Introdução - A incidência das fendas lábio – palatinas, é de 1 para cada 700 nascidos vivos na população mundial, trata-se de uma má-formação congênita que pode ocorrer devido a fatores endógenos ou exógenos. Objetivo – Relacionar o índice de massa corporal (IMC) materno com o nascimento de bebês com fendas. Métodos – Trata-se de um estudo tipo caso-controle. Foram incluídas 800 mães com idade entre 18 e 35 anos, que não apresentaram suspeita ou confirmação de diabete mellitus ou gravídica e bebês com peso entre 2.500 e 4.500 gramas nascidos entre a 37ª e a 42ª semana de gestação que não apresentaram nenhum outro tipo de deficiência que não a estudada. Para a coleta dos dados aplicou – se questionários a 400 mães de crianças normais distribuídas em quatro postos de saúde da cidade de Santo André (controles), e 400 mães de bebês com fendas labiais e/ou palatinas que estavam em tratamento no FUNCRAF, que é um centro especializado no tratamento da deformidade estudada, nesta mesma cidade (casos). Resultados - Entre os casos encontrou - se 148 (37,00%) mulheres com IMC acima de 26 e entre os controles foram 132 (33,00%). Com relação ao uso de álcool/drogas observou-se que 82 (20,50%) mulheres entre os casos e 58 (14,50%) no grupo controle eram usuárias. Duzentas e onze (52,70%) mães de bebês com fendas relataram ter histórico de má - formação na família dela ou do pai da criança. Este número foi de 103 (25,70%) no grupo controle. No grupo controle observou-se que 330 (82,50%) eram brancas ou pardas, 43 (10,75%) negras e 27 (6,70%) amarelas, entre os casos foram 294 (73,50%) brancas ou pardas, 65 (16,25%) negras e 40 (10,00%) amarelas. Conclusões - O IMC alto não esteve relacionado ao nascimento de bebês com fendas. Ter sido usuária de álcool/drogas no primeiro trimestre de gestação relacionou-se ao nascimento de crianças com a má-formação. O risco de surgimento desta deformidade foi 3,6 vezes maior quanto existiu histórico de qualquer má-formação familiar; a raça/etnia da mãe também apresentou associação com a presença de fendas, a raça branca é a menos associada seguida pela parda e negra e, finalmente pela amarela que foi a que apresenta maior associação. / Introduction – The incidence of cleft lips and palate is 1 to 700 live births in the world population, it is a congenital malformation that can happens due to endogens or exogenesis factors. Objectives – Association between maternal body mass index (BMI) and the risk of cleft lips or palate. Methods – That is a case – control study. We include 800 mothers between 18 and 35 years old without suspicious of gestational or preexisting diabetes and babies between 2,500 e 4, 000 g was born between the 37 and 42 pregnancy week without other congenital malformation that is not the studied. Some questions were asked for 400 normal children’s mothers from four health centers from Santo André (controls), and 400cleft lips or palate children’s mothers from FUNCRAF that is a health center just to treatment of this malformation, from Santo André (cases). Results – Among the cases we have 148 (37.00%) mothers with BMI above 26 and among the controls it was 132 (33.00%). About alcohol and drugs use we have 82 (20.50%) women among cases and 58 (14.50%) on control group. Two hundred eleven (52.70%) malformations children’s mothers declare to have malformation parental history against 103 (25.70%) on control group. On control group we have 330 (82.50%) white , 43 (10.75%) black and 27 (6.70%) yellow, among the cases 294 (73.50%) white, 65 (16.25%) black and 40 (10.00%) yellow. Conclusions – The increase of BMI is not likely to be a risk factor for clefts, the consumption of alcohol/drugs is a risk factor for this malformation; the risk is 3.6 times highest for clefts when there is malformation history; a racial association with clefts was observed, the white women presents the lowest association and the yellow presents the highest one.

Made available in DSpace on 2016-01-26T12:51:25Z (GMT). No. of bitstreams: 1 marcosluiztostesdossantos_dissert.pdf: 2066322 bytes, checksum: 9abf4b93ab3ce79b49c60b4edd0f3b0c (MD5) Previous issue date: 2007-11-06 / Brain arteriovenous malformations (BAVM) are morphological and neurovascular abnormalities characterized by direct communication between arteries and veins, without interposition of capillary bed, therefore without resistance to blood flow. OBJECTIVE: The purpose of this research was to characterize morphologically brain arteriovenous malformations aiming correlation with clinical presentation. CASUISTIC AND METHOD: A total of 170 patients with brain AVM, 78(46%) males and 92(54%) females, were studied from January 2001 to January 2007 at the Vascular and Endovascular Neurosurgery Unit of the Hospital de Base of São José do Rio Preto, SP. Univariate and multivariate analyses were conducted to test the associations among demographic (sex, age), clinical (hemorrhage, seizure, focal neurological deficit, and headache), and morphological features (anatomical localization; superficial, deep, infratentorial or supratentorial location; nidus size; number of feeding arteries, compartments, and draining veins; type of venous drainage; presence of stenosis, venous ectasias, and arterial aneurysms; Spetzler-Martin classification). RESULTS: The main clinical presentations at the moment of diagnosis included hemorrhage in 89 (52%) patients, headache in 79 (46%), focal neurological deficit in 54 (32%), and seizure in 52 (31%). According to the Spetzler-Martin classification, grade I was found in 15 (9%) patients, grade II in 49 (28%), grade III in 55 (33%), grade IV in 41 (24%), and grade V in 10 (6%) patients. There was a statistically significant association among hemorrhage and small nidus size (p = 0.002), single feeding artery (p = 0.007), single draining vein (p = 0.003), and single compartment (p = 0.040). Seizure was positively correlated with medium (3-6 cm) and large nidus size (>6cm), and negatively with small nidus size (<3cm) (p = 0.021). CONCLUSIONS: Brain AVM with small nidus size, Spetzler-Martin grade I, single feeding artery and draining vein are associated with hemorrhage. Spetzler-Martin grade V was negatively associated with hemorrhage. In the braim AVM there is no association between aneurysm and hemorrhage. On the other hand, seizure show positive correlation with large nidus size and negative with small nidus size. / Malformações arteriovenosas (MAV) encefálicas são anomalias morfológicas neurovasculares caracterizadas por comunicação direta entre artérias e veias, sem interposição do leito capilar, portanto sem resistência ao fluxo sangüíneo. OBJETIVO: O objetivo desta pesquisa foi caracterizar morfologicamente MAV encefálicas, visando correlação com apresentação clínica. CASUÍSTICA E MÉTODO: Foram estudados 170 pacientes portadores de MAV encefálicas, sendo 78 (46%) do sexo feminino e 92 (54%) do masculino, no período de janeiro de 2001 a janeiro de 2007, atendidos na unidade de Neurocirurgia Vascular e Endovascular do Hospital de Base de São Jose do Rio Preto, SP. Análises univariada e multivariada foram efetuadas para testar associações entre características demográficas (sexo, idade), clínicas (hemorragia, convulsão, déficit focal, cefaléia) e morfológicas (localização anatômica; posição superficial, profunda, infratentorial ou supratentorial; tamanho do nidus; número de aferências, compartimentos e eferências; padrão de drenagem venosa; presença de estenose, ectasias venosas e aneurismas arteriais; classificação de Spetzler-Martin). RESULTADOS: As principais formas de apresentação clínica no momento do diagnóstico incluíram hemorragia em 89 (52%) pacientes, cefaléia em 79 (46%), déficit focal em 54 (32%) e convulsão em 52 (31%). De acordo com a classificação de Spetzler & Martin, 15 (9%) pacientes tinham MAV grau I, 49 (28%) grau II, 55 (33%) grau III, 41 (24%) grau IV, e 10 (6%) grau V. Houve associação estatisticamente significativa entre hemorragia e tamanho pequeno do nidus (p = 0,002), aferência única (p = 0,007), eferência única (p = 0,003) e compartimento único (p = 0,040). Convulsão foi correlacionada positivamente com nidus de tamanho médio (3-6 cm) e grande (>6cm) e negativamente com tamanho pequeno (<3cm) (p = 0,021). CONCLUSÕES: MAV encefálicas com nidus de tamanho pequeno, grau I, aferência e eferência únicas estão associados à hemorragia. MAV encefálicas grau V estão associadas negativamente à hemorragia. Na MAV encefálica observa-se ausência de associação entre aneurisma e hemorragia. Por outro lado, convulsão mostra correlação positiva com nidus de tamanho grande e negativa com nidus de tamanho pequeno.

Introdução - A incidência das fendas lábio – palatinas, é de 1 para cada 700 nascidos vivos na população mundial, trata-se de uma má-formação congênita que pode ocorrer devido a fatores endógenos ou exógenos. Objetivo – Relacionar o índice de massa corporal (IMC) materno com o nascimento de bebês com fendas. Métodos – Trata-se de um estudo tipo caso-controle. Foram incluídas 800 mães com idade entre 18 e 35 anos, que não apresentaram suspeita ou confirmação de diabete mellitus ou gravídica e bebês com peso entre 2.500 e 4.500 gramas nascidos entre a 37ª e a 42ª semana de gestação que não apresentaram nenhum outro tipo de deficiência que não a estudada. Para a coleta dos dados aplicou – se questionários a 400 mães de crianças normais distribuídas em quatro postos de saúde da cidade de Santo André (controles), e 400 mães de bebês com fendas labiais e/ou palatinas que estavam em tratamento no FUNCRAF, que é um centro especializado no tratamento da deformidade estudada, nesta mesma cidade (casos). Resultados - Entre os casos encontrou - se 148 (37,00%) mulheres com IMC acima de 26 e entre os controles foram 132 (33,00%). Com relação ao uso de álcool/drogas observou-se que 82 (20,50%) mulheres entre os casos e 58 (14,50%) no grupo controle eram usuárias. Duzentas e onze (52,70%) mães de bebês com fendas relataram ter histórico de má - formação na família dela ou do pai da criança. Este número foi de 103 (25,70%) no grupo controle. No grupo controle observou-se que 330 (82,50%) eram brancas ou pardas, 43 (10,75%) negras e 27 (6,70%) amarelas, entre os casos foram 294 (73,50%) brancas ou pardas, 65 (16,25%) negras e 40 (10,00%) amarelas. Conclusões - O IMC alto não esteve relacionado ao nascimento de bebês com fendas. Ter sido usuária de álcool/drogas no primeiro trimestre de gestação relacionou-se ao nascimento de crianças com a má-formação. O risco de surgimento desta deformidade foi 3,6 vezes maior quanto existiu histórico de qualquer má-formação familiar; a raça/etnia da mãe também apresentou associação com a presença de fendas, a raça branca é a menos associada seguida pela parda e negra e, finalmente pela amarela que foi a que apresenta maior associação. / Introduction – The incidence of cleft lips and palate is 1 to 700 live births in the world population, it is a congenital malformation that can happens due to endogens or exogenesis factors. Objectives – Association between maternal body mass index (BMI) and the risk of cleft lips or palate. Methods – That is a case – control study. We include 800 mothers between 18 and 35 years old without suspicious of gestational or preexisting diabetes and babies between 2,500 e 4, 000 g was born between the 37 and 42 pregnancy week without other congenital malformation that is not the studied. Some questions were asked for 400 normal children’s mothers from four health centers from Santo André (controls), and 400cleft lips or palate children’s mothers from FUNCRAF that is a health center just to treatment of this malformation, from Santo André (cases). Results – Among the cases we have 148 (37.00%) mothers with BMI above 26 and among the controls it was 132 (33.00%). About alcohol and drugs use we have 82 (20.50%) women among cases and 58 (14.50%) on control group. Two hundred eleven (52.70%) malformations children’s mothers declare to have malformation parental history against 103 (25.70%) on control group. On control group we have 330 (82.50%) white , 43 (10.75%) black and 27 (6.70%) yellow, among the cases 294 (73.50%) white, 65 (16.25%) black and 40 (10.00%) yellow. Conclusions – The increase of BMI is not likely to be a risk factor for clefts, the consumption of alcohol/drugs is a risk factor for this malformation; the risk is 3.6 times highest for clefts when there is malformation history; a racial association with clefts was observed, the white women presents the lowest association and the yellow presents the highest one.

La fermeture percutanée est le traitement de référence des communications interatriales (CIA). Après son implantation, une cicatrisation du dispositif est classiquement attendue après quelques mois ; il semble cependant qu’un recouvrement incomplet ou partiel puisse être observé dans de rares cas, sans que l’on en connaisse les mécanismes impliqués. Cette cicatrisation imparfaite du dispositif est associée à la survenue de complications retardées. Dans le cadre de cette thèse nous avons étudié la cicatrisation de ces prothèses de CIA, en nous focalisant sur les processus de recouvrement et d’endothélialisation des dispositifs, à travers une approche translationnelle incluant expérimentations in vitro, modèle animal chronique et étude clinique. A la fin de ce travail, il est possible de conclure que : 1) il existe des cas de complications au long cours après fermeture de CIA, liées à un défaut de recouvrement du dispositif, 2) sur une large cohorte pédiatrique avec un suivi allant jusqu’à 18 ans après l’implantation, l’incidence de ces complications est faible 3) les modèles animaux, utilisés seuls, ne peuvent suffire à expliquer ni à avancer dans la compréhension de ce phénomène, 4) il n’existe pas de différences significatives concernant le processus de recouvrement entre les 3 prothèses analysées au cours de ce travail, 5) une évaluation non invasive et individualisée du recouvrement prothétique , grâce aux techniques d’imagerie, est une perspective prometteuse. Ces données montrent qu’une meilleure compréhension du processus de recouvrement prothétique passe par la réalisation conjointe d’études fondamentales et cliniques. Cependant, le développement d’outils permettant une évaluation individualisée du recouvrement doit être poursuivi, du fait de leur fort potentiel de translation clinique et de leur capacité à optimiser la prise en charge du patient. / The percutaneous device closure is the gold treatment of atrial septal defect (ASD). After implantation, device healing is classically expected following several months; however, an incomplete or partial covering of the device may be observed without a full knowledge of the underlying mechanisms. In this thesis we studied the healing of these intracardiac prostheses, focusing on the covering and endothelialization processes of devices, approach through a translational approach including in vitro experiments, chronic animal model and clinical study. At the end of this work, it is possible to conclude that 1) there are cases of long-term complications after closure of CIA, related to a lack of recovery of the device, 2) in a large cohort of pediatric with a follow up of up to at 18 years after implantation, the incidence of these complications is low 3) animal models, used alone, can not suffice to explain or improve the understanding of this complex process, 4) there is no significant differences in the covering process between the 3 prostheses analyzed during this work, 5) a non-invasive and individualized assessment of prosthetic recovery, using imaging techniques, is a promising perspective with significant potential for clinical translation . These data show that a better understanding of device healing process needs the joint undertake of basic and clinical studies. Moreover, the development of tools for individualized assessment of device covering should be pursued in parallel, due to their high translational potential, in order to optimize patient management.

<p>To assess the impact of congenital malformations in Down syndrome (DS) on morbidity, mortality and outcome at birth, information on all children with DS born in the northern part of Sweden in 1973-80 (n=211) and 1995-98 (n=88) was collected. Most common were congenital heart defects (CHD), dominated by atrioventricular septal defects (AVSD). Up to age 10 years, morbidity and mortality were more than 10 times higher in DS children with CHD than in healthy DS children. The DS children seemed more vulnerable at birth than Swedish children in general: they had increased frequencies of Cesarean sections, premature birth, asphyxia, and low birthweight, and higher proportions of children small for gestational age, regardless of the presence of CHD. Infant mortality decreased from 14.2% to 2.3% between the two periods.</p><p>All children with AVSD with and without DS born in Sweden 1973-1997 (n=801) were followed up retrospectively to 2001. Children with isolated AVSD without complex additional CHDs were studied more closely (n=502). A reduction in age at operation and postoperative mortality (from 28 to 1%) was observed. No significant difference in 5-year postoperative mortality between genders or between DS and non-DS children was found. The 5-year postoperative mortality in DS decreased from 35% in 1973-77 to about 10% in 1993-97. </p><p>CHD had a major influence on morbidity, infectionrate and mortality in DS, but not on DS birth variables. The formerly high mortality in CHD is now reduced. In isolated AVSD measures seem equally successful in DS and non-DS children. Mortality is still 3 times higher in DS children with isolated AVSD than in healthy DS children. </p>

To assess the impact of congenital malformations in Down syndrome (DS) on morbidity, mortality and outcome at birth, information on all children with DS born in the northern part of Sweden in 1973-80 (n=211) and 1995-98 (n=88) was collected. Most common were congenital heart defects (CHD), dominated by atrioventricular septal defects (AVSD). Up to age 10 years, morbidity and mortality were more than 10 times higher in DS children with CHD than in healthy DS children. The DS children seemed more vulnerable at birth than Swedish children in general: they had increased frequencies of Cesarean sections, premature birth, asphyxia, and low birthweight, and higher proportions of children small for gestational age, regardless of the presence of CHD. Infant mortality decreased from 14.2% to 2.3% between the two periods. All children with AVSD with and without DS born in Sweden 1973-1997 (n=801) were followed up retrospectively to 2001. Children with isolated AVSD without complex additional CHDs were studied more closely (n=502). A reduction in age at operation and postoperative mortality (from 28 to 1%) was observed. No significant difference in 5-year postoperative mortality between genders or between DS and non-DS children was found. The 5-year postoperative mortality in DS decreased from 35% in 1973-77 to about 10% in 1993-97. CHD had a major influence on morbidity, infectionrate and mortality in DS, but not on DS birth variables. The formerly high mortality in CHD is now reduced. In isolated AVSD measures seem equally successful in DS and non-DS children. Mortality is still 3 times higher in DS children with isolated AVSD than in healthy DS children.

No description available.

Les gènes Hox sont essentiels à la mise en place de l’identité des cellules le long de l’axe antéropostérieur des embryons et pourraient agir en aval de l’acide rétinoïque pendant la formation du cœur. Nous montrons que les gènes Hoxb1, Hoxa1 et Hoxa3 définissent des sous-domaines du second champ cardiaque. L’analyse de lignage génétique révèle que les progéniteurs cardiaques Hoxb1+ contribuent aux oreillettes et à la partie inférieure de la voie efférente, futur myocarde sous-pulmonaire. Les progéniteurs Hoxa1+ contribuent à la partie distale de la voie efférente, suggérant un rôle de ces gènes Hox antérieurs dans sa régionalisation proximo-distale. Alors qu’aucune anomalie cardiaque n’avait été décrite chez les mutants Hoxb1, notre étude détaillée des fœtus Hoxb1-/- révèle des défauts d’alignement des gros vaisseaux ainsi que des communications interventriculaires. L’utilisation d’un marqueur du myocarde sous-pulmonaire, montre une contribution anormale des cellules du second champ cardiaque à cette région chez les mutants. Nous montrons que ces défauts sont la conséquence de la dérégulation des voies de signalisation présentes dans le second champ cardiaque. En accord avec ces observations, les embryons ont une voie efférente plus courte. L’étude des mutants Hoxa1 révèle des malformations des arcs pharyngés puis des anomalies de la crosse aortique chez les fœtus. L’analyse des doubles mutants, montre une augmentation de la pénétrance et de la sévérité de ces défauts, suggérant une interaction synergique entre Hoxa1 et Hoxb1 lors de la formation des gros vaisseaux. Ces résultats révèlent un rôle crucial des gènes Hox antérieurs dans le développement du cœur. / Hox genes are known to be involved in the establishment of cell position and identity along the anterior-posterior axis in embryos and could act as key downstream effectors of retinoic acid during heart development. In situ hybridization experiments show that Hoxb1, Hoxa1 and Hoxa3 define sub-domains within the second heart field (SHF). Our genetic lineage analysis reveals the contribution of Hoxb1+ cardiac progenitors to the atria and to the inferior wall of the outflow tract (OFT), which then gives rise to the myocardium at the base of the pulmonary trunk. Interestingly, Hoxa1+ progenitors contribute to the distal part of the OFT suggesting that these anterior Hox genes could play a role in its proximo-distal patterning. No cardiac anomalies had been reported so far in Hoxb1 mutant mice. However, our detailed study shows that mutant fetuses exhibit OFT misalignment and ventricular septal defects associated or not with ventricular wall and epicardium anomalies. Using a marker of the sub-pulmonary myocardium, we observe an abnormal contribution of SHF cells in Hoxb1-/- hearts. This defect is the consequence of the dysregulation of the signaling pathways controlling SHF regulation. Accordingly, those embryos exhibit a shorter OFT. The study of Hoxa1 mutant embryos reveals pharyngeal arch arteries patterning defects causing anomalies of the aortic arch and right subclavian artery at fetal stages. Using compound mutants, we show an increase in the penetrance and severity of these defects, suggesting a synergistic interaction between Hoxa1 and Hoxb1 during aortic arch patterning. Together, these data support a crucial role for anterior Hox genes in cardiac development.

Children with focal intractable epilepsy caused by MCD, FCD and TSC are in a high risk of development of cognitive delay, as a result of both drug resistant epilepsy and genetically determined abnormal structure of the neuronal networks. Epilepsy surgery represents an established and safe treatment method of focal drug resistant epilepsy, and increases the chances for these patients to be rid of epileptic seizures, anti-epileptic medication and cognitive comorbidities. Current data on genetic background of focal MCD and FCD and their comorbidities provide space to expand the diagnostic process in epilepsy surgery candidates. However, available information on genetic causes of MCD and FCD do not allow us to infer prognostic estimates on chances of seizure freedom and optimal cognitive development. Future studies should elucidate these uncertainties.

No description available.