Orientador: Sergio Tadeu Martins Marba / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-13T01:41:15Z (GMT). No. of bitstreams: 1 Vinagre_LuisEduardodeFigueiredo_M.pdf: 699641 bytes, checksum: f53b941c432fcc025a8d30c2ff8a4493 (MD5) Previous issue date: 2009 / Resumo: O objetivo deste trabalho foi avaliar o efeito do uso antenatal do corticosteróide na incidência da hemorragia peri-intraventricular global e em seus graus, levando-se em consideração o efeito do número de doses e o intervalo entre a administração da primeira ou segunda dose e o parto, em recém-nascidos com peso de nascimento entre 500 e 1.500 g. Para tanto foi realizado um estudo analítico retrospectivo, no qual foram incluídos 176 recém-nascidos internados em um hospital terciário do Município de Campinas no período de janeiro de 2000 a dezembro de 2001. Os recém-nascidos foram divididos em dois grupos: um em que se fez uso antenatal do corticosteróide que incluiu 143 participantes e outro que não recebeu este tratamento que abrangeu 33 participantes. Os dados foram analisados inicialmente através de tabelas descritivas e também foram utilizados, quando indicado, o teste do quiquadrado, o teste exato de exato de Ficher, o teste t de Student, o teste de Mann-Whitney e odds ratio. O nível de significância aceito foi de p<0,05 (intervalo de confiança de 95%). Os grupos foram comparáveis na maioria das variáveis; entretanto, houve diferença estatística em relação à idade materna (p = 0,0313), na hipertensão arterial materna (p < 0,0001), no trabalho de parto (p = 0,0059), tipo de parto (p = 0,0152) e infecção neonatal (p = 0,0093). Não houve diferença estatisticamente significativa entre os grupos em relação à idade gestacional, peso de nascimento e escore de Apgar. A incidência global da hemorragia periintraventricular foi de 12,5%, sendo 11,2% para o grupo que fez uso antenatal do corticosteróide e 18,2% para o grupo que não fez uso do tratamento. Este resultado não alcançou significância estatística (OR: 0,57 com IC 95% = 0,19 - 1,80). Não foi observada significância estatística também, ao analisar o período de tempo entre a administração da dose de corticosteróide e o parto e em relação ao número de doses. Apesar da literatura demonstrar um efeito protetor do uso antenatal do corticosteróide na prevenção da hemorragia peri-intraventricular, este trabalho não evidenciou tal efeito. A baixa incidência global da hemorragia peri-intraventricular, juntamente com a elevada taxa de mães hipertensas e de recém-nascidos pequenos para idade gestacional podem ter interferido na análise do uso antenatal do corticosteróide na prevenção desta patologia, ou mais algum outro fator, não identificado, que contribuiu na redução da hemorragia peri-intraventricular, esteve associado ao uso do corticosteróide, ocultando o seu efeito protetor / Abstract: The aim of this study is to evaluate the effects of antenatal corticosteroid therapy on the incidence of intraventricular hemorrhage and in its grade, regarding the effect of number of doses and the timing between the application of the first or second dose and delivery, in newborn with birth weight between 500 and 1,500 grams. An analytic retrospective trial was carried out enrolling 176 newborn admitted at a tertiary center hospital in Campinas city, São Paulo, Brazil, from January 2000 to December 2001. The newborns have been divided into two groups: one received antenatal corticosteroid therapy (143/176) and another (33/176) who have not received the treatment. Data were analyzed through descriptive chart, also when indicated, quisquare test and Fisher exact test, Student's t-test, Mann-Whitney test and odds ratio. The groups were comparable in majority of the variables; nevertheless there was statistically significant difference in maternal age, (p = 0,0313), maternal hypertension (p < 0,0001), labor (p = 0,0059), method of delivery (p = 0,0152) and neonatal sepse (p = 0,0093). There was no statistically significant difference among the groups regarding the gestational age, birth weight and in 5 minutes Apgar score. The global incidence of intraventricular hemorrhage was 12,5%. The incidence for the group which had been treated with antenatal corticosteroid therapy was 11,2%, and the other group it was 18,2%. This outcome didn't reach statistic significance (OR: 0,57; CI 95% = 0,19 - 1,80). Also, there was no statistic significance in the time between the dose application and delivery, and in regarding the number of doses. Despite literature demonstrating a protective effect of the use of antenatal corticosteroid therapy for prevention of intraventricular hemorrhage, this study showed no such effect. The low overall incidence of intraventricular hemorrhage along with high rate of maternal hypertension and small-for-gestational-age infant may have interfered in the analysis of the antenatal corticosteroid therapy in the prevention of this disease, or some other factor that contributes to reduce intraventricular hemorrhage, that couldn't be predicted, was associated with antenatal corticosteroid, obscuring its protective effect / Mestrado / Pediatria / Mestre em Saude da Criança e do Adolescente

Hemorragia pós-parto (HPP) é tradicionalmente definida como perda sanguínea maior ou igual a 500 ml em partos vaginais e acima de 1000 ml em partos cesarianos e/ou queda de 10% do hematócrito comparado ao exame feito à admissão da parturiente e/ou sangramento importante que requeira hemotransfusão. Estima-se que 25 a 30% das mortes maternas são decorrentes da HPP. Além disso, este quadro pode causar impacto na qualidade de vida de mulheres e neonatos, devido às complicações, além da necessidade de intervenções. Objetivo: Estimar prevalência de HPP, efeito do tipo de parto e intervenções obstétricas sobre os valores hematimétricos (hematócrito e hemoglobina) em uma amostra de mulheres primíparas atendidas em hospital de ensino. Metodologia: A amostra constituiu-se de 100 primíparas, independente da via de parto. A coleta de dados foi realizada a partir de dados retrospectivos obtidos de prontuários (impresso e eletrônico), cartão de pré-natal, dentre outras fontes de consulta, respaldadas por formulário testado previamente em estudo piloto. Resultados: A prevalência de HPP na amostra de estudo foi de 16%. Através da análise simples (teste F), encontrou-se significância estatística para as seguintes variáveis: diabetes, síndromes hipertensivas, anemia diagnosticada durante a gestação, analgesia, tipo de parto e peso do recém-nascido. Porém através da regressão linear múltipla, observou-se significância apenas para as variáveis: diabetes e analgesia. Mulheres portadoras de diabetes apresentaram maiores perdas hemáticas; enquanto que mulheres que realizaram analgesia durante o trabalho de parto, apresentaram menores perdas. Dentre as complicações mais frequentes no período compreendido do puerpério imediato à alta hospitalar detectou-se: necessidade de ocitócito terapêutico adicional (20 UI); nível de hemoglobina < 9 mg/dl; lipotímia; necessidade de suplementação com sulfato ferroso (em dose terapêutica); 22 mulheres apresentaram algum tipo de sintoma (fraqueza, desânimo, entre outros); 62 mulheres apresentaram anemia no período puerperal. Houve correlação positiva (0,89) entre os níveis de queda do hematócrito e da hemoglobina, sendo que para queda de hematócrito >= 10%, a queda de hemoglobina foi de 2,99 mg/dl. Não foram constatadas outras associações significativas. Considerações finais: Acreditamos que a dosagem de hemoglobina e hematócrito 48 horas pós-parto é uma importante ferramenta para auxiliar no diagnóstico precoce e mais fidedigno dos quadros, devendo esta prática ser adotada como rotina nas instituições. Ressaltamos mais uma vez que análise laboratorial não exime o profissional de avaliação clínica rigorosa e minuciosa. Assim, esta prática vem complementar a assistência clínica no puerpério e em hipótese alguma se deve substituí-la. Dada a magnitude do problema e a escassez de estudos sobre a temática acreditamos que todos os trabalhos sobre a questão são louváveis e podem contribuir para a melhoria da assistência ao ciclo gravídico-puerperal. / Postpartum hemorrhage (PPH) is traditionally defined as blood loss greater than or equal to 500 ml in vaginal parturition and over 1000 ml in cesarean sections and/or 10% drop in hematocrit compared to examination by the admission of the mother and/or major bleeding requiring blood transfusion. It is estimated that 25-30% of maternal deaths are due to PPH. Moreover, this framework can impact quality of life of women, newborns, due to its complications, and the need for interventions. Objective: To estimate the prevalence of PPH and effect of type of delivery and obstetric interventions on the hematological values (hemoglobin and hematocrit) in a sample of primiparous women attended at a teaching hospital. Methodology: The sample consisted of 100 primiparous, regardless of mode of delivery. Data collection was performed with retrospective data obtained from medical records, pregnancy card, among other sources of information, backed-up by a form previously tested in a pilot study. Results: The prevalence of PPH in the study sample was 16%. Through simple analysis (F test), statistical significance was found for the following variables: diabetes, hypertensive disorders, anemia diagnosed during pregnancy, analgesia, mode of delivery and weight of the newborn. But through multiple linear regression, we found significance only for the variables: diabetes and analgesia. Women with diabetes had higher blood loss, whereas women who underwent analgesia during labor, showed smaller losses. The following complications were identified: need for additional oxytocin therapy (20UI), hemoglobin < 9 mg/dl, syncope, need for supplementation with iron (terapheutic dose), 22 women had some type of symptoms (weakness, prostration, etc), 62 women had anemia in the postpartum period. A positive correlation (0.89) between the levels of low hematocrit and hemoglobin, while those for the fall of hematocrit >= 10%, the drop in hemoglobin was 2.99 mg/dl. No association with other variables was found. Final considerations: We believe that dosage of hemoglobin and hematocrit 48 hours after delivery is an important tool for early diagnosis and the most reliable for detection of the frameworks, so, should this practice be adopted as routine in institutions. We emphasize once again that laboratoring testing does not relieve the professional of a rigorous and thorough clinical evaluation. Thus, this practice come to complement the clinical care in puerperium and in no way should replace it. Given the magnitude of the problem and the scarcity of studies on the subject believe that all study on the issue is commendable and may contribute to the improvement of care in pregnancy and childbirth.

Em função da categoria dos estressores, vias neurais específicas são envolvidas e respostas distintas podem ser induzidas. A literatura tem reportado que o estrógeno (E 2 ) através de seus receptores de tipos (ER) e (ER) influencia a atividade do eixo hipotálamo hipófise adrenal (HPA). Além disso, há evidências de que o E2 exerça efeitos protetores em situação de choque hemorrágico. O objetivo deste trabalho foi verificar a participação dos receptores ER e ER na atividade do eixo HPA durante estresse hemorrágico. Foram utilizadas ratas Wistar ovariectomizadas que receberam injeções s.c. de DMSO (veículo), PPT (agonista ER) ou DPN (agonista ER), durante 3 dias. No segundo dia, as ratas foram canuladas para coleta seriada de sangue na manhã seguinte. Os animais receberam (controle) ou não (hemorrágicos) reposição imediata com salina. Os hormônios corticosterona (CORT), ocitocina (OT) e vasopressina (AVP) foram dosados por radioimunoensaio. Ao final do experimento, os ratos foram perfundidos e os cérebros processados para imuno-histoquímica de FOS, tirosina hidroxilase (TH) e hormônio liberador de corticotrofina (CRH). Nos animais tratados com veículo, a hemorragia gradual moderada aumentou a secreção de CORT, OT e AVP, a expressão de neurônios TH ativados na região A1C1 e de FOS no mpPVN. O PPT reduziu a secreção de CORT, na situação controle atuando no LC e mpPVN; e também após hemorragia atuando no LC, NTS, A1C1 e mpPVN. O DPN reduziu a secreção de CORT apenas após estresse hemorrágico atuando no LC, A1C1 e mpPVN. O PPT bloqueou o aumento da secreção de OT e aumentou a secreção de AVP, após hemorragia. O DPN, por sua vez, reduziu a concentração plasmática de OT e aumentou a concentração plasmática de AVP, independentemente da hemorragia. Em conclusão: o estrógeno pode exercer uma ação inibitória sobre a secreção basal de CORT somente através da ação do ER sobre o LC e mpPVN; a secreção de CORT aumenta em resposta à hemorragia gradual moderada e o estrógeno pode exercer um controle inibitório nessa resposta através de ER atuando sobre LC, NTS, A1C1 e mpPVN, bem como através de ER atuando sobre LC, A1C1 e mpPVN. / Depending on the stressors category, specific neural pathways are involved and different responses can be selected. It has been reported in the literature that estrogen (E2 ) can affect hypothalamus pituitary adrenal (HPA) axis activity through its receptors type (ER) and (ER). Moreover, there is evidence that E 2 has protecting properties after hemorrhagic shock. The aim of this work was to assess the participation of ER and ER on HPA axis activity during hemorrhagic stress. It was used ovariectomized Wistar rats that received s.c. injections of: DMSO (vehicle), PPT (ER agonist) or DPN (ER agonist), during 3 days. In the second day the rats were catheterized for serial blood collect in the next morning. Animals received (control) or not (hemorrhagic) immediate reposition with same volume of isotonic saline. The hormones corticosterone (CORT), oxytocin (OT) and vasopressin (AVP) were measured by radioimmunoassay. At the end of the experiment, animals were perfused and their brains were processed for immuno-histochemistry for FOS, tyrosine hydroxylase (TH) and corticotropin releasing hormone (CRH). In vehicle treated animals, the gradual hemorrhage enhanced CORT, OT and AVP secretion, TH activated neurons expression in A1C1 and FOS expression in mpPVN. PPT decreased plasma CORT in control situation acting on LC and mpPVN, and also after hemorrhage acting on LC, NTS, A1C1 and mpPVN. DPN reduced plasma CORT only after hemorrhagic stress acting on LC, A1C1 and mpPVN. PPT blocked the increase of OT secretion and increased AVP secretion, after hemorrhage. The agonist DPN reduced OT and increased AVP levels, despite hemorrhage. In conclusion: E2 can exert an inhibitory effect on CORT basal secretion only through ER action on LC and mpPVN; CORT secretion increases after gradual moderate hemorrhage and E2 inhibit this secretion through ER action on LC, NTS, A1C1 and mpPVN, as well through ER action on LC, A1C1 and mpPVN.

Abstract Primary intracerebral hemorrhage (ICH) comprises 10–15% of all strokes. Arterial hypertension and warfarin use are well documented risk factors for ICH, but aspirin use also seems to predispose to ICH. The annual incidence of primary ICH in western populations is 12–31 / 100,000. Mortality is high: 14–52% during the first month and 14–80% during the first year after ICH. The size and location of the hemorrhage, a midline shift in head computed tomography, intraventricular spread of the hemorrhage, level of consciousness on admission, and high blood glucose independently predict mortality. For a risk factor study, 98 consecutive patients admitted into the Department of Neurology, Oulu University Hospital, because of ICH between January 1993 and September 1995 were compared with 206 control subjects drawn from a population register. Thromboxane and prostacyclin biosynthesis were measured from serial urine samples of 43 patients. For outcome studies, all subjects (n = 208) with incident ICH during the study period in the population of Northern Ostrobothnia, Finland, were identified. Untreated hypertension was the main modifiable risk factor for ICH. Use of aspirin appeared to be a significant risk factor for ICH in the subjects with a history of epistaxis. Enhanced thromboxane and prostacyclin biosynthesis were observed in the acute phase and 3 months after ICH. Regular use of aspirin preceding ICH doubled the 3-month mortality rate compared with nonusers of aspirin/warfarin. Aspirin use also associated with early hematoma growth. Patients with ICH showed increased long-term mortality up to 7 years after ICH compared to controls. No excess mortality was observed among those with good recovery at 3 months, but those who were severely disabled at 3 months after ICH showed marked excess mortality.

Abstract The purpose of the study was to analyze the angiographic and clinical results of endovascularly treated intracranial aneurysms in Oulu University Hospital, Finland. The study population consisted of 416 consecutive patients (467 aneurysms, 332 ruptured), who were referred for endovascular treatment of intracranial aneurysm(s) between December 1993 and July 2004. Technical failures were analyzed for an assesment of technical feasibility. Angiographic results were assessed using modified Raymond Classification. Clinical results were analyzed from patient files using the Glasgow Outcome Scale (GOS). Patient, aneurysm, and procedure related variables were tested with an intention to find the predictors of the angiographic and clinical outcome. The clinical effects on presenting symptoms were analyzed for a subgroup of patients with a symptomatic unruptured aneurysm (n = 30). The mean results on technical feasibility, complications, and angiographic results were separately assessed for three time periods (1993–1997, 1998–2000 and 2001–2004) to demonstrate potential significant changes in outcome. Endovascular treatment of saccular aneurysms was technically feasible in 91.4% of the treatments. Initially, 25.7% of the aneurysms were completely occluded, 57.9% had a neck remnant, and 16.3% remained incompletely occluded. In follow-up, the rates for complete occlusions, neck remnants and incomplete occlusions were 37.6%, 49.7% and 12.7%, respectively. Small aneurysm size predicted complete aneurysm occlusion, while a wide aneurysm neck and location in the posterior circulation predicted incomplete occlusion. In follow-up (mean 38.2 months), 78.1% of the patients with a ruptured aneurysm and 92.3% of the patients with an unruptured aneurysm had resumed independent life (GOS 4-5). The predictors of good outcome were young age, good preprocedural clinical condition, small amount of blood in CT scan, and uncomplicated procedure. Ten of the treated aneurysms involved intracranial bleeding in follow-up, and the annual risk for bleeding after endovascular treatment was 0.95% among the patients with ruptured aneurysms and 0.33% among those with unruptured aneurysms. The risk of bleeding was associated with larger aneurysm size and lower occlusion grade. In the subgroup of symptomatic unruptured aneurysms, 53.4% of the patients showed either resolution or improvement of the symptoms after treatment. The rates of procedural complications, morbidity, and mortality were 16.5%, 6.7%, and 1.7%, respectively. The risk for procedural complications was higher when the balloon remodeling technique was used and lower in retreatments. Technical feasibility (85.6%, 90.6%, and 95.7%, respectively) and the percentage of complete occlusions (initially 16.5%, 23.0%, and 32.9%, respectively) were significantly improved by increased experience, while no statistical difference was detected in the total procedural complication rates (15.4%, 15.7%, and 18.3%, respectively) or the combined procedural morbidity and mortality rates (8.0%, 8.3%, and 9.1%, respectively). All six dissecting aneurysms treated with parent artery occlusion or the stent remodeling technique resulted in complete occlusions. The present results confirmed endovascular treatment of intracranial aneurysms as a feasible, safe, and effective method in preventing further bleeding of aneurysms. Increased experience in a single center improved the feasibility of the treatment as well as the angiographic results.

No description available.

Objective Postpartum hemorrhage (PPH) is a major cause of maternal mortality world-wide; misoprostol is a relatively cheap, easily administered, and an efficient medication to be given after the delivery of the baby to prevent PPH, thus posing it as a first choice in resource-poor communities. The aim of this study is to answer questions regarding the most appropriate dose (400 µg versus 600 µg), effect of labour settings (community or clinical), and management of labour on misoprostol effectiveness and safety in preventing PPH. Methods We developed a search strategy and conducted a search within five key databases. Two reviewers screened the articles for predefined inclusion/exclusion criteria, quality, and performed data extraction. Discrepancy was dealt with by reaching consensus. In article 1, we only included randomized controlled trials, we performed a random-effects Bayesian network meta-analysis comparing 400 µg to 600 µg misoprostol over five outcomes of interest: blood loss ≥500 ml, blood loss ≥1000 ml, using additional uterotonics, shivering, and pyrexia. In article 2, we included any experimental trial, we performed a random effects model meta-analysis, pooling the incidence of PPH from each misoprostol arm. Subsequently, a meta-regression model was performed on identified potential effect-modifiers, including clinical settings and labour management. Results Of 444 identified records, 46 trials met the inclusion/exclusion criteria in article 1, and 56 trials in article 2. The odds ratio (OR) of misoprostol 400 µg vs. 600 µg for bleeding ≥ 500 ml is 0.86 [95% Credible Intervals: 0.46 − 1.54], for bleeding ≥ 1000 ml the OR is 0.83 [95% CrI 0.54 – 1.26], for additional uterotonics is 0.75 [95% CrI 0.40 – 1.40], for pyrexia and shivering an OR of 0.57 [95% CrI 0.15 – 2.18] and 0.63 [95% CrI 0.29 – 1.31] respectively. The overall incidence of PPH was 6.62 per 100 pregnancies (95%CI 4.71 per 100 – 8.53 per 100). Labour settings and other aspects of active management of labour had no statistically significant effect on the incidence of post-partum hemorrhage. Conclusion We found no difference between the administration of misoprostol 400 µg or 600 µg for the prevention of PPH and side effects of misoprostol, as well as no effect of labour settings and management of labour on misoprostol effectiveness.

Intracerebral hemorrhage (ICH) is a severe form of stroke, with a high mortality rate and often resulting in irreversible neurological deterioration. Although animal studies have provided insight into the etiology of the disease, many of the causative genes and mechanisms implicated in cerebral-vascular malformations are unknown. Treatment options remain ineffective. With the present models, the pathophysiological consequences of ICH can only be assessed in situ and after histological analysis. Furthermore, common deficiencies of the current models include the heterogeneity, low expression and low reproducibility of the desired phenotype. Hence, there is a requirement for novel approaches to model ICH pathogenesis. Zebrafish (Danio rerio) has gained recognition as a vertebrate model for stroke research. Through a combination of pharmacological blockers, metabolite rescue, genetic approaches, and confocal imaging analysis, I demonstrate a requirement for the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) pathway in regulating developmental cerebral-vascular stabilization. A transient loss in HMGCR function induces ICH, characterised by progressive dilation of blood vessels, vascular permeability and vessel rupture. These effects are likely due to reduced prenylation of Rho GTPases, evidenced by morpholino-mediated blocking of the prenylation pathway and in vivo assessment of endothelial-specific localization of cdc42, a Rho GTPase family protein. These results are in conformity with recent clinical and experimental evidence. I have further shown that this model consistently replicates common pathoghysiological processes associated with ICH. The hemorrhages are associated with the disruption of the blood-brain barrier, vessel disintegration, hematoma expansion and edema into the adjacent brain regions. Also, enhanced apoptosis, activation of inflammatory mediators in the periphery of the hematoma, enriched heme oxygenase 1 (HO-1) expression and localised thrombosis were observed in these embryos. I show that the patterning and distribution of catecholaminergic neurons, response to sensory stimulus and swimming speed were impaired as a consequence of ICH. These results suggest that HMGCR contributes to cerebral-vascular stabilisation through Rho GTPase mediated-signalling and that zebrafish can serve as a powerful paradigm for the systemic analysis of the etiological and pathophysiological underpinnings of ICH and can help establish the basis for future studies into screening for putative therapeutics and elucidating mechanisms aiding functional recovery.

Orientador: Yvens Barbosa Fernandes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T09:26:09Z (GMT). No. of bitstreams: 1 Zullo_JoaoFlavioDaniel_M.pdf: 4994617 bytes, checksum: 7f874ff0599b4cec270f92a8010dc856 (MD5) Previous issue date: 2014 / Resumo: As hemorragias intracerebrais supratentoriais espontâneas, correspondem a cerca de 10 a 20% de todos os acidentes vasculares cerebrais (AVC), acometendo mais de 4 milhões de pessoas por ano em todo o mundo(13). Apresenta as mais altas taxas de morbi-mortalidade dentre os diferentes tipos de AVC, sendo que a mortalidade desta patologia alcança índices ao redor de 30-40% dos doentes, além de grande número de pacientes com seqüelas graves, sendo que seu principal fator de risco é a hipertensão arterial sistêmica (HAS). Desde o trabalho de McKissock(1) at al em 1961, vem se tentando descobrir qual a melhor maneira para tratar pacientes que apresentam tais hemorragias. Com esse intuito, avaliamos 67 pacientes atendidos no HC/Unicamp e no Hospital Estadual de Sumaré/Unicamp (HES) entre os anos de 2007 e 2012, sendo 41 com hemorragias de núcleos da base e 26 com hematomas lobares. Estudamos a influência de vários fatores no prognóstico dos pacientes com hemorragias intracerebrais supratentoriais espontâneas, como idade, nível de consciência à admissão hospitalar (usando-se a escala de coma de Glasgow), profundidade do hematoma em relação à superfície cerebral, volume do hematoma, presença de hemorragia intraventricular, desvio de linha média, tempo entre ictus hemorrágico e cirurgia e tipo de tratamento (craniotomia ou conservador). O nível de consciência na chegada ao hospital é fator determinante com relação ao prognóstico funcional avaliado em 30 dias após o ictus, independente da modalidade de tratamento adotada, porém com diferentes nuances dependendo da localização da lesão (núcleos da base ou lobar). Algumas particularidades, como tamanho do hematoma, podem determinar o resultado prognóstico funcional, assim como o tratamento cirúrgico, hemoventrículo e desvio de linha média (DLM) tendem a influenciar o prognóstico / Abstract: Spontaneous supratentorial intracerebral hemorrhages correspond to 10 to 20% of all stroke cases, affecting more than 4.000.000 people/year worldwide(13). It shows the highest rates of morbidity and mortality among the different types of stroke. The mortality of this disease achieves around 30- 40% of all patients, besides a large number of pacientes with severe sequels. Its main risk factor is high blood pressure. Since McKissock(1) at al published his work in 1961, researchers are trying to figure out the best way to treat patients with this type of hemorrhage. Aiming this situation, we evaluated 67 patients treated at HC/Unicamp and State Hospital of Sumaré (HES)/Unicamp between 2007 and 2012, with 41 basal ganglia and 26 lobar hematomas. We studied the influence of several factors on the prognosis of patients with spontaneous supratentorial intracerebral hemorrhage, such as age, consciousness at hospital admision (using the Glasgow Coma Scale), hematoma depth, hematoma volume, intraventricular hemorrhage, midline shift, time between bleeding and surgery and treatment option (craniotomy or conservative). The consciousness on arrival at the hospital is a determinant factor relative to functional outcome in 30 days after bleeding, regardless of treatment modality adopted, but with different nuances depending on the lesion location (basal ganglia or lobar). Some special features, like the size of the hematoma, can determine the funcional outcome, as well as surgery, ventricular hemorrhage and midline shift have a trend to influence prognosis / Mestrado / Neurologia / Mestre em Ciências Médicas

Os mecanismos responsáveis pelas manifestações hemorrágicas durante a leptospirose severa ainda são pouco compreendidos. Este trabalho avaliou os efeitos diretos e indiretos das leptospiras sobre moléculas do sistema de coagulação. Foi verificado que leptospiras virulentas são eficientes em bloquear a atividade da enzima trombina por meio do sequestro de seu sítio de ligação ao substrato, gerando uma menor formação do coágulo de fibrina, acarretando em sangramento e consequente disseminação do patógeno para outros sítios de infecção. Foi mostrado também que a inflamação causada pela resposta imune contra as bactérias causa uma ativação da coagulação, muito provavelmente via expressão de Fator Tissular, o que ocasiona um consumo e consequente esgotamento dos fatores e inibidores de coagulação, culminando em hemorragia e formação de trombos, os quais podem levar à falência de órgãos. Estes resultados melhoram o entendimento da patogênese da leptospirose e podem favorecer o desenvolvimento de terapias para as manifestações hemorrágicas. / The mechanisms responsible for the hemorrhagic manifestations during severe leptospirosis are still poorly understood. This work evaluated the direct and indirect effects of leptospires upon molecules of the coagulation system. It has been shown that virulent leptospires are effective in blocking the activity of the enzyme thrombin by sequestration of its substrate binding site, generating less fibrin clot formation, leading to bleeding and consequent dissemination of the pathogen to other sites of infection. It has also been shown that the inflammation caused by the immune response against the bacteria causes an activation of the coagulation, most probably via expression of Tissue Factor, which causes a consumption and consequent depletion of coagulation factors and inhibitors, culminating in hemorrhage and thrombus formation, which can lead to organ failure. These results improve the understanding of the pathogenesis of leptospirosis and may favor the development of therapies for hemorrhagic manifestations.