Predictive genetic testing of at-risk relatives requires analysis of all CCM genes after identification of an unclassified CCM1 variant in an individual affected with cerebral cavernous malformations.

The mutation detection rate for familial cerebral cavernous malformations (CCM) is extremely high, being about 90 % if direct sequencing of the three genes, CCM1, CCM2, and CCM3, is used in conjunction with quantitative analyses to detect larger CCM1-3 deletions/duplications. We here report on an individual who had presented with more than 30 cerebral and spinal cavernous malformations, two intracranial meningiomas, and disease manifestation only in the mid-forties. A CCM1 missense variant of unclear relevance was found during the first sequencing step. Thereafter, direct sequencing of all three CCM genes revealed the typical pathogenic loss-of-function mutation c.598C > T/p.Q200* in the CCM3 gene. Our results demonstrate that mutation analyses of all three CCM genes in the index patient regardless of previous identification of an unclassified CCM1 variant is crucial for reliable predictive testing of at-risk relatives.

Mechanical recanalization with flow restoration in acute ischemic stroke: the ReFlow (mechanical recanalization with flow restoration in acute ischemic stroke) study.

OBJECTIVES: This study sought to assess the feasibility and safety of a recently described technique of mechanical recanalization with the help of a stent-like device. BACKGROUND: In the special group of acute stroke patients with an intracranial large vessel occlusion, intravenous tissue-type plasminogen activator on its own leads to a good clinical outcome (mRS ≤ 2) in only 15% to 25% of cases. The aforementioned technique of mechanical recanalization showed very promising clinical results. METHODS: Forty patients presenting within 6 h from stroke symptom onset were enrolled. Mechanical recanalization was performed using a Solitaire FR revascularization device. The primary endpoint of the study was the clinical outcome rated with the help of the modified Rankin Scale (mRS) after 90 days. RESULTS: Twenty-four patients (60%) showed a good clinical outcome (mRS ≤ 2) at 90 days. One symptomatic hemorrhage was detected on follow-up computed tomography. The death rate was 12.5% (5 patients). Successful recanalization (Thrombolysis In Cerebral Infarction score ≥ 2b) of the target vessel was achieved in 95% of the patients with a mean of 1.8 runs with the device. CONCLUSIONS: The ReFlow (Mechanical Recanalization With Flow Restoration in Acute Ischemic Stroke) study shows that mechanical recanalization with flow restoration is highly effective in stroke patients with a large intracranial vessel occlusion presenting within 4.5 h after symptom onset. (Mechanical Recanalization With Flow Restoration in Acute Ischemic Stroke [ReFlow]; NCT01210729).

Diagnosis and treatment of patients with stroke in a mobile stroke unit versus in hospital: a randomised controlled trial.

BACKGROUND: Only 2-5% of patients who have a stroke receive thrombolytic treatment, mainly because of delay in reaching the hospital. We aimed to assess the efficacy of a new approach of diagnosis and treatment starting at the emergency site, rather than after hospital arrival, in reducing delay in stroke therapy. METHODS: We did a randomised single-centre controlled trial to compare the time from alarm (emergency call) to therapy decision between mobile stroke unit (MSU) and hospital intervention. For inclusion in our study patients needed to be aged 18-80 years and have one or more stroke symptoms that started within the previous 2·5 h. In accordance with our week-wise randomisation plan, patients received either prehospital stroke treatment in a specialised ambulance (equipped with a CT scanner, point-of-care laboratory, and telemedicine connection) or optimised conventional hospital-based stroke treatment (control group) with a 7 day follow-up. Allocation was not masked from patients and investigators. Our primary endpoint was time from alarm to therapy decision, which was analysed with the Mann-Whitney U test. Our secondary endpoints included times from alarm to end of CT and to end of laboratory analysis, number of patients receiving intravenous thrombolysis, time from alarm to intravenous thrombolysis, and neurological outcome. We also assessed safety endpoints. This study is registered with ClinicalTrials.gov, number NCT00153036. FINDINGS: We stopped the trial after our planned interim analysis at 100 of 200 planned patients (53 in the prehospital stroke treatment group, 47 in the control group), because we had met our prespecified criteria for study termination. Prehospital stroke treatment reduced the median time from alarm to therapy decision substantially: 35 min (IQR 31-39) versus 76 min (63-94), p<0·0001; median difference 41 min (95% CI 36-48 min). We also detected similar gains regarding times from alarm to end of CT, and alarm to end of laboratory analysis, and to intravenous thrombolysis for eligible ischaemic stroke patients, although there was no substantial difference in number of patients who received intravenous thrombolysis or in neurological outcome. Safety endpoints seemed similar across the groups. INTERPRETATION: For patients with suspected stroke, treatment by the MSU substantially reduced median time from alarm to therapy decision. The MSU strategy offers a potential solution to the medical problem of the arrival of most stroke patients at the hospital too late for treatment. FUNDING: Ministry of Health of the Saarland, Germany, the Werner-Jackstädt Foundation, the Else-Kröner-Fresenius Foundation, and the Rettungsstiftung Saar.

Carotid artery stenting in acute stroke.

OBJECTIVES: The purpose of this study is to demonstrate the technical success of carotid artery stenting in acute extracranial internal carotid artery (ICA) occlusion as well as the benefit in clinical outcome. BACKGROUND: Stroke caused by acute occlusion of the ICA is associated with a significant level of morbidity and mortality. For this type of lesion, treatment with standard intravenous thrombolysis alone leads to a good clinical outcome in only 17% of the cases, with a death rate as high as 55%. Recanalization of the occluded ICA can lead to an improvement in acute symptoms of stroke, prevent possible deterioration, and reduce long-term stroke risk. At present, there is no consensus treatment for patients with acute ischemic stroke presenting with severe clinical symptoms due to atherosclerotic occlusion of the extracranial ICA. METHODS: Carotid artery stenting was performed in 22 patients with acute atherosclerotic extracranial ICA occlusion within 6 h of stroke symptom onset. In 18 patients, there was an additional intracranial occlusion at the level of the terminal segment of the ICA (n = 4) and at the level of the middle cerebral artery (n = 14). Intracranial occlusions were either treated with the Penumbra system or the Solitaire stent-based recanalization system, or a combination of mechanical recanalization and intra-arterial thrombolysis. Recanalization results were assessed by angiography immediately after the procedure. The neurologic status was evaluated before and after the treatment with a follow-up as long as 90 days using the National Institutes of Health Stroke Scale and the modified Rankin Scale. RESULTS: Successful revascularization of extracranial ICA with acute stent implantation was achieved in 21 patients (95%). There was no acute stent thrombosis. After successful recanalization of the origin of the ICA, the intracranial recanalization with Thrombolysis In Myocardial Infarction flow grade 2/3 was achieved in 11 of the 18 patients (61%). The overall recanalization rate (extracranial and intracranial) was 14 of 22 patients (63%). Nine patients (41%) had a modified Rankin Scale score of ≤2 at 90 days. The mortality rate was 13.6% at 90 days. CONCLUSIONS: Carotid artery stenting in acute atherosclerotic extracranial ICA occlusion with severe stroke symptoms is feasible, safe, and useful within the first 6 h after symptom onset.

Bringing the hospital to the patient: first treatment of stroke patients at the emergency site.

BACKGROUND: Early treatment with rt-PA is critical for favorable outcome of acute stroke. However, only a very small proportion of stroke patients receive this treatment, as most arrive at hospital too late to be eligible for rt-PA therapy. METHODS AND FINDINGS: We developed a "Mobile Stroke Unit", consisting of an ambulance equipped with computed tomography, a point-of-care laboratory system for complete stroke laboratory work-up, and telemedicine capabilities for contact with hospital experts, to achieve delivery of etiology-specific and guideline-adherent stroke treatment at the site of the emergency, well before arrival at the hospital. In a departure from current practice, stroke patients could be differentially treated according to their ischemic or hemorrhagic etiology even in the prehospital phase of stroke management. Immediate diagnosis of cerebral ischemia and exclusion of thrombolysis contraindications enabled us to perform prehospital rt-PA thrombolysis as bridging to later intra-arterial recanalization in one patient. In a complementary patient with cerebral hemorrhage, prehospital diagnosis allowed immediate initiation of hemorrhage-specific blood pressure management and telemedicine consultation regarding surgery. Call-to-therapy-decision times were 35 minutes. CONCLUSION: This preliminary study proves the feasibility of guideline-adherent, etiology-specific and causal treatment of acute stroke directly at the emergency site.

Canavalia ensiformis, un cultivo desarrollado mediante un esfuerzo de investigación interdisciplinaria / Canavalia ensiformis, a cultive

Las leguminosas constituyen no solamente una fuente natural de alimento sino también de una variedad de productos derivados y compuestos de amplia utilización industrial y farmacéutica. Su papel enriquecedor del suelo, producto de su capacidd fijadora de nitrógeno del aire, le confiere de por sí un lugar trascendente en la agricultura. En el trópico, el uso de las leguminosas forrajeras y de granos de mayor productividad ha estado limitado, en gran parte, por la escasa disponibilidad de conocmientos en relación al potencial de producción y utilización de las mismas en la alimentación. Las producciones animales intensivas en Venezuela dependen fundamentalmente de la importación de fuentes proteicas - soya - principalmente, para confirmar los alimentos balanceados. El presente trabajo resume los principales esfuerzos de organización e investigación conducidos por el denominado ®Grupo interdisciplinario Canavalia¼ (GIC), conformado por investigadores de distintas instituciones nacionales e internacionales, que han permitido transformar un cultivo - la canavalia ensiformis - silvestre y desconocido, en una leguminosa de granos que puede ser hoy incorporada a la producción comercial en Venezuela. Se ha definido las prácticas agronómicas y culturales más apropiadas, seleccionando nuevas variedades, mecanizado el cultivo y se cuenta con recomendaciones parael procesamiento y utilización de la planta, en todas sus partes, en alimentación animal. Estos logros, sin duda significativos, no habrían sido posible en tan corto plazo si no se hubieran abordado con un enfoque interdisciplinario de investigación. Es de esperar que el GIC sirva de inspiración y estímulo parapromover por parte de los entes financiadores de Ciencia y Tecnología en Venezuela, el abordaje de los grandes problemas nacionales en base a la conformación de grupos interdisciplinarios de trabajo

Valor nutricional y contenido de factores antinutricionales de harinas precocidas de granos de Canavalia ensiformis / Nutritional value and antinutritional factors content of precooked flours prepared from Canavalia ensiformis

Precooked flours obtained five Canavalia ensiformis varieties were prepared by dehydration in double drums. On a dry matter basis, significant differences (P < 0.05) among varieties were detected for crude protein content (25 to 30 percent), starch (36 to 40 percent) and dietary fiber (13 to 15 percent). Hemagglutinins were eliminated as result of the high temperature (146 degrees C/4 min) employed during the drying process. Similar results were not obtained for trypsin inhibitors and canavanine considering that small amounts of these compounds remained in the precooked flours prepared from canavalia seeds. A 10 percent decrease in available lysine was observed. Biological assays yielded Protein Efficiency Ratio (PER) values of 0, 8-1 and Neat Proteic Relation (NPR) values of 2-3-2.6. True digestibility of protein values were improved from 87 to 90 percent. All cultivars had similar starch digestive utilization coefficient (96 percent) and starch fraction (4 percent) resistant to enzymatic hydrolysis in the rat digestive tract

Problemario de genética general / Problemary of general genetic / Textos y manuales de enseñanza

Este problemario tiene como objetivo: 1) Ayudar a los estudiantes en el aprendizaje de los conceptos básicos de genética y principalmente en la resolución de problemas. 2) Colaborar con los docentes y 3) Complementar los libros de texto de genética general. Para ello se ha dividido cada tema en cinco secciones: guía de estudio, resumen, problemas resueltos, problemas y preguntas propuestas. En el apéndice se incluyen las respuestas de los problemas y preguntas propuestas, así como también algunos conocimientos estadísticos necesarios