Hepatocellular carcinoma in the noncirrhotic liver: Clinical features and outcomes in Veracruz, Mexico. / Carcinoma hepatocelular en hígado no cirrótico: características clínicas y resultados en Veracruz, México.

INTRODUCTION AND AIM: Hepatocellular carcinoma (HCC) is the most frequent primary tumor of the liver. HCC in the noncirrhotic liver accounts for 15-20% of all HCC. Noncirrhotic HCC is a clinically different entity because of the non-neoplastic liver parenchyma involved. Our aim was to describe the presentation, treatment, and predictive survival results of noncirrhotic HCC in Veracruz. MATERIAL AND METHOD: A retrospective study, spanning 13 years, was conducted on patients with noncirrhotic HCC. It analyzed their clinical characteristics, fibrosis/cirrhosis biologic index (NAFLD, MELD, ALBI, APRI, CDS, FIB-4, GUCI, Lok) results, disease treatment, and survival. RESULTS: From a total of 168 cases of HCC, 33 (19.6%) noncirrhotic patients were included in the study. Of those patients, the mean patient age was 67.3 years (51.5% men), 9.1% had hepatitis C virus infection, and 27.3% were alcoholics. Less than 20% of the patients had biologic indexes suggestive of fibrosis/cirrhosis. Mean tumor size was 7.7cm and 42.4% of the patients had alpha-fetoprotein levels>15ng/ml. A total of 52.5% of the tumors were classified as Okuda II and 30.3% of the patients had advanced disease (the Milan criteria). Liver resection was performed on 51.5% of the patients, radiofrequency ablation on 18.2%, and transarterial chemoembolization on 9.1%. The overall 5-year survival rate was 55.4%. Liver resection resulted in the best 5-year survival rate (72.7%). Age>67 years and elevated alpha-fetoprotein levels were associated with poorer survival (P<.05, log-rank). CONCLUSIONS: The characteristics and survival rate of HCC in the noncirrhotic liver were similar to those reported in other studies. Liver resection provided the highest survival rates. The liver fibrosis biologic indexes were not risk factors for survival.

Preferencias del tratamiento en pacientes con Espondiloartritis axial / Treatment preferences in patients with axial spondyloarthritis

Introducción: Una de las premisas del Treat to Target (T2T) es la decisión conjunta del tratamiento entre el reumatólogo y el paciente. Por esta razón las preferencias del paciente juegan un rol fundamental en el éxito del tratamiento a corto y largo plazo. El objetivo de este estudio fue evaluar las preferencias de tratamiento de los pacientes con Espondiloartritis axial (EsPax) e identificar factores asociados a su elección. Material y métodos: Estudio de corte transversal de la cohorte ESPAXIA de pacientes ≥18 años de edad con EsPax (según criterios ASAS 2009). Se consignaron datos sociodemográficos, comorbilidades, características de la enfermedad, y tratamientos recibidos. Se administró un cuestionario especialmente diseñado, en modalidad de elección múltiple y/o respuesta categorizada según orden de importancia de los enunciados. Análisis estadístico: Estadística descriptiva. Test T de Student, test de Chi2 y análisis de regresión logística múltiple. Se consideró significativo un valor de p<0,05. Resultados: Se incluyeron 70 pacientes con una edad mediana (m) de 46,5 años (RIC: 38-57) y un tiempo m de evolución de 13,5 años (RIC: 7,75-23,25). Los aspectos más importantes en la elección del tratamiento fueron: la capacidad de mejoría en la calidad de vida, seguido por mejoría en la inflamación articular, el dolor y la función física. Las vías de administración elegidas en orden decreciente de frecuencia fueron: vía oral (VO) 51,4%, subcutánea (SC) 41,4%, intramuscular (IM) 4,3% y endovenosa (EV) 2,9%. El intervalo entre dosis más votado en la VO fue 1 comprimido semanal (61,1%), y en la SC, 1 aplicación mensual (34,5%). La elección de la VO, se asoció con: preferencia por la autoaplicación, preferencia de aplicación en el hogar y mayor nivel de escolaridad. La elección de la vía SC, fue más frecuente en los pacientes con EA. Los pacientes que recibían tratamiento biológico por vía SC, así como aquellos que tenían la actividad de su enfermedad más controlada, tuvieron mayor conformidad con el tratamiento. Conclusión: La vía de administración de la medicación preferida en nuestra cohorte de pacientes con EsPax fue la oral. Los pacientes con mayor conformidad de tratamiento fueron aquellos que recibían el tratamiento biológico por vía SC y los que tenían menor actividad de la enfermedad.

Background: One of the premises of the Treat to Target (T2T) is the shared treatment decision between the rheumatologist and the patient. For this reason, patient preferences play a fundamental role in the success of treatment in the short and long term. The aims of this study were to evaluate the treatment preferences of patients with Axial Spondyloarthritis (axSpA) and to identify the factors associated with their choice. Material and methods: Cross sectional study. Patients ≥18 years old that fulfilled the ASAS 2009 criteria for axSpA were included. Sociodemographic data, comorbidities, disease characteristics, and treatments received were recorded. A specially designed questionnaire in both, multiple choice modality and response mode listed in order of priority of the statements was administered. Statistical analysis: Descriptive statistics. Student's T-test, Chi2 test and multiple logistic regression analysis. A value of p <0.05 was considered significant. Results: Seventy patients were included with a median age (m) of 46.5 years (IQR: 38-57), 55 males (78.6%) and a median disease duration of 13.5 years (IQR: 7.75-23.25). The relevant aspects for choosing a treatment were: the ability to improve the quality of life (32.9%), followed by improvement in joint inflammation (22.9%), pain (21.4%) and physical function (14.3%). The chosen administration routes in decreasing order of frequency were: oral (51.4%), subcutaneous (SC) (41.4%), intramuscular (IM) 4.3% and intravenous (IV) 2.9%. The preferred frequency of oral administration was one tablet per week (61.1%) and SC administration, once a month (34.5%). The choice of oral route was associated with: preference for self-administration, preference for receiving the medication at home and higher level of education. The choice of the SC route was independently associated with the type of axSpA (AS) and a lower educational level. The patients under biological SC treatment and with lower disease activity, showed higher level of treatment satisfaction. Conclusion: The most preferred way of administration by patients with axSpA was the oral route. Lower disease activity and SC biological treatment were associated with treatment greater compliance.

[Beliefs and perceptions of the diagnosis and treatment of fibromyalgia in a group of rehabilitation and physical medicine specialists in Colombia]. / Conceptos y percepciones acerca del diagnóstico y tratamiento de la fibromialgia en un grupo de médicos especialistas en medicina física y rehabilitación en Colombia.

INTRODUCTION: Fibromyalgia is a chronic disease characterised by the presence of musculoskeletal pain, usually associated with other symptoms, including depression, fatigue, and sleep disorders. There is no objective information on the beliefs and perceptions of the diagnosis and treatment of fibromyalgia among rehabilitation and physical medicine specialists. The aim of this study was to describe these beliefs and perceptions among a group of physical medicine and rehabilitation specialists in Colombia. METHODS: We performed a cross-sectional study. A focus group was held with the participation of 2 rheumatologists, one physical medicine and rehabilitation specialist and an expert in qualitative research. The group designed a survey to assess the beliefs and perceptions of physical medicine and rehabilitation specialists of the diagnosis and treatment of fibromyalgia. The self-administered, anonymous questionnaire was completed during meetings of the Colombian Association of Physical Medicine and Rehabilitation. RESULTS: The questionnaire was completed by 99 physical medicine and rehabilitation specialists. Of these, 17.1% (n=17) believed there was insufficient evidence to consider fibromyalgia a disease, 86.8% (n=86) used the ACR 1990 criteria to diagnose patients with fibromyalgia, and 33.3% (n=33) used the criteria of the 2010 classification. The most commonly used drugs for the management of fibromyalgia were antidepressants, prescribed by 84.8% of the surveyed physicians, followed by analgesics (75.7%) and anticonvulsants (66.6%). Concerning multidisciplinary management, 50.6% referred these patients to a rheumatologist and 40.7% to a psychiatrist. In all, 77.2% of rehabilitation specialists believed that patients with fibromyalgia should be managed by their specialty. CONCLUSION: This study provides information on perceptions of the diagnosis and treatment of fibromyalgia among a group of Colombian rehabilitation specialists and found frequent use of the ACR 1990 classification. Among these physicians, the use of drugs, especially antidepressants and analgesics, was high. Most believed that patients with fibromyalgia should be treated by rehabilitation specialists.

Tolerancia, sobrevida y adherencia al tratamiento con Metotrexato en pacientes con artritis reumatoidea / Tolerance, survival and adherence to Methotrexate treatment in patients with rheumatoid arthritis

Introducción: Metotrexato (MTX) es la medicación más utilizada en pacientes con Artritis Reumatoidea (AR). Sin embargo, varios autores han cuestionado su éxito debido a la frecuente presencia de eventos adversos y la consiguiente falta de adherencia al tratamiento. Objetivos: Determinar la sobrevida al tratamiento con MTX, eventos adversos y causas de discontinuación en pacientes con AR. Material y métodos: Se incluyeron pacientes ≥18 años de edad con diagnóstico de AR (criterios ACR/EULAR 2010), en forma consecutiva, que hubiesen iniciado en algún momento tratamiento con MTX. Se consignaron datos sociodemográficos, clínicos y terapéuticos. Se determinó fecha de inicio y suspensión de MTX, forma de administración, tratamientos concomitantes, consumo de café y tabaco, como también presencia de eventos adversos (EA). La adherencia se evaluó utilizando el cuestionario Compliance Questionnaire Rheumatology de 5 ítems (CQR5). Análisis estadístico: Estadística descriptiva. Test Chi² o test exacto de Fisher. Sobrevida del tratamiento por Kaplan-Meier y log Rank. Regresión logística múltiple. Una p <0,05 se consideró significativa. Resultados: Se incluyeron 118 pacientes, 101 mujeres (85,6%), con una edad mediana (m) de 56 años (RIC 49-64) y tiempo m de evolución de 10 años (RIC 6-18). Ochenta y cinco pacientes (72%) recibieron MTX por vía oral. 43,2% presentaron EA asociados al MTX, donde solo 20 pacientes (16,9%) tuvieron que discontinuar. La intolerancia digestiva fue el EA más frecuente (27,1%), seguida por alteraciones del laboratorio (12,7%). 86,6% de los pacientes presentaron una adherencia ≥80%. La supervivencia mediana acumulada del tratamiento con MTX fue de 348 meses (IC 95%: 235-460,9). En los análisis uni y multivariados no se encontró asociación de la sobreviva del MTX con variables sociodemográficas, características de la enfermedad, tratamiento concomitante, vía de administración, consumo de café y nivel de adherencia. Conclusión: En nuestra cohorte, la adherencia y sobrevida del tratamiento con MTX fueron buenas. La sobrevida acumulada fue de casi 30 años. La presencia de EA no determinó la suspensión del tratamiento en la mayoría de los casos.

Background: Methotrexate (MTX) is the most frequently used medication in patients with Rheumatoid Arthritis (RA). However, several authors have questioned its success due to the presence of adverse events and the lack of adherence. Objectives: To determine cumulative survival of MTX, frequency and type of adverse events and causes of discontinuation in patients with RA. Methods: Consecutive patients 18 years and older with a diagnosis of RA (ACR/EULAR 2010 criteria), who had begun treatment with MTX during their disease were included. Sociodemographic, clinical and therapeutic data were collected. Date of initiation and suspension of MTX, route of administration, concomitant treatments, consumption of coffee and tobacco, presence of adverse events (AE) were all consigned. Adherence was evaluated using the Compliance Questionnaire Rheumatology questionnaire 5-item summary version (CQR5). Statistical analysis: Descriptive statistics. Chi² test or Fisher's exact test; Survival of treatment by Kaplan-Meier and log Rank. Multiple logistic regression. A p value <0.05 was considered significant. Results: We included 118 patients, 101 were women (85.6%), with a median age (m) of 56 years (IQR 49-64) and disease duration m 10 years (IQR 6-18). Thirty-five patients (29.7%) were smokers and 56 patients (47.5%) consumed coffee. Eighty-five patients (72%) received MTX orally. 43.2% presented AE associated with MTX, but only 20 patients (16.9%) had to discontinue MTX. Gastrointestinal intolerance was the most frequent AE (27.1%), followed by laboratory test abnormalities (12.7%). 86.6% of the patients presented an adherence ≥80%. The median cumulative survival of MTX treatment was 348 months (95% CI: 235-460.9). In the univariate and multivariate analysis, there was no association of survival of MTX with sociodemographic variables, disease characteristics, concomitant treatment, route of administration, coffee consumption nor level of adherence. Conclusions: In our cohort, adherence and survival of MTX treatment were good. The cumulative survival was almost 30 years. The presence of AE did not determine the suspension of treatment in most cases.

Seasonal composition, abundance and biomass of the subestuarine fish assemblage in Solís Chico (Río de la Plata estuary, Uruguay) / Composição, abundância e biomasa sazonal da assembleia de peixes no subestuário do Solís Chico (Estuário do Río de la Plata, Uruguay)

Abstract The large estuaries can present long narrow branches called subestuaries or tidal creeks. These types of subsystems are distributed along the Uruguayan coast of the Río de la Plata estuary and are very important as nursery and refuge areas for fish. For the first time, the seasonal composition and abundance of the fish community of the Solís Chico subestuary was studied by using beach and gill nets. Fourteen species, mainly euryhaline (86%) presented a significant representation of juvenile stages. The fish community was dominated by Odontesthes argentinensis, Platanichthys platana, Mugil liza, Brevoortia aurea, Micropogonias furnieri and Paralichthys orbignyanus, similar to adjacent subestuaries. While Micropogonias furnieri and B. aurea were the most abundant species, some other species were rarely caught. A seasonal variation of the fish assemblage abundance was detected, with higher values in autumn showing a positive correlation with temperature. Species that complete their life cycle in the Río de la Plata estuary, some of which are relevant to fisheries (64% of the analyzed species) were captured in the Solís Chico subestuary. The importance of this environment as a transitional system for some estuarine fish species is advised.

Resumo Os grandes estuários podem apresentar longos ramos estreitos chamados subestuários e riachos de maré. Estes subsistemas estão distribuídos ao longo da costa uruguaia no estuário do Río de la Plata e são muito importantes como áreas de reprodução e refúgio para os peixes. Pela primeira vez, a composição sazonal e abundância da comunidade de peixes do subestuário Solís Chico foi estudada usando redes de arrasto de praia e rede de emalhar. Quatorze espécies com predominância das eurialinas foram capturadas, havendo uma representação significativa das fases juvenis e espécies alvo para a pesca. A comunidade de peixes foi dominada por Odontesthes argentinensis, Platanichthys platana, Mugil liza, Brevoortia aurea, Micropogonias furnieri e Paralichthys orbignyanus, semelhante aos subestuários adjacentes. Enquanto, M. furnieri e B. aurea foram as espécies com maior número de individuos. Solís Chico apresentou espécies exclusivas com baixa abundância e ocorrência. Foi verificada uma variação sazonal da abundância de peixes, com valores maiores no outono, mostrando uma correlação positiva com a temperatura. Algumas espécies relevantes para a pesca que completam seu ciclo de vida no estuário do Río de la Plata foram capturadas (64% das espécies estudadas) no subestuário Solís Chico, indicando a importância deste ambiente como um sistema transitório para algumas espécies estuarinas de peixes.

Seasonal composition, abundance and biomass of the subestuarine fish assemblage in Solís Chico (Río de la Plata estuary, Uruguay).

The large estuaries can present long narrow branches called subestuaries or tidal creeks. These types of subsystems are distributed along the Uruguayan coast of the Río de la Plata estuary and are very important as nursery and refuge areas for fish. For the first time, the seasonal composition and abundance of the fish community of the Solís Chico subestuary was studied by using beach and gill nets. Fourteen species, mainly euryhaline (86%) presented a significant representation of juvenile stages. The fish community was dominated by Odontesthes argentinensis, Platanichthys platana, Mugil liza, Brevoortia aurea, Micropogonias furnieri and Paralichthys orbignyanus, similar to adjacent subestuaries. While Micropogonias furnieri and B. aurea were the most abundant species, some other species were rarely caught. A seasonal variation of the fish assemblage abundance was detected, with higher values in autumn showing a positive correlation with temperature. Species that complete their life cycle in the Río de la Plata estuary, some of which are relevant to fisheries (64% of the analyzed species) were captured in the Solís Chico subestuary. The importance of this environment as a transitional system for some estuarine fish species is advised.

Assessment of an image-guided neurosurgery system using a head phantom.

OBJECTIVE: To acknowledge the challenges and limitations of image-guided neurosurgery systems, we compared the application accuracy of two different image registration methods for one commercial system. (VectorVision, BrainLab, Germany). METHODS: We used an anthropomorphic head phantom for radiosurgery and a custom built add-on to simulate surgical targets inside the brain during an image-guided neurosurgery. We used two image registration methods, fiducial registration using attachable surface markers for computed tomography (CT) and surface registration using infrared laser face scanning. After simulation, we calculated the three-dimensional (3D) distance between the predicted position of a target, and its actual position using a registered pointer and an infrared camera. Deviations were measured for both superficial fiducial markers and internal surgical targets by five different users. RESULTS: Deviations from the location of fiducial markers after each registration method were 2.15 ± 0.93 mm after CT surface marker registration and 1.25 ± 0.64 mm after infrared face scanner registration. The mean target registration errors were 2.95 ± 1.4 mm using fiducial registration and 2.90 ± 1.3 mm using surface registration. The largest deviations (6.2 mm) were found for the targets in the skull base and posterior cranial fossa. Fiducial deviations and target registration errors were statistically uncorrelated. The total application accuracy was 4.87 ± 0.97 mm after CT surface marker registration and 4.14 ± 0.64 mm after infrared face scanner registration. CONCLUSIONS: Despite others have reported differences, we did not find significant variations between both registration methods for the target registration error, although application accuracy was slightly better after surface face registration. Superficial registration errors, but not the target registration error, can be routinely evaluated in the operating room. Since both errors were uncorrelated, surgeons may neglect the achievable accuracy of the procedure. The described method is recommended to assess application accuracy in the operating room.

Effect of correction methods of radiochromic EBT2 films on the accuracy of IMRT QA.

Radiochromic films are dosimeters with more favorable characteristics than other two-dimensional (2D) radiation detectors. Transmission film scanners using a linear charge-coupled device (CCD) array have a drawback of variation in response along the detector array, which may result in a nonuniform transmission of signal over the scanned image. This study uses 2D gamma index analysis to compare two methods for correcting the nonuniform response of EBT2: the first method was based on the new red:blue method proposed by the manufacturer (to compensate for small nonuniformities in the film coating) and the second method, proposed by Menegotti et al. (2008), was based on dose-dependent matrix correction factors. The gamma index analysis shows that both the methods are comparably accurate for all the criteria values used for evaluation (1 mm/1%, 2 mm/2%, 3 mm/3%). Centers around the world use both the methods to correct EBT2 local heterogeneities, but it is important to note that the former method has several advantages such as less time consumption and easy implementation.

Hemorragia alveolar difusa asociada a vasculitis ANCA positiva, manejo con plasmaféresis. reporte de un caso / ANCA vasculitis associated diffuse alveolar hemorrhage treated with plasmapheresis: a case report

Presentamos el caso de una paciente femenina de 43 años con vasculitis tipo ANCA con severo compromiso pulmonar por desarrollo de hemorragia alveolar difusa (HAD) e insuficiencia respiratoria. Debido al rápido deterioro clínico y pobre respuesta a inmunosupresores (ciclofosfamida y metilprednisolona) se le practicó plasmaféresis resultando en rápida mejoría, permitiendo la liberación en la ventilación mecánica y mejoría radiológica. En la actualidad se puede sugerir esta terapia en pacientes con diagnóstico de vasculitis tipo ANCA con compromiso pulmonar severo.

We describe a 43 years old woman who was diagnosed of ANCAassociated vasculitides (AAV) with onset of diffuse alveolarhemorrhage and poor pulmonary function. She developed a clinicaldeterioration in spite of cyclophosphamide and methylprednisolonetreatment, and plasmapheresis was performed. She was successfullytreated with timely plasma exchange and immunosuppressivetreatment. Early plasmapheresis with immunosuppressant therapycan rescue this fatal complication.

Antivenom for snakebite envenoming in Sri Lanka: the need for geographically specific antivenom and improved efficacy.

Sri Lanka is a tropical developing island nation that endures significant economic and medical burden as a result of snakebite envenomation, having not only a high prevalence of envenomations, but also one of the highest incidence rates (200 snakebites/100,000 people/year) of venomous snakebite in the world (Kasturiratne et al., 2005). Ironically, the very snakes responsible for this human morbidity and mortality are a valuable biomedical and ecological national resource, despite the medical and economic consequences of envenomation. Currently, no snake antivenom is produced using venoms from native Sri Lankan snakes as immunogens, and there is a true need for an efficacious Sri Lanka, poly-specific snake antivenom. An approach to fulfilling this need via combining the scientific, technological and economical resources from Costa Rica and the United States with the knowledge and talent of Sri Lankan official governmental agencies, legal counsels, environmental, medical and veterinary academic institutions, and religious and cultural leaders has been initiated, coordinated and funded by Animal Venom Research International (AVRI), a nonprofit charity. This bridging of nations and the cooperative pooling of their resources represents a potential avenue for antivenom development in a developing country that suffers the consequences of few specific resources for the medical management of venomous snakebite. The desired final outcome of such an endeavor for Sri Lanka is, most importantly, improved medical outcomes for snakebite patients, with enhanced and expanded science and technology relating to snake venoms and antivenoms, and the collateral benefits of reduced economic cost for the country.

Antiplasmodial effect of the venom of Crotalus durissus cumanensis, crotoxin complex and Crotoxin B.

The antiplasmodial activity of phospholipases A(2) (PLA(2)) isolated from different animals has been studied. We explored the in vitro anti Plasmodium falciparum effect of a fraction containing crotoxin, Crotoxin B and whole venom of the rattlesnake Crotalus durissus cumanensis. Fraction II (crotoxin complex) was obtained by size exclusion chromatography, whereas Crotoxin B was purified by RP-HPLC. The whole venom is active against the parasite at concentrations of 0.17±0.03 µg/ml, fraction II at 0.76±0.17 µg/ml and Crotoxin B at 0.6±0.04 µg/ml. Differences were observed in the cytotoxic activity against peripheral mononuclear cells, with Crotoxin B exhibiting the highest cytotoxicity. The concentration of Crotoxin B required to exert cytotoxic activity was higher than that required to exert antiplasmodial activity. Lethality in mice confirmed the higher toxicity and neurotoxicity of whole venom and fraction II, whereas Crotoxin B was not lethal at the doses tested. These results suggest the potential of Crotoxin B as a lead compound for antimalarial activity.

Immunochemical and biological characterization of monoclonal antibodies against BaP1, a metalloproteinase from Bothrops asper snake venom.

BaP1 is a P-I class of Snake Venom Metalloproteinase (SVMP) relevant in the local tissue damage associated with envenomations by Bothrops asper, a medically-important species in Central America and parts of South America. Six monoclonal antibodies (MoAb) against BaP1 (MABaP1) were produced and characterized regarding their isotype, dissociation constant (K(d)), specificity and ability to neutralize BaP1-induced hemorrhagic and proteolytic activity. Two MABaP1 are IgM, three are IgG1 and one is IgG2b. The K(d)s of IgG MoAbs were in the nM range. All IgG MoAbs recognized conformational epitopes of BaP1 and B. asper venom components but failed to recognize venoms from 27 species of Viperidae, Colubridae and Elapidae families. Clone 7 cross-reacted with three P-I SVMPs tested (moojeni protease, insularinase and neuwiedase). BaP1-induced hemorrhage was totally neutralized by clones 3, 6 and 8 but not by clone 7. Inhibition of BaP1 enzymatic activity on a synthetic substrate by MABaP1 was totally achieved by clones 3 and 6, and partially by clone 8, but not by clone 7. In conclusion, these neutralizing MoAbs against BaP1 may become important tools to understand structure-function relationships of BaP1 and the role of P-I class SVMP in snakebite envenomation.

Preclinical assessment of the neutralizing capacity of antivenoms produced in six Latin American countries against medically-relevant Bothrops snake venoms.

Species of the genus Bothrops induce the vast majority of snakebite envenomings in Latin America. A preclinical study was performed in the context of a regional network of public laboratories involved in the production, quality control and development of antivenoms in Latin America. The ability of seven polyspecific antivenoms, produced in Argentina, Brazil, Peru, Bolivia, Colombia and Costa Rica, to neutralize lethal, hemorrhagic, coagulant, defibrinogenating and myotoxic activities of the venoms of Bothrops neuwiedi (diporus) (Argentina), Bothrops jararaca (Brazil), B. neuwiedi (mattogrossensis) (Bolivia), Bothrops atrox (Peru and Colombia) and Bothrops asper (Costa Rica) was assessed using standard laboratory tests. Despite differences in the venom mixtures used in the immunization of animals for the production of these antivenoms, a pattern of extensive cross-neutralization was observed between these antivenoms and all the venoms tested, with quantitative differences in the values of effective doses. This study reveals the capacity of these antivenoms to neutralize, in preclinical tests, homologous and heterologous Bothrops venoms in Central and South America, and also highlight quantitative differences in the values of Median Effective Doses (ED50s) between the various antivenoms.

Immunochemical and biological characterization of monoclonalantibodies against BaP1, a metalloproteinase from Bothrops aspersnake venom

BaP1 is a P-I class of Snake Venom Metalloproteinase (SVMP) relevant in the local tissue damage associated with envenomations by Bothrops asper, a medically-important species in Central America and parts of South America. Six monoclonal antibodies (MoAb) against BaP1 (MABaP1) were produced and characterized regarding their isotype, dissociation constant (Kd), specificity and ability to neutralize BaP1-induced hemorrhagic and proteolytic activity. Two MABaP1 are IgM, three are IgG1 and one is IgG2b. The Kds of IgG MoAbs were in the nM range. All IgG MoAbs recognized conformational epitopes of BaP1 and B. asper venom components but failed to recognize venoms from 27 species of Viperidae, Colubridae and Elapidae families. Clone 7 cross-reacted with three P-I SVMPs tested (moojeni protease, insularinase and neuwiedase). BaP1-induced hemorrhage was totally neutralized by clones 3, 6 and 8 but not by clone 7. Inhibition of BaP1 enzymatic activity on a synthetic substrate by MABaP1 was totally achieved by clones 3 and 6, and partially by clone 8, but not by clone 7. In conclusion, these neutralizing MoAbs against BaP1 may become important tools to understand structure–function relationships of BaP1 and the role of P-I class SVMP in snakebite envenomation.

The Caenorhabditis elegans genome: a multifractal analysis.

The Caenorhabditis elegans genome has several regular and irregular characteristics in its nucleotide composition; these are observed within and between chromosomes. To study these particularities, we carried out a multifractal analysis, which requires a large number of exponents to characterize scaling properties. We looked for a relationship between the genetic information content of the chromosomes and multifractal parameters and found less multifractality compared to the human genome. Differences in multifractality among chromosomes and in regions of chromosomes, and two group averages of chromosome regions were observed. All these differences were mainly dependent on differences in the contents of repetitive DNA. Based on these properties, we propose a nonlinear model for the structure of the C. elegans genome, with some biological implications. These results suggest that examining differences in multifractality is a viable approach for measuring local variations of genomic information contents along chromosomes. This approach could be extended to other genomes in order to characterize structural and functional regions of chromosomes.

Diagnostic approach in suspected recurrent primary brain tumors using (18)FDG-PET/MRI, perfusion MRI, visual and quantitative analysis, and three dimensional stereotactic surface projections. First experience in Mexico.

UNLABELLED: Thirty patients with primary cerebral tumors WHO III and IV previously treated, undergoing evaluation for tumoral recurrence, they underwent (18)FDG-PET study, MRI and PMRI. PET uptake was determined by visual inspection and was quantified by use of standard uptake values, the ratio of tumor uptake to normal tissue and were z scored using automated voxel-based comparison. PMRI was quantified by use of ratios of cerebral blood volume (rCBV). The accuracies were determined by comparing imaging data with histologic findings and clinical follow up of up to 21 mo. RESULTS: Sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy were 100 %, 82 %, 90 %, 100 % and 93 % respectively for the PET/MRI fusion and 68 %, 82 %, 87 %, 60 % and 73 % respectively for PMRI. There were two false positive cases for PET/MRI fusion that were confirmed by biopsy: chronic inflammation; and foreign body granulomas. The receiver operating characteristic (ROC) curve analysis showed statistically significant difference (p = 0.0225). CONCLUSIONS: (18)FDG SUVs, glucose uptake ratios and 3D stereotactic surface projections in brain tumors were not a reliable measure for evaluating recurrent tumors. PET/MRI fusion was more sensitive and accurate than PMRI for imaging recurrent primary brain tumors. The region of interest can be visually analyzed on the PET/MRI fusion images and described as recurrent tumor when any activity (lower, equal or greater than the contralateral cortex) is presented in the zone of hyperintensity seen on the post-gadolinium T1-weighted MRI.

Cellular pathology induced by snake venom phospholipase A2 myotoxins and neurotoxins: common aspects of their mechanisms of action.

A large variety of snake toxins evolved from PLA(2) digestive enzymes through a process of 'accelerated evolution'. These toxins have different tissue targets, membrane receptors and mechanisms of alteration of the cell plasma membrane. Two of the most commonly induced effects by venom PLA(2)s are neurotoxicity and myotoxicity. Here, we will discuss how these snake toxins achieve a similar cellular lesion, which is evolutionarily highly conserved, despite the differences listed above. They cause an initial plasma membrane perturbation which promotes a large increase of the cytosolic Ca(2+) concentration leading to cell degeneration, following modes that we discuss in detail for muscle cells and for the neuromuscular junction. The different systemic pathophysiological consequences caused by these toxins are not due to different mechanisms of cell toxicity, but to the intrinsic anatomical and physiological properties of the targeted tissues and cells.

Isolation and characterization of a serine proteinase with thrombin-like activity from the venom of the snake Bothrops asper

A serine proteinase with thrombin-like activity was isolated from the venom of the Central American pit viper Bothrops asper. Isolation was performed by a combination of affinity chromatography on aminobenzamidine-Sepharose and ion-exchange chromatography on DEAE-Sepharose. The enzyme accounts for approximately 0.13 percent of the venom dry weight and has a molecular mass of 32 kDa as determined by SDS-PAGE, and of 27 kDa as determined by MALDI-TOF mass spectrometry. Its partial amino acid sequence shows high identity with snake venom serine proteinases and a complete identity with a cDNA clone previously sequenced from this species. The N-terminal sequence of the enzyme is VIGGDECNINEHRSLVVLFXSSGFL CAGTLVQDEWVLTAANCDSKNFQ. The enzyme induces clotting of plasma (minimum coagulant dose = 4.1 µg) and fibrinogen (minimum coagulant dose = 4.2 µg) in vitro, and promotes defibrin(ogen)ation in vivo (minimum defibrin(ogen)ating dose = 1.0 µg). In addition, when injected intravenously in mice at doses of 5 and 10 µg, it induces a series of behavioral changes, i.e., loss of the righting reflex, opisthotonus, and intermittent rotations over the long axis of the body, which closely resemble the `gyroxin-like' effect induced by other thrombin-like enzymes from snake venoms.