Perfusion and diffusion MRI of glioblastoma progression in a four-year prospective temozolomide clinical trial

RESUME BUT Cette étude a été menée sur le suivi de patients traités pour un glioblastome nouvellement diagnostiqué. Son objectif a été de déterminer l'impact des séquences de perfusion et de diffusion en imagerie par résonance magnétique (IRM). Un intérêt particulier a été porté au potentiel de ces nouvelles techniques d'imagerie dans l'anticipation de la progression de la maladie. En effet, l'intervalle de temps libre de progression est une mesure alternative de pronostic fréquemment utilisée. MATERIEL ET METHODE L'étude a porté sur 41 patients participant à un essai clinique de phase II de traitement par temozolomide. Leur suivi radiologique a comporté un examen IRM dans les 21 à 28 jours après radiochimiothérapie et tous les 2 mois par la suite. L'évaluation des images s'est faite sur la base de l'évaluation de l'effet de masse ainsi que de la mesure de la taille de la lésion sur les images suivantes : T1 avec produit de contraste, T2, diffusion, perfusion. Afin de déterminer la date de progression de la maladie, les critères classiques de variation de taille adjoints aux critères cliniques habituels ont été utilisés. RESULAT 311 examens IRM ont été revus. Au moment de la progression (32 patients), une régression multivariée selon Cox a permis de déterminer deux paramètres de survie : diamètre maximal en T1 (p>0.02) et variation de taille en T2 (p<0.05). L'impact de la perfusion et de la diffusion n'a pas été démontré de manière statistiquement significative. CONCLUSION Les techniques de perfusion et de diffusion ne peuvent pas être utilisées pour anticiper la progression tumorale. Alors que la prise de décision au niveau thérapeutique est critique au moment de la progression de la maladie, l'IRM classique en T1 et en T2 reste la méthode d'imagerie de choix. De manière plus spécifique, une prise de contraste en T1 supérieure à 3 cm dans son plus grand diamètre associée à un hypersignal T2 en augmentation forment un marqueur de mauvais pronostic.

In vivo study of an injectable poly(acrylonitrile)-based hydrogel paste as a bulking agent for the treatment of urinary incontinence.

Urinary incontinence can be treated by endoscopic injection of bulking agents, however, no optimal therapeutic effect has been achieved upon this treatment yet. In the present study, the development of a injectable poly(acrylonitrile) hydrogel paste is described, and its efficacy and histological behavior, once injected into the submucosal space of the minipig bladder, are evaluated. A device was developed to mix poly(acrylonitrile) hydrogel powder with glycerin, used as carrier, prior to injection into the submucosal space of the bladder. Several paste deposits, depending on the size of the bladder, were injected per animal. The implants were harvested at days 7, 14, 21, 28, 84 and 168 and analyzed morphologically and by histology. The persistence of the implants was demonstrated. However, at later time points the implants were split up and surrounded by granulomatous tissue, which was gradually replaced by histiocytes and adipocytes. Transitory focal urothelial metaplasia was observed only at day 7 and moderate foreign body reaction was detected predominantly between the second and fifth week. This study demonstrated the feasibility to develop an injectable paste of poly(acrylonitrile) hydrogel thought to provide the expected bulking effect, necessary for the treatment of urinary incontinence.

ORGANIC PHOSPHORUS FRACTIONS IN SOIL FERTILIZED WITH CATTLE MANURE

Inorganic phosphorus (Pi) usually controls the P availability in tropical soils, but the contribution of organic P (Po) should not be neglected, mainly in systems with low P input or management systems that promote organic matter accumulation. The aims of this study were to evaluate the changes in the Po fractions over time in soil fertilized and not fertilized with cattle manure and to correlate Po forms with available P extracted by anion exchange resin. The experiment was carried out under field conditions, in a sandy-clay loam Haplustox. The experimental design was a 2 × 9 randomized complete block factorial design, in which the first factor was manure application (20 t ha-1) or absence, and the second the soil sampling times (3, 7, 14, 21, 28, 49, 70, 91, and 112 days) after manure incorporation. Labile, moderately labile and non-labile Po fractions were determined in the soil material of each sampling. Manure fertilization increased the Po levels in the moderately labile and non-labile fractions and the total organic P, but did not affect the Po fraction proportions in relation to total organic P. On average, 5.1 % of total Po was in the labile, 44.4 % in the moderately labile and 50.5 % in the non-labile fractions. Available P (resin P) was more affected by the manure soluble Pi rather than by the labile Po forms. The labile and non-labile Po fractions varied randomly with no defined trend in relation to the samplings; for this reason, the data did not fit any mathematical model.

Blood lymphocyte subsets in rats with adjuvant arthritis

To determine the phenotype of peripheral blood lymphocytes during the time-course of adjuvant arthritis (AA) to detect alterations that could be involved in the pathogenesis of the arthritic process. METHODS--Phenotype analysis was performed on days 7, 14, 21, 28, 42, 56 and 70 after arthritis induction using monoclonal antibodies to CD5, CD4 and CD8 subsets, and flow cytometry. The proportion of activated lymphocytes and lymphocytes was also assessed with monoclonal antibodies to IL-2R (CD25), to Ia antigen and by polyclonal antibodies to rat Ig. RESULTS--Adjuvant arthritis produced leukocytosis with neutrophilia. Rats with AA showed a marked increase in the number of both CD4+ and CD8+ cells. The ratio CD4/CD8 decreased because the rise in CD8+ cells was more pronounced than the increase in CD4+ cells. Changes in lymphocyte counts showed two well-defined periods: the first, from day 14 to day 28, during which the inflammation of the joints reached a maximum and changes in lymphocyte subsets were more pronounced, that is, there was a threefold increase in CD8+ lymphocytes over normal counts, and the second, from day 42 to day 70, in which modified parameters improved considerably but remained different from controls. CONCLUSION--Alterations were detected in the phenotype of peripheral blood lymphocytes in AA, which provides an additional marker of disease activity.

Mecánica de la succión: comparación entre la lactancia artificial y la lactancia materna

Introducción: Hay poco conocimiento sobre la similitud de la mecánica entre la lactancia materna y la artificial. Evaluamos la mecánica de la succión en neonatos con lactancia materna exclusiva, lactancia artificial exclusiva y lactancia mixta. Nuestra hipótesis fue que el patrón fisiológico de los movimientos de succión varía según el tipo de alimentación. Según esta hipótesis, los niños con lactancia materna exclusiva realizan unos movimientos al mamar distintos a los de la succión de una tetina, realizados por niños con lactancia artificial. Los niños con lactancia mixta mezclan ambos tipos de movimientos de succión. Métodos: Estudio transversal de neonatos de 21-28 días de edad con lactancia materna o artificial exclusiva (124 parejas madre-hijo), y ensayo de campo, abierto, cruzado y aleatorizado, realizado en neonatos de 21-28 días (110 parejas madre-hijo) y en lactantes de 3-5 meses de edad (125 parejas madre-hijo) con lactancia mixta. Las variables principales fueron los movimientos de succión y las pausas. Resultados: Los neonatos de 21-28 días de edad alimentados con lactancia artificial exclusiva mostraron un menor número de movimientos de succión y el mismo número de pausas, pero de mayor duración, que los neonatos con lactancia materna exclusiva. Entre los niños que recibieron lactancia mixta, el número de movimientos de succión al recibir alimentación con biberón fue similar y las pausas menos numerosas y de menor duración respecto a lo observado al amamantar, tanto a los 21-28 días como a los 3-5 meses de edad. En este grupo de lactancia mixta, la cifra media de tomas de lactancia materna fue de 5,83 ± 1,93 a los 21-28 días de vida y de 4,42 ± 1,67 a los 3-5 meses de edad. En el análisis de equivalencia, realizado sobre los niños que recibieron lactancia mixta, el intervalo de confianza del 95% de la razón de movimientos con lactancia artificial y con lactancia materna se situó fuera del rango de equivalencia, indicó un número de movimientos de succión menor en un 5,9-8,7% al tomar el biberón, así como un menor número de pausas y una duración más breve de ellas en este mismo grupo. Conclusiones: En la lactancia mixta, la comparación entre las tomas de biberón y las de pecho se situó fuera del rango de equivalencia, aunque las diferencias fueron pequeñas. Los niños con lactancia mixta mezclan ambos tipos de movimientos (lactancia materna y lactancia artificial) durante la fase de aprendizaje y adoptan su propio patrón.

Efeitos de materiais orgânicos e da umidade do solo na patogenicidade de Rhizoctonia solani Kühn GA-4 HGI ao feijoeiro

Foram avaliados, em casa de vegetação, os efeitos das seguintes variáveis sobre a patogenicidade de Rhizoctonia solani GA-4 HGI a plantas de feijão (Phaseolus vulgaris L.), em solo artificialmente infestado: presença de materiais orgânicos com diferentes relações C:N (torta de mamona e bagaço de cana); níveis de decomposição da matéria orgânica, e condições de umidade do solo incorporado. A umidade do solo até o momento da semeadura foi mantida sob duas condições: 20% ou acima de 80% da capacidade de campo. Foram realizadas semeaduras aos 0, 7, 14, 21, 28 e 35 dias após inoculação e incorporação. As avaliações foram realizadas 14 dias após cada semeadura. O material com baixa relação C:N propiciou o aumento da incidência de R. solani no feijoeiro, enquanto o material com alta relação C:N não interferiu na incidência do patógeno. A incidência de R. solani no feijoeiro, em solo incorporado, foi independente da condição de umidade.

Mecánica de la succión: comparación entre la lactancia artificial y la lactancia materna

Introducción: Hay poco conocimiento sobre la similitud de la mecánica entre la lactancia materna y la artificial. Evaluamos la mecánica de la succión en neonatos con lactancia materna exclusiva, lactancia artificial exclusiva y lactancia mixta. Nuestra hipótesis fue que el patrón fisiológico de los movimientos de succión varía según el tipo de alimentación. Según esta hipótesis, los niños con lactancia materna exclusiva realizan unos movimientos al mamar distintos a los de la succión de una tetina, realizados por niños con lactancia artificial. Los niños con lactancia mixta mezclan ambos tipos de movimientos de succión. Métodos: Estudio transversal de neonatos de 21-28 días de edad con lactancia materna o artificial exclusiva (124 parejas madre-hijo), y ensayo de campo, abierto, cruzado y aleatorizado, realizado en neonatos de 21-28 días (110 parejas madre-hijo) y en lactantes de 3-5 meses de edad (125 parejas madre-hijo) con lactancia mixta. Las variables principales fueron los movimientos de succión y las pausas. Resultados: Los neonatos de 21-28 días de edad alimentados con lactancia artificial exclusiva mostraron un menor número de movimientos de succión y el mismo número de pausas, pero de mayor duración, que los neonatos con lactancia materna exclusiva. Entre los niños que recibieron lactancia mixta, el número de movimientos de succión al recibir alimentación con biberón fue similar y las pausas menos numerosas y de menor duración respecto a lo observado al amamantar, tanto a los 21-28 días como a los 3-5 meses de edad. En este grupo de lactancia mixta, la cifra media de tomas de lactancia materna fue de 5,83 ± 1,93 a los 21-28 días de vida y de 4,42 ± 1,67 a los 3-5 meses de edad. En el análisis de equivalencia, realizado sobre los niños que recibieron lactancia mixta, el intervalo de confianza del 95% de la razón de movimientos con lactancia artificial y con lactancia materna se situó fuera del rango de equivalencia, indicó un número de movimientos de succión menor en un 5,9-8,7% al tomar el biberón, así como un menor número de pausas y una duración más breve de ellas en este mismo grupo. Conclusiones: En la lactancia mixta, la comparación entre las tomas de biberón y las de pecho se situó fuera del rango de equivalencia, aunque las diferencias fueron pequeñas. Los niños con lactancia mixta mezclan ambos tipos de movimientos (lactancia materna y lactancia artificial) durante la fase de aprendizaje y adoptan su propio patrón.

Pneumocystis jirovecii genotype associated with increased death rate of HIV-infected patients with pneumonia.

Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations have been associated with failure of sulfa prophylaxis; their effect on the outcome of patients with P. jirovecii pneumonia (PCP) remains controversial. P. jirovecii DHPS polymorphisms and genotypes were identified in 112 cases of PCP in 110 HIV-infected patients by using PCR single-strand conformation polymorphism. Of the 110 patients observed, 21 died; 18 of those deaths were attributed to PCP. Thirty-three percent of the PCP cases involved a P. jirovecii strain that had 1 or both DHPS mutations. The presence or absence of DHPS mutations had no effect on the PCP mortality rate within 1 month, whereas P.jirovecii type 7 and mechanical ventilation at PCP diagnosis were associated with an increased risk of death caused by PCP. Mechanical ventilation at PCP diagnosis was also associated with an increased risk of sulfa treatment failure at 5 days.

Alterações anatômicas e físico-químicas associadas ao armazenamento refrigerado de pêssegos 'Aurora-1' e 'Dourado-2 '

O presente trabalho objetivou avaliar as características anatômicas e físico-químicas de pêssegos (Prunus persica (L.) Batsch) 'Aurora-1' e 'Dourado-2', armazenados em diferentes temperaturas e períodos. No primeiro experimento, os frutos foram armazenados a 0, 3 e 6ºC por 14, 21, 28 e 35 dias (mais dois dias de simulação à comercialização, sob 25ºC). No segundo experimento, os frutos foram armazenados a 0 e 3ºC por 7, 14, 21, 28 e 35 dias (mais dois dias de simulação à comercialização, sob 25ºC). O delineamento experimental empregado foi inteiramente ao acaso, em esquema fatorial, com quatro repetições em parcelas de seis frutos. Pêssegos 'Dourado-2', após sete dias de armazenamento a 3ºC ou 14 dias de armazenamento a 0ºC, apresentaram lanosidade caracterizada pela queda brusca na firmeza e pouca sucosidade. Os sintomas no mesocarpo foram caracterizados pelo afastamento das paredes de células adjacentes e acúmulo de substâncias pécticas no interior das células e dos espaços intercelulares. Pêssegos 'Aurora-1' sofreram redução na firmeza sem comprometer a qualidade dos frutos, podendo ser conservados por até 35 dias a 0 e 3ºC; mesmo aos 35 dias de armazenamento, o mesocarpo não apresentou alterações típicas da lanosidade. Aos 35 dias de armazenamento a 6ºC, os frutos de ambas cultivares estavam sobremaduros.

Rastreabilidade de farinha de vísceras de aves por isótopos estáveis em penas de frangos de corte

O objetivo deste trabalho foi detectar a presença de farinha de vísceras de aves (FV) na alimentação de frangos de corte, por meio da análise de penas por isótopos estáveis de carbono (13C/12C) e nitrogênio (15N/14N) e espectrofotometria de massas. Setecentos e vinte pintos machos Cobb foram submetidos aos seguintes tratamentos: ração vegetal (RV) à base de milho e farelo de soja, de 1 a 42 dias de idade; ração com 8% de farinha de vísceras de frango (FV), de 1 a 42 dias de idade; ração vegetal de 1 a 21 dias e ração com FV de 22 a 42 dias; ração vegetal de 1 a 35 dias e ração com FV de 36 a 42 dias; ração com FV de 1 a 21 dias, e ração vegetal de 22 a 42 dias; ração com FV de 1 a 35 dias, e ração vegetal de 36 a 42 dias. Foram colhidas amostras de penas de quatro aves por tratamento aos 7, 14, 21, 28, 35 e 42 dias de idade, que foram submetidas à análise isotópica de carbono (13C/12C) e nitrogênio (15N/14N) por espectrometria de massas. A aplicação da técnica dos isótopos estáveis de C e N a penas de frango de corte, após a utilização de farinha de vísceras na alimentação de frangos de corte, pelo período de até 21 dias, permite detectar a inclusão da FV na dieta.

Ammonium and nitrate in soil and upland rice yield as affected by cover crops and their desiccation time

The objective of this work was to evaluate the effect of cover crops and their desiccation times on upland rice yield and on the levels of nitrate and ammonium in a no-tillage soil. The experiment was carried out in a randomized blocks, with split plots and three replicates. Cover crops (plots) were sowed in the off-season (March 2009). In November 2009, at 30, 20, 10 and 0 days before rice sowing (split plots), herbicide was applied on the cover crops (fallow, Panicum maximum, Urochloa ruziziensis, U. brizantha and millet). Straw and soil were sampled (0 - 10 cm) at the sowing day, and after 7, 14, 21, 28 and 35 days. Straws from millet and fallow were degraded more rapidly and provided the lowest level of nitrate in the soil. Urochloa ruziziensis, U. brizantha and P. maximum produced higher amounts of dry matter, and provided the highest levels of nitrate in the soil. Millet provides the lowest nitrate/ammonium ratio and the highest upland rice yield. Desiccations carried out at 30 and 20 days before sowing had the largest levels of nitrate in the soil at the sowing date. Nitrogen content and forms in the soil are affected by cover crops and their desiccation times.

A multi-temporal approach to model endangered species distribution in Europe: the case of the Eurasian otter in Italy

We analysed the relationship between changes in land cover patterns and the Eurasian otter occurrence over the course of about 20 years (1985-2006) using multi-temporal Species Distribution Models (SDMs). The study area includes five river catchments covering most of the otter's Italian range. Land cover and topographic data were used as proxies of the ecological requirements of the otter within a 300-m buffer around river courses. We used species presence, pseudo-absence data, and environmental predictors to build past (1985) and current (2006) SDMs by applying an ensemble procedure through the BIOMOD modelling package. The performance of each model was evaluated by measuring the area under the curve (AUC) of the receiver-operating characteristic (ROC). Multi-temporal analyses of species distribution and land cover maps were performed by comparing the maps produced for 1985 and 2006. The ensemble procedure provided a good overall modelling accuracy, revealing that elevation and slope affected the otter's distribution in the past; in contrast, land cover predictors, such as cultivations and forests, were more important in the present period. During the transition period, 20.5% of the area became suitable, with 76% of the new otter presence data being located in these newly available areas. The multi-temporal analysis suggested that the quality of otter habitat improved in the last 20 years owing to the expansion of forests and to the reduction of cultivated fields in riparian belts. The evidence presented here stresses the great potential of riverine habitat restoration and environmental management for the future expansion of the otter in Italy

Treatment of brain metastases from non-small cell lung cancer with whole-brain radiotherapy (wbrt) in combination with gefitinib (gft) or temozolomide (tmz): a randomized multicenter phase ii trial of the swiss group of clinical cancer research (sakk #70/03)

BACKGROUND: Patients with BM rarely survive .6 months and are commonly excluded from clinical trials. We aimed at improving outcome by exploring 2 combined modality regimens with at the time novel agents for which single-agent activity had been shown. METHODS: NSCLC patients with multiple BM were randomized to WBRT (10 × 3 Gy) and either GFT 250 mg p.o. daily or TMZ 75 mg/m2 p.o. daily ×21/28 days, starting on Day 1 of RT and to be continued until PD. Primary endpoint was overall survival, a Simon's optimal 2-stage design was based on assumptions for the 3-month survival rate. Cognitive functioning and quality of life were also evaluated. RESULTS: Fifty-nine patients (36 M, 23 F; 9 after prior chemo) were included. Median age was 61 years (range 46-82), WHO PS was 0 in 18 patients, 1 in 31 patients, and 2 in 10 patients. All but 1 patients had extracranial disease; 33 of 43 (TMZ) and 15 of 16 (GFT) had adenocarcinoma histology. GFT arm was closed early after stage 1 analysis when the prespecified 3-mo survival rate threshold (66%) was not reached, causes of death were not GFT related. Main causes of death were PD in the CNS 24%, systemic 41%, both 8%, and toxicity 10% [intestinal perforation (2 patients), pneumonia (2), pulmonary emboli (1), pneumonitis NOS (1), seizure (1)]. We summarize here other patients' characteristics for the 2 trial arms: TMZ (n ¼ 43)/GFT (n ¼ 16); median treatment duration: 1.6 /1.8 mo; Grade 3-4 toxicity: lymphopenia 5 patients (12%)/0; fatigue 8 patients (19%)/2 patients (13%). Survival data for TMZ/GFT arms: 3-month survival rate: 58.1% (95% CI 42.1-73)/62.5% (95% CI 35- 85); median OS: 4.9 months (95% CI 2.5-5.6)/6.3 months (95% CI 2.2- 14.6); median PFS: 1.8 months (95% CI 1.5-1.8)/1.8 (95% CI 1.1-3.9); median time to neurol. progr.: 8.0 months (95% CI 2.2-X)/4.8 (95% CI 3.9-10.5). In a model to predict survival time including the variables' age, PS, number of BM, global QL, total MMSE score, and subjective cognitive function, none of the variables accounted for a significant improvement in survival time. CONCLUSIONS: The combinations of WBRT with GFT or TMZ were feasible. However, in this unselected patient population, survival remains poor and a high rate of complication was observed. Four patients died as a result of high-dose corticosteroids. Preliminary evaluation of cognitive function andQL failed to show significant improvement. Indications and patient selection for palliative treatment should be revisited and careful monitoring and supportive care is required. Research and progress for this frequent clinical situation is urgently needed. Trial partly supported by AstraZeneca (Switzerland), Essex Chemie (Switzerland) and Swiss Federal Government.