Objectif: élaborer un index prédictif de la prééclampsie basé sur les données les plus significatives de lanamnèse, de la clinique, de la biologie et des tests fonctionnels afin didentifier les patientes qui présentent un risque élevé de développer une prééclampsie (PE). Méthodes: Etude cas-contrôle comparant, en dehors de toute grossesse, des patientes ayant présenté, lors dune grossesse antérieure, une prééclampsie (n=101) avec des patientes dont la grossesse a eut un décours strictement normal, à parier pour la gestité, la parité, lâge, lassuétude au tabac et le délai depuis cette grossesse (n=50). Les paramètres analysés sont lanamnèse, lexamen clinique, la biologie sanguine (coagulopathie, trombophilie, hyperhomocystéinémie, vitamines B, marqueurs rénaux et vasculaires); et approches morphologie et fonctionnelle (système cardiovasculaire et rénal). Etude statistique de régressions logistiques a été appliquée à lensemble des données afin de nen dégager que les plus représentatives dans chacune des directions suivies par létude (anamnèse, biologie, épreuve fonctionnelle). Résultats: Lidentification des patientes à haut risque de prééclampsie peut être faite efficacement (88 % de sensibilité et 88 % de spécificité en se basant sur les trois index de risques construits respectivement sur les données anamnestiques et cliniques, sur les données de la biologie et sur les épreuves fonctionnelles. Conclusion: Il ny a actuellement aucun dépistage possible des patientes à risque de prééclampsie en dehors de la grossesse. Cette étude permet lélaboration dun index prédictif de la prééclampsie en préconceptionnel et par la même ouvre les portes à une prévention primaire.

L'objectif de notre première étude était d'identifier les déterminants génétiques et environnementaux du risque de maladie thromboembolique veineuse (MTEV) chez les femmes sous contraceptifs oraux combinés (COC). Après ajustement pour les facteurs confondants, les principaux déterminants environnementaux de la MTEV étaient le tabagisme (OR = 1,65) et un indice de masse corporelle supérieur à 35 kg.m2 (OR = 3,46). En outre, la thrombophilie héréditaire sévère (OR = 2,13) et les groupes sanguins non-O (OR = 1,98). Nous avons confirmé que l’histoire familiale au premier degré de MTEV prédit mal la thrombophilie. En conclusion, cette étude confirme l'influence du tabagisme et de l'obésité et pour la première fois l'impact du groupe sanguin ABO sur le risque de MTEV chez les femmes sous COC. Elle confirme également la faible sensibilité de l'histoire familiale de MTEV pour dépister les thrombophilies héréditaires.Le but de la deuxième étude était d'étudier, chez les utilisatrices de COC, l'impact des polymorphismes génétiques nouvellement identifiés par les études pangénomiques associés au risque de MTEV dans la population générale. Neuf polymorphismes situés sur les gènes KNG1, F11, F5, F2, PROCR, FGG, TSPAN15 et SLC44A2 ont été génotypés dans un échantillon de 766 cas et 464 témoins dans le cadre de l’étude PILGRIM. Seul le polymorphisme rs2289252 situé sur le F11 était significativement associé au risque de MTEV. La présence de l’allèle rs2289252-A du F11 était associée à un risque accru de MTEV (OR =1,6). En outre, la combinaison de l’allèle rs2289252-A et du groupe sanguin non-O, était associée à un risque d’OR de 4. / The aim of our first study was to identify the genetic and environmental determinants of venous thromboembolism (VTE) risk in a large sample of women using combined oral contraceptives (COC). A total of 968 women with a personal history of VTE during COC use were compared with 874 women under COC, but no personal history of VTE. After adjustment for confounding factors, the main environmental determinants of VTE were smoking odds ratio (OR = 1.65) and a body mass index greater than 35 kg.m-2 (OR = 3.46). In addition, severe hereditary thrombophilia (OR = 2.13) and non-O blood groups (OR = 1.98) have been shown to be important genetic risk factors for VTE under COC. First-degree family history of VTE predicts thrombophilia poorly. In conclusion, this study confirms the influence of smoking and obesity and for the first time the impact of ABO blood group on the risk of VTE in women under COC It also confirms the low sensitivity of the family history of VTE to detect hereditary thrombophilia. The purpose of the second study was to study, in COC users, the impact of newly identified genetic polymorphisms by genome-wide as associated with the risk of VTE in the general population. Nine polymorphisms on the KNG1, F11, F5, F2, PROCR, FGG, TSPAN15 and SLC44A2 genes were genotyped in a sample of 766 patients and 464 controls in the PILGRIM study. Only the rs2289252 polymorphism on the F11 was significantly associated with the risk of VTE. The presence of the F11 rs2289252-A allele was associated with an increased risk of VTE (OR = 1.6). In addition, the combination of the rs2289252-A allele and the non-O blood group was associated with an OR risk of 4.

Made available in DSpace on 2014-06-11T19:32:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-11-14Bitstream added on 2014-06-13T21:04:42Z : No. of bitstreams: 1 tofano_vac_dr_botfm.pdf: 984641 bytes, checksum: d4fcddf13acc4d52c783e4c30966c9b0 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A trombose venosa profunda (TVP) caracteriza-se pela formação aguda de um trombo no interior das veias profundas. É uma doença de alta incidência e de grande importância clínica e epidemiológica devido à sua morbimortalidade, sendo atualmente, considerada multifatorial. São vários os fatores de risco genéticos e/ou adquiridos relacionados à TVP e a compreensão da interação destes, permite melhor entender esta doença, não só devido aos seus sintomas de fase aguda mas, principalmente, por sua complicação mais temida, a embolia pulmonar e, a longo prazo, a síndrome pós-trombótica (SPT), que apresenta importante morbidade, inclusive com repercussões sócio-econômicas. A avaliação a longo prazo, clínica e ultrassonográfica, de pacientes com diagnóstico de TVP, visando verificar a incidência e gravidade da SPT é necessária para a compreensão da evolução destes pacientes. Desconhecemos a existência de trabalhos em nosso meio, que avaliem a evolução tardia da TVP. Objetivo: Determinar a evolução a longo prazo de pacientes com TVP de membros, portadores de trombofilia e verificar se existem diferenças na evolução de pacientes trombofílicos e não trombofílicos. Método: Num estudo coorte retrospectivo foram avaliados os prontuários de 275 pacientes atendidos no Hospital das Clínicas da Faculdade de Medicina de Botucatu-Unesp, dos quais foram identificados 60 pacientes trombofílicos, sendo possível contactar 40 deles para consulta, dos quais 39 pacientes aceitaram participar do estudo. Foram selecionados 25 pacientes com diagnóstico de TVP, não trombofílicos, pareados para sexo e idade, para comparação com o grupo trombofílico. Durante a consulta foi preenchido um protocolo que continha as seguintes variáveis: dados demográficos, profissão, antecedentes pessoais e antecedentes obstétricos (se mulher), antecedentes familiares com relação... / Deep vein thrombosis (DVT) is characterized by the acute formation of a thrombus in the interior of the deep veins. It is a disease of high incidence and great clinical and epidemiological importance due to its morbimortality, being presently considered multifactorial. The genetic and/or acquired risk factors related to DVT are various and understanding their interaction allows a better comprehension of this illness, due to both symptoms of the acute stage and, mainly, its most feared complication, the pulmonary embolism and, in long term, the post-thrombotic syndrome (PTS), which presents important morbidity, inclusively with social and economical repercussions. The long-term clinical and ultrasound evaluation of patients with DVT diagnosis, aiming to verify the incidence and seriousness of PTS, is necessary to understand the evolution of these patients. We are not aware of the existence of works in our area which evaluate the late evolution of DVT. Objective: To determine the long-term evolution of patients with DVT of limbs, carriers of thrombophilia, and verify the existence of differences in the evolution of thrombophilic and non-thrombophilic patients. Method: In a retrospective cohort study, the medical registers of 275 patients attended at the Clinics Hospital of the School of Medicine of the Paulista State University, in Botucatu, São Paulo, Brazil, were evaluated, from which 60 thrombophilic patients were identified. It was possible to contact 40 of them for appointment, from which 39 patients accepted to participate in the study. 25 non-thrombophilic patients, paired for sex and age, were selected with DVT diagnosis, for comparison with the thrombophilic group. During the appointment, a protocol was filled in, containing the following variables: demographic data, occupation, personal antecedents and obstetric antecedents (if woman), familiar antecedents concerning thrombosis... (Complete abstract click electronic access below)

Orientador: Izolete Aparecida Thomazini Santos / Banca: Paulo Eduardo de Abreu Machado / Banca: Márcia Aparecida Sperança / Resumo: A perda gestacional recorrente idiopática é multifatorial, pois envolve fatores de risco clínicos e biológicos. A trombofilia pode ser definida como uma predisposição para trombose. Anormalidades na hemostasia que estão associadas com trombofilias clínicas incluem defeitos hereditários, tais como os anticoagulantes naturais Antitrombina III, Proteína S e Proteína C ou fatores de coagulação, as mutações do fator V Leiden, gene da protrombina G20210A, metilenotetrahidrofolato redutase MTHFR C677T, e defeitos adquiridos, tal como Síndrome Antifosfolípide e a Hiperhomocisteinemia. O presente trabalho foi realizado com 70 mulheres, sendo que 35 mulheres apresentavam 3 ou mais abortos recorrentes inexplicáveis, e 35 mulheres voluntárias clinicamente normais, para todas as mulheres foram feitas as investigações para os anticoagulantes naturais da coagulação e investigação para as mutações do fator V Leiden, gene da protrombina G20210A e metilenotetrahidrofolato redutase MTHFR C677T e as deficiências adquiridas. Em nosso estudo, encontramos resultados estatísticamente significantes para a síndrome do anticorpo antifosfolípide (trombofilia adquirida). Em nosso estudo observamos um grande número de defeitos trombofílicos adquiridos sendo que alguns estão em associação com a mutação do fator V Leiden e MTHFR C677T, porém mais pesquisas são necessárias para confirmar ou contestar as causas das trombofilias,e avaliar a eficiência e segurança da tromboprofilaxia em mulheres grávidas. / Abstract: The idiopathic appealing gestational loss is multifactorial because it involves clinical and biological risk factors. Thrombophilia can be defined as a predisposition for thrombosis. Abnormalities in homeostasis that are associated with clinical thrombophilia include hereditary defects, such as natural anticoagulants as Antithrombin III, S Protein and C Protein or coagulation factors, mutations of V Leiden factor, gene of G20210A prothrombin, MTHFR C677T methilene redutase tetrahydropholat, and acquired defects just as Antiphospholipid Syndrome and Hyperhomocisteinemy. The present work was accomplished with 70 women, and 35 women showed 3 or more inexplicable appealing abortions, and 35 women voluntary clinically normal. For all women were made investigations for natural anticoagulants of coagulation and investigations for mutations of V Leiden factor, gene of G20210A prothrombin, MTHFR C677T methilene redutase tetrahydropholat, and acquired defects. In study we found statistically significant results for antiphospholipid antibody syndrome (acquired thrombophilia). In our study it was observed a great number of thrombophilics acquired defects, and some of then are associated to mutation of V Leiden factor and MTHFR C677T, however more researches are necessary to confirm or to answer the causes of the thrombophilia and to evaluate the efficiency and safety of the thromboprophylaxis in pregnant women. / Mestre

Orientador: Francisco Humberto de Abreu Maffei / Banca: Hamilton Almeida Rollo / Banca: Adilson F. Paschôa / Banca: Newton Key Hokama / Banca: Cyrillo C. Filho / Resumo: A trombose venosa profunda (TVP) caracteriza-se pela formação aguda de um trombo no interior das veias profundas. É uma doença de alta incidência e de grande importância clínica e epidemiológica devido à sua morbimortalidade, sendo atualmente, considerada multifatorial. São vários os fatores de risco genéticos e/ou adquiridos relacionados à TVP e a compreensão da interação destes, permite melhor entender esta doença, não só devido aos seus sintomas de fase aguda mas, principalmente, por sua complicação mais temida, a embolia pulmonar e, a longo prazo, a síndrome pós-trombótica (SPT), que apresenta importante morbidade, inclusive com repercussões sócio-econômicas. A avaliação a longo prazo, clínica e ultrassonográfica, de pacientes com diagnóstico de TVP, visando verificar a incidência e gravidade da SPT é necessária para a compreensão da evolução destes pacientes. Desconhecemos a existência de trabalhos em nosso meio, que avaliem a evolução tardia da TVP. Objetivo: Determinar a evolução a longo prazo de pacientes com TVP de membros, portadores de trombofilia e verificar se existem diferenças na evolução de pacientes trombofílicos e não trombofílicos. Método: Num estudo coorte retrospectivo foram avaliados os prontuários de 275 pacientes atendidos no Hospital das Clínicas da Faculdade de Medicina de Botucatu-Unesp, dos quais foram identificados 60 pacientes trombofílicos, sendo possível contactar 40 deles para consulta, dos quais 39 pacientes aceitaram participar do estudo. Foram selecionados 25 pacientes com diagnóstico de TVP, não trombofílicos, pareados para sexo e idade, para comparação com o grupo trombofílico. Durante a consulta foi preenchido um protocolo que continha as seguintes variáveis: dados demográficos, profissão, antecedentes pessoais e antecedentes obstétricos (se mulher), antecedentes familiares com relação... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Deep vein thrombosis (DVT) is characterized by the acute formation of a thrombus in the interior of the deep veins. It is a disease of high incidence and great clinical and epidemiological importance due to its morbimortality, being presently considered multifactorial. The genetic and/or acquired risk factors related to DVT are various and understanding their interaction allows a better comprehension of this illness, due to both symptoms of the acute stage and, mainly, its most feared complication, the pulmonary embolism and, in long term, the post-thrombotic syndrome (PTS), which presents important morbidity, inclusively with social and economical repercussions. The long-term clinical and ultrasound evaluation of patients with DVT diagnosis, aiming to verify the incidence and seriousness of PTS, is necessary to understand the evolution of these patients. We are not aware of the existence of works in our area which evaluate the late evolution of DVT. Objective: To determine the long-term evolution of patients with DVT of limbs, carriers of thrombophilia, and verify the existence of differences in the evolution of thrombophilic and non-thrombophilic patients. Method: In a retrospective cohort study, the medical registers of 275 patients attended at the Clinics Hospital of the School of Medicine of the Paulista State University, in Botucatu, São Paulo, Brazil, were evaluated, from which 60 thrombophilic patients were identified. It was possible to contact 40 of them for appointment, from which 39 patients accepted to participate in the study. 25 non-thrombophilic patients, paired for sex and age, were selected with DVT diagnosis, for comparison with the thrombophilic group. During the appointment, a protocol was filled in, containing the following variables: demographic data, occupation, personal antecedents and obstetric antecedents (if woman), familiar antecedents concerning thrombosis... (Complete abstract click electronic access below) / Doutor

Introduction: Spontaneous abortion (SA) is the most common complication in pregnancy. The aim of the study was to investigate the causality of selected genetic factors - Apolipoprotein E (Apo E) gene polymorphisms, factor V Leiden (FVL), Prothrombin (PT G20210A) and nongenetics factors - Thyroid stimulating hormone (TSH), free thyroxine (fT4), antibodies against thyroid peroxidase (a-TPO) in the role of early SA. Materials and methods: For genotyping of APO E polymorphism was used PCR-RFLP. The detection of mutations in genes FV and FII was performed using by HRM. Laboratory markers of thyroid (TSH, a-TPO and fT4) were determined by an automated analyzer using chemiluminescent immunoassay. Results: APOE genotypes of investigated group of 410 samples abortioned embryonic/ fetal tissues were not significantly different from 2 606 adult controls (P = 0.653). In observed infertile group of 75 women with isolated SA was FVL detected in heterozygous constitution with a prevalence of 12 %. The prevalence of FVL in a group of women with early insulated SA was significantly higher than 76 controls (12 % vs. 2.6 %, P = 0.031). The difference of PTG20210A prevalence between women with isolated SA and controls was not significant (4 % vs. 5.3 %, P = 1). The prevalence of elevated TSH levels (higher than 2.5...

Orientador: Ana Terezinha Guillaumon / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T00:25:35Z (GMT). No. of bitstreams: 1 Paschoa_AdilsonFerraz_D.pdf: 1209751 bytes, checksum: 841d1a79e90d1ef1c6bb14b58b807236 (MD5) Previous issue date: 2006 / Resumo: O tromboembolismo venoso (TEV) afeta de 1 a 3 indivíduos por mil habitantes/ano. O conhecimento atual das trombofilias permite a associação com cerca de 40% dos casos de TEV. Há controvérsias quanto ao valor da pesquisa laboratorial de trombofilia para o benefício dos doentes com tromboembolismo venoso. Procuraram-se as variáveis preditivas para a pesquisa positiva de trombofilia e avaliar o impacto desses resultados nas decisões clínicas. Foram avaliados 84 doentes consecutivos com TEV confirmado por métodos de imagem no período entre janeiro de 2001 e novembro de 2003. Após o período previsto de anticoagulação definido por critérios clínicos, os doentes foram submetidos à pesquisa das principais causas de trombofilia. Os resultados laboratoriais permitiram a dois examinadores independentes reavaliar caso-a-caso a indicação de ¿mudança de conduta¿, caracterizada pela interferência no tempo de profilaxia secundária ou ¿atenção especial¿ para medidas de maior vigilância diante de situações de risco ou para a extensão da pesquisa aos familiares assintomáticos. A trombofilia foi encontrada em 35 dos 84 casos (41,66%), sendo que em 27 (32,12%) havia uma causa genética. O fator V Leiden foi a alteração mais freqüente (15,47%), seguida do conjunto de deficiência dos anticoagulantes naturais (11,9%). Não houve diferença significativa da freqüência de trombofilia relacionada à faixa etária nem diferença de idade de aparecimento do primeiro evento trombótico entre doentes trombofílicos e não trombofílicos. Houve significância estatística para ocorrência de trombofilia nos doentes com tromboflebite superficial, recorrência e na associação com fatores de risco não cirúrgicos. A ¿mudança de conduta¿ foi atribuída a 6 dos 84 doentes (7,14%), estatisticamente significativa para aqueles com recorrência em relação aos que tiveram apenas um episódio de TEV. A ¿atenção especial¿ foi atribuída a 34 dos 84 casos (40,47%).A tromboflebite superficial de aparecimento espontâneo, a ocorrência de TEV relacionada a causas não cirúrgicas e a recorrência foram os principais achados preditivos de trombofilia. A ¿mudança de conduta¿ aplicou-se a uma pequena porcentagem de doentes, e refletiu predominantemente a confirmação da necessidade de prolongamento da profilaxia secundária. A ¿atenção especial¿ diante de situações de risco e a extensão da profilaxia primária a familiares de primeiro grau assintomáticos expostos a situações de risco parecem-nos a melhor indicação para a pesquisa laboratorial da trombofilia. Palavras-chave: trombofilia, fator V Leiden, mutação G20210A, proteína S, proteína C, antitrombina, hiperhomocisteinemia, anticorpos antifosfolípides, tromboembolismo venoso / Abstract: The venous thromboembolism (VTE) affects 1 to 3 individuals per a thousand habitants/year. Nowadays its possible to associated VTE with a cause of thrombophilia in about 40% of patients. There are some inconclusive points about the real benefit of the laboratorial investigation on thrombophilia for patients with VTE. We tried to identify the variables that point to the positive test results and the impact of these results on clinical decisions.The screening for the more common causes of thrombophilia was applied to 84 consecutive patients with VTE confirmed by image examination between January 2001 and November 2003. After test results, two independent observers evaluated, in a case by case basis, the indication of a ¿change on prophylaxis¿, in order to modify the period of anticoagulant intake (secondary prophylaxis), or ¿special attention¿ when considering to have a higher medical surveillance before risk situations or for the extension of the research to the first degree asymptomatic relatives.Thrombophilia was found in 41.66% (35/84), and in 32.12% (27/84) it involved agenetic cause. The factor V Leiden was the more prevalent alteration, identified in 15.47% of the cases, followed by the natural anticoagulants disfunction (11.9%). There was no significative difference of thrombophilia frequency between ages, nor a difference of age in the onset of the first thrombotic event between thrombophilic and non-thrombophilic patients. There was a higher prevalence of thrombophilia in patients with superficial thrombophlebitis of spontaneous onset, in cases of recurrence and when associated with non-surgical predisponent factors. The ¿change on prophylaxis¿ resulted in 7.14% (6/84), and there was statistically significance for patients with recurrent episodes when compared to patients with just one. The ¿special attention¿ was applied in 40.47% (34/84). Spontaneous superficial thrombophlebitis, occurrence of VTE related to nonsurgical causes and recurrence, were the main findings which suggested thrombophilia. The ¿change of prophylaxis¿ was applied to a small percentage of patients. The ¿special attention¿ for risk situations and the extension of the primary prophylaxis to the asymptomatic family members seem to be the best indication for the laboratorial research on thrombophilia. Key words: thrombophilia, factor V Leiden, G20210A mutation, protein C, protein S, antithrombin, hyperhomocysteinaemia, antiphospholipids antibodies, venous thromboembolism / Doutorado / Cirurgia / Doutor em Cirurgia

Abstract The incidence of pre-eclampsia (PE) is 2–7% in different populations and in the worst cases PE may threaten the survival of both mother and newborn; its pathogenesis is not resolved. Field literature today considers PE an angiogenic disorder. Coordinated vascularization is essential for placental development. We wanted to find novel factors in the etiology of PE, and focused our attention on angiogenesis, inherited thrombophilia and folate-homocysteine metabolism. Homocysteine inhibits endothelial cell proliferation, which is closely related to angiogenesis. We performed gene expression profiling of placental tissue using microarray chips, studied the prevalence of factor V Leiden (FVL), prothrombin (F5) G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in patients with severe pregnancy complications and normal controls, compared the expression of the placental adiponectin, leptin and their receptor genes and the relationship of each to trophoblast apoptosis and further, studied the effect of folic acid fortified mineral water on plasma homocysteine concentration during pregnancy. Gene expression profiling revealed downregulation of nine and upregulation of four genes. Interestingly, in one PE patient with cord compression during delivery the profile resembled that observed in normals. The expression level of the leptin and the adiponectin receptor 1 (ADIPOR1) genes was significantly higher in PE. No other significant expression changes were observed. The rate of apoptosis was higher in patients with PE. The FVL prevalence was 9.5%, in PE cases and 1.8% in the controls; a difference of 7.7%, (95% CI 2.0–13.4%). No statistical difference was found in other polymorphisms.. Maternal serum folate concentration increased in our intervention group, but decreased in the control group (p < 0.05). The plasma homocysteine concentrations decreased more in the intervention group (p < 0.001). The expression of angiogenesis-related placental genes can be altered in PE and cord compression cases. The activity of adipocytokine genes in PE may mean that they have a role in placental angiogenesis and apoptosis. Women with FVL may have an increased risk of PE. Fortified mineral water will help us to ensure that especially pregnant women achieve adequate folate intake.

Abstract Patent foramen ovale (PFO) is a common finding in the general population and is present in approximately one quarter of adults. The potential role of PFO in the pathogenesis of ischaemic brain infarction of unknown aetiology in young adults has been investigated during the past 15 years, and associations with other diseases have been proposed. The most plausible mechanism of stroke associated with PFO is paradoxical embolism, but there is uncertainty about this because a venous source of emboli is seldom identified. If the theory of venous emboli is relevant, prothrombotic states should be associated with PFO and ischaemic stroke. Relatively little is known about the risk factors of cryptogenic brain infarction, although this subgroup of stroke is relatively common. As the present diagnostic methods for detecting PFO have certain limitations, new non-invasive, simple and reliable methods would be useful. Two new methods examined here, the dye dilution method and ear oximetry, were both found to be feasible and to be highly specific and sensitive in relation to the present gold standard, contrast transoesophageal echocardiography. A case-control study among adult patients with PFO and cryptogenic brain infarction showed the presence of a prothrombotic state, particularly factor V Leiden and prothrombin G2021OA gene mutation, to be associated with an increased risk of stroke, and migraine was also identified as a risk factor. Associations with the classical risk factors for venous thrombosis and Valsalva manoeuvre-like activities at the onset of stroke were also observed. The results lend support to the theory that paradoxical embolism is one of the pathogenic mechanisms behind cryptogenic brain infarction with associated PFO. In another case-control study among adult patients with cryptogenic brain infarction but without associated PFO, prothrombotic states were not identified as risk factors, except that an association was found between elevated factor VIII activity and stroke. The major independent risk factors for such cryptogenic strokes were current cigarette smoking, hypertension and a low level of high density lipoprotein cholesterol.

No description available.