A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America

Background: Genetic counselling and testing for Lynch syndrome (LS) have recently been introduced in several Latin America countries. We aimed to characterize the clinical, molecular and mismatch repair (MMR) variants spectrum of patients with suspected LS in Latin America. Methods: Eleven LS hereditary cancer registries and 34 published LS databases were used to identify unrelated families that fulfilled the Amsterdam II (AMSII) criteria and/or the Bethesda guidelines or suggestive of a dominant colorectal (CRC) inheritance syndrome. Results: We performed a thorough investigation of 15 countries and identified 6 countries where germline genetic testing for LS is available and 3 countries where tumor testing is used in the LS diagnosis. The spectrum of pathogenic MMR variants included MLH1 up to 54%, MSH2 up to 43%, MSH6 up to 10%, PMS2 up to 3% and EPCAM up to 0.8%. The Latin America MMR spectrum is broad with a total of 220 different variants which 80% were private and 20% were recurrent. Frequent regions included exons 11 of MLH1 (15%), exon 3 and 7 of MSH2 (17 and 15%, respectively), exon 4 of MSH6 (65%), exons 11 and 13 of PMS2 (31% and 23%, respectively). Sixteen international founder variants in MLH1, MSH2 and MSH6 were identified and 41 (19%) variants have not previously been reported, thus representing novel genetic variants in the MMR genes. The AMSII criteria was the most used clinical criteria to identify pathogenic MMR carriers although microsatellite instability, immunohistochemistry and family history are still the primary methods in several countries where no genetic testing for LS is available yet. Conclusion: The Latin America LS pathogenic MMR variants spectrum included new variants, frequently altered genetic regions and potential founder effects, emphasizing the relevance implementing Lynch syndrome genetic testing and counseling in all of Latin America countries.Radium Hospital Foundation (Oslo, Norway) in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript, Helse Sør-Øst (Norway) in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript, the French Association Recherche contre le Cancer (ARC) in the analysis, and interpretation of data, the Groupement des Entreprises Françaises dans la Lutte contre le Cancer (Gefluc) in the analysis, and interpretation of data, the Association Nationale de la Recherche et de la Technologie (ANRT, CIFRE PhD fellowship to H.T.) in the analysis, and interpretation of data and by the OpenHealth Institute in the analysis, and interpretation of data. Barretos Cancer Hospital received financial support by FINEP-CT-INFRA (02/2010)info:eu-repo/semantics/publishedVersio

P2-ROV a portable/polar ROV

P2-ROV is a portable polar ROV. Designed to be transported via-helicopter and easily handled by a small team of scientists it is specially addressed to work under the shelf ice of Antarctica by exploiting the holes drilled in the ice by means of a special 350 mm auger; the shape of the vehicle reminds that of a torpedo contained in a 340 mm diameter. Highly automated, P2-ROV is designed to work in hovering in order to monitor the peculiar Platelet Ice and to collect biological samples. For this purpose it will be equipped with a mechanical arm with an embedded suction pump which permits to collect larvae and fish eggs of the species that live and breed in the Platelet Ice. During these operations P2-ROV is remotely controlled, with a tether that transmits mutual information and electrical power, by operators safely standing on the Pack Ice. P2-ROV, light and manageable, is highly modular thanks to the open-frame chassis that allows for quick installation and shifting of tools, equipment and sensors. Even thrusters are interchangeable and displace-able modules. In this way the vehicle can be reconfigured at every mission according to the specific needs

Sampling Surfaces with SESAMO

The sea surface autonomous modular unit (SESAMO) catamaran was satisfactorily exploited for sampling the sea-surface microlayer and immediate subsurface in the Terra Nova Bay area of the Ross Sea during the XIX Italian expedition to Antarctica in January–February 2004. The SESAMO prototype robot, designed to collect data and samples for the study of the sea-air interface, is the result of the synergy between the robotics group of Consiglio Nazionale delle Ricerche–Istituto di Studi sui Sistemi Intelligenti per l”Automazione (CNR-ISSIA), Genoa branch, and the scientific end users of Consiglio Nazionale delle Ricerche–Istituto per la Dinamica dei Processi Ambientali (CNR-IDPA, or Institute for the Dynamics of Environmental Processes) in the framework of a project of the Italian National Program of Research in Antarctica (PNRA). At sea, operations showed that a relatively simple robot could satisfactorily work in a natural, outdoor environment, dramatically facilitating the job of the human operator

PARENTERAL ISRADIPINE REDUCES BLOOD-PRESSURE IN HYPERTENSIVE CRISIS

The efficacy and tolerability of an infusion of isradipine, a calcium antagonist of the dihydropyridine type, were tested in patients in hypertensive crisis. Ten patients with symptomatic and significant elevations in blood pressure were infused for 12 h with isradipine at 1.2, 2.4, 4.8, and 7.2 mug/kg/h (3 h of each infusion level).No untoward effects or adverse reactions were noted. No alterations were observed on electrocardiographic tracings, and blood pressure was significantly reduced only at doses of 7.2 mug/kg/h.Thus, isradipine as an infusion is useful and safe for hypertensive crisis, starting at a rate of 7.2 mug/kg/h. Higher doses may yet prove to be safe, well tolerated, and even more efficacious.ESCOLA PAULISTA MED SCH,DIV HYPERTENS NEPHROL,RUA BOTUCATU 740,BR-04023 SAO PAULO,BRAZILESCOLA PAULISTA MED SCH,DIV HYPERTENS NEPHROL,RUA BOTUCATU 740,BR-04023 SAO PAULO,BRAZILWeb of Scienc

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America

Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path_MLH1 and path_MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%–80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency