The purpose of this work was to improve the diagnosis of intracranial hemorrhage with MRI, using, among others, T2*-w GE sequences. Various sequences were tested in rabbits at two magnetic field strengths. Then, the most effective technique was applied to stroke patients. Experimental studies: The MR detectability of small experimental haematomas in the brain and of blood in the cerebrospinal fluid (CSF) spaces of 30 rabbits was evaluated. MRI examinations were performed at determined intervals. The last MR images were compared to formalin fixed brain sections and, in 16 rabbits, also to the histological findings. T2*-weighted GE sequences revealed all the intraparenchymal haematomas at 1.5 T, appearing strongly hypointense. Their signal patterns remained unchanged during the follow-up. Blood in the CSF spaces was best detected at 1.5T with T2*-weighted GE sequences during the first 2 days. FLAIR and SE sequences were rather insensitive. Clinical studies: MR examinations were performed at 1.5T, including T1- and T2-w SE, FLAIR and T2*-w GE sequences. In the first clinical study, 66 intraparenchymal hematomas (IPH) of different sizes and ages were examined. T2*-w GE sequence was the most sensitive. On all the sequences, we found a big variety of signal patterns, without a clear relationship to the age of the hematomas. In a second clinical study, MR examinations were performed to 83 patients with acute stroke: 43 presented acute IPH and 40 were used as controls. Old microhemorrhages (OMHs) were found in 60% of the patients with IPH, and in 15% of the controls. Conclusion: T2*-weighted GE sequences are capable of revealing very small intraparenchymal hemorrhages at any stage, and blood in CSF spaces during at least the first 2 days. The age of IPHs cannot reliably be estimated with MRI. We have found a correlation between the presence of OMHs and acute intraparenchymal hematomas.

This study was undertaken to investigate the involutional changes of the uterus and uterine cavity by ultrasound (US), gray-scale and Doppler, after normal delivery, and to compare with the corresponding findings from women with puerperal complications, particularly retained placental tissue (RPT). The overall design was exploratory and prospective, with the use of descriptive statistics for analysis. Forty-two women with uncomplicated vaginal term delivery were examined on post-partum days 1, 3, 7, 14, 28 and 56. The AP diameters of the uterus and uterine cavity and morphological findings were recorded. The maximum AP diameters of the uterus and uterine cavity diminished from 92.0 mm on day 1 to 38.9 mm at day 56 and from 15.8 mm at day 1 to 4.0 mm at day 56, respectively. The uterus was most often empty in the early and late puerperium while a mixed echo pattern over the whole cavity was found during mid puerperium (I). Seventy-nine women with secondary post partum hemorrhage (SPH) were examined on the day they presented with clinical symptoms. US revealed an echogenic mass in the uterine cavity in 17 of 18 patients treated surgically and histology confirmed placental tissue in 14 of these. Sixty-one patients with either an empty cavity or mixed echo pattern had an uneventful puerperal course after conservative treatment (II). AP diameters and morphological findings for 55 women with endometritis, 28 after caesarean section and 20 after manual evacuation of the placenta overlapped extensively with normal references (III). The physiological vascular involution studied in 45 women after normal delivery showed that PI and RI indices did not change significantly until day 28 postpartum. The presence of at least one uterine artery notch was found in 13.3% of the women at day 1 and in 90.6% at day 56 postpartum (IV). PI and RI values were measured and compared with reference values in 20 women with clinical suspicion of RPT who were to undergo surgical evacuation. Mean resistance indices were below the 10th percentile for eight of these 20 women, but overlapping was considerable. Doppler US has limited value as a diagnostic tool for RPT. The absence of a hyper-vascular area in the myometrium does not exclude RPT but an echogenic mass in the cavity is a sign of RPT (V).

Transcatheter Arterial Embolization (TAE) is a method in which a catheter is inserted into an artery under fluoroscopy guidance. By using material that creates a thrombus, inserted through the catheter, the artery can be occluded and the bleeding stopped. Endoscopy is the treatment of choice in upper gastrointestinal (GI) bleeding, but 10% to 30% of patients rebleed and needs other treatment options. Post Partum Hemorrhage (PPH) may evolve rapidly and can become life threatening. Obstetrical treatment will manage most cases, but in some cases emergency surgery is needed and in the worst case hysterectomy. The primary aim of this thesis was to evaluate the clinical usefulness, improve the TAE technique and compare the outcome of TAE with surgery used as “salvage therapy” in patients with upper GI bleeding. Evaluate TAE technique and the long-term effect on the menstrual cycle and fertility in severe PPH. To evaluate the clinical usefulness 13 patients were treated with TAE after endoscopic treatment failure and 5 were treated for recurrent hemorrhage after emergency surgery. The clinical outcome and mortality rate of 40 patients treated with TAE was compared with 51 patients treated with surgery of upper GI bleedings. In 13 patients the ulcer was marked with placement of a metallic clip at endoscopy to be able to locate the exact site of the bleeding ulcer during the TAE procedure. A retrospective study of 20 patients with severe PPH treated with bilateral TAE of the uterine artery was performed. TAE was found to be effective and an alternative to emergency surgery for control of massive upper GI bleeding. The 30-day mortality was lower in the TAE group (3%) compared to the surgical group (14%). By marking the bleeding ulcer at endoscopy using a metallic clip the site of bleeding could be identified on angiography without extravasation of contrast media. No major impact on fertility or menstruation cycle was found in patients treated with TAE in PPH. TAE in PPH is safe and have no major long-term side effect. By using TAE in PPH hysterectomy can be avoided.

During brain activity neurons release the major excitatory transmitter glutamate, which is taken up by astrocytes and converted to glutamine. Glutamine returns to neurons for re-conversion to glutamate. This glutamate-glutamine cycle is energy demanding. Glutamate turnover in injured brain was studied using an animal iron-induced posttraumatic epilepsy model and using neurointensive care data from 33 patients with spontaneous subarachnoid hemorrhage (SAH). Immunoblotting revealed that the functional form of the major astrocytic glutamate uptake protein GLT-1 was decreased 1-5 days following a cortical epileptogenic iron-injection, presumably due to oxidation-induced aggregation. Using microdialysis it was shown that the GLT-1 decrease was associated with increased interstitial glutamate levels and decreased interstitial glutamine levels. The results indicate a possible posttraumatic and post-stroke epileptogenic mechanism. Analysing 3600 microdialysis hours from patients it was found that the interstitial lactate/pyruvate (L/P) ratio correlate with the glutamine/glutamate ratio (r =-0.66). This correlation was as strong as the correlation between L/P and glutamate (r=0.68) and between lactate and glutamate (r=0.65). Pyruvate and glutamine correlated linearly (r=0.52). Energy failure periods, defined as L/P>40, were associated with high interstitial glutamate levels. Glutamine increased or decreased during energy failure periods depending on pyruvate. Energy failure periods were clinically associated with delayed ischemic neurological deficits (DIND) or development of radiologically verified infarcts, confirming that L/P>40 is a pathological microdialysis pattern that can predict ischemic deterioration after SAH. DIND-associated microdialysis patterns were L/P elevations and surges in interstitial glutamine. Glutamine and pyruvate correlated with the cerebral perfusion pressure (r=0.25, r=0.24). Glutamine and the glutamine/glutamate ratio correlated with the intracranial pressure (r=-0.29, r=0.40). Glutamine surges appeared upon substantial lowering of the intracranial pressure by increased cerebrospinal fluid drainage. Increased interstitial glutamine and pyruvate levels may reflect augmented astrocytic glycolysis in recovering brain tissue with increased energy demand due to a high glutamate-glutamine turnover.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2007. / Title from PDF title page (viewed on Feb. 19, 2010). Includes bibliographical references.

Dengue, a group of four similar viruses transmitted through the bite of a mosquito, is estimated to infect upwards of 100 million annually in over 100 nations throughout the global equatorial belt. Distribution of global dengue is highly skewed as Southeast Asian and Western Pacific regions endure 75% of the global dengue burden. Similar to other regional countries, Malaysia has been rapidly urbanizing, which has supported a hyperendemic dengue state. The biological pathway by which dengue infection causes a wide range of clinical manifestations, spanning asymptomatic to life-threatening severe complications, is not comprehensively understood. Historically, severe dengue complications have primarily occurred in children. Consequentially, the majority of the dengue biological pathway research has been conducted on children; however, extrapolation of research findings to adults may be inappropriate as dengue manifestations have differed between age groups. As developing countries undergo epidemiologic transitions and dengue continues to spread geographically to non-endemic regions, youth and adult populations have been subjected to more of the severe dengue burden. Epidemiology and laboratory-based evidence has supported both memory T-cell and antibody independent enhancement hypotheses to explain the biological pathway of severe dengue. Both hypotheses employ the central idea that a primary infection alters immune components so that during a secondary heterotypic dengue infection, an individual is more at risk for severe complications. Monocytes, immune cells that are pivotal in both hypotheses, have been highly examined through in vivo and in vitro experimentation; however, epidemiological evidence for monocyte involvement is incomplete. The primary objective of the study was to examine if a difference in absolute monocyte count, considering independent risk factors, is present in individuals with primary and secondary dengue infections. A secondary dengue infection was found to raise absolute monocyte count during the defervescence phase of dengue illness in individuals aged 15 years and older 0.71 ± 0.15 (x10^9) compared to those experiencing primary dengue infection. Gender and distance of study participants' residences from Hospital Ampang were found to be risk factors for the relationship of interest; whereas, age and race were not found to be significant risk factors. The study helps expand current knowledge of the severe dengue biological pathway with respect to immunological differences between primary and secondary dengue infections. Further research is needed to confirm and expand the findings of this initial study, specifically to include infecting dengue serotype, education, and socioeconomic status which are known dengue risk factors.

Sur l’île de La Réunion, la prévalence du diabète de type 2 est 3,5 fois plus élevée que celle de la France hexagonale. Parmi les diverses complications qu’engendre le diabète, les AVC qui en résultent sont responsables d’une forte mortalité faisant des maladies cardiovasculaires un problème de santé publique majeur sur l’île. Les AVC ischémiques proviennent de l’occlusion d’une artère cérébrale par un thrombus généré localement ou qui s’est détaché d’une plaque d’athérothrombose généralement localisée au niveau des bifurcations carotidiennes. Les plaques compliquées sont souvent caractérisées par des hémorragies intraplaques, responsables de l’extravasation des cellules sanguines. Différents marqueurs moléculaires, protéiques et physiques peuvent refléter ces processus et renseigner le médecin sur l’instabilité de la plaque du patient. Il est donc important d’étudier ces marqueurs de risque de rupture de plaques carotidiennes chez les patients diabétiques, afin d’en prévenir les complications et la mortalité associée. L’hémorragie intraplaque, notamment pourvoyeuse d’érythrocytes et de neutrophiles libérant leurs contenus cytoplasmiques, participe activement à la déstabilisation de la plaque d’athérothrombose chez le diabétique. Cette thèse a permis l’étude de l’influence de ces marqueurs à travers une étude clinique et de proposer un nouveau concept de phagocytose des érythrocytes glyqués par les cellules endothéliales in vitro. Ainsi, les résultats préliminaires de l’étude clinique nous permettent de supposer que la clairance des globules rouges des patients diabétiques est altérée, ce qui leurs permettraient de résider sur une période plus longue dans les plaques de ces patients. De cette manière, les globules rouges pourraient y être pris en charge par d’autres types cellulaires comme les cellules endothéliales. Nous avons tout d’abord mis au point un modèle de glycation des érythrocytes in vitro reflétant un diabète mal équilibré. Nous avons ensuite mis en évidence que les globules rouges glyqués pouvaient être phagocytés par les cellules endothéliales humaines, conduisant à une prolifération limitée et à la surexpression de l’HO-1. Ces données suggèrent qu’une ingestion des érythrocytes glyqués par les cellules endothéliales pourrait amplifier la déstabilisation des plaques d’athérothrombose carotidiennes des diabétiques. / Type 2 diabetes prevalence in Reunion Island, a French overseas department, is 3.5 higher than in France mainland. Among the various diseases caused by diabetes, stroke induces high mortality making cardiovascular diseases a major public health problem on the island. Ischemic stroke results from a cerebral artery occlusion by a thrombus that is locally produced or has detached from an atherothrombotic plaque usually located at the carotid bifurcations. Complicated plaques can are often characterized by intraplaque hemorrhages, responsible for blood cell extravasation. Several molecular and physical markers can reflect these processes and inform the physician about the instability of the patient's plaque. It is therefore of major importance to study the markers of carotid plaque rupture in diabetic patients in order to prevent complications and associated mortality. Intraplaque hemorrhage, providing erythrocytes and neutrophils releasing their cytoplasmic contents, plays an active role in destabilizing atherothrombotic plaque in diabetic subjects. The objectives of the present thesis were to study these markers in a clinical study and to suggest a new concept of red blood cell phagocytosis by endothelial cells in vitro. According to the first results of the clinical study, we can suggest that in diabetic patients, the clearance of red blood cells is impaired. This prolonged residence of red blood cells in atherosclerotic plaques from diabetic patients. In this way, red blood cells could be phagocytosed by othercell types such as endothelial cells. In this work, we have also set up an in vitro model of erythrocyte glycation that reflects a clinical situation of poorly controlled diabetes. We have demonstrated that glycated red blood cell phagocytosed by human endothelial cells, leading to their limited proliferation and to HO-1 overexpression. These data suggest an ingestion of glycated erythrocytes by endothelial cells may amplify the destabilization of carotid atherothrombotic plaques in diabetics.

O presente trabalho propõe um diálogo entre a teologia e a medicina a partir da análise da cura da mulher que sofria de hemorragia (Lc 8.43-48). A pesquisa se orienta pelo padrão metodológico e exegético praticado pela Faculdades EST e seus orientadores de pesquisa. O trabalho descreve, de forma sucinta, a questão do significado da cura no contexto do primeiro século, a história da medicina, apresentando seu conceito e sua origem, no que implica a doença para o povo primitivo da Mesopotâmia e a doença no Oriente, a mitologia grega e o desenvolvimento da medicina na Grécia, a medicina romana e a medicina entre o povo hebreu. Ele se ocupa também com o autor do Evangelho, que a tradição da igreja atribui a Lucas, o médico, originário de Antioquia da Síria, com a doença que acometia a mulher de Lucas 8.43-48, com o significado físico da doença hemorrágica, com as possíveis causas da hemorragia, com a implicação social e religiosa da doença. O trabalho apresenta uma interpretação exegética do texto em foco, com suas prerrogativas de interpretação, com a análise das variantes textuais e com análise literária do Evangelho de Lucas. O trabalho enfoca também a iniciativa da mulher hemorrágica e sua cura através da ação milagrosa de Jesus. O trabalho também reflete sobre o milagre da cura e a cura como milagre, sobre o milagre na Bíblia, no Antigo e Novo Testamentos e, especificamente, sobre o milagre da cura da mulher hemorrágica e o seu significado físico e social. Por fim, o trabalho elenca um número razoável de obras, com as quais os leitores e pesquisadores do assunto poderão obter outras informações sobre o tema. / This paper proposes a dialog between theology and medicine based on the analysis of the cure of the woman suffering from hemorrhages (Lk 8:43-48). The research is guided by the exegetical and methodological practice of Faculdades EST and its research orientators. The work describes in a brief way, the issue of the meaning of curing in the context of the first century, the history of medicine, presenting its concept and its origin, as it applies to what illness meant to the primitive people of Mesopotamia and to illness in the East, in Greek mythology and the development of medicine in Greece, Roman medicine and medicine among the Hebrew people. It also deals with the author of the Gospel which the tradition of the church attributes to Luke, the doctor, originally from Syrian Antioch, with the illness which plagued the woman in Luke 8:43-48, with the physical meaning of the hemorrhagic illness, with the possible causes of the hemorrhage, with the social and religious implication of the illness. The work presents an exegetical interpretation of the text in focus, with its prerogatives of interpretation, with the analysis of textual variants and the literary analysis of the Gospel of Luke. The work also focuses on the initiative of the hemorrhagic woman and her cure through the miraculous action of Jesus. The work also reflects on the miracle of the cure and the cure as a miracle, about miracle in the Bible, in the Old and New Testament, and specifically about the miracle of the cure of the hemorrhagic woman and its physical and social meaning. Finally, the work lists a reasonable number of works where the readers and the researchers can obtain more information on the theme.

A lagarta da espécie Lonomia obliqua é medicamente importante, cujo veneno, presente nas espículas, causa uma síndrome hemorrágica caracterizada por equimoses, alterações da coagulação, dentre outros sintomas. Isto sugere a presença de peptídeos bioativos com potencial farmacêutico, devido à capacidade de modular o comportamento das células endoteliais. O objetivo deste estudo é analisar os potenciais efeitos do veneno de Lonomia obliqua na angiogênese. Uma linhagem celular endotelial (HUVEC) foi exposta a diferentes concentrações do extrato de espículas da Lonomia obliqua (Lonomia obliqua Bristle extract - LOBE) 5 μg/mL, 10 μg/mL, 20 μg/mL e 50 μg/mL. Empregando citometria de fluxo, observou-se que nenhuma das doses afetou o ciclo celular, viabilidade ou apoptose das células endoteliais após 24h de exposição. Os esferóides das células HUVEC foram plaqueados numa matriz 3D de colágeno e observou-se que LOBE (10 μg/mL, 20 μg/mL e 50 μg/mL) induz um aumento na migração celular, consistente com o processo de angiogênese. A análise da dinâmica da VE-caderina indica que a exposição imediata a LOBE (10 μg/mL) induz um desprendimento da junção célula-célula, o que corrobora com a hemorragia observada nas vítimas de envenenamento. Através de espectrometria de massa, observou-se que LOBE possui vários potenciais peptídeos bioativos. Grupos destes peptídeos foram isolados por fracionamento com metanol a partir do veneno bruto. Os peptídeos presentes, em cada uma das 10 frações, foram caracterizados por espectrometria de massa e foram analisados os efeitos de cada fração sobre a angiogênese. Os resultados sugerem que alguns dos efeitos do envenenamento por Lonomia obliqua são devidos à presença de peptídeos bioativos que modulam o comportamento das células endoteliais. / The caterpillar of the species Lonomia obliqua is medically important, whose venom present in the bristles leads to an hemorrhagic syndrome characterized by ecchymosis, coagulation disorders and others symptoms. This suggests the presence of bioactive peptides with pharmaceutical potencial due to the ability to modulate the behavior of endothelial cells. The aim of this study is to analyze the potential effects of Lonomia obliqua venom on angiogenesis. An endothelial cell line (HUVEC) was exposed to different concentrations (5 μg/mL, 10 μg/mL, 20 μg/mL and 50 μg/mL) of Lonomia obliqua bristle extract (LOBE). Using flow cytometry, it was observed that none of the doses affected endothelial cell cycle, cell viability or apoptosis after 24h of exposition. Spheroids of HUVEC cells were plated in a 3D-collagen matrix and it was observed that LOBE (10 μg/mL, 20 μg/mL and 50 μg/mL) induced an increase on cell migration consistent with the angiogenesis process. Analysis of VE-cadherin dynamics indicates that the immediate exposition to LOBE (10 μg/mL) induced a loosening of cell-cell junction, which corroborates with the hemorrhage observed in the victims. By mass spectroscopy, it was observed that LOBE possesses several potentially bioactive peptides. Groups of these peptides were isolated by a methanol-based fractioning of the crude venom. The peptides present in each of the 10 fractions were characterized by mass spectroscopy and it was analyzed the effects of each fraction on angiogenesis. The results suggest that some of the effects of Lonomia obliqua envenomation are due to the presence of bioactive peptides that modulate the behavior of endothelial cells.

O uso de Derivação Ventricular Externa (DVE) é necessário para o tratamento de muitas doenças, como Traumatismo Cranioencefálico (TCE) e Hemorragia Subaracnoide (HSA). As meningites e ventriculites são complicações frequentes desse uso. Neste trabalho buscamos determinar sensibilidade, especificidade e ponto de corte para o Índice de Celularidade (IC) em pacientes com TCE, HSA e acidente vascular cerebral hemorrágico (AVCh). Nossa população de estudo foi composta por pacientes com diferentes doenças de base e poucos resultados de cultura de líquor positiva. Para diagnóstico das infecções foram utilizados os critérios do CDC. A análise global do IC mostrou uma área sob a curva de 0,982. O ponto de corte geral do IC com o valor de 2,9 tem uma sensibilidade de 95% e uma especificidade de 92,9%. Nos pacientes com HSA obtivemos uma área sob a curva de 1,0 com o IC de 2,7. A sensibilidade e especificidade foram de 100%. Também foi analisada a variação relativa do IC. Para esta análise, a área sob a curva foi de 0,882 e um aumento de 4,33 vezes no IC demonstrou ser indicativo de infecção (p=0,002), dados estes semelhantes aos da literatura. Também foi feito Heatmap do IC, mostrando que ele dificilmente volta ao normal em pacientes com meningite, mesmo após o tratamento. Logo, o IC mostrou-se valioso para diagnóstico de infecção e inadequado para o acompanhamento do tratamento. Esperamos utilizar em nossa instituição o novo ponto de corte proposto por este trabalho com o intuito de melhorar desfechos clínicos. / The use of an external ventricular drain (EVD) is required for the treatment of many diseases, such as traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH). Meningitis and ventriculitis are frequent complications arising from the use of EVD therapy. This study aimed to determine the sensitivity, specificity, and cutoff point for cellularity index (CI) in patients with TBI, SAH, and hemorrhagic stroke. Our study population consisted of patients with different underlying diseases and few culture-positive CSF samples. The diagnosis of infections was based on CDC criteria. Overall CI analysis showed an area under the curve (AUC) of 0.982. The cutoff of 2.9 for overall CI provided a sensitivity of 95% and a specificity of 92.9%. In patients with SAH, the AUC was 1.0 for a CI of 2.7; furthermore, sensitivity and specificity were 100%. The relative variation of the CI was also assessed. This analysis revealed an AUC of 0.882, and a 4.33-fold increase was found be indicative of infection (p=0.002), findings similar to those of the literature. Additionally, a heatmap analysis demonstrated that the CI is unlike to return to normal in patients with meningitis, even after treatment. Therefore, this index showed to be valuable for the diagnosis of infection, but was inadequate for monitoring treatment. We hope to use the new cutoff point proposed by this study in our institution to improve patient clinical outcomes.