Prognostic value of brain perfusion by MRI in the initial study of high grade gliomas.

OBJECTIVES: To evaluate if the tumour perfusion at the initial MRI scan is a marker of prognosis for survival in patients diagnosed with High Grade Gliomas (HGG). To analyse the risk factors which influence on the mortality from HGG to quantify the overall survival to be expected in patients. PATIENTS AND METHODS: The patients diagnosed with HGG through a MRI scan in a third-level hospital between 2017 and 2019 were selected. Clinical and tumour variables were collected. The survival analysis was used to determine the association between the tumour perfusion and the survival time. The relation between the collected variables and the survival period was assessed through Wald's statistical method, measuring the relationship via Cox's regression model. Finally, the type of relationship that exists between the tumour perfusion and the survival was analysed through the Lineal Regression method.Those statistical analysis were carried out using the software SPSS v.17. RESULTS: 38 patients were included (average age: 61.1 years old). The general average survival period was 20.6 months. A relationship between the tumour perfusion at the MRI scan and the overall survival has been identified, in detail, a group with intratumor values of relative cerebral blood volume (rCBV)>3.0 has shown a significant decline in the average survival period with regard to the average survival period of the group with values <3.0 (14.6 months vs. 22.8 months, p = 0.046). It has also been proved that variables like Karnofsky's scale and the response time since the intervention significantly influence on the survival period. CONCLUSIONS: It has become evident that the tumour perfusion via MRI scan has a prognostic value in the initial analysis of HGG. The average survival period of patients with rCBV less than or equal to 3.0 is significantly higher than those patients whose values are higher, which allows to be more precise with the prognosis of each patient.

Guidelines for the management of coagulation disorders in patients with cirrhosis.

Coagulation management in the patient with cirrhosis has undergone a significant transformation since the beginning of this century, with the concept of a rebalancing between procoagulant and anticoagulant factors. The paradigm that patients with cirrhosis have a greater bleeding tendency has changed, as a result of this rebalancing. In addition, it has brought to light the presence of complications related to thrombotic events in this group of patients. These guidelines detail aspects related to pathophysiologic mechanisms that intervene in the maintenance of hemostasis in the patient with cirrhosis, the relevance of portal hypertension, mechanical factors for the development of bleeding, modifications in the hepatic synthesis of coagulation factors, and the changes in the reticuloendothelial system in acute hepatic decompensation and acute-on-chronic liver failure. They address new aspects related to the hemorrhagic complications in patients with cirrhosis, considering the risk for bleeding during diagnostic or therapeutic procedures, as well as the usefulness of different tools for diagnosing coagulation and recommendations on the pharmacologic treatment and blood-product transfusion in the context of hemorrhage. These guidelines also update the knowledge regarding hypercoagulability in the patient with cirrhosis, as well as the efficacy and safety of treatment with the different anticoagulation regimens. Lastly, they provide recommendations on coagulation management in the context of acute-on-chronic liver failure, acute liver decompensation, and specific aspects related to the patient undergoing liver transplantation.

Valor pronóstico de la perfusión cerebral por RM en el estudio inicial de los gliomas de alto grado / Prognostic value of brain perfusion by MRI in the initial study of high grade gliomas

Objetivos: Valorar si la perfusión tumoral en el estudio diagnóstico inicial de RM es un marcador pronóstico para la supervivencia en pacientes diagnosticados de gliomas de alto grado. Analizar los factores de riesgo que influyen en la mortalidad por gliomas de alto grado para poder cuantificar la supervivencia global esperada del paciente. Pacientes y métodos: Se seleccionaron las RM de todos los pacientes diagnosticados de glioma de alto grado en un hospital de tercer nivel entre los años 2017 y 2019. Se recogieron variables clínicas y tumorales. Se usó el análisis de supervivencia para determinar la asociación entre la perfusión tumoral y el tiempo de supervivencia. Se estudió la relación entre las variables recogidas y la supervivencia mediante el estadístico de Wald, cuantificando esta relación mediante la regresión de Cox. Por último, se analizó el tipo de relación existente entre la perfusión tumoral y la supervivencia a través del estudio de regresión lineal. Estos análisis estadísticos se realizaron con el software SPSS v.17. Resultados: Se incluyeron 38 pacientes (media de edad 61,1años). La supervivencia media global fue de 20,6meses. Se observó asociación entre la perfusión tumoral en la RM diagnóstica y la supervivencia global, mostrando el grupo con valores intratumorales de volumen sanguíneo cerebral relativo (rVSC) >3,0 una disminución significativa en el tiempo medio de supervivencia respecto al grupo con valores <3,0 (14,6meses vs 22,8meses, p=0,046). También han demostrado influir significativamente en la supervivencia media variables como la escala de Karfnosky y el tiempo de recidiva desde la intervención. Conclusiones: Se ha evidenciado que la perfusión tumoral por RM tiene valor pronóstico en el estudio inicial de los gliomas de alto grado.(AU)

Objectives: To evaluate if the tumour perfusion at the initial MRI scan is a marker of prognosis for survival in patients diagnosed with high grade gliomas (HGG). To analyse the risk factors which influence on the mortality from HGG to quantify the overall survival to be expected in patients. Patients and methods: The patients diagnosed with HGG through a MRI scan in a third-level hospital between 2017 and 2019 were selected. Clinical and tumour variables were collected. The survival analysis was used to determine the association between the tumour perfusion and the survival time. The relation between the collected variables and the survival period was assessed through Wald's statistical method, measuring the relationship via Cox's regression model. Finally, the type of relationship that exists between the tumour perfusion and the survival was analysed through the lineal regression method.Those statistical analysis were carried out using the software SPSS v.17. Results: Thirty-eight patients were included (average age: 61.1years old). The general average survival period was 20.6months. A relationship between the tumour perfusion at the MRI scan and the overall survival has been identified, in detail, a group with intratumor values of relative cerebral blood volume (rCBV) >3.0 has shown a significant decline in the average survival period with regard to the average survival period of the group with values <3.0 (14.6months vs. 22.8months, P=.046). It has also been proved that variables like Karnofsky's scale and the response time since the intervention significantly influence on the survival period. Conclusions: It has become evident that the tumour perfusion via MRI scan has a prognostic value in the initial analysis of HGG. The average survival period of patients with rCBV less than or equal to 3.0 is significantly higher than those patients whose values are higher, which allows to be more precise with the prognosis of each patient.(AU)

Approach to the patient with cholestasis and jaundice syndrome. Joint AMH, AMG, and AMEG scientific position statement.

The term cholestasis refers to bile acid retention, whether within the hepatocyte or in the bile ducts of any caliber. Biochemically, it is defined by a level of alkaline phosphatase that is 1.67-times higher than the upper limit of normal. Cholestatic diseases can be associated with an inflammatory process of the liver that destroys hepatocytes (hepatitis), withjaundice (yellowing of the skin and mucus membranes, associated with elevated serum bilirubin levels), or with both, albeit the three concepts should not be considered synonymous. Cholestatic diseases can be classified as intrahepatic or extrahepatic, depending on their etiology. Knowing the cause of the condition is important for choosing the adequate diagnostic studies and appropriate treatment in each case. A complete medical history, together with a thorough physical examination and basic initial studies, such as liver ultrasound and liver function tests, aid the clinician in deciding which path to follow, when managing the patient with cholestasis. In a joint effort, the Asociación Mexicana de Hepatología (AMH), the Asociación Mexicana de Gastroenterología (AMG) and the Asociación Mexicana de Endoscopia Gastrointestinal (AMEG) developed the first Mexican scientific position statement on said theme.

Sofosbuvir-velpatasvir in Mexican patients with hepatitis C: A retrospective review.

INTRODUCTION: The sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking. METHODS: A retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment. RESULTS: Overall SVR was 98.8% (95% CI 97.35-100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported. CONCLUSION: Treatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.

Asociación Mexicana de Hepatología A.C. Clinical guideline on hepatitis B.

Hepatitis B virus (HBV) infection continues to be a worldwide public health problem. In Mexico, at least three million adults are estimated to have acquired hepatitis B (total hepatitis B core antibody [anti-HBc]-positive), and of those, 300,000 active carriers (hepatitis B surface antigen [HBsAg]-positive) could require treatment. Because HBV is preventable through vaccination, its universal application should be emphasized. HBV infection is a major risk factor for developing hepatocellular carcinoma. Semi-annual liver ultrasound and serum alpha-fetoprotein testing favor early detection of that cancer and should be carried out in all patients with chronic HBV infection, regardless of the presence of advanced fibrosis or cirrhosis. Currently, nucleoside/nucleotide analogues that have a high barrier to resistance are the first-line therapies.

Asociación Mexicana de Hepatología A.C. Clinical guideline on hepatitis B. / Asociación Mexicana de Hepatología A.C. Guía Clínica de Hepatitis B.

Hepatitis B virus (HBV) infection continues to be a worldwide public health problem. In Mexico, at least three million adults are estimated to have acquired hepatitis B (total hepatitis B core antibody [anti-HBc]-positive), and of those, 300,000 active carriers (hepatitis B surface antigen [HBsAg]-positive) could require treatment. Because HBV is preventable through vaccination, its universal application should be emphasized. HBV infection is a major risk factor for developing hepatocellular carcinoma. Semi-annual liver ultrasound and serum alpha-fetoprotein testing favor early detection of that cancer and should be carried out in all patients with chronic HBV infection, regardless of the presence of advanced fibrosis or cirrhosis. Currently, nucleoside/nucleotide analogues that have a high barrier to resistance are the first-line therapies.

Sofosbuvir-velpatasvir in Mexican patients with hepatitis C: A retrospective review. / Sofosbuvir-velpatasvir en pacientes mexicanos con hepatitis C: una revisión retrospectiva.

INTRODUCTION: The sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking. METHODS: A retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment. RESULTS: Overall SVR was 98.8% (95% CI 97.35-100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported. CONCLUSION: Treatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.

The Mexican consensus on alcoholic hepatitis. / Consenso Mexicano de hepatitis alcohólica.

Alcoholic hepatitis is a frequent condition in the Mexican population. It is characterized by acute-on-chronic liver failure, important systemic inflammatory response, and multiple organ failure. The severe variant of the disease implies elevated mortality. Therefore, the Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Hepatología brought together a multidisciplinary team of health professionals to formulate the first Mexican consensus on alcoholic hepatitis, carried out utilizing the Delphi method and resulting in 37 recommendations. Alcohol-related liver disease covers a broad spectrum of pathologies that includes steatosis, steatohepatitis, different grades of fibrosis, and cirrhosis and its complications. Severe alcoholic hepatitis is defined by a modified Maddrey's discriminant function score ≥ 32 or by a Model for End-Stage Liver Disease (MELD) score equal to or above 21. There is currently no specific biomarker for its diagnosis. Leukocytosis with neutrophilia, hyperbilirubinemia (> 3 mg/dL), AST > 50 U/l (< 400 U/l), and an AST/ALT ratio > 1.5-2 can guide the diagnosis. Abstinence from alcohol, together with nutritional support, is the cornerstone of treatment. Steroids are indicated for severe disease and have been effective in reducing the 28-day mortality rate. At present, liver transplantation is the only life-saving option for patients that are nonresponders to steroids. Certain drugs, such as N-acetylcysteine, granulocyte-colony stimulating factor, and metadoxine, can be adjuvant therapies with a positive impact on patient survival.

Gastroprotective potential of Buddleja scordioides Kunth Scrophulariaceae infusions; effects into the modulation of antioxidant enzymes and inflammation markers in an in vivo model.

ETHNOPHARMACOLOGICAL RELEVANCE: A common plant used to treat several gastric disorders is Buddleja scordioides Kunth, commonly known as salvilla. AIM OF THE STUDY: To detect inflammatory markers, in order to evaluate the gastroprotective potential of salvilla infusions, as this could have beneficial impact on the population exposed to gastric ulcers and colitis. MATERIALS AND METHODS: The present work attempted infusions were prepared with B. scordioides (1% w/w) lyophilized and stored. Total phenolic content and GC-MS analysis were performed. Wistar rats were divided into five groups (n=8), a negative vehicle control, an indomethacin group, and three experimental groups, named preventive, curative, and suppressive. All rats were sacrificed under deep ether anesthesia (6h) after the last oral administration of indomethacin/infusion. The rat stomachs were promptly excised, weighed, and chilled in ice-cold and 0.9% NaCl. Histological analysis, nitrites quantification and immunodetection assays were done. RESULTS: B. scordioides infusions markedly reduced the visible hemorrhagic lesions induced by indomethacin in rat stomachs, also showed down-regulation of COX2, IL-8 and TNFα and up-regulation of COX-1 with a moderate down-regulation of NFkB and lower amount of nitrites. However, this behavior was dependent on the treatment, showing most down-regulation of COX-2, TNFα and IL-8 in the curative treatment; more down-regulation of NF-kB in the preventive treatment; and more up-regulation of COX-1 for the suppressor and preventive treatments. CONCLUSION: The anti-inflammatory potential of B. scordioides infusions could be related with the presence of polyphenols as quercetin in the infusion and how this one is consumed.

Greenhouse gas emissions from stabilization ponds in subtropical climate.

Waste stabilization ponds (WSPs) are a cost-efficient method to treat municipal and non-toxic industrial effluents. Numerous studies have shown that WSPs are a source of greenhouse gas (GHG). However, most reports concerned anaerobic ponds (AP) and few have addressed GHG emissions from facultative (FP) and aerobic/maturation ponds (MPs). In this paper, GHG emissions from three WSP in series are presented. These WSPs were designed as anaerobic, facultative and aerobic/maturation and were treating agricultural wastewater. CH4 fluxes from 0.6 +/- 0.4 g CH4 m(-2) d(-1) in the MP, to 7.0 +/- 1.0 g CH4 m(-2) d(-1) in the (AP), were measured. A linear correlation was found between the loading rates of the ponds and CH4 emissions. Relatively low CO2 fluxes (0.2 +/- 0.1 to 1.0 +/- 0.8 g CO2 m(-2) d(-1)) were found, which suggest that carbonate/bicarbonate formation is caused by alkaline pH. A mass balance performed showed that 30% of the total chemical oxygen demand removed was converted to CH4. It has been concluded that the WSP system studied emits at least three times more GHG than aerobic activated sludge systems and that the surface loading rate is the most important design parameter for CH4 emissions.

Chronic administration of thiamine pyrophosphate decreases age-related histological atrophic testicular changes and improves sexual behavior in male Wistar rats.

Aging is a multifactorial universal process and constitutes the most important risk factor for chronic-degenerative diseases. Although it is a natural process, pathological aging arises when these changes occur quickly and the body is not able to adapt. This is often associated with the generation of reactive oxygen species (ROS), inflammation, and a decrease in the endogenous antioxidant systems, constituting a physiopathological state commonly found in chronic-degenerative diseases. At the testicular level, aging is associated with tissue atrophy, decreased steroidogenesis and spermatogenesis, and sexual behavior disorders. This situation, in addition to the elevated generation of ROS in the testicular steroidogenesis, provides a critical cellular environment causing oxidative damage at diverse cellular levels. To assess the effects of a reduction in the levels of ROS, thiamine pyrophosphate (TPP) was chronically administered in senile Wistar rats. TPP causes an activation of intermediate metabolism routes, enhancing cellular respiration and decreasing the generation of ROS. Our results show an overall decrease of atrophic histological changes linked to aging, with higher levels of serum testosterone, sexual activity, and an increase in the levels of endogenous antioxidant enzymes in TPP-treated animals. These results suggest that TPP chronic administration decreases the progression of age-related atrophic changes by improving the intermediate metabolism, and by increasing the levels of antioxidant enzymes.

The fermented non-digestible fraction of common bean (Phaseolus vulgaris L.) triggers cell cycle arrest and apoptosis in human colon adenocarcinoma cells.

Cancer is a leading cause of death worldwide with colorectal cancer (CRC) ranking as the third contributing to overall cancer mortality. Non-digestible compounds such as dietary fiber have been inversely associated with CRC in epidemiological in vivo and in vitro studies. In order to investigate the effect of fermentation products from a whole non-digestible fraction of common bean versus the short-chain fatty acid (SCFAs) on colon cancer cells, we evaluated the human gut microbiota fermented non-digestible fraction (hgm-FNDF) of cooked common bean (Phaseolus vulgaris L.) cultivar Negro 8025 and a synthetic mixture SCFAs, mimicking their concentration in the lethal concentration 50 (SCFA-LC50) of FNDF (hgm-FNDF-LC50), on the molecular changes in human colon adenocarcinoma cells (HT-29). Total mRNA from hgm-FNDF-LC50 and SCFA-LC50 treated HT-29 cells were used to perform qPCR arrays to determine the effect of the treatments on the transcriptional expression of 84 genes related to the p53-pathway. This study showed that both treatments inhibited cell proliferation in accordance with modulating RB1, CDC2, CDC25A, NFKB and E2F genes. Furthermore, we found an association between the induction of apoptosis and the modulation of APAF1, BID, CASP9, FASLG, TNFR10B and BCL2A genes. The results suggest a mechanism of action by which the fermentation of non-digestible compounds of common bean exert a beneficial effect better than the SCFA mixture by modulating the expression of antiproliferative and pro-apoptotic genes in HT-29 cells to a greater extent, supporting previous results on cell behavior, probably due to the participation of other compounds, such as phenolic fatty acids derivatives and biopetides.

Fermented nondigestible fraction from common bean (Phaseolus vulgaris L.) cultivar Negro 8025 modulates HT-29 cell behavior.

The aim of the study was to evaluate the effect of a fermented nondigestible fraction (FNDF) of cooked bean (Phaseolus vulgaris L.) cultivar Negro 8025 on human colon adenocarcinoma HT-29 cell survival. Negro 8025 was chosen for in vitro fermentation based on comparison of chemical composition with 2 other cultivars: Azufrado Higuera and Pinto Durango. Negro 8025 had 58% total dietary fiber, 27% resistant starch, and 20 mg of (+)-catechin equivalents per gram of sample. Short-chain fatty acids (SCFAs) production and pH of the medium were measured after fermentation as indicators of colon protection through induced arrest on cell culture and apoptosis. Butyrate and pH of FNDF of Negro 8025 were higher than the control fermented raffinose extract. The FNDF inhibited HT-29 cell survival in a time- and concentration-dependent manner. The lethal concentration 50 (LC(50)) was 13.63% FNDF (equivalent to 7.36, 0.33, and 3.31 mmol of acetic, propionic, and butyric acids, respectively). DNA fragmentation, an apoptosis indicator, was detected by the TdT-mediated dUTP nick end labeling method in cells treated with the LC(50)-FNDF and a synthetic mixture of SCFAs mimicking LC(50)-FNDF. Our results suggest that common bean is a reliable source of fermentable substrates in colon, producing compounds with potential chemoprotective effect on HT-29 colon adenocarcinoma cells, so it may present an effective alternative to mitigate colon cancer development.

Dietary supplementation of lutein reduces colon carcinogenesis in DMH-treated rats by modulating K-ras, PKB, and ß-catenin proteins.

In colon cancer, disturbances have been detected in genes coding for proteins involved in cellular proliferation, such as K-ras, ß-catenin, extracellular signal-regulated kinases (ERKs), and the protein kinase B (PKB). Although carotenoids such as lutein have an important role to prevent and treat some types of cancer, there are very few studies about the effect of lutein against colon cancer and its activity at the molecular level. Therefore, the aim of this study was to evaluate the chemoprotective activity of lutein against colon cancer induced by dimethylhydrazine (DMH). The results showed a significant increase in protein expression for K-ras and ß-catenin in tumors of DMH-treated rats. Simultaneously, we detected changes in the phosphorylation state of ERK1/2 and PKB in DMH-treated animals. Lutein given in the diet (0.002%), before (prevention) and after (treatment) DMH administration, diminished the number of tumors by 55% and 32%, respectively. Moreover, lutein significantly decreased in tumors the expression of K-ras (25%) and ß-catenin (28%) and the amount of pPKB (32%), during the prevention, and 39%, 26%, and 26% during the treatment stage, respectively. This study demonstrates the chemoprotective effect of lutein against colon cancer by modulating the proliferative activity of K-ras, PKB, and ß-catenin proteins.

Seguimiento mediante angio-resonancia magnética de aneurismas cerebrales embolizados: concordancia entre lectores / MR angiography follow-up of embolized cerebral aneurysms: interobserver agreement

Objetivo: valorar el grado de concordancia entre lectores en los estudios de angio-resonancia magnética (angio-RM) realizados como seguimiento de aneurismas intracraneales embolizados. Asimismo, comprobar si el uso de contraste paramagnético mejora el grado de concordancia. Material y métodos: se recogen los estudios de angio-RM realizados desde julio de 2004 a diciembre de 2006 como seguimiento de aneurismas cerebrales embolizados. Estas exploraciones se analizaron de forma independiente por 2 neurorradiólogos con experiencia en RM. Se obtuvieron 2 secuencias para cada paciente, una sin contraste, mediante parámetros 3D time-of-flight, y otra con contraste paramagnético. Los hallazgos se dividieron en: a) invalorable; b) oclusión completa, y c) resto aneurismático. El grado de concordancia entre lectores para las angio-RM sin y con contraste se midió mediante el cálculo del coeficiente kappa y se clasificó en: k<0,2 insignificante; k=0,21–0,4 bajo; k=0,41–0,6 moderado; k=0,61–0.8 bueno, y k>0,81 excelente. Resultados: se obtuvieron 200 angio-RM, 100 realizadas sin contraste y 100 con contraste, en un total de 48 pacientes a los 6, 12 y/o 24 meses tras la embolización. El grado de concordancia entre lectores fue bueno, tanto para las angio-RM sin contraste como para las con contraste, si bien fue superior para los estudios con contraste (k=0,660, p<0,001 y k=0,779, p<0,001, respectivamente). Conclusiones: la angio-RM presenta una buena concordancia entre lectores en el seguimiento de aneurismas intracraneales embolizados. El uso de contraste paramagnético ha supuesto un mayor grado de concordancia observado (AU)

Objective: To determine the interobserver agreement in the interpretation of MR angiography (MRA) studies for surveillance of embolized intracranial aneurysms. To determine whether contrast administration improves interobserver agreement. Material and methods: Two experienced neuroradiologists independently reviewed all follow-up MRA studies performed between July 2004 and December 2006 of cerebral aneurysms embolized with coils. All MRA studies included both unenhanced 3D time-of-flight (3D TOF) and contrast-enhanced MRA (CE-MRA) images. Studies were classified as: a) not assessable; b) complete occlusion; c) residual aneurysm. Interobserver agreement for unenhanced and enhanced MRA studies was determined using the kappa statistic. Kappa values were considered insignificant when<0.2, low when between 0.21 and 0.4, and moderate when between 0.41–0.6; values >0.6 were considered good agreement and >0.8 excellent agreement. Significance was set at p<0.005. Results: We reviewed a total of 200 MRA studies (100 3D TOF studies and 100 CE-MRA studies) performed in 48 patients (25 women, 23 men) at 6, 12, and/or 24 months after embolization. Interobserver agreement was good in both 3D TOF and CE-MRA studies, although it was better in CE-MRA studies (k=0.660, p<0.001 and k=0.779, p<0.001, respectively). Conclusions: Interobserver agreement is good for follow-up MRA studies of embolized intracranial aneurysms. Gadolinium administration improves interobserver agreement (AU)

[MR angiography follow-up of embolized cerebral aneurysms: interobserver agreement]. / Seguimiento mediante angio-resonancia magnética de aneurismas cerebrales embolizados: concordancia entre lectores.

OBJECTIVE: To determine the interobserver agreement in the interpretation of MR angiography (MRA) studies for surveillance of embolized intracranial aneurysms. To determine whether contrast administration improves interobserver agreement. MATERIAL AND METHODS: Two experienced neuroradiologists independently reviewed all follow-up MRA studies performed between July 2004 and December 2006 of cerebral aneurysms embolized with coils. All MRA studies included both unenhanced 3D time-of-flight (3D TOF) and contrast-enhanced MRA (CE-MRA) images. Studies were classified as: a) not assessable; b) complete occlusion; c) residual aneurysm. Interobserver agreement for unenhanced and enhanced MRA studies was determined using the kappa statistic. Kappa values were considered insignificant when<0.2, low when between 0.21 and 0.4, and moderate when between 0.41-0.6; values >0.6 were considered good agreement and >0.8 excellent agreement. Significance was set at p<0.005. RESULTS: We reviewed a total of 200 MRA studies (100 3D TOF studies and 100 CE-MRA studies) performed in 48 patients (25 women, 23 men) at 6, 12, and/or 24 months after embolization. Interobserver agreement was good in both 3D TOF and CE-MRA studies, although it was better in CE-MRA studies (kappa=0.660, p<0.001 and kappa=0.779, p<0.001, respectively). CONCLUSIONS: Interobserver agreement is good for follow-up MRA studies of embolized intracranial aneurysms. Gadolinium administration improves interobserver agreement.

[Paralysis of cranial nerves as a form of presentation of dissection of the internal carotid artery]. / Parálisis de pares craneales bajos como forma de presentación de la disección de la arteria carótida interna.

INTRODUCTION: Dissection of the internal carotid artery (DIC) is a known cause of cerebral infarct, especially in young patients. The classical clinical syndrome consists of unilateral pain of the head or neck, homolateral oculo-sympathetic paresis and ischaemic symptoms of the cerebral hemisphere involved. Presentation as paralysis of cranial nerves is rare and occurs in less than 12% of cases. The neurological involvement seems to be due to compression caused by the increased diameter of the artery involved. CASE REPORTS: Two patients are reported with paralysis of the lower cranial nerves secondary to DIC. In the first case there was paralysis of the left cranial nerves IX, X, and XII which was diagnosed on angiography using computerized tomography with spiral acquisition. The second patient had clinical involvement of cranial nerves IX, X, XI and XII and magnetic resonance angiography showed the dissection. Both cases were confirmed after digital subtraction angiography. CONCLUSION: Diagnosis of DIC requires a high level of suspicion in cases with atypical onset. The use of new techniques of non invasive imaging diagnosis such as computerized tomography and magnetic resonance angiography permit effective diagnosis of this disorder.

Role of phase 2 enzyme induction in chemoprotection by dithiolethiones.

One of the major mechanisms of protection against carcinogenesis, mutagenesis, and other forms of toxicity mediated by carcinogens is the induction of enzymes involved in their metabolism, particularly phase 2 enzymes such as glutathione S-transferases (GSTs), UDP-glucuronosyl transferases, and quinone reductases. Animal studies indicate that induction of phase 2 enzymes is a sufficient condition for obtaining chemoprevention and can be achieved by administering any of a diverse array of naturally-occurring and synthetic chemopreventive agents. Indeed, monitoring of enzyme induction has led to the recognition or isolation of novel, potent chemopreventive agents such as 1,2-dithiole-3-thiones, terpenoids and the isothiocyanate sulforaphane. For example, oltipraz, a substituted 1,2-dithiole-3-thione originally developed as an antischistosomal agent, possesses chemopreventive activity against different classes of carcinogens targeting multiple organs. Mechanistic studies in rodent models for chemoprevention of aflatoxin B(1) (AFB(1))-induced hepatocarcinogenesis by oltipraz indicates that increased expression of phase 2 genes is of central importance, although inhibition of phase 1 activation of AFB(1) can also contribute to protection. Exposure of rodents to 1,2-dithiole-3-thiones triggers nuclear accumulation of the transcription factor Nrf2 and its enhanced binding to the "antioxidant response element" (ARE), leading to transcriptional activation of a score of genes involved in carcinogen detoxication and attenuation of oxidative stress. Nrf2-deficient mice fail to induce many of these genes in response to dithiolethiones; moreover, basal expression of these genes is typically repressed. To test the hypothesis that enzyme induction is a useful strategy for chemoprevention in humans, three key elements are necessary: a candidate agent, an at-risk population and modulatable intermediate endpoints. Towards this end, a placebo-controlled, double blind clinical trial of oltipraz was conducted in residents of Qidong, PR China who are exposed to dietary aflatoxins and who are at high risk for the development of liver cancer. Oltipraz significantly enhanced excretion of a phase 2 product, aflatoxin-mercapturic acid, a derivative of the aflatoxin-glutathione conjugate, in the urine of study participants administered 125 mg oltipraz by mouth daily. Administration of 500 mg oltipraz once a week led to a significant reduction in the excretion of the primary oxidative metabolite of AFB(1), AFM(1), when measured shortly after drug administration. While this study highlighted the general feasibility of inducing phase 2 enzymes in humans, a longer term intervention is addressing whether protective alterations in aflatoxin metabolism can be sustained for extended periods of time in this high-risk population.