A population-based study in South East Wales (population 668,100) identified 69 families with 135 affected members with von Recklinghausen neurofibromatosis (NF-1), giving a disease prevalence of 20/105 of population. In these families penetrance of the NF-1 gene was 100% by the age of five years. 41/135 cases were judged to represent new disease mutations and the mutation rate was estimated to lie between 3.1x10-5 and 10.4x10-5. A parental age effect for new mutations was not demonstrated, nor was a maternal effect on disease severity. The clinical features and natural history of NF-1 in this cohort were used to derive data for genetic counselling and recommendations for the management of affected individuals. For counselling purposes the complications of NF-1 can be usefully divided into 4 categories (the frequency of each, based on this study, are shown in parentheses): intellectual handicap (33% overall, moderate/severe retardation 3.2%, minimal retardation/ learning difficulties 29.8%); complications developing in childhood and causing lifelong morbidity, e. g. facial plexiform neurofibromas, scoliosis, pseudoarthrosis (8.5%); 'treatable' complications which can develop at any age, e. g. benign disorders of the nervous system, visceral and endocrine tumours, renal artery stenosis (15.7%) and malignant or CNS tumours (4.4-5.2%). The study population indicates that sufferers are not being diagnosed sufficiently early, nor receiving appropriate follow-up and counselling. It is recommended that patients with NF-1 have regular clinical assessments to monitor for the development of complications, although none occur often enough to warrant biochemical or radiological screening. As many of the complications develop early in life, children should have biannual review; in adults, unless a particular complication indicates more frequent review,annual clinical examination is sufficient. Alongside the population survey, genetic linkage studies were undertaken in selected large families to determine the chromosomal localisation of the NF-1 gene. At the outset of this work, two families had been reported in which NF-1 and Myotonic Dystrophy (DM) appeared to co-segregate, suggesting that the two genes were closely linked and on chromosome 19. However, linkage studies of 3 chromosome 19 markers linked to DM showed significantly negative lod scores, therefore excluding this possibility. Other chromosomes were then studied using random unique sequence DNA probes and samples from the largest families were made available to collaborators in the USA for linkage studies using possible candidate genes (ß nerve growth factor and oncogenes). No marker studied showed evidence of linkage. The negative data were used to produce an exclusion map for NF-1, using the computer program 'EXCLUDE'. The presentation of this work was one of the factors which precipitated the formation of an international consortium for NF-1 linkage in February 1987; the first task of the consortium was to produce an expanded exclusion map. A small positive lod score for a marker on chromosome 17, taken with the exclusion data, showed that NF-1 was seven times more likely to be on chromosome 17 than any other chromosome; this was rapidly confirmed by two North American groups, one of which was using samples from the 5 largest families presented in the thesis. Subsequent linkage analysis of pericentromeric chromosome 17 markers in the Welsh family panel showed no evidence of non-allelic heterogeneity and identified closely linked flanking markers for the NF-1 gene suitable for prenatal/presymptomatic diagnosis. The chromosomal localisation of NF-1 represents a major step towards the eventual understanding of the disease pathogenesis and the development of possible treatments.

Dementia and Alzheimer's disease (AD) are highly debilitating conditions that afflict millions of elderly persons. In recent decades, biological evidence has implicated chronic stress in the etiology of these conditions. As a result, the relationship between widowhood, one of the most stressful life events, and dementia and AD has also received attention. However, studies are mixed regarding this association, and few have investigated whether this relationship is moderated by the context surrounding widowhood. This study extends this literature by investigating whether widowhood increases risk for dementia and AD and whether this risk is moderated by contextual factors including age at widowhood, remarriage after widowhood, manner of death, number of dependent and adult children at the time of widowhood, gender, presence of epsilon 4 allele of apolipoprotein E (APOE), and history of depression and antidepressant use. To do this, this investigation utilized data from the Cache County Memory Study (CCMS), a large population-based epidemiological study of dementia and AD, and the Utah Population Database (UPDB), one of the world's foremost linked genealogical databases. In Cox regression analyses that modeled time to onset of dementia and AD, gender was found to moderate the relationship between incident widowhood and dementia (HR = 1.74, 95% CI: 0.97-3.10), in that widowhood trended towards decreased risk among men (HR =0.72, CI: 0.45-1.16) but increased risk among women (HR = 1.21, CI: 0.83-1.75) in stratified models. In addition, history of depression and antidepressant use moderated the association between incident widowhood and dementia (HR = 2.63, 95% CI: 1.26-5.50) and AD (HR = 1.68, 95% CI: 1.11-2.53), in that widowhood was associated with decreased risk for dementia and AD among the never depressed (HR = 0.66, CI: 0.42-1.02 and HR = 0.54, CI: 0.31-0.92, respectively), a trend towards increased risk for AD among those with a history of antidepressant use but no depression (HR = 1.80, CI: 0.86-3.75), and with increased risk for dementia and AD among those with a history of both (HR = 1.93, CI: 0.98-3.81 and HR = 1.89, CI: 0.80-4.43). These findings advance clinical and scientific knowledge concerning the effects of widowhood on risk for dementia and AD, and underscore the importance of context in understanding this relationship.

Moterų narkomanija gana nauja ir mažai tyrinėta tema socialinių mokslų srityje. Pastaruoju metu vis didesnis dėmesys skiriamas narkotinės priklausomybės vystymuisi lyties aspektu, daug diskutuojama apie priklausomybę nuo narkotikų sergančių moterų poreikių specifiškumą, reikiamos pagalbos užtikrinimą. / Women’s drug addiction is quite a new and little investigated theme in the field of social sciences. Recently, more and more attention has been given to the development of drug addiction in respect to gender, and such themes as drug addiction, drug-addicted women’s specificity of needs and provision of help have been discussed a lot.

Šiuolaikiniame ir vis labiau skubančiame pasaulyje naujovės bei išradimai uţvaldo vis didesnę rinkos dalį. Mokslininkai, dizaineriai ir kitų specialybių ţmonės stengiasi kaip išmanydami palengvinti vartotojų ir tiekėjų rinką. Tik ar viskas, ką jie siūlo rinkai, yra sveika mūsų organizmui?Ar maistas, gėrimai, kosmetika, technologinės naujovės, vis labiau tobulėjanti farmacija ir kita, ką mes su mielu noru priimame, nėra mums nuodinga? Reikia atkreipti didesnį dėmesį į patį ţmogų. / The main issue analysed in this work is the harm done to a human body by the six factors: drugs, genetically modified organisms (GMO), air pollution, cosmetics, radiation and preservatives. Health is the most important human value and the majority of nowadays world solutions may reduce it faster than we think it could. Hereinafter these main factors crippling our health will be shortly discussed.

Orientadores: Carlos Alberto Petta, Denise Engelbrecht Zantut-Wittmann / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-08T17:23:05Z (GMT). No. of bitstreams: 1 Arruda_MauriciodeSouza_D.pdf: 343806 bytes, checksum: 09bf586ba699ac3a35538ead5e7277a9 (MD5) Previous issue date: 2007 / Resumo: O objetivo deste estudo de corte transversal foi comparar a prevalência de doença tiroideana auto-imune e disfunção tiroideana entre mulheres portadoras de endometriose e um grupo de controle. Foram avaliadas 148 mulheres, com diagnóstico cirúrgico de endometriose, acompanhadas no Ambulatório de Endometriose do Centro de Atenção Integral à Saúde da Mulher da Universidade Estadual de Campinas, no período de dezembro de 2005 a abril de 2006, e comparadas a 158 mulheres atendidas no Ambulatório de Planejamento Familar da mesma intituição e no mesmo período. As pacientes foram entrevistadas durante uma de suas consultas nos respectivos Ambulatórios. Foram avaliadas: i) a função tiroideana através das dosagens dos hormônios Tiroestimulante e Tiroxina livre, e ii) a presença de doença tiroideana auto-imune através dos anticorpos anti-tiroglobulina e anti-tiroperoxidase. A associação entre as variáveis independentes, o grupo de estudo e as doenças tiroidianas foi avaliada através dos testes qui-quadrado e exato de Fisher, teste de Mann-Whitney e cálculo de odds ratio com seu respectivo intervalo de confiança 95%. A prevalência de hipotiroidismo foi de 12,2% (18 mulheres) no grupo com endometriose e 7,8% (12 mulheres) no grupo de controle (OR 1,49; IC 95%, 0,69 ¿ 3,2). A prevalência de hipotiroidismo auto-imune foi de 6,0% (9/148) e 5,0% (8/158), nos dois grupos, respectivamente (p <0,005). Identificamos 4,0% (6 mulheres) de hipotiroidismo instalado entre as mulheres com endometriose e 3,2% (5 casos) nas mulheres do grupo de controle. A prevalência de doença tiroidiana auto-imune foi de 8,8% (13/148 mulheres) entre as mulheres com endometriose e 15,8% (25/158) entre as mulheres no grupo de controle (OR 0,52; IC 95%, 0,25 ¿ 1,06). Em conclusão, os resultados obtidos neste estudo não sustentam a hipótese de que mullheres com endometriose apresentam maior prevalência de disfunção tiroidiana ou doença tiroidiana autoimune. Assim, entendemos não haver necessidade de rastreamento diferenciado para hipotiroidismo ou para disfunção tiroidiana nas mulheres com endometriose / Abstract: The objective of this cross sectional study was to compare the prevalence of autoimmune thyroid disease and thyroid dysfunction between women with endometriosis and a control group. One hundred forty eight women with surgically confirmed endometriosis attended at the endometriosis outpatient clinic at the Department of Obstetrics and Gynaecology, School of Medicine, Universidade Estadual de Campinas (Unicamp) were evaluated from December 2005 to April 2006 and compared to 158 women from the family planning outpatient clinic at the same institution, during the same time period. All patients were interviewed in one of their regular visit. Thyroid function and autoimmunity were evaluated by measuring serum level of thyroid stimulating hormone, free thyroxin and the antibodies antithyroperoxidase and antithyroglobulin. The association of independent variables and the study group with thyroid disorder and with thyroid dysfunction was assessed by X2 test and Fisher test. Prevalence of thyroid disorders and thyroid dysfuncion among women with endometriosis were calculated and compared with the control group using Mann-Whitney test and the odds ratio was calculated with the 95% confidence interval. The prevalence of hypothyroidism was 12.2 % (18 women) among women with endometriosis and 7.8% (12 women) in the control group (OR 1.49; CI 95%, 0.69 ¿ 3.23). The prevalence of autoimmune hypothyroidism was 6% (9/148) and 5% (8/158) in both groups, respectively. We identified 4% (6 women) with overt hypothyroidism in the group of women with endometriosis and 3.2% (5 cases) among women from the control group. The prevalence of autoimmune thyroid disease was 8.8 % (13 women) among women with endometriosis and 15.8% (25 women) in the control group (OR 0.52; CI 95%, 0.25 ¿ 1.06). Our data do not support the hypotesis that women with endometriosis present a higher prevalence of autoimmune thyroid disease or thyroid dysfuction. Therefore, we believe there is no need for a specific screening of thyroid diseases among women with endometriosis / Doutorado / Tocoginecologia / Doutor em Tocoginecologia

Résumé non transmis / Summary not transmitted

La réponse de l’organisme contre un agent pathogène nécessite la mise en jeu d’interactions complexes entre cellules immunitaires et environnement. La matrice extra-cellulaire est remodelée au cours de la réponse immunitaire pour permettre la migration des cellules vers le site infectieux. Les peptides issus de la dégradation de la matrice peuvent influencer les fonctions biologiques des cellules immunitaires. Dans les pathologies impliquant des tissus riches en élastine, les cellules de la réponse inflammatoire et immunitaire, notamment les polynucléaires neutrophiles (PN) et les cellules dendritiques se retrouvent dans un environnement riche en produits issus de la dégradation de l’élastine. Le travail de thèse présenté ici nous a permis de montrer que les peptides d’élastine (PE) régulent les fonctions des PN de sujets sains en augmentant de façon significative leur capacité migratoire, leur capacité à produire des cytokines pro-inflammatoire et à phagocyter les agents pathogènes. Les effets régulateurs des PE sont moindres chez les sujets BPCO et varient en fonction de l’état clinique des patients. Les propriétés biologiques des PN de patients BPCO en exacerbation ne sont pas affectées par les PE. Cette différence de réponse aux PE des PN de patients BPCO à l’état stable ou à l’état exacerbé est proportionnellement liée au niveau d’expression du récepteur S-Gal à la surface des PN. Dans un second travail nous avons montré que les PE sont capables d’attirer les CD au niveau du site infectieux sans influencer la maturation des cellules induite par une activation antigénique. L’effet des PE sur la migration des CD met en jeu le récepteur S-Gal présent à la surface des cellules. Par ailleurs, les PE orientent la réponse cytokinique des CD activées par le LPS vers un profil de type Th-2 et favorisent l’émergence d‟un profil tolérogénique des CD. Ces effets régulateurs des PE sont médiés via l’interaction PE/S-Gal et conduisent au développement d’une réponse adaptative T régulatrice. L’ensemble de ces résultats suggère que les PE participent activement à la régulation de la réponse immunitaire innée et adaptative / Organisme defense against pathogens needs complexe interactions interactions between immune cells and environnement. The extracellular matrix is being remodeled to aloww cells to migrate to infectious site. Peptides generated by this degradation can influence biological fonctions of immune cells. In pathologies involving elastin rich tissue degradation inflammatory and immune cells, especially neutrophils and dendritic cells are in an environnement including numbers of matrix degradation products. This work shows that Elastin Peptides (EP) can regulate the fonctions of neutrophils from healthy subjects, by increasing significantly their migration, their cytokines production and their phagocytic capacity. These EP effects are howeever less important en stable COPD subject and depends on the clinical state of these patients. Indeed the biological properties of neutrophils from COPD patients in exacerbation are not affected by EP. This discrepancy considering the clinical state can be explained by the level of the S-Gal receptor expression. In a second part we have shown the ability of the EP to attract dendritic cell (DC) on the infection site without couetracting DC maturation. This effect involves the S-Gal receptor present on the surface of the cells. EP can also oriente the cytokine production by LPS-induced toward a Th-2 profil and favorise the emergence of DC with tolerogenic features. These effects are mediated throug EP/S-Gal interaction and leads to the developement of a T regulatory response. All of these results suggest that EP are involved in the regulation of innate and adaptative immunity.

Made available in DSpace on 2015-03-05T20:04:15Z (GMT). No. of bitstreams: 0 Previous issue date: 24 / Nenhuma / O estudo se propõe a conhecer a percepção de reação do sujeito frente à doença osteomuscular e os fatores que influenciam essa reação. Uma entrevista semiestruturada captou os relato de 15 sujeitos com doença osteomuscular, a maioria mulheres, de 20 a 40 anos. As entrevistas gravadas e transcritas foram analisadas a partir de quatro categorias principais: reação, aspectos sobre a doença, percepção do corpo e fatores sociais. As reações à doença osteomuscular são seletivas. Quando negativas os quadros característicos foram de irritação e depressão. Quando positivas foram demonstradas pela autopoiese, ressignificação do sujeito, valorização de si e busca por saúde como dignidade. Os apoios afetivos, como a religiosidade, a família e o convívio com outras pessoas apresentaram-se como fatores de influência positiva. E as condições sociais, como o fator econômico relacionado à escolaridade, ao trabalho e ao acesso aos serviços de saúde influenciaram negativamente. O fisioterapeuta pode auxiliar na reação positiva / The Study aim to know the Perception of subjectif Reaction face to a Osteomuscular Disease and the Factors which influence these Reaction. The Research interviews 15 Subjects with Osteomuscular Desease, most of them Wemen 20 to 40 years old. Four Categories were used to analyse the registered and transcripted Interviews: Reaction, Desease aspects, Body Perception and Social Factors. The Reactions to Osteomuscular Desease are selectives. The Display of negative Reaction are Irritation and Depression. Positive Reaction appeared by Autopiesis, subjectif Reframe, self Valuation and Search of Health with dignity. Affectives Supports, as Religiosity, Family, Living together with other Persons showed as Factors of positive Influence. The Social Conditions, as economic Income, Educational Level, Job, Access to Health Services, demonstrated negative Influence. The Physioterapist can improve the positive Reaction through the Health Education, the good Relation with the patients and the Incentive to the Body Perception

Orientador: Carlos Antonio Caramori / Resumo: A doença hepática gordurosa não alcoólica (DHGNA) é a alteração mais comum do metabolismo hepático, associada à obesidade, resistência à insulina e à síndrome metabólica. Compreende amplo espectro de alterações, que tem em comum a esteatose, em indivíduos que não consomem álcool. Além da sobrecarga de ingestão calórica, outros fatores como alterações do metabolismo do ferro podem estar relacionados à patogênese ou progressão da DHGNA. Analisamos no presente estudo as possíveis relações de marcadores do metabolismo do ferro com a intensidade das lesões hepáticas na DHGNA em indivíduos obesos. Foram estudados 88 indivíduos adultos, de ambos os gêneros, obesos (IMC >30), com diagnóstico histológico de DHGNA, acompanhados no ambulatório de Gastroenterologia e Hepatologia da FMB-Unesp. Os marcadores do metabolismo do ferro avaliados foram: níveis séricos de ferro, ferritina e transferrina, bem como o índice de saturação da transferrina (IST). A presença e intensidade da deposição de ferro no parênquima hepático foram investigadas pelo método histoquímico do Azul da Prússia (Perls). A intensidade da esteatose e o grau de fibrose foram avaliados nas biópsias hepáticas. Dos 88 indivíduos avaliados, 31 (35,2 %) apresentaram aumento dos níveis séricos de ferritina e 12 (13,6%) apresentaram valores de IST acima de 45 %. A avaliação histológica, das biópsias hepáticas, demonstrou a presença de fibrose em 48/88 casos (54,54%), sendo 21/88 (23,86%) de intensidade leve e 27/88 (30,68%) caso... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor

Orientador: Carlos Antonio Caramori / Resumo: A doença hepática gordurosa não alcoólica (DHGNA) é a alteração mais comum do metabolismo hepático, associada à obesidade, resistência à insulina e à síndrome metabólica. Compreende amplo espectro de alterações, que tem em comum a esteatose, em indivíduos que não consomem álcool. Além da sobrecarga de ingestão calórica, outros fatores como alterações do metabolismo do ferro podem estar relacionados à patogênese ou progressão da DHGNA. Analisamos no presente estudo as possíveis relações de marcadores do metabolismo do ferro com a intensidade das lesões hepáticas na DHGNA em indivíduos obesos. Foram estudados 88 indivíduos adultos, de ambos os gêneros, obesos (IMC > 30), com diagnóstico histológico de DHGNA, acompanhados no ambulatório de Gastroenterologia e Hepatologia da FMB-Unesp. Os marcadores do metabolismo do ferro avaliados foram: níveis séricos de ferro, ferritina e transferrina, bem como o índice de saturação da transferrina (IST). A presença e intensidade da deposição de ferro no parênquima hepático foram investigadas pelo método histoquímico do Azul da Prússia (Perls). A intensidade da esteatose e o grau de fibrose foram avaliados nas biópsias hepáticas. Dos 88 indivíduos avaliados, 31 (35,2 %) apresentaram aumento dos níveis séricos de ferritina e 12 (13,6%) apresentaram valores de IST acima de 45%. A avaliação histológica, das biópsias hepáticas, demonstrou a presença de fibrose em 48/88 casos (54,54%), sendo 21/88 (23,86%) de intensidade leve e 27/88 (30,68%) ca... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor