Introdução: A homocistinúria clássica é um erro inato do metabolismo causado pela atividade deficiente da cistationina β-sintase (CβS). É caracterizada pela elevação sérica de homocisteína e metionina e redução dos níveis de cisteína. As manifestações clínicas clássicas envolvem os sistemas ocular, vascular, nervoso central e ósseo. Entretanto, observações recentes sugerem que alterações na composição corporal, especialmente a redução de tecido adiposo, também pode ser uma manifestação frequente e clinicamente relevante nesta doença. Além disso, a gravidade do fenótipo clínico parece ser influenciada por outros genes além do CβS. O objetivo deste estudo foi investigar alterações na composição corporal e detectar mutações comuns nos genes CβS, MTHFR e F5 em pacientes com homocistinúria clássica; relacionando dados clínicos, bioquímicos e genéticos. Métodos: Realizada avaliação da composição corporal em 8 pacientes através de duas técnicas: antropometria (aferição das dobras cutâneas triciptal, biciptal, subescapular e suprailíaca) e bioimpedância elétrica (BIA). A partir dos resultados obtidos, calculou-se o percentual de gordura pelas fórmulas de Siri (antropometria) e Kushner (BIA). O índice de massa corporal (IMC) também foi calculado. Os níveis de metionina, homocisteína e cisteína foram mensurados por HPLC. A avaliação genotípica foi realizada em 11 pacientes através de PCR-RFLP. Pesquisadas as mutações p.I278T, p.T191M, p.G307S e c.844ins68 no gene CβS; c.677TC>T e c.1298A>C no gene MTHFR; e p.R506Q no gene F5 (Fator V de Leiden). Resultados: Cinco pacientes apresentaram baixo percentual de gordura por pelo menos um dos métodos; o restante apresentou percentual médio. De acordo com o IMC, apenas dois pacientes foram classificados em baixo peso. O percentual de gordura total não se relacionou com os achados bioquímicos ou ósseos, mas medida isolada da dobra cutânea triciptal correlacionou-se positivamente com os níveis de cisteína (p=0,03) Além disso, os níveis de homocisteína e metionina correlacionaram-se negativamente com o IMC, enquanto que a cisteína teve associação positiva (p<0.05). Houve tendência do escore T de fêmur associar-se negativamente com homocisteína e positivamente com cisteína (p=0,09). Entre as mutações do gene CβS, a p.1278T foi a única encontrada (n= 3/9 famílias); entretanto, em 2/3 famílias estava em cis com a c.844ins68. Assim, em apenas um caso tinha caráter patogênico. Não foi possível estabelecer associação entre mutações em MTHFR e F5 e a gravidade do fenótipo. Conclusões: Os resultados sugerem que deficiência de CβS gera alterações significativas na composição corporal – observou-se redução do percentual de gordura independentemente do IMC. Este pode ser um mecanismo patogênico importante envolvido na etiologia da 2 osteoporose na homocistinúria clássica, mas estudos adicionais são necessários para demonstrar esta relação. Os achados sugerem que as mutações patogênicas no gene CBS sejam raras ou privadas nesta amostra, e não corroboram a ação dos genes MTHFR e F5 como modificadores da doença. / Introduction: Classical homocystinuria is an inborn error of metabolism caused by the deficient activity of cystathionine β-synthase (CβS). It is characterized by plasma increase in homocysteine and methionine and a decrease in cysteine levels. Its classical clinical manifestations involve the following systems: ocular, vascular, central nervous, and skeletal. However, recent observations have suggested that changes in the body composition, especially a reduction of the adipose tissue, may also be a frequent manifestation of the disease and clinically relevant to it. Moreover, the severity of its clinical phenotype may be influenced by other genes besides CβS. The objective of the present study was to investigate alterations in the body composition and to detect common mutations in CβS, MTHFR and F5 genes in patients with classical homocystinuria and to correlate them to the clinical, biochemical, and genetic data. Methods: Body composition was assessed in 8 patients using the techniques of anthropometry (measurement of the following skinfolds: triciptal, biciptal, subscapular, and suprailiac) and electrical bioimpedance (BIA). Based on the results obtained, the percentage of body fat was calculated using the formulas of Siri (anthropometry) and Kushner (BIA). The body mass index (BMI) was also calculated. The levels of methionine, homocysteine, and cysteine were measured by HPLC. The genotypic evaluation was done in 11 patients by PCR-RFLP. The following mutations were investigated: p.I278T, p.T191M, p.G307S, and c.844ins68 in the CβS gene; c.677TC>T and c.1298A>C in the MTHFR gene; and p.R506Q in the F5 gene (Factor V Leiden). Results: Five patients presented low percentage of body fat by at least one of the methods; the other patients presented a medium percentage. According to the BMI, only 2 patients were classified as being underweight. The percentage of total body fat was not related to either bone or biochemical findings, but the isolate measurement of the triciptal skinfold was positively correlated to the levels of cysteine (p=0.03). Also, the levels of homocysteine and methionine were negatively correlated to the BMI, while cysteine had a positive association (p<0.05). The T score of the femur tended to associate negatively with homocysteine and positively with cysteine (p=0.09). The genetic evaluation revealed only one pathogenic mutation in CβS (p.I278T). An association between mutations in MTHFR and F5 and phenotype severity could not be established. Conclusions: The present results suggest that the deficiency of CβS causes significant alterations in the body composition; a reduction of the percentage of body fat was observed independently from the BMI. This may be an important pathogenic mechanism involved in the etiology of osteoporosis in classical homocystinuria. The present findings suggest that in this sample the 4 pathogenic mutations in the CBS gene are rare or private and do not corroborate with the action of the MTHFR and F5 genes as disease modifiers. Further studies are needed.

This thesis was about the relationship of the Factor V Leiden mutation and activated protein C resistance. I looked up patients with Leiden mutation and activated protein C resistance. I monitored the frequency of thromboembolism and miscarriages in the personal and family case history of patients. Subsequently, I looked up if other risk factors which affect clinical manifestations in patients with this mutation can be found.

Introdução: A homocistinúria clássica é um erro inato do metabolismo causado pela atividade deficiente da cistationina β-sintase (CβS). É caracterizada pela elevação sérica de homocisteína e metionina e redução dos níveis de cisteína. As manifestações clínicas clássicas envolvem os sistemas ocular, vascular, nervoso central e ósseo. Entretanto, observações recentes sugerem que alterações na composição corporal, especialmente a redução de tecido adiposo, também pode ser uma manifestação frequente e clinicamente relevante nesta doença. Além disso, a gravidade do fenótipo clínico parece ser influenciada por outros genes além do CβS. O objetivo deste estudo foi investigar alterações na composição corporal e detectar mutações comuns nos genes CβS, MTHFR e F5 em pacientes com homocistinúria clássica; relacionando dados clínicos, bioquímicos e genéticos. Métodos: Realizada avaliação da composição corporal em 8 pacientes através de duas técnicas: antropometria (aferição das dobras cutâneas triciptal, biciptal, subescapular e suprailíaca) e bioimpedância elétrica (BIA). A partir dos resultados obtidos, calculou-se o percentual de gordura pelas fórmulas de Siri (antropometria) e Kushner (BIA). O índice de massa corporal (IMC) também foi calculado. Os níveis de metionina, homocisteína e cisteína foram mensurados por HPLC. A avaliação genotípica foi realizada em 11 pacientes através de PCR-RFLP. Pesquisadas as mutações p.I278T, p.T191M, p.G307S e c.844ins68 no gene CβS; c.677TC>T e c.1298A>C no gene MTHFR; e p.R506Q no gene F5 (Fator V de Leiden). Resultados: Cinco pacientes apresentaram baixo percentual de gordura por pelo menos um dos métodos; o restante apresentou percentual médio. De acordo com o IMC, apenas dois pacientes foram classificados em baixo peso. O percentual de gordura total não se relacionou com os achados bioquímicos ou ósseos, mas medida isolada da dobra cutânea triciptal correlacionou-se positivamente com os níveis de cisteína (p=0,03) Além disso, os níveis de homocisteína e metionina correlacionaram-se negativamente com o IMC, enquanto que a cisteína teve associação positiva (p<0.05). Houve tendência do escore T de fêmur associar-se negativamente com homocisteína e positivamente com cisteína (p=0,09). Entre as mutações do gene CβS, a p.1278T foi a única encontrada (n= 3/9 famílias); entretanto, em 2/3 famílias estava em cis com a c.844ins68. Assim, em apenas um caso tinha caráter patogênico. Não foi possível estabelecer associação entre mutações em MTHFR e F5 e a gravidade do fenótipo. Conclusões: Os resultados sugerem que deficiência de CβS gera alterações significativas na composição corporal – observou-se redução do percentual de gordura independentemente do IMC. Este pode ser um mecanismo patogênico importante envolvido na etiologia da 2 osteoporose na homocistinúria clássica, mas estudos adicionais são necessários para demonstrar esta relação. Os achados sugerem que as mutações patogênicas no gene CBS sejam raras ou privadas nesta amostra, e não corroboram a ação dos genes MTHFR e F5 como modificadores da doença. / Introduction: Classical homocystinuria is an inborn error of metabolism caused by the deficient activity of cystathionine β-synthase (CβS). It is characterized by plasma increase in homocysteine and methionine and a decrease in cysteine levels. Its classical clinical manifestations involve the following systems: ocular, vascular, central nervous, and skeletal. However, recent observations have suggested that changes in the body composition, especially a reduction of the adipose tissue, may also be a frequent manifestation of the disease and clinically relevant to it. Moreover, the severity of its clinical phenotype may be influenced by other genes besides CβS. The objective of the present study was to investigate alterations in the body composition and to detect common mutations in CβS, MTHFR and F5 genes in patients with classical homocystinuria and to correlate them to the clinical, biochemical, and genetic data. Methods: Body composition was assessed in 8 patients using the techniques of anthropometry (measurement of the following skinfolds: triciptal, biciptal, subscapular, and suprailiac) and electrical bioimpedance (BIA). Based on the results obtained, the percentage of body fat was calculated using the formulas of Siri (anthropometry) and Kushner (BIA). The body mass index (BMI) was also calculated. The levels of methionine, homocysteine, and cysteine were measured by HPLC. The genotypic evaluation was done in 11 patients by PCR-RFLP. The following mutations were investigated: p.I278T, p.T191M, p.G307S, and c.844ins68 in the CβS gene; c.677TC>T and c.1298A>C in the MTHFR gene; and p.R506Q in the F5 gene (Factor V Leiden). Results: Five patients presented low percentage of body fat by at least one of the methods; the other patients presented a medium percentage. According to the BMI, only 2 patients were classified as being underweight. The percentage of total body fat was not related to either bone or biochemical findings, but the isolate measurement of the triciptal skinfold was positively correlated to the levels of cysteine (p=0.03). Also, the levels of homocysteine and methionine were negatively correlated to the BMI, while cysteine had a positive association (p<0.05). The T score of the femur tended to associate negatively with homocysteine and positively with cysteine (p=0.09). The genetic evaluation revealed only one pathogenic mutation in CβS (p.I278T). An association between mutations in MTHFR and F5 and phenotype severity could not be established. Conclusions: The present results suggest that the deficiency of CβS causes significant alterations in the body composition; a reduction of the percentage of body fat was observed independently from the BMI. This may be an important pathogenic mechanism involved in the etiology of osteoporosis in classical homocystinuria. The present findings suggest that in this sample the 4 pathogenic mutations in the CBS gene are rare or private and do not corroborate with the action of the MTHFR and F5 genes as disease modifiers. Further studies are needed.

Introdução: A homocistinúria clássica é um erro inato do metabolismo causado pela atividade deficiente da cistationina β-sintase (CβS). É caracterizada pela elevação sérica de homocisteína e metionina e redução dos níveis de cisteína. As manifestações clínicas clássicas envolvem os sistemas ocular, vascular, nervoso central e ósseo. Entretanto, observações recentes sugerem que alterações na composição corporal, especialmente a redução de tecido adiposo, também pode ser uma manifestação frequente e clinicamente relevante nesta doença. Além disso, a gravidade do fenótipo clínico parece ser influenciada por outros genes além do CβS. O objetivo deste estudo foi investigar alterações na composição corporal e detectar mutações comuns nos genes CβS, MTHFR e F5 em pacientes com homocistinúria clássica; relacionando dados clínicos, bioquímicos e genéticos. Métodos: Realizada avaliação da composição corporal em 8 pacientes através de duas técnicas: antropometria (aferição das dobras cutâneas triciptal, biciptal, subescapular e suprailíaca) e bioimpedância elétrica (BIA). A partir dos resultados obtidos, calculou-se o percentual de gordura pelas fórmulas de Siri (antropometria) e Kushner (BIA). O índice de massa corporal (IMC) também foi calculado. Os níveis de metionina, homocisteína e cisteína foram mensurados por HPLC. A avaliação genotípica foi realizada em 11 pacientes através de PCR-RFLP. Pesquisadas as mutações p.I278T, p.T191M, p.G307S e c.844ins68 no gene CβS; c.677TC>T e c.1298A>C no gene MTHFR; e p.R506Q no gene F5 (Fator V de Leiden). Resultados: Cinco pacientes apresentaram baixo percentual de gordura por pelo menos um dos métodos; o restante apresentou percentual médio. De acordo com o IMC, apenas dois pacientes foram classificados em baixo peso. O percentual de gordura total não se relacionou com os achados bioquímicos ou ósseos, mas medida isolada da dobra cutânea triciptal correlacionou-se positivamente com os níveis de cisteína (p=0,03) Além disso, os níveis de homocisteína e metionina correlacionaram-se negativamente com o IMC, enquanto que a cisteína teve associação positiva (p<0.05). Houve tendência do escore T de fêmur associar-se negativamente com homocisteína e positivamente com cisteína (p=0,09). Entre as mutações do gene CβS, a p.1278T foi a única encontrada (n= 3/9 famílias); entretanto, em 2/3 famílias estava em cis com a c.844ins68. Assim, em apenas um caso tinha caráter patogênico. Não foi possível estabelecer associação entre mutações em MTHFR e F5 e a gravidade do fenótipo. Conclusões: Os resultados sugerem que deficiência de CβS gera alterações significativas na composição corporal – observou-se redução do percentual de gordura independentemente do IMC. Este pode ser um mecanismo patogênico importante envolvido na etiologia da 2 osteoporose na homocistinúria clássica, mas estudos adicionais são necessários para demonstrar esta relação. Os achados sugerem que as mutações patogênicas no gene CBS sejam raras ou privadas nesta amostra, e não corroboram a ação dos genes MTHFR e F5 como modificadores da doença. / Introduction: Classical homocystinuria is an inborn error of metabolism caused by the deficient activity of cystathionine β-synthase (CβS). It is characterized by plasma increase in homocysteine and methionine and a decrease in cysteine levels. Its classical clinical manifestations involve the following systems: ocular, vascular, central nervous, and skeletal. However, recent observations have suggested that changes in the body composition, especially a reduction of the adipose tissue, may also be a frequent manifestation of the disease and clinically relevant to it. Moreover, the severity of its clinical phenotype may be influenced by other genes besides CβS. The objective of the present study was to investigate alterations in the body composition and to detect common mutations in CβS, MTHFR and F5 genes in patients with classical homocystinuria and to correlate them to the clinical, biochemical, and genetic data. Methods: Body composition was assessed in 8 patients using the techniques of anthropometry (measurement of the following skinfolds: triciptal, biciptal, subscapular, and suprailiac) and electrical bioimpedance (BIA). Based on the results obtained, the percentage of body fat was calculated using the formulas of Siri (anthropometry) and Kushner (BIA). The body mass index (BMI) was also calculated. The levels of methionine, homocysteine, and cysteine were measured by HPLC. The genotypic evaluation was done in 11 patients by PCR-RFLP. The following mutations were investigated: p.I278T, p.T191M, p.G307S, and c.844ins68 in the CβS gene; c.677TC>T and c.1298A>C in the MTHFR gene; and p.R506Q in the F5 gene (Factor V Leiden). Results: Five patients presented low percentage of body fat by at least one of the methods; the other patients presented a medium percentage. According to the BMI, only 2 patients were classified as being underweight. The percentage of total body fat was not related to either bone or biochemical findings, but the isolate measurement of the triciptal skinfold was positively correlated to the levels of cysteine (p=0.03). Also, the levels of homocysteine and methionine were negatively correlated to the BMI, while cysteine had a positive association (p<0.05). The T score of the femur tended to associate negatively with homocysteine and positively with cysteine (p=0.09). The genetic evaluation revealed only one pathogenic mutation in CβS (p.I278T). An association between mutations in MTHFR and F5 and phenotype severity could not be established. Conclusions: The present results suggest that the deficiency of CβS causes significant alterations in the body composition; a reduction of the percentage of body fat was observed independently from the BMI. This may be an important pathogenic mechanism involved in the etiology of osteoporosis in classical homocystinuria. The present findings suggest that in this sample the 4 pathogenic mutations in the CBS gene are rare or private and do not corroborate with the action of the MTHFR and F5 genes as disease modifiers. Further studies are needed.

No description available.

Die Krise der Philosophie, die Nietzsche diagnostiziert hat, ist eine Krise der Abstraktheit der Philosophie, einer Philosophie, die nicht mehr als existenziale Luft des Lebens und als existenziale Atmung des Menschen funktioniert. Für Nietzsche ist die Konkretheit als Begriff im Verhältnis mit der wirklichen Lebenswelt des Menschen nicht bloß die Diagnose der Krise des Lebens, sondern eine Philosophie der Heilung, die der Handlung eines Arztes entspricht. In Nietzsches Philosophie als Gesundheitsphilosophie wird die Krankheit als eine Chance bestimmt, wieder gesund werden zu können. Das heißt, die Krankheit ist ein wichtiger Grund für die Hoffnung auf Gesundheit und die Gesundheit ist eine wichtige Antwort auf den Sinn der Krankheit. / The Crisis of Philosophy that Nietzsche has diagnosed, is a Crisis of the Abstractness of Philosophy, a Philosophy that no longer functions as the existential air of Life and existential Breath of Humans. For Nietzsche the Concreteness as understood as a Conceptual unit is in Proportion with the real Life and World of Humans not only the diagnosis of the Crisis of Life, but a Philosophy of Healing, which corresponds to the Cure of a Doctor. In Nietzsche''s Philosophy as a Philosophy of Health the disease is determined as a chance to be Healthy once more. Disease is an important reason for the Hope of Health and Health is an important Response to the sense of the disease.

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.

Trombophilia means an increased disposition to creation of trombs. Health complication incurred as a consequence of hypercoagulation can be very serious. When a trombophilic mutation is found at a patient, it brings necassity of thrombosis - control in risk situations (e.g. pregnancy, operation) for the rest of the patient's life. There were filed 300 people (206 women and 94 men) with trombophilic mutations into my study of clinical signification of trombophilic mutations. These people were examinated in years 2008 - 2010. Most of positive medical findings - 266 people, were recorded in the area of MTHFR (C677T i A1298C) mutations. There were less findings in the field of FV Leiden and FII prothrombin mutations. Multipath trombophilic mutations were found at 99 patients. I accordance with foreign literature, our results advert to clinical consequences of trombophilic mutations like: repeated spontanious aborts, cerebrovascular akcident (CA), ischaemic heart disease (IHD), thrombosis, flebothrombosis, pulmonary embolism, varicose veins, aseptic necrosis of hip bone, arterial sclerosis and aortic stenosis. Mutations MTHFR C677T and MTHFR A1298C we found mainly at patients with CA, IM and IHD. Leiden mutation was most often found at patients with thrombosis, flebothrombosis and pulmonary embolism. We...

La recherche sur les questions touchant aux leaders de groupes sectaires et à la violence sectaire a mené à l’étude du rôle joué par l’autorité charismatique, tel que défini par Weber (1922) et repris par Dawson (2010). À ce sujet, d’éminents spécialistes des études sur les sectes sont d’avis qu’un vide important dans la recherche sur l’autorité charismatique dans le contexte de groupes sectaires et de nouveaux mouvements religieux reste à combler (ajouter les références ‘d’éminents spécialistes’). Ce mémoire vise à contribuer à l’étude cet aspect négligé, le rôle de l’autorité charismatique dans le recours è la violence dans les groupes sectaires, par une étude de cas historique d’un groupe de la Réformation protestante du XVIe siècle, le Royaume anabaptiste de Münster (AKA), sous l’influence d’un leader charismatique, Jan van Leiden. Cette recherche s’intéresse plus spécifiquement aux divers moyens utilisés par Jan van Leiden, pour asseoir son autorité charismatique et à ceux qui ont exercé une influence sur le recours à des actes de violence. L’étude de cas est basé sur le matériel provenant de deux comptes-rendus des faits relatés par des participants aux événements qui se sont déroulés à pendant le règne de Leiden à la tête du AKA. L’analyse du matériel recueilli a été réalisé à la lumière de trois concepts théoriques actuels concernant le comportement cultuel et le recours à la violence.. L’application de ces concepts théoriques a mené à l’identification de quatre principales stratégies utilisées par Jan van Leiden pour établir son autorité charismatique auprès de ses disciples, soit : 1) la menace du millénarisme, 2) l’exploitation d’une relation bilatérale parasitique avec ses disciples, 3) l’utilisation de l’extase religieuse et de la prophétie, 4) l’utilisation du désir de voir survenir des changements sociaux et religieux. En plus de ces quatre stratégies, trois autres dimensions ont été retenues comme signes que le recours à la violence dans le Royaume anabaptiste de Münster résultait de l’établissement de l’autorité charismatique de son leader, soit : 1) la violence liée au millénarisme, 2) la notion d’identité et de violence partagée, 3) des facteurs systémiques, physiques et culturels menant à la violence. / Research surrounding questions regarding cultic behaviors, leadership and issues of sectarian violence has lead to the study of charismatic leadership. Prominent cultic scholars have identified that there remains a rather large void in research when analyzing charismatic leadership within the context of sectarian groups and new religious movements. This thesis will attempt to bridge that gap through a historical case study analysis of a 16th century protestant reformation group, the Anabaptist Kingdom of Münster (AKM), under the influence of a charismatic leader, Jan van Leiden. More specifically, this research will focus on the various means utilized by the group’s leader, to establish charismatic leadership and how this affected the group’s recourse to acts of violence. The case material was obtained through two primary source accounts from participants in the events that unfolded in Münster during Leiden’s reign. The analysis of this material was made using three current theoretical concepts on cultic behavior and violence, that is Casoni (2000), Robbins (2002) and Dawson (2010). It appears that four major strategies were utilized by Jan van Leiden to establish his charismatic leadership over his followers: (1) the threat of millenarianism, (2) the exploitation of a bilateral parasitic relationship with his followers, (3) the use of religious ecstasy and prophecy, and (4) the use of their desire for social and religious change. By contrasting the results of the analyses undertaken in chapters three and four, three factors that have played a crucial role in Leiden’s charismatic leadership, as it relates to the recourse to violence in the AKM, will be identified. These are: (1) millennial violence, (2) shared identity, and (3) macro-level dimensions.

Objetivo: A trombose da veia porta é uma causa importante de hiper-tensão porta em crianças e adolescentes, porém, em uma proporção importante dos casos, não apresenta fator etiológico definido. O objetivo desse estudo é determinar a freqüência de deficiência das proteínas inibidoras da coagulação – proteínas C, S e antitrombina − e das mutações fator V Leiden, G20210A no gene da protrombina e C677T da metileno-tetraidrofolato redutase em crianças e adolescentes com trom-bose da veia porta, definir o padrão hereditário de uma eventual deficiência das pro-teínas inibidoras da coagulação nesses pacientes e avaliar a freqüência da deficiên-cia dessas proteínas em crianças e adolescentes com cirrose. Casuística e Métodos: Foi realizado um estudo prospectivo com 14 crianças e adolescentes com trombose da veia porta, seus pais (n = 25) e dois gru-pos controles pareados por idade, constituídos por um grupo controle sem hepato-patia (n = 28) e um com cirrose (n = 24). A trombose da veia porta foi diagnosticada por ultra-sonografia abdominal com Doppler e/ou fase venosa do angiograma celíaco seletivo. A dosagem da atividade das proteínas C, S e antitrombina foi determinada em todos os indivíduos e a pesquisa das mutações fator V Leiden, G20210A da pro-trombina e C677T da metileno-tetraidrofolato redutase, nas crianças e adolescentes com trombose da veia porta, nos pais, quando identificada a mutação na criança, e nos controles sem hepatopatia. Resultados: Foram avaliados 14 pacientes caucasóides, com uma média e desvio padrão de idade de 8 anos e 8 meses ± 4 anos e 5 meses e do diagnóstico de 3 anos e 8 meses ± 3 anos e seis meses. Metade dos pacientes pertenciam ao gênero masculino. O motivo da investigação da trombose da veia porta foi hemorra-gia digestiva alta em 9/14 (64,3%) e achado de esplenomegalia ao exame físico em 5/14 (35,7%). Anomalias congênitas extra-hepáticas foram identificadas em 3/14 (21,4%) e fatores de risco adquiridos em 5/14 (35,7%) dos pacientes. Nenhum pa-ciente tinha história familiar de consangüinidade ou trombose venosa. A deficiência das proteínas C, S e antitrombina foi constatada em 6/14 (42,9%) (p < 0,05 vs con-troles sem hepatopatia), 3/14 (21,4%) (p > 0,05) e 1/14 (7,1%) (p > 0,05) pacientes com trombose da veia porta, respectivamente. A deficiência dessas proteínas não foi identificada em nenhum dos pais ou controles sem hepatopatia. A mutação G20210A no gene da protrombina foi identificada em um paciente com trombose da veia porta e em um controle sem hepatopatia (p = 0,999), mas em nenhum desses foi identificado a mutação fator V Leiden. A mutação C677T da metileno-tetraidrofo-lato redutase foi observada na forma homozigota, em 3/14 (21,4%) dos pacientes com trombose da veia porta e em 5/28 (17,9%) controles sem hepatopatia (p = 0,356). A freqüência da deficiência das proteínas C, S e antitrombina nos pacientes com cir-rose foi de 14/24 (58,3%), 7/24 (29,2%) e 11/24 (45,8%), respectivamente (p < 0,05 vs controles sem hepatopatia), sendo mais freqüente nos pacientes do subgrupo Child-Pugh B ou C, que foi de 11/12 (91,7%), 5/12 (41,7%) e 9/12 (75%), respectivamente (p < 0,05 vs controles sem hepatopatia). Conclusões: A deficiência de proteína C foi freqüente nas crianças e adolescentes com trombose da veia porta e não parece ser de origem genética. A deficiência de proteína S, antitrombina e as presenças das mutações G20210A da protrombina e C677T da metileno-tetraidrofolato redutase foram observadas mas não apresentaram diferença estatística significativa em relação ao grupo controle sem hepatopatia. O fator V Leiden não foi identificado. Os resultados deste estudo sugerem que a deficiência da proteína C pode ocorre como conseqüência da hiper-tensão porta. Os distúrbios pró-trombóticos hereditários não parecem apresentar um papel importante em relação à trombose nas crianças e adolescentes estudadas. / Objective: Portal vein thrombosis is a major cause of portal hypertension in children and adolescents; yet, its etiology is not clearly defined in a considerable number of cases. The present study aims at determining the prevalence of blood coagulation disorders – protein C, protein S and antithrombin – and factor V Leiden, G20210A prothrombin, and C677T methylenetetrahydrofolate reductase mutations in children and adolescents with portal vein thrombosis, as well as assessing the hereditary character of these disorders in these patients, and also evaluating the prevalence of blood coagulation disorders in children and adolescents with cirrhosis. Study design: A prospective study was carried out, including children and adolescents with portal vein thrombosis (n = 14), their parents (n = 25), two age-matched control groups, one without liver disease (n = 28), and another with cirrhosis (n = 24). Portal vein thrombosis was diagnosed through abdominal Doppler ultrasonography and/or venous phase of selective coeliac angiograms. The activity of protein C, protein S and antithrombin was evaluated for all individuals; the presence of factor V Leiden, G20210A prothrombin, and C677T methylenetetrahydrofolate reductase gene mutations was investigated in children and adolescents with portal vein thrombosis, in parents when their respective children presented any of these mutations, and in the control group without liver disease. Results: 14 Caucasian patients were assessed. The mean and standard deviation for age were 8 years and 8 months ± 4 years and 5 months while the mean and standard deviation for diagnosis were 3 years and 8 months ± 3 years and six months. Half of the patients were males. Initial clinical manifestations upon diagnosis were digestive hemorrhage in 9/14 (64.3%) and splenomegaly on physical examination in 5/14 individuals (35.7%). Patients presented extrahepatic anomalies in 3/14 (21.4%) and acquired risk factors in 5/14 (35.7%) of the cases. None of the patients had a family history of consanguinity or venous thrombosis. The frequency of protein C, protein S and antithrombin deficiency was observed in 6/14 (42.9%) (p < 0.05 vs. controls without liver disease), 3/14 (21.4%) (p > 0.05) and 1/14 (7.1%) (p > 0.05) of patients, respectively. None of the portal vein thombosis patients or controls presented protein C, S or antithrombin deficiency. One portal vein patient and one control (p = 0.999) presented G20210A prothrombin mutation. None of these patients presented the factor V Leiden. The homozygous form of C677T methylenetetrahydrofolate reductase mutation was observed in 3/14 patients with portal vein thrombosis (21.4%) and in 5/28 controls (17.9%) (p = 0.356). The frequency of coagulation inhibitor deficiency was high in cirrhotic patients (14/24 (58.3%) PC, 7/24 (29.2%) PS and 11/24 (45.8%) AT; p < 0.05 vs. controls), especially in Child-Pugh B and C patients (11/12 (91.7%) PC, 5/12 (41.7%) PS and 9/12 (75%) AT; p < 0.05 vs. controls). Conclusions: Protein C deficiency was frequent in children and adolescents with portal vein thrombosis and does not seem to be an inherited condition. Protein S and antithrombin deficiency, and G20210A prothrombin and C677T methylenetetrahydrofolate reductase mutations were observed but did not present statistically significant differences when compared to the controls without liver disease. Factor V Leiden was not observed. The results suggest the protein C deficiency may originates from portal hypertension. The hereditary prothrombotic disorders do not seem to play a vital role in thrombosis in children and adolescents with portal vein thrombosis.