQR, 0 to 5.1] log CFU/g veg; P = 0.01), no statistical differences were found with VAN-HD. In addition, FOF+IPM sterilized more vegetations than VAN-SD (11/15 [73%] versus 5/16 [31%]; P = 0.02). The GISA-ATCC 700788 load in the vegetations was significantly lower after FOF+IPM or FOF+CRO treatment than with VAN-SD (2 [IQR, 0 to 2] and 0 [IQR, 0 to 2] versus 6.5 [IQR, 2 to 6.9] log CFU/g veg; P < 0.01). The number of sterilized vegetations after treatment with FOF+CRO was higher than after treatment with VAN-SD or VAN-HD (8/15 [53%] versus 4/20 [20%] or 4/20 [20%]; P = 0.03). To assess the effect of FOF+IPM on penicillin binding protein (PBP) synthesis, molecular studies were performed, with results showing that FOF+IPM treatment significantly decreased PBP1, PBP2 (but not PBP2a), and PBP3 synthesis. These results allow clinicians to consider the use of FOF+IPM or FOF+CRO to treat MRSA or GISA IE.

Componentes da Produção de Forragem em Pastagens dos Capins Tanzânia e Mombaça Adubadas com Quatro Doses de NPK

O trabalho foi conduzido na FCAV-Unesp, em Jaboticabal-SP, para avaliar os efeitos de quatro doses combinadas de NPK sobre os componentes da produção e das perdas de matéria seca (MS) em pastagens dos cultivares Tanzânia e Mombaça de Panicum maximum Jacq., manejadas com 28 dias de descanso e com altura média de 30 cm de resíduo pós-pastejo. As avaliações foram realizadas em parcelas de 96 m² segundo um fatorial 2 (cultivares) x 4 (doses de NPK), em blocos completos ao acaso, com três repetições. As adubações estudadas corresponderam ao decréscimo em 30 % e aos acréscimos em 30 e 60 % de uma dose padrão com 145; 21,6 e 180 kg/ha de N, P2O5 e K2O, respectivamente (referente a 1,2; a 0,08; e a 1,2 % de N, P e K na MS, com produção estimada em 12000 kg/ha). A MS verde (MSV) em pré-pastejo e no resíduo aumentou linearmente com a adubação, com maiores valores obtidos para o cv. Mombaça (9183 e 5227 kg/ha, respectivamente) do que para o cv. Tanzânia (6275 e 3808 kg/ha, respectivamente). A participação de lâminas foliares na MSV em pré-pastejo foi menor no cv. Tanzânia (51 %) do que no cv. Mombaça (54 %). A densidade de perfilhos não variou com a adubação. O aumento do peso de perfilho com a elevação das doses de NPK resultou em maiores produções de MSV. A MS senescida (média de 3108 kg/ha de MS) não diferiu entre cultivares. de modo geral, quanto maior a dose de adubo aplicado, maiores foram a taxa de acúmulo diário de MSV e a MSV perdida por pisoteio. O cv. Mombaça apresentou maior potencial de resposta à adubação do que o cv. Tanzânia, com taxas de lotação de 6,2 e 4,0 UA/ha, respectivamente.

Resposta nutricional do porta-enxerto delimoeiro 'citrumelo' à aplicacão de nitrogênio, fósforo e potássio

The effect of the application of three doses N, P and K on substrates on the nutritional status of root stock of 'Citrumelo' lemon (Citrus paradisi x Poncirus trifoliata) was evaluated. The experiment followed a fully randomized factorial design (3x3) (three nutrients x three doses plus a control) with three replicates. The treatments consisted of D1 = half standard dose, D2 = one standard dose and D3 = twice standard dose, in addition to the control that did not received fertilization at all. At four months after the emergence of the root stock of lemon 'Citrumelo' the plants tissue (leaves) were determined for nutrients analysis to obtain its accumulation. The results showed that plants of lemon 'Citrumelo' 'Swingle' are responsive to the application of N, P and K. The application of nitrogen showed a linear accumulation pattern of N and K, while the applications of phosphorus and potassium provided a quadratic response.

Folha diagnótica para avaliação do estado nutricional do feijoeiro

The bean is a nutrient demanding plant, either due to the small and shallow root system or due to the short cycle. A study with doses of lime and boron was conducted and correlations were made between two types of leaf (+ 1 and + 3) of the bean with the contents of these elements in plants and production, aiming to establish the most appropriate leaf for diagnosis of nutritional status. The experiment was conducted in greenhouse conditions employing bean seeds cv. BRS Talisma. Lime rates considering the saturation of bases (70%), were calculated as zero, half the standard dose, dose to increase V = 70% (default), one and a half and twice the standard dose, while the boron amounts used were: zero, 0.6, 1.2, 1.8 and 2.4 mg B dm(-3). At the time of flowering, diagnostic leaves + 1 and + 3 (mature leaves from the apex) were collected along with sampling of a plant (aerial part) per pot and the measurement of production. Through correlations it was verified that nutrients, calcium, magnesium and boron in the leaf + 3 showed higher correlation coefficients with levels in the plant and production data.

Treatment of pediatric myelodysplastic syndromes and juvenile myelomonocytic leukemia: the Brazilian experience in the past decade

Background: Therapy strategies for myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) vary considerably. Objective: To review the treatment of Brazilian children who were diagnosed with MDS or JMML in the past decade and reported to the Brazilian Cooperative Group on Pediatric Myelodysplastic syndromes (BCG-MDS-PED). Results: of 173 children reported to the BCG-MDS-PED from January 1997 to January 2003 with a suspected diagnosis of MDS or JMML, 91 had the diagnosis confirmed after central review of the bone marrow aspirate and biopsy. Information on previous treatments was available for 78 MDS/JMML patients. Treatment varied from different schedules of low-dose (14%) and standard-dose chemotherapy (50%), granulocyte-colony-stimulating factor (G-CSF 7%), interferon (5%), steroids (2%) and erythropoietin (2%) to allogeneic stem-cell transplantation (SCT) (14%). No survival advantage could be demonstrated based on Hasle's classification or based on treatment. Conclusion: This report reflects the current practice in treating Brazilian children with MDS/JMML without specific Cooperative Group guidelines. Treatment modalities were very heterogeneous. The strategies for implementing a national protocol should consider international guidelines and focus on local experience and available resources. (C) 2004 Elsevier Ltd. All rights reserved.

Methotrexate improves the health-related quality of life of children with juvenile idiopathic arthritis

Objectives: To examine the change in health-related quality of life (HRQOL) and its determinants in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX). Methods: Patients were extracted from the PRINTO clinical trial which aimed to evaluate the efficacy and safety profile of MTX administered in standard, intermediate or higher doses (10, 15 and 30 mg/m2/week respectively). Children with polyarticular-course JIA, who were less than 18 years and had a complete HRQOL assessment were included. Results: A total of 521 children were included. At baseline, patients with JIA showed poorer HRQOL (p<0.01) than healthy children. In 207/412 (50%) and 63 (15%) children, HRQOL values were 2 standard deviations below the mean of healthy controls in the physical and psychosocial summary scale, respectively. After 6 months of treatment with standard dose MTX, there was a statistically significant improvement in all HRQOL health concepts, particularly the physical ones. Similar improvements were observed in those who did not respond to a standard dose of MTX and were subsequently randomised to a higher dose. The presence of marked disability at baseline was associated with a fivefold increased risk of retaining poor physical health after 6 months of active treatment with standard dose MTX. Other less important determinants of retaining poor physical well-being were the baseline level of systemic inflammation, pain intensity and an antinuclear-antibody-negative status. Conclusions: MTX treatment produces a significant improvement across a wide range of HRQOL components, particularly in the physical domains, in patients with JIA.

Caracterização física e química do solo e avaliação do desenvolvimento de plantas de eucalipto em função do espaçamento e da adubação, visando a colheita precoce para utilização em bioenergia

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Resposta sorológica de bezerras da raça Tabapuã recém-vacinadas com amostra B19 de Brucella abortus

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Produção e perdas de forragem em pastagens dos cultivares Tanzânia e Mombaça de Panicum maximum Jacq. adubadas com doses crescentes de NPK

Pós-graduação em Zootecnia - FCAV

Nutrição do porta-enxerto 'Flying Dragon'

Pós-graduação em Agronomia (Produção Vegetal) - FCAV

Nutrição do porta-enxerto 'Flying Dragon'

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Dasatinib Overrides Imatinib Resistance Mediated by the F359I Residue Mutation in Two Patients with Chronic Myeloid Leukemia

Despite the beneficial effects of imatinib mesylate, some patients may either not respond or respond suboptimally. Here, we report two chronic myelogenous leukemia patients; one had a suboptimal response according to European LeukemiaNet criteria (a major molecular response was not achieved after 18 months of standard-dose imatinib therapy) and the other had failure with a standard dose of imatinib. At the time of the suboptimal response in patient 1 and the failure in patient 2, we were able to detect the F359I mutation in the BCR-ABL tyrosine kinase domain using DNA sequencing in both patients. Therefore, it was decided to change the therapeutic regimen to dasatinib at a dose of 100 mg once daily in both patients. This change resulted in the achievement of complete cytogenetic remission in patient 1 after 4 months and a major molecular response within 2 and 3 months in both patients. Detection of the F359I mutation in our two cases likely explains the suboptimal response to imatinib in case 1 and the failure in case 2. This implies that in such cases dasatinib should be considered to effectively suppress the mutated clones. Copyright (C) 2011 S. Karger AG, Basel