Background: Patent Foramen Ovale (PFO), a remnant of the foetal circulation, is emerging as a new cause of disease. It has been found to be associated with cryptogenic stroke in young adults, peripheral arterial embolism and neurological decompression sickness in divers. The detection of PFO remains a diagnostic challenge; transoesophageal echocardiogram being currently considered the ‘gold standard’. The development of a non-invasive technique is crucial for the identification of a venous-to-arterial shunt (v-aCS) which may permit paradoxical embolism. Little is known about the genetic basis of PFO and our limited knowledge is based on animal studies and gene mutations detected in patients with other cardiac septal defects. Methods: Study 1: PFO Detection and Evaluation: This study was designed to evaluate transcranial Doppler (TCD), transthoracic echocardiogram (TTE) and transoesophageal echocardiogram (TOE) with administration of contrast via arm and femoral veins. We then developed a standardized protocol for PFO detection and quantification using TCD. Study 2: PFO and Migraine: The PFO detection protocol developed from the first study formed the diagnostic technique to detect v-aCS in an adequately powered matched case control study to explore the association between PFO and migraine. Study 3: The Genetic basis of PFO: This study was designed to explore the genetic basis of a PFO using a candidate gene approach. Results: Study 1 - PFO Detection Study: When compared with TOE with femoral vein contrast injection as the ‘gold standard’, TCD with arm vein contrast was 100% sensitive and 97.4% specific for detecting a PFO. We defined a PFO positive (+ve) study on TCD as > 15 microbubbles entering the cerebral circulation, on TCD following arm vein injection and >16 microbubbles with a femoral contrast injection. A ‘major’ PFO+ve v-aCS was defined as >35 microbubbles with arm vein injection or >90 microbubbles with femoral vein injection. We then developed a new diagnostic pathway for PFO detection in clinical practice. Study 2 - PFO Migraine study: A significant difference in prevalence of v-aCS between migraine with aura M+A) and their matched controls was demonstrated with adjusted OR=3.72 (1.48-9.38) p=0.005 for a PFO+ve v-aCS, and a highly significant difference between M+A and controls for a ‘major’ PFO+ve v-aCS with adjusted OR = 6.38 (1.89 – 21.48) p = 0.003. There was significant association with APC resistance and migraine on thrombophilia screen. Study 3 - The PFO Genetics Study: This study detected mutations of GATA4 and NKX2-5 in both PFO+ve cases and PFO-ve controls. Two novel non synonymous mutations of GATA4, c.461T>A and c.994G>A were found only in PFO positive individuals and may be associated with a PFO. All the PFO+ve cases with a GATA4 gene mutation had a major PFO+ve v-aCSConclusion:TCD detects PFO with a sensitivity of 100% and specificity of 92.3% and is the most reliable non-invasive technique for PFO detection. When arm vein injections are used both cough and valsalva provocation is essential. There was a highly significant association between PFO+ve v- aCS and M+A, especially with a ‘major’ PFO+ve v-aCS. GATA 4 mutations though infrequent were found PFO+ve cases and all had major v-aCS.

The role of patent foramen ovale (PFO) in stroke was debated for decades. Randomized clinical trials (RCTs) have shown fewer recurrent events after PFO closure in patients with cryptogenic stroke (CS). However, in clinical practice, treating stroke patients with coexisting PFO raises some questions. This brief review summarizes current knowledge and challenges in handling stroke patients with PFO and identifies issues for future research. The rationale for PFO closure was initially based on the concept of paradoxical embolism from deep vein thrombosis (DVT). However, RCTs did not consider such details, limiting their impact from a pathophysiological perspective. Only a few studies explored the coexistence of PFO and DVT in CS with varying results. Consequently, the PFO itself might play a role as a prothrombotic structure. Transesophageal echocardiography thus appears most appropriate for PFO detection, while a large shunt size or an associated atrial septum aneurysm qualify for a high-risk PFO. For drug-based treatment alone, studies did not find a definite superiority of oral anticoagulation over antiplatelet therapy. Remarkably, drug-based treatment in addition to PFO closure was not standardized in RCTs. The available literature rarely considers patients with transient ischemic attack (TIA), over 60 years of age, and competing etiologies like atrial fibrillation. In summary, RCTs suggest efficacy for closure of high-risk PFO only in a small subgroup of stroke patients. However, research is also needed to reevaluate the pathophysiological concept of PFO-related stroke and establish strategies for older and TIA patients and those with competing risk factors or low-risk PFO.

Crocodiles are ectothermic, intermittent breathing reptiles with low metabolic rates. Additionally, they are diving animals that can stay submerged for long periods, which poses special demands on their cardiovascular system. The crocodilian heart is four-chambered with completely separated ventricles, making it unique among other reptiles. It has special anatomical structures that give it the capability to shunt blood away from the lungs, which results in mixing of deoxygenated and oxygenated blood. The purpose of this study was to morphologically describe the heart and review its functions and the significance of its circulatory patterns. Dissection of two crocodilian hearts was performed for morphological characterization of the heart, including the special features that contribute to the shunting: the left aorta, the foramen of Panizza and the cog-teeth-like valves. Obstruction of the pulmonary outflow tract by the cog-teeth-like valves decreases pulmonary blood flow and generates an increased right ventricular pressure, diverting venous blood into the ‘extra’ left aorta and the systemic circulation. Thus, during shunting conditions, venous blood from the left aorta and arterial blood from the right aorta is mixed. The functional significance of this shunting pattern has been extensively discussed and several hypotheses have been proposed. A recent study showed that the absence of the right-to-left shunt does not affect the diving physiology of crocodiles negatively, but it did result in cardiac hypertrophy, indicating that the shunt might have a significance for the circulation and physiology of extant crocodiles.

Background: Stroke is a leading cause of significant physical, cognitive, and psychiatric morbidity. One risk factor for stroke is paradoxical embolization through a patent foramen ovale (PFO). In cardiac clinical practice, power M-mode Transcranial Doppler (TCD) evaluation is the gold standard for diagnosis of PFO, or right-to-left cardiac shunt (RLS). Brain micro-embolization due to diagnostic bubble contrast echocardiography may cause neurological symptoms in patients with PFO. However, the neurocognitive effects of TCD have not been studied. Objective: The purpose of this study was to evaluate cognitive outcomes in patients who undergo routine diagnostic bubble contrast TCD. The aims of the study were (1) to determine if cognitive function declines pre- to post-TCD evaluation and, (2) to assess the relationship between cognitive function and severity of the RLS measured using the Spencer Grading System. Methods: One hundred and four participants referred to Sorensen Cardiovascular Group for diagnosis of RLS were evaluated for changes in cognitive functioning at three time points. A dual baseline (pre-test and baseline test) was administered to mitigate practice effects between the first and second administrations. All pre and post-TCD comparisons were analyzed using the baseline test and post-TCD test, controlling for the effects of practice, if present. Results: Practice effects were observed for the working memory task, with significant improvement in working memory scores occurring between the first (pre-test) and second (baseline) administrations. The main effect for shunt group (no shunt vs. moderate-to-severe shunt) and the shunt group by time interactions were not significant for processing speed, attention, or working memory, adjusting for practice effects, age, and education. Migraine did not predict group status for mood or shunt variables. Conclusion: Cardiac patients with both small and large RLS did not experience a decline in processing speed, attention, or working memory ability following TCD, suggesting that TCD-induced microemboli do not result in immediate cognitive deficits in these domains. These findings support the use of TCD for routine evaluation of PFO, even in patients with severe RLS, although findings are limited to young (30s), medically healthy, predominately Caucasian individuals assessed immediately following TCD. Results do not exclude the possibility of cognitive impairment at follow-up, on other cognitive tests, or in other cognitive domains.

Introduction: Au moins 30% des AVC ischémiques chez les jeunes demeurent inexpliqués malgré une investigation extensive. Le rôle de certains états prothrombotiques (ÉP) dans la thrombose artérielle reste incertain, possiblement à cause du petit nombre de patients, de populations hétérogènes ou d’ÉP analysés individuellement dans les études antérieures, alors que leur prévalence est basse. Méthodologie : Étude cas-témoins sur une cohorte rétrospective (2002-2011). Les patients âgés de ≤50ans lors d’un AVC ischémique furent identifiés sur une base de données hospitalière. Après exclusion des individus ayant une investigation étiologique incomplète, un syndrome antiphospholipide ou aucun ÉP testé, la cohorte fut divisée en groupes cas (AVC idiopathique) et témoins (étiologie identifiée). La prevalence de chaque ÉP fut comparée entre les groupe, ainsi que la présence de ≥2 ÉP (analyse primaire), sans et avec ajustement pour les facteurs de risque non-prothrombotiques (régression logistique). En analyse de sous-groupe, la présence de ≥1 ÉP fut comparée entre les cas avec versus sans foramen ovale perméable (FOP), entre les cas ou contrôles porteurs d’un FOP avec versus sans migraine, de même qu’entre les cas versus témoins de sexe féminin en incluant la contraception orale parmi les ÉP. Résultats : 502 jeunes avec AVC ischémique furent identifiés. Après exclusion de 108 patients, 184 cas et 210 témoins furent comparés, (âge moyen : 39,2 ans, 51% hommes). La prévalence des ÉP ne différait pas entre les cas et contrôles : déficits en protéine S (0,6%), protéine C (3,4%), antithrombine (1,2%), mutation de la prothrombine (2,5%), facteur V Leiden (4,6%), et anticardiolipines (titre 15-40 unités GPL ou MPL; 3,3%). La présence de ≥2 ÉP n’était pas associée à l’AVC idiopathique, avant (p=0,48) ou après ajustement (p=0,74). La présence de ≥1 ÉP ne différait pas entre les sous-groupes étudiés. Conclusion: Il n’y a pas d’association entre les ÉP, isolés ou en association, avec l’AVC ischémique idiopathique chez les jeunes, même en presence de FOP ou de migraine. / Background: Despite extensive workup, more than 30% of ischemic strokes in young adults remain idiopathic. The role of some prothrombotic factors (PF) in arterial thrombosis remains unclear in previous studies. This may be due to small sample sizes, heterogeneous characteristics of populations studied, or analyzing individual PF with low prevalence. Methods: We conducted a case-control study using a retrospective cohort (2002-2011). From a hospital database, we identified patients with ischemic stroke at age ≤50 years. We excluded patients with incomplete baseline investigation or antiphospholipid syndrome, and those without prothrombotic testing. We compared the prevalence of each PF, as well as the presence of ≥2 PF (primary analysis) between cases with idiopathic stroke and controls with defined stroke etiology, before and after adjusting for non-prothrombotic risk factors. By subgroup analysis, we compared the presence of ≥1 PF between cases with versus without patent foramen ovale (PFO), between cases or controls with PFO with versus without migraine, as well as between women (cases versus controls), including oral contraceptives among PF. Results: 502 young ischemic stroke patients were identified. We excluded 108 patients. We analyzed 184 cases and 210 controls (Mean age : 39.2 y-o, 51% male). Prevalence of individual PF did not differ between cases and controls : protein S (0.6%), protein C (3.4%), antithrombin (1.2%) deficiencies, mutant prothrombin (2.5%), factor V Leiden (4.6%), and total anticardiolipin (titers 15-40 units GPL or MPL; 3,3%). There was no association between the presence of ≥2 PF and idiopathic stroke, before (p=0,48) and after adjusting for non-prothrombotic risk factors (p= 0,74). No differences were observed between subgroups for the presence of ≥1 PF. Conclusion: There is no association between prothrombotic risk factors (analyzed individually or as a group) and idiopathic ischemic stroke in the young, even in those with a PFO or with migraine.

No description available.

O controle da extrusão apical durante a reintervenção endodôntica é essencial para o sucesso do novo tratamento. Nesse contexto, o presente estudo teve como objetivo comparar a quantidade de material sólido extruído na desobturação de canais radiculares variando-se a técnica de esvaziamento e o limite de obturação. Foram utilizados 40 incisivos inferiores previamente tratados divididos em dois grupos de acordo com o limite de obturação estabelecido. Cada grupo foi subdividido em dois subgrupos levando-se em conta a técnica de desobturação empregada; manual (subgrupos A1 e B1) e mecânico-rotatória com limas de Ni-Ti (Quantec LX) (subgrupos A2 e B2). O material sólido extruído foi coletado por meio do sistema de filtração Millipore, levado à secagem em dessecador de sílica e pesado em balança analítica de precisão. Os resultados obtidos foram submetidos a ANOVA para dois fatores de variação sendo em seguida empregado o Teste de Tukey (&#945; = 5%). A técnica de desobturação mecânico-rotatória produziu menor extrusão (0,66mg) que a manual (1,11mg), havendo diferença estatística significante entre elas (p < 0,05). Os canais preenchidos até o vértice radiográfico apresentaram maior quantidade de extrusão (1,38mg) do que os obturados 1 mm aquém do forame (0,39mg), observando-se diferença estatística significante entre eles (p < 0,05). A menor quantidade extrusão foi observada no subgrupo A2 (0,20mg), em que foi empregada a técnica rotatória de desobturação em canais obturados 1mm aquém do forame apical, sendo constatada diferença estatisticamente significante deste subgrupo com os demais (p < 0,05). A extrusão de material sólido durante a desobturação de canais radiculares é influenciado pela técnica empregada e pelo limite apical de obturação. / The apical extrusion control during the endodontic retreatment is essential for the success of the new treatment. The purpose of this study was to compare the quantity of solid apically extruded material during filling removal according the gutta-percha removal technique and root filling limit. Forty mandibular incisors with a single straight canal were selected. The canals were previously endodontically treated and then divided into two groups according the filling level. Each group was subdivided in two groups considering the retreatment technique: stainless steel hand files (subgroups A1 and B1) versus niquel-titanium rotatory instruments (subgroups A2 and B2). The extruded solid material was collected by Millipore filtration system, dried in silica desiccators and weighed in an eletrobalance. The results were analyzed using ANOVA with two variation factors and Tukey Test (&#945; = 5%). The niquel-titanium rotatory instruments produced less extrusion (0,66mg) than the stainless steel hand files (1,11mg), with significant statistical difference between them (p < 0,05). The canals filled until the radiographic apex showed larger amount of extruded material (1,38mg) than those filled 1 mm beyond the foramen (0,39mg). It was observed significant statistical difference between them (p < 0,05). The smaller extruded debris amount was observed in subgroup A2 (0,20mg), in which one the rotary technique was used to remove the gutta-percha of canals filled 1mm beyond the apical foramen. It was verified significant statistical difference of this subgroup with the other ones (p < 0,05). The extrusion of solid material during the gutta-percha removal is influenced by the technique as well as the apical filling limit.

O controle da extrusão apical durante a reintervenção endodôntica é essencial para o sucesso do novo tratamento. Nesse contexto, o presente estudo teve como objetivo comparar a quantidade de material sólido extruído na desobturação de canais radiculares variando-se a técnica de esvaziamento e o limite de obturação. Foram utilizados 40 incisivos inferiores previamente tratados divididos em dois grupos de acordo com o limite de obturação estabelecido. Cada grupo foi subdividido em dois subgrupos levando-se em conta a técnica de desobturação empregada; manual (subgrupos A1 e B1) e mecânico-rotatória com limas de Ni-Ti (Quantec LX) (subgrupos A2 e B2). O material sólido extruído foi coletado por meio do sistema de filtração Millipore, levado à secagem em dessecador de sílica e pesado em balança analítica de precisão. Os resultados obtidos foram submetidos a ANOVA para dois fatores de variação sendo em seguida empregado o Teste de Tukey (&#945; = 5%). A técnica de desobturação mecânico-rotatória produziu menor extrusão (0,66mg) que a manual (1,11mg), havendo diferença estatística significante entre elas (p < 0,05). Os canais preenchidos até o vértice radiográfico apresentaram maior quantidade de extrusão (1,38mg) do que os obturados 1 mm aquém do forame (0,39mg), observando-se diferença estatística significante entre eles (p < 0,05). A menor quantidade extrusão foi observada no subgrupo A2 (0,20mg), em que foi empregada a técnica rotatória de desobturação em canais obturados 1mm aquém do forame apical, sendo constatada diferença estatisticamente significante deste subgrupo com os demais (p < 0,05). A extrusão de material sólido durante a desobturação de canais radiculares é influenciado pela técnica empregada e pelo limite apical de obturação. / The apical extrusion control during the endodontic retreatment is essential for the success of the new treatment. The purpose of this study was to compare the quantity of solid apically extruded material during filling removal according the gutta-percha removal technique and root filling limit. Forty mandibular incisors with a single straight canal were selected. The canals were previously endodontically treated and then divided into two groups according the filling level. Each group was subdivided in two groups considering the retreatment technique: stainless steel hand files (subgroups A1 and B1) versus niquel-titanium rotatory instruments (subgroups A2 and B2). The extruded solid material was collected by Millipore filtration system, dried in silica desiccators and weighed in an eletrobalance. The results were analyzed using ANOVA with two variation factors and Tukey Test (&#945; = 5%). The niquel-titanium rotatory instruments produced less extrusion (0,66mg) than the stainless steel hand files (1,11mg), with significant statistical difference between them (p < 0,05). The canals filled until the radiographic apex showed larger amount of extruded material (1,38mg) than those filled 1 mm beyond the foramen (0,39mg). It was observed significant statistical difference between them (p < 0,05). The smaller extruded debris amount was observed in subgroup A2 (0,20mg), in which one the rotary technique was used to remove the gutta-percha of canals filled 1mm beyond the apical foramen. It was verified significant statistical difference of this subgroup with the other ones (p < 0,05). The extrusion of solid material during the gutta-percha removal is influenced by the technique as well as the apical filling limit.