Implicit Motor Imagery for Chronic Pelvic Pain: A Cross-Sectional Case-Control Study.

Implicit motor imagery (IMI), with an image laterality discrimination (LD) task, has been proposed as a useful therapeutic tool to restore body schema in patients with chronic pelvic pain (CPP). The aim of this study was to analyse the existence of differences between patients with CPP and healthy individuals in order to justify the use of IMI. An observational, cross-sectional study with non-probabilistic sampling was designed as a one-to-one matched case-control study. Through a web link designed for this purpose, a total of 40 abdominoperineal images were shown to 130 participants during the laterality task. Outcome measures were pain intensity (visual analogue scale, VAS), accuracy, response time (RT), and CPPQ-Mohedo score (Chronic Pelvic Pain Questionnaire-Mohedo). This was an observational, cross-sectional study with a total of 64 CPP patients and 66 healthy individuals. The comparative analysis between groups revealed significant differences in accuracy, CPPQ-Mohedo and VAS (p < 0.001), but not in RT; in patients with CPP, accuracy was correlated with a lower CPPQ-Mohedo score and RT and, the greater the pain intensity, the higher the CPPQ-Mohedo score and RT, and the lower the accuracy. In the LD task, the patients with CPP made more mistakes than the healthy individuals. IMI could be a useful and complementary tool in the therapeutic approach for patients with CPP.

Intervención psicológica grupal, basada en la aceptación y el entrenamiento en comunicación, con familiares de personas con trastorno mental grave / Group psychological intervention, based on acceptance and communication training, with relatives of people with severe mental disorders

Se evaluó la eficacia de un programa de intervención grupal para la disminución de problemas psicológicos de familiares que conviven con pacientes con trastorno mental grave. Participaron ocho madres y un padre cuyos hijos recibían tratamiento en un Hospital de Día de Salud Mental. Se les aplicó el 'Inventario de ansiedad de Beck', el 'Inventario de depresión de Beck-II', la 'Escala de estrés percibido', el “Cuestionario de salud SF- 36', el 'Inventario de estrategias de afrontamiento' y el 'Inventario de aserción'. Asistieron a 20 sesiones de tratamiento psicológico grupal, basado en la aceptación y el desarrollo de competencias. Tras la intervención, los participantes disminuyeron significativamente el nivel de depresión, aumentaron la conducta asertiva y el uso de estrategias de afrontamiento orientadas a la solución de problemas. Los familiares valoraron el programa como útil, aplicaron lo aprendido en su vida cotidiana, disminuyeron los niveles de malestar psicológico y la mayoría realizó acciones en la dirección de lo que valora en su vida. En conclusión, el programa fue eficaz para disminuir la depresión en los familiares y aumentar estrategias de afrontamiento adaptativas. No obstante, son necesarios más estudios para superar algunas limitaciones como el tamaño de la muestra y la ausencia del grupo control

The effectiveness of a group intervention program to reduce psychological problems in relatives living with patients with severe mental disorders was evaluated. Attended eight mothers and one father whose adult children were receiving treatment in a Mental Health Day Hospital. They followed the Beck Anxiety Inventory, the Beck Depression Inventory-II, the Perceived Stress Scale, the SF-36 Health Survey, the Coping Strategies Inventory, and the Assertiveness Inventory. They attended 20 sessions of group psychological acceptance and development of skills based treatment. Following the completion of the program, the level of depression in the parents decreased significantly, assertive conduct increased, as did the use of coping strategies aimed at the solution of problems. The relatives rated the program as useful, applied what they have learned to their daily lives, decreased the levels of psychological discomfort, and the majority applied what they have learned to what they value most. Concluding the program was successful in decreasing depression among patients’ relatives and in increasing their adaptive coping skills. Nevertheless, more studies are needed in order to overcome some limitations such as the size of the cohort and the lack of a control group

Ozonation of benzotriazole and methylindole: Kinetic modeling, identification of intermediates and reaction mechanisms.

The ozonation of 1H-benzotriazole (BZ) and 3-methylindole (ML), two emerging contaminants that are frequently present in aquatic environments, was investigated. The experiments were performed with the contaminants (1µM) dissolved in ultrapure water. The kinetic study led to the determination of the apparent rate constants for the ozonation reactions. In the case of 1H-benzotriazole, these rate constants varied from 20.1 ± 0.4M(-1)s(-1) at pH=3 to 2143 ± 23 M(-1)s(-1) at pH=10. Due to its acidic nature (pKa=8.2), the degree of dissociation of this pollutant was determined at every pH of work, and the specific rate constants of the un-dissociated and dissociated species were evaluated, being the values of these rate constants 20.1 ± 2.0 and 2.0 ± 0.3 × 10(3)M(-1)s(-1), respectively. On the contrary, 3-methylindole does not present acidic nature, and therefore, it can be proposed an average value for its rate constant of 4.90 ± 0.7 × 10(5)M(-1)s(-1) in the whole pH range 3-10. Further experiments were performed to identify the main degradation byproducts (10 mg L(-1) of contaminants, 0.023 gh(-1) of ozone). Up to 8 intermediates formed in the ozonation of 3-methylindole were identified by LC-TOFMS, while 6 intermediates were identified in the ozonation of 1H-benzotriazole. By considering these intermediate compounds, the reaction mechanisms were proposed and discussed. Finally, evaluated rate constants allowed to predict and modeling the oxidation of these micropollutants in general aquatic systems.

La asertividad y la salud de familiares cuidadores de pacientes con trastorno mental grave / Assertiveness and health of family caregivers of patients with severe mental illness

Actualmente, las pruebas empíricas relativas al comportamiento asertivo de los familiares cuidadores de pacientes con trastorno mental grave (TMG) y a los efectos relacioneados con su déficit son escasas. El objetivo de este trabajo fue evaluar la asertividad de 140 familiares cuidadores de 54 pacientes con TMG y la relación entre asertividad y salud física y psicológica. Se utilizó el "Inventario de aserción" (Gambrill y Richey, 1075), el «Inventario de ansiedad, de Beck» el "Inventario de depresión de Beck-II", la "Escala de estrés percibido" y el "Cuestionario de salud SF-36". El 77,15 de los familiares se comportaba de forma asertiva y no hubo diferencias significativas según las variables sociodemográficas. La asertividad estaba relacionada con la ansiedad, la depresión, el estrés percibido y la valoración global del estado de salud, así como con seis (de los ocho) aspectos evaluados por el SF-36. La falta de asertividad era un factor de riesgo para todas estas variables. Estos hallazgos apoyan la importancia de incluir el entrenamiento asertivo en el tratamiento de los familiares de pacientes con TMG

At present, empirical evidence is scarce related to assertive behavior of family caregivers of patients with severe mental illness (SMI) and to the effects related to their deficits. The aim of this study was to examine the assertiveness of 140 family caregivers of 94 patients with SMI, and to examine the relationship between assertiveness and physical and psychological health. The Assertion Inventory (Granbrill and Richey, 1975), the Beck Anxiety Inventory, the Beck Depression Inventory-II, the Perveived Stress Scale, and the Health Questionnaire SF-36 were used. 77,1% of the participants were assertive and there were no significant differences in base to socio-demographic variables. Assertiveness was related to anxiety, depression, stress, and general wellbeing as well as six (out of eight) areas assessed by the SF-36. The lack of assertiveness was a risk factor for all these variable. These findings support the importance of including assertiveness training in the treatment of the families of patients with SMI BY staff at mental health units

La asertividad y su relación con problemas emocionales y el desgaste en profesionales sanitarios / Assertiveness and its relationship to emotional problems and burnout in healthcare workers

Este trabajo tuvo como objetivo analizar la relación entre la asertividad y los problemas emocionales (depresión, ansiedad y ansiedad social) y el desgaste profesional en médicos, enfermeras y celadores-conductores de dispositivos de cuidados críticos y urgencias (DCCU). Se evaluó a 315 profesionales sanitarios con el "Inventario de aserción", el "Inventario de depresión de Beck II", el "Inventario de ansiedad de Beck" y el "Inventario de burnout, de Maslach". Se encontró que el 17,7% no era asertivo, el 16,6% tenía ansiedad social, el 12,9% depresión y el 11,7% ansiedad. Hubo algunas diferencias de sexo. Adicionalmente, el 52,7% sufría despersonalización, el 46,7% falta de realización personal en el trabajo y el 24,4% agotamiento emocional. La asertividad se relacionó de forma significativa con la ansiedad social, el agotamiento y la falta de realización personal y el análisis de regresión indicó que la falta de asertividad era un factor de riesgo para estas tres cuestiones. Estos resultados apoyan la importancia de incluir el entrenamiento asertivo como parte de la formación de los profesionales de los DCCU

The main aim of this study was to examine the relationship between assertiveness and emotional problems (depression, anxiety and social anxiety) and burnout in physician, nurses, orderlies and ambulance drivers in the Critical Care and Emergency Services (CCES). 315 Healthcare workers completed the Assertion Inventory, the Beck Depression Inventory II, the Beck Anxiety Inventory, and the Maslach Burnout Inventory. The results show that 17.7% were not assertive, 16.6% had social anxiety, 12.9% suffered from depression, and 11.7% from anxiety. There were some sex differences. Furthermore, 52.7% had depersonalization, 46.7% felt a lack of personal accomplishment, and 24.4% suffered from emotional exhaustion. Assertiveness was significantly associated with social anxiety, exhaustion and lack of personal accomplishment. Regression analysis indicated that the lack of assertiveness was a risk factor for these three psychological difficulties. These results support the importance of including assertiveness training as part of the training of CCES professionals

Perfil de seguridad de las terapias biológicas intravenosas en una cohorte de pacientes con artritis reumatoide. Monitorización clínica por enfermería (estudio Sebiol) / Safety profile of biological intravenous therapy in a rheumatoid arthritis patients cohort. Clinical nursing monitoring (Sebiol study)

Introducción. El uso de biológicos ha permitido conocer de manera exhaustiva su seguridad gracias a registros como BIOBADASER. El presente trabajo permite, con un estudio observacional de cohortes, describir el perfil de seguridad perinfusional de dichos tratamientos por vía intravenosa. Objetivos. Conocer el perfil de seguridad en la práctica clínica, tras la administración de biológicos por vía intravenosa y durante las 24 h posteriores. Material y métodos. Cohorte transversal de 114 pacientes con AR tratados con agentes biológicos (criterios ACR) durante un mes de 2009 por enfermería de hospital de día de 12 centros hospitalarios catalanes. Se analizaron la edad, el sexo, los tratamientos actuales y previos, los datos de vacunación previa y la premedicación. Se registró también cualquier acontecimiento adverso (AA) durante la administración o en las 24 h posteriores. Se clasificó según el diccionario internacional MedDRAv11.0 y se describieron la intensidad (leve, moderada, severa), la relación con la administración del fármaco según el algoritmo de Karch y Lasagna (no relacionada, improbable, posible, probable, definitiva) y las medidas emprendidas. El análisis estadístico se realizó mediante SPSS 18.0. Resultados. Ciento once con criterios de inclusión (edad media ± desviación estándar 56,06 ± 12,12 años), 90 mujeres (81,1%) y evolución de 11,97 ± 7,95 años; 24 pacientes (21,6%) con antecedentes de alergia. Se observaron 12 AA en 7 pacientes, 9 de ellos durante la administración y 3 en las 24 h posteriores. No hubo ningún acontecimiento adverso grave y uno de los AA se calificó de intensidad moderada (urticaria). El resto de los AA fueron de intensidad leve (AU)

Introduction: The Biologics used in the management of rheumatoid arthritis (RA) in recent years, have comprehensively permitted to understand its security, as shown in registries such as BIOBADASER. The present manuscript represents an observational cohort study to describe the safety perinfusional profile of those intravenous treatments. Objectives: To confirm the safety profile of biological therapies in routine clinical practice, after the administration of intravenous drugs and 24 hours post-administration. Material and methods: We evaluated a cross-sectional cohort of 114 patients with RA (according to the American College of Rheumatology ACR criteria), attending within one month in 2009 the nursing clinics of day care hospital of 12 Catalonian hospitals. All patients were treated with intravenous biological agents. We recorded the age, sex, current and previous drug treatments, we also collected data about previous vaccination and premedication received and any adverse event occurring at the time of drug administration or within 24 hours. If an adverse event occurred, was categorized by MedDRAv11.0 International Dictionary, and categorized in terms of intensity (mild, moderate, severe), relationship to drug administration according to Karch and Lasagna algorithm (unrelated, unlikely, possible, probable, definite) and the further measures taken. Results: 111 patients met the inclusion criteria, with a mean age of 56.06 years (SD: 12.12), 90 of them women (81.1%) and mean time since diagnosis of the disease of 11.97 years (SD: 7.95). 24 patients (21.6%) had a history of allergy. 12 adverse events were observed in 7 patients, 9 of which at the time of administration and 3 in 24 hours after. There were no serious adverse events and only one of the adverse events (AEs) was rated as moderate (urticaria). The remaining AA were mild (AU)

Modeling the photodegradation of emerging contaminants in waters by UV radiation and UV/H2O2 system.

Five emerging contaminants (1-H-Benzotriazole, N,N-diethyl-m-toluamide or DEET, Chlorophene, 3-Methylindole, and Nortriptyline HCl), frequently found in surface waters and wastewaters, were selected to be photooxidized in several water matrices. Previous degradation experiments of these compounds individually dissolved in ultra pure water were performed by using UV radiation at 254 nm and the Fenton's reagent. These oxidation systems allowed the determination of the quantum yields and the rate constants for the radical reaction between each compound and hydroxyl radicals. Later, the simultaneous photodegradation of mixtures of the selected ECs in several types of water (ultrapure water, reservoir water, and two effluents from WWTPs) was carried out and a kinetic study was conducted. A model is proposed for the ECs elimination, and the theoretically calculated concentrations with this model agreed well with the experimental results obtained, which confirmed that it constitutes an excellent tool to predict the elimination of these compounds in waters.

Safety profile of biological intravenous therapy in a rheumatoid arthritis patients cohort. Clinical nursing monitoring (Sebiol study).

INTRODUCTION: The Biologics used in the management of rheumatoid arthritis (RA) in recent years, have comprehensively permitted to understand its security, as shown in registries such as BIOBADASER. The present manuscript represents an observational cohort study to describe the safety perinfusional profile of those intravenous treatments. OBJECTIVES: To confirm the safety profile of biological therapies in routine clinical practice, after the administration of intravenous drugs and 24 hours post-administration. MATERIAL AND METHODS: We evaluated a cross-sectional cohort of 114 patients with RA (according to the American College of Rheumatology ACR criteria), attending within one month in 2009 the nursing clinics of day care hospital of 12 Catalonian hospitals. All patients were treated with intravenous biological agents. We recorded the age, sex, current and previous drug treatments, we also collected data about previous vaccination and premedication received and any adverse event occurring at the time of drug administration or within 24 hours. If an adverse event occurred, was categorized by MedDRAv11.0 International Dictionary, and categorized in terms of intensity (mild, moderate, severe), relationship to drug administration according to Karch and Lasagna algorithm (unrelated, unlikely, possible, probable, definite) and the further measures taken. RESULTS: 111 patients met the inclusion criteria, with a mean age of 56.06 years (SD: 12.12), 90 of them women (81.1%) and mean time since diagnosis of the disease of 11.97 years (SD: 7.95). 24 patients (21.6%) had a history of allergy. 12 adverse events were observed in 7 patients, 9 of which at the time of administration and 3 in 24 hours after. There were no serious adverse events and only one of the adverse events (AEs) was rated as moderate (urticaria). The remaining AA were mild.

Photolysis of model emerging contaminants in ultra-pure water: kinetics, by-products formation and degradation pathways.

The photolysis of five frequent emerging contaminants (Benzotriazole, Chlorophene, N,N-diethyl-m-toluamide or DEET, Methylindole, and Nortriptyline HCl) was investigated in ultrapure water under monochromatic ultraviolet radiation at 254 nm and by a combination of UV and hydrogen peroxide. The results revealed that the photolysis rates followed first-order kinetics, with rate constant values depending on the nature of the specific compound, the pH, and the presence or absence of the scavenger tert-butanol. Quantum yields were also determined and values in the range of 53.8 × 10⁻³ - 9.4 × 10⁻³ mol E⁻¹ for Benzotriazole, 525 × 10⁻³ - 469 × 10⁻³ mol E⁻¹ for Chlorophene, 2.8 × 10⁻³ - 0.9 × 10⁻³ mol E⁻¹ for DEET, 108 × 10⁻³ - 165 × 10⁻³ mol E⁻¹ for Methylindole, and 13.8 × 10⁻³ - 15.0 × 10⁻³ mol E⁻¹ for Nortriptyline were obtained. The study also found that the UV/H2O2 process enhanced the oxidation rate in comparison to direct photolysis. High-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS) technique was applied to the concentrations evaluation and further identification of the parent compounds and their by-products, which allowed the proposal of the degradation pathways for each compound. Finally, in order to assess the aquatic toxicity in the photodegradation of these compounds, the Vibrio fischeri acute toxicity test was used, and the results indicated an initial increase of this parameter in all cases, followed by a decrease in the specific case of Benzotriazole, DEET, Methylindole, and Chlorophene.

Glioblastoma multiforme cerebral hemisférico: análisis de sobrevida de 65 casos tratados en el Departamento de Oncología del Hospital de Clínicas, desde 1980 a 2000 / Glioblastoma multiforme in the cerebral hemisphere: survival analysis of 65 cases seen at the Oncology Department of the Clínicas Hospital from 1980 through 2000

Introducción: el glioblastoma multiforme (GBM) representa la forma más agresiva de los gliomas. La sobrevida a cinco años con el tratamiento quirúrgico exclusivo es nula. El agregado radioterapia (RT) y quimioterapia (QT) prolongan la so-brevida. Objetivo: evaluar el impacto del tratamiento en la sobrevida de pacientes portadores de GBM.Pacientes y métodos: se incluyeron los pacientes con diagnóstico histológico de GBM asistidos en la Unidad de Neuro-Oncología del Hospital de Cínicas, de 1980 a 2000. Se recabaron datos patronímicos, clínicos, paraclínicos y evolutivos de las historias clínicas. Se calculó la sobrevida mediante el método de Kaplan Meier y Mantel Cox.Resultados: se estudiaron 65 pacientes con una edad mediana de 58 años (rango: 6-79). Recibieron cirugía 100%(completa en 22 pacientes, subtotal en 9, parcial en 32 y biopsia en 2). El 92% recibió RT posoperatoria y 25% QT. La mediana de sobrevida fue de 46,6 semanas y la sobrevida global al año fue de 28%. La probabilidad de sobrevida al año fue 0 en los pacientes que recibieron cirugía exclusiva; 0,23 en los que se agregó RT, y 0,62 en los tratados con QT (p=0,0001). El análisis multivariable identificó como variables independientes: el tratamiento multimodal incluyendo quimioterapia(p=0,003) y buen estado neurológico posoperatorio (p=0,007).Conclusiones: la mediana de sobrevida de esta serie fue similar a lo descrito en la literatura, existiendo una sobrevida mayor en los pacientes con buen estado neurológico tratadoscon cirugía seguida de RT y QT.

Introduction: glioblastoma multiforme (GBM) is the most agressive kind of gliomas. The 5-year survival rate for exclusive surgical treatment is null. Additional chemotherapy and radiotherapy increases survival.Objective: to evaluate the impact of treatment in the survival of patients suffering from GBM.Method: patients with a histological diagnosis of GBM who were seen at the Neuro-Oncology Unit of the Clínicas Hospital, from 1980 through 2000. Clinical, paraclinical and patronymic data was collected, the same as information on the evolution of medical records. Survival rates were calculated through the Kaplan Meier and Mantel Cox method. Results: 65 patients with an average age of 58 years old were studied, (range: 6-79). All of them underwent surgery (complete in 22 patients, subtotal in 9, partial in 32 and biopsy in 2 patients). Ninety two percent of patients were treated with radiotherapy and 25% with chemotherapy. Median survival was 46.6 weeks and global survival one year after was 28%. The probability for survival one year after was 0 in patients who were treated only with surgery; 0.23 in those who also received radiotherapy and 0.62 with chemotherapy QT (p=0,0001).Multivariable analysis identified the following independent variables: multimodal treatment including chemotherapy (p=0,003) and a good postoperative general condition (p=0,007). Conclusions: median survival in this series was similar to that described in literature, there existing a longer survival rate for patients with a good neurologic condition who are treated with radiotherapy and chemotherapy after surgery.

Introdução: o glioblastoma multiforme (GBM) é a forma mais agressiva dos gliomas. A sobrevida a os cinco anos é nula quando o paciente recebe exclusivamente tratamento cirúrgico. Observa-se um aumento da sobrevida quando ademais da cirurgia se agrega radioterapia (RT) e quimioterapia (QT).Objetivo: avaliar o impacto do tratamento na sobrevida de pacientes portadores de GBM. Pacientes e métodos: foram incluídos todos os pacientes com diagnóstico histológico de GBM atendidos na Unidade de Neuro-Oncologia do Hospital de Clínicas, de 1980 a 2000. Dos prontuários dos pacientes foram coletados os dados de identificação, clínicos, resultados de exames e estudos e os relacionados com a evo-lução do caso. A sobrevida foi calculada utilizando o método de Kaplan Meier e Mantel Cox.Resultados: foram estudados 65 pacientes com idade média de 58 anos (rango: 6-79 anos). Todos os pacientes (100%) foram submetidos à cirurgia (completa em 22 pacientes, subtotal em 9, parcial em 32 e biopsia em 2). Noventa e dois por centos (92%) receberam RT pós-operatória e 25% QT. A mediana de sobrevida foi de 46,6 semanas e a sobrevida global aos 12 meses foi de 28%. A probabilidade de sobrevida aos 12 meses foi zero nos pacientes que foram submetidos exclusivamente à cirurgia; 0,23 nos que se agregaram RT, e 0,62 nos tratados com QT (p=0,0001). A análise multivariada identificou como variáveis independentes: o tratamento multimodal incluindo quimioterapia (p=0,003) e bom estado neurológico pós-operatório (p=0,007).Conclusões: a mediana de sobrevida desta serie foi similar às descritas na literatura, existindo uma sobrevida maior nos pacientes com bom estado neurológico tratados com cirurgia seguida de RT e QT.

Combined chemical oxidation and membrane filtration techniques applied to the removal of some selected pharmaceuticals from water systems.

The elimination of five selected pharmaceuticals (amoxicillin, hydrochlorothiazide, metoprolol, naproxen and phenacetin) dissolved in different water systems (two natural water matrices and a secondary effluent) was carried out by sequential processes constituted by membrane filtration and chemical oxidation stages. Different configurations of those two stages were applied. In a first group, a pretreatment consisting in a membrane filtration (ultrafiltration or nanofiltration) was conducted; and the permeate and retentate effluents produced were afterwards treated by chemical oxidation, using ozone or chlorine. In a second group, the pretreatment consisted in a chemical oxidation stage (by using ozone, chlorine, O(3)/H(2)O(2), UV or UV/H(2)O(2)) followed by a nanofiltration process. The main objective of this set of experiments was the comparison of the efficiencies reached by using different systems and configurations in order to optimize the elimination of those pollutants from the selected water matrices. Results of removals and rejection coefficients for the five pharmaceuticals showed that the combined treatments involving UV radiation (254 nm monochromatic radiation during 30 min) followed by nanofiltration were very effective, with global removals over 80 % in most of the experiments. Ozonation (initial dose of 2.25 mg L(-1)) followed by nanofiltration also showed high levels of efficiency, with removals over 70 % in the permeate stream generated in experiments carried out with natural waters. The opposite sequence, nanofiltration followed by ozonation, reached removals over 97 % in the natural waters by using an ozone dose of 2.25 mg L(-1); and over 90 % in the secondary effluent with an initial ozone dose of 3.75 mg L(-1).

Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers.

Oligodendroglioma is characterized by unique clinical, pathological, and genetic features. Recurrent losses of chromosomes 1p and 19q are strongly associated with this brain cancer but knowledge of the identity and function of the genes affected by these alterations is limited. We performed exome sequencing on a discovery set of 16 oligodendrogliomas with 1p/19q co-deletion to identify new molecular features at base-pair resolution. As anticipated, there was a high rate of IDH mutations: all cases had mutations in either IDH1 (14/16) or IDH2 (2/16). In addition, we discovered somatic mutations and insertions/deletions in the CIC gene on chromosome 19q13.2 in 13/16 tumours. These discovery set mutations were validated by deep sequencing of 13 additional tumours, which revealed seven others with CIC mutations, thus bringing the overall mutation rate in oligodendrogliomas in this study to 20/29 (69%). In contrast, deep sequencing of astrocytomas and oligoastrocytomas without 1p/19q loss revealed that CIC alterations were otherwise rare (1/60; 2%). Of the 21 non-synonymous somatic mutations in 20 CIC-mutant oligodendrogliomas, nine were in exon 5 within an annotated DNA-interacting domain and three were in exon 20 within an annotated protein-interacting domain. The remaining nine were found in other exons and frequently included truncations. CIC mutations were highly associated with oligodendroglioma histology, 1p/19q co-deletion, and IDH1/2 mutation (p < 0.001). Although we observed no differences in the clinical outcomes of CIC mutant versus wild-type tumours, in a background of 1p/19q co-deletion, hemizygous CIC mutations are likely important. We hypothesize that the mutant CIC on the single retained 19q allele is linked to the pathogenesis of oligodendrogliomas with IDH mutation. Our detailed study of genetic aberrations in oligodendroglioma suggests a functional interaction between CIC mutation, IDH1/2 mutation, and 1p/19q co-deletion.

Bromination of selected pharmaceuticals in water matrices.

The bromination of five selected pharmaceuticals (metoprolol, naproxen, amoxicillin, phenacetin, and hydrochlorothiazide) was studied with these compounds individually dissolved in ultra-pure water. The apparent rate constants for the bromination reaction were determined as a function of the pH, obtaining the sequence amoxicillin>naproxen>>hydrochlorothiazide≈phenacetin≈metoprolol. A kinetic mechanism specifying the dissociation reactions and the species formed for each compound according to its pK(a) value and the pH allowed the intrinsic rate constants to be determined for each elementary reaction. There was fairly good agreement between the experimental and calculated values of the apparent rate constants, confirming the goodness of the proposed reaction mechanism. In a second stage, the bromination of the selected pharmaceuticals simultaneously dissolved in three water matrices (a groundwater, a surface water from a public reservoir, and a secondary effluent from a WWTP) was investigated. The pharmaceutical elimination trend agreed with the previously determined rate constants. The influence of the main operating conditions (pH, initial bromine dose, and characteristics of the water matrix) on the degradation of the pharmaceuticals was established. An elimination concentration profile for each pharmaceutical in the water matrices was proposed based on the use of the previously evaluated apparent rate constants, and the theoretical results agreed satisfactorily with experiment. Finally, chlorination experiments performed in the presence of bromide showed that low bromide concentrations slightly accelerate the oxidation of the selected pharmaceuticals during chlorine disinfection.

International retrospective study of over 1000 adults with anaplastic oligodendroglial tumors.

Treatment for newly diagnosed anaplastic oligodendroglial tumors is controversial. Radiotherapy (RT) alone and in combination with chemotherapy (CT) are the most well studied strategies. However, CT alone is often advocated, especially in cases with 1p19q codeletion. We retrospectively identified 1013 adults diagnosed from 1981-2007 treated initially with RT alone (n = 200), CT + RT (n = 528), CT alone (n = 201), or other strategies (n = 84). Median overall survival (OS) was 6.3 years and time to progression (TTP) was 3.1 years. 1p19q codeletion correlated with longer OS and TTP than no 1p or 19q deletion. In codeleted cases, median TTP was longer following CT + RT (7.2 y) than following CT (3.9 y, P = .003) or RT (2.5 y, P < .001) alone but without improved OS; median TTP was longer following treatment with PCV alone than temozolomide alone (7.6 vs. 3.3 y, P = .019). In cases with no deletion, median TTP was longer following CT + RT (3.1 y) than CT (0.9 y, P = .0124) or RT (1.1 y, P < .0001) alone; OS also favored CT + RT (median 5.0 y) over CT (2.2 y, P = .02) or RT (1.9 y, P < .0001) alone. In codeleted cases, CT alone did not appear to shorten OS in comparison with CT + RT, and PCV appeared to offer longer disease control than temozolomide but without a clear survival advantage. Combined CT + RT led to longer disease control and survival than did CT or RT alone in cases with no 1p19q deletion. Ongoing trials will address these issues prospectively.

Leptomeningeal disease in oligodendroglial tumors: a population-based study.

In this population-based study, we determined the frequency and clinical characteristics of leptomeningeal disease (LMD) developing in the context of oligodendroglial tumors (oligodendrogliomas and oligoastrocytomas). LMD occurred in only 3.9% (8/204) of oligodendroglial tumors and in patients with more recurrences [mean 2.88 vs. 1.27 in LMD and non-LMD, respectively (p = 0.001)]. In contrast to LMD from systemic solid tumors, the median survival following the diagnosis of LMD in oligodendroglial tumors was surprisingly long at 22 months (95% CI 11-33 months). Treatment with oral chemotherapy seemed as effective as more aggressive treatments (e.g. repeat RT or intrathecal chemotherapy) in these patients.

Determination of the methylation status of MGMT in different regions within glioblastoma multiforme.

Epigenetic silencing of the MGMT gene through promoter methylation correlates with improved survival in Glioblastoma Multiforme (GBM) patients receiving concurrent chemoradiotherapy. Although the clinical benefit is primarily seen in patients with methylated MGMT promoter, some unmethylated patients also respond to Temozolomide. One possible explanation may be intratumoral heterogeneity. This study was designed to assess the methylation status of the MGMT promoter in different areas of GBM and determine if methylation status varied depending on the fixation technique (paraffin-embedding versus fresh frozen) used to store tissue. Using intraoperative navigation, biopsies were obtained from three distinct regions: the enhancing outer area, the non-enhancing inner core, and an area immediately outside the enhancing region. Only patients with GBM were included for evaluation and analysis. Samples taken from each area were divided with half stored by flash freezing and the other half stored using paraffin fixation. Methylation Specific-PCR (MS-PCR) was used for analysis of MGMT promoter methylation. Thirteen patients were included. Ten were male with a median age of 62 years. In each patient, samples were taken from the enhancing rim and the necrotic centre. However, it was not considered safe or feasible to obtain samples from the area immediately adjacent to the enhancing tumor rim in one case. All patients were homogeneous for methylation status throughout their tumor and tissue taken adjacent to it when frozen tissue was used. However, four patients had discrepancies in the MGMT promoter status between the frozen and paraffin-embedded blocks and one patient was not homogeneous within the tumor when paraffin-embedded tissue was used. MGMT promoter methylation status was homogeneous in all GBM tumors. Our observation that methylation status varied depending if the DNA was extracted from paraffin-embedded versus frozen tissue is concerning. Although the reason for this is unclear, we postulate that the timing from resection to fixation or the process of fixation itself may potentially alter methylation status in paraffin-embedded tumors.

The prognostic value of hemoglobin in patients with anal cancer treated with chemoradiotherapy.

PURPOSE: This study aimed to evaluate the impact of hemoglobin level on clinical outcome (local response, progression-free survival, and overall survival) in patients with carcinoma of the anal canal treated with definitive chemoradiotherapy. METHODS: This is a retrospective study of patients with anal cancer treated between 1992 and 2005 with definitive chemoradiotherapy at Tom Baker Cancer Centre. Patient treatment, laboratory, and outcome data were extracted from the chart. RESULTS: Seventy-two patients treated with definitive chemoradiotherapy were identified. The median age was 56 years, the male-to-female ratio was 1:2, and the median tumor size was 3.5 cm. At 6 weeks after the completion of chemoradiotherapy, 62% of patients (38/61) had complete clinical response, and 34% (21/61) had achieved a partial clinical response. At 3 months after treatment, complete clinical response was observed in 78% (49/63) and a partial response in 16% (10/63). The median pretreatment hemoglobin level was 138.5 g/L, and the median on-treatment hemoglobin level was 129 g/L. Distant relapse was associated with hemoglobin levels in the lowest quartiles, pretreatment and on-treatment (P = .007 and P = .008, respectively). Hemoglobin levels were not associated with response at 6 weeks or 3 months. A pretreatment hemoglobin level of <130 g/L was associated with worse progression-free and overall survival (P < .0001, both). A hemoglobin on-treatment level of <121 g/L was associated with progression-free and overall survival (P < .0001 and P = .019, respectively), when stratified by gender. CONCLUSIONS: Hemoglobin status was correlated with progression-free and overall survival, and distant relapse, but not clinical response, in patients with carcinoma of the anal canal treated with chemoradiotherapy. The clinically relevant cut point, and the value of correcting hemoglobin levels before or during treatment, remains to be elucidated.

Kinetics of aqueous chlorination of some pharmaceuticals and their elimination from water matrices.

Apparent rate constants for the reactions of four selected pharmaceutical compounds (metoprolol, naproxen, amoxicillin, and phenacetin) with chlorine in ultra-pure (UP) water were determined as a function of the pH. It was found that amoxicillin (in the whole pH range 3-12), and naproxen (in the low pH range 2-4) presented high reaction rates, while naproxen (in the pH range 5-9), and phenacetin and metoprolol (in the pH range 2.5-12 for phenacetin, and 3-10 for metoprolol) followed intermediate and slow reaction rates. A mechanism is proposed for the chlorination reaction, which allowed the evaluation of the intrinsic rate constants for the elementary reactions of the ionized and un-ionized species of each selected pharmaceutical with chlorine. An excellent agreement is obtained between experimental and calculated rate constants by this mechanism.The elimination of these substances in several waters (a groundwater, a surface water from a public reservoir, and two effluents from municipal wastewater treatment plants) was also investigated at neutral pH. The efficiency of the chlorination process with respect to the pharmaceuticals elimination and the formation THMs was also established. It is generally observed that the increasing presence of organic and inorganic matter in the water matrices demand more oxidant agent (chlorine), and therefore, less chlorine is available for the oxidation of these compounds. Finally, half-life times and oxidant exposures (CT) required for the removal of 99% of the four pharmaceuticals are also evaluated. These parameters are useful for the establishment of safety chlorine doses in oxidation or disinfection stages of pharmaceuticals in treatment plants.

An analysis of image texture, tumor location, and MGMT promoter methylation in glioblastoma using magnetic resonance imaging.

In glioblastoma (GBM), promoter methylation of the DNA repair gene O(6)-methylguanine-DNA methyltransferase (MGMT) is associated with benefit from chemotherapy. Correlations between MGMT promoter methylation and visually assessed imaging features on magnetic resonance (MR) have been reported suggesting that noninvasive detection of MGMT methylation status might be possible. Our study assessed whether MGMT methylation status in GBM could be predicted using MR imaging. We conducted a retrospective analysis of MR images in patients with newly diagnosed GBM. Tumor texture was assessed by two methods. First, we analyzed texture by expert consensus describing the tumor borders, presence or absence of cysts, pattern of enhancement, and appearance of tumor signal in T2-weighted images. Then, we applied space-frequency texture analysis based on the S-transform. Tumor location within the brain was determined using automatized image registration and segmentation techniques. Their association with MGMT methylation was analyzed. We confirmed that ring enhancement assessed visually is significantly associated with unmethylated MGMT promoter status (P=0.006). Texture features on T2-weighted images assessed by the space-frequency analysis were significantly different between methylated and unmethylated cases (P<0.05). However, blinded classification of MGMT promoter methylation status reached an accuracy of only 71%. There were no significant differences in the locations of methylated and unmethylated GBM tumors. Our results provide further evidence that individual MR features are associated with MGMT methylation but better algorithms for predicting methylation status are needed. The relevance of this study lies on the application of novel techniques for the analysis of anatomical MR images of patients with GBM allowing the evaluation of subtleties not seen by an observer and facilitating the standardization of the methods, decreasing the potential for interobserver bias.

Population-based study of pseudoprogression after chemoradiotherapy in GBM.

INTRODUCTION: Chemoradiotherapy followed by monthly temozolomide (TMZ) is the standard of care for patients with glioblastoma multiforme (GBM). Case reports have identified GBM patients who experienced transient radiological deterioration after concurrent chemoradiotherapy which stabilized or resolved after additional cycles of adjuvant TMZ, a phenomenon known as radiographic pseudoprogression. Little is known about the natural history of radiographic pseudoprogression. METHODS: We retrospectively evaluated the incidence of radiographic pseudoprogression in a population-based cohort of GBM patients and determined its relationship with outcome and MGMT promoter methylation status. RESULTS: Out of 43 evaluable patients, 25 (58%) exhibited radiographic progression on the first MRI after concurrent treatment. Twenty of these went on to receive adjuvant TMZ, and subsequent investigation demonstrated radiographic pseudoprogression in 10 cases (50%). Median survival (MS) was better in patients with pseudoprogression (MS 14.5 months) compared to those with true radiologic progression (MS 9.1 months, p=0.025). The MS of patients with pseudoprogression was similar to those who stabilized/responded during concurrent treatment (p=0.31). Neither the extent of the initial resection nor dexamethasone dosing was associated with pseudoprogression. CONCLUSIONS: These data suggest that physicians should continue adjuvant TMZ in GBM patients when early MRI scans show evidence of progression following concurrent chemoradiotherapy, as up to 50% of these patients will experience radiologic stability or improvement in subsequent treatment cycles.