Thesis (M.A.)--Northern Kentucky University, 2006. / Made available through ProQuest. Publication number: AAT 1435881. ProQuest document ID: 1136092761. Includes bibliographical references (p. 28-29)

Made available in DSpace on 2016-05-17T16:51:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-07-30. Added 1 bitstream(s) on 2016-05-17T16:54:51Z : No. of bitstreams: 1 000860050.pdf: 11797088 bytes, checksum: 46b5b09d31d666095fb160a815ac01ae (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A trombose jugular nos equinos ocorre comumente em situações iatrogênicas, secundárias a quadros de endotoxemia e coagulação vascular disseminada, podendo levar ao óbito. A profilaxia com agentes antitrombóticos tem reduzido a gravidade dos casos. No entanto, em situações em que há cronicidade do quadro, com intensa aderência do trombo ao vaso, a terapêutica alopática pode ser insatisfatória sendo necessária a intervenção cirúrgica. O objetivo deste trabalho é avaliar a aplicabilidade da trombectomia com Anel de Vollmar e observar a ação da passagem do Cateter de Fogarty através de trombos aderidos - crônicos. Foram utilizados 10 equinos hígidos divididos em dois grupos de cinco animais cada, sendo estes tratados com anel de Vollmar e Cateter de Fogarty (GVF) e somente com o Cateter de Fogarty (GF), após 13 dias da indução de trombose jugular unilateral direita. Durante vinte e oito dias (D0-27), os animais foram avaliados em momentos específicos, quanto aos parâmetros físicos, termográficos, laboratoriais, ultrassonográficos e venográficos, compreendendo quatro períodos de avaliação: o momento pré-indução à tromboflebite (MPIT); período de indução da tromboflebite (MIT), que teve 72 horas de duração; o período de tromboflebite (MT), onde os animais foram avaliados por dez dias; e avaliados em grupos divididos (GF x GVF) após a aplicação das técnicas de correção de trombose, o período pós-operatório (MPT). Dados quantitativos foram comparados seguindo media e desvio padrão. As análises laboratoriais foram avaliadas pela comparação dos dados de momento e tratamento, pela análise de variância. Já os dados ultrassonográficos, foram avaliados em duas etapas, sendo a comparação de momento e segmento e momento e tratamento. Em ambas as análises, valores de significância inferiores a p<0,05 foram submetidos ao teste de Tukey. Através da análise... / The jugular thrombosis in horses commonly occurs in iatrogenic situations secondary to endotoxemia, and disseminated intravascular coagulation, which may lead to death. Prophylactic treatment with antithrombotic agents has reduced the severity of the cases. However, in situations where there chronic cases, with intense adhesion of thrombus to the vessel, drug therapy may be unsatisfactory and surgical intervention is required. The objective of this study is to evaluate the applicability of thrombectomy with Vollmar ring and watch the action of the passage of the Fogarty catheter through adhered thrombi. 10 healthy horses were used and divided into two groups of five animals each, treated with Vollmar ring and Fogarty catheter (GVF) and only with the Fogarty catheter (GF), after 13 days from unilateral right jugular vein thrombosis induction. During twenty-eight days (D0-28), the animals were evaluated at specific times, as the physical parameters, thermography, laboratory, ultrasound and phlebography, comprising four evaluation periods: the pre-induction of thrombophlebitis time (MPIT); Induction period of thrombophlebitis (MIT), which is 72 hours duration; thrombophlebitis the period (MT), where the animals was evaluated for ten days; and evaluated in divided groups (GF x GVF) after application of thrombosis correction techniques, the postoperative period (MPT). Quantitative data were compared following mean and standard deviation. Laboratory tests were evaluated by comparing the treatments by analysis of variance ANOVA. Already sonographic data were evaluated in two phases, the comparison point and segment and treatments. In both analyzes, significance values below p <0.05 were submitted to Tukey test. By analyzing the data, we observed laboratory findings and similar physiological parameters between the groups, no escape from physiological patterns or present differences than expected by the use of ...

Objetivo: Avaliar a incidência de tromboembolismo e as condições clínicolaboratoriais associadas em pacientes pediátricos internados em um hospital terciário. Pacientes e métodos: Estudo retrospectivo onde foram revisados os prontuários de todas as 6140 crianças de 0 à 13 anos que internaram entre fevereiro de 2007 à janeiro de 2009. Foram identificadas 31 crianças que tiveram 34 casos de tromboembolismo confirmado por diagnóstico de imagem, e estas foram incluídas no banco de dados para análise. Resultados: A incidência de tromboembolismo foi de 43,3 (intervalo de confiança de 95%: 30,0-60,4) para cada 10.000 internações. Vinte e seis (83,9%) crianças tinham condições clínicas associadas, sendo que 11 (35,4%) tinham apenas 1 condição associada, 5 (16,1%) tinham 2 condições associadas, 6 (19,3%) tinham 3 condições associadas, 4 (12,9%) tinham 4 condições associadas e 5 (16,1%) não tinham condições associadas. As frequências das principais condições clínico-laboratoriais foram: sepse, 41,9%; trombofilias, 35,5%; cardiopatia acianótica, 29,9%; e cateter central, 22,5%. Conclusão: O presente estudo evidenciou uma incidência de tromboembolismo muito mais alta do que a descrita na literatura, provavelmente devido ao estudo ter sido realizado em um hospital terciário, com maior complexidade e complicações associadas mostrando a importância de considerar este diagnóstico. Observamos também uma alta taxa de trombofilias nos pacientes que tiveram tromboembolismo, salientando que a associação de fatores de risco e predisposição genética ou fatores intrínsecos devem ser considerada no diagnostico e manejo destes pacientes. / Objective: To assess the incidence of thromboembolism and associated clinical conditions and laboratory abnormalities in a sample of pediatric patients admitted to a tertiary referral center. Methods: This was a retrospective chart review study. The medical records of all 6140 children between the ages of 0 and 13 years admitted to the study facility from February 2007 through January 2009 were reviewed. A total of 34 cases of imaging-confirmed thromboembolism were identified in 31 children and included for analysis. Results: The incidence of thromboembolism was 43.3 (95%CI, 30.0–60.4) per 10,000 admissions. Twenty-six children (83.9%) had associated clinical conditions: 11 (35.4%) had only 1 associated condition, 5 (16.1%) had 2 associated conditions, 6 (19.3%) had 3 associated conditions, 4 (12.9%) had 4 associated conditions, and 5 (16.1%) had no associated conditions. The main associated conditions were sepsis (41.9%), thrombophilia (35.5%), acyanotic heart disease (29.9%), and central venous catheterization (22.5%). Conclusion: In the sample studied herein, the incidence of thromboembolism was much higher than that reported in the literature, most likely due to the study setting (tertiary referral hospital) and its implications (greater case complexity and frequency of complications), stressing the importance of considering the diagnosis. Furthermore, among patients who developed thromboembolism, there was a high rate of thrombophilia, highlighting the importance of the association between risk factors and genetic predispositions or intrinsic factors in the diagnosis and management of these patients.

Síndrome de Turner é causada por alterações no cromossomo X. Afeta de 1:2000 a 1:3000 recém-nascidas femininas. Apesar de ser uma doença genética, aspectos como crescimento deficiente e insuficiência ovariana são de interesse da Endocrinologia. Manifestações clínicas importantes também incluem malformações cardíacas, linfáticas e renais e estão implicadas em maior morbidade da doença. Muito embora já tenha sido descrita há quase 80 anos, novos aspectos genéticos relacionados à etiopatogenia da doença vem sendo descritos. As abordagens terapêuticas relativas aos tratamentos hormonais têm sido discutidas e novos diagnósticos clínicos, incluindo alterações cardíacas, hepáticas e casos de trombose vem sendo descritos recentemente. / Turner Syndrome is caused by X chromosome anomalies. It affects 1:2000 to 1:3000 live born females. Some aspects of the syndrome such as growth failure and ovarian failure are of interest to the Endocrinologist. Other important features of this disorder include cardiac, lymphatic and renal malformations, the cause of high morbidity. Although recognized and described for almost 80 years, new genetic information has been added to update the understanding of the etiopathogenesis of the disorder. Hormone therapies and novel clinical findings, cardiac, hepatic and thrombotic, recently described, are reviewed.

Atherosclerotic plaque ruptures have been determined as the most common underlying cause of acute coronary syndromes and stroke. Currently, the standard of care for plaque rupture risk is based on the amount of luminal stenosis presented in a particular vessel; however, X-ray angiographic studies have shown that plaques at risk of rupture generally show <50% luminal narrowing. These findings explicate the need for other, more accurate methods of identifying problem lesions prior to the rupture event. Unfortunately, the study of thrombotic events and vulnerable plaque lesions in humans is difficult due to the spontaneity of rupture and the lengthy time course of disease progression. To further the understanding of plaque rupture risk in light of vulnerability detection, a rabbit model of atherothrombosis was used in conjunction with magnetic resonance imaging (MRI). MRI has been validated as a suitable imaging modality for in vivo, non-invasive detection of atherosclerosis and has provided quantitative predictors of plaques at risk of rupture. Additionally, the rabbit model has been shown, histologically, to present 6 of the 8 human plaque types classified by the American Heart Association. The first portion of this dissertation work focuses on using MRI to serially image rabbits undergoing the atherosclerotic protocol in order to assess rupture risk at the various time points. Previous work has determined that an increase in the vessel remodeling ratio (which hides a large plaque in the vessel wall) and contrast uptake (which indicates inflammation) are both characteristics of increased rupture risk. By obtaining these parameters at various time points in the disease progression, it was possible to determine when a certain plaque displays a heightened risk of rupture. The second portion of this work tested the efficacy of a pro-resolving molecule, lipoxin (an endogenous molecule), in reducing atherosclerotic disease state, specifically rupture with a luminal thrombus. Using chronic administration of this molecule in the same rabbit model of atherosclerosis yielded a faint reduction in atherosclerotic severity based on the parameters of decreased vessel lipid content and decreased thrombotic events presented in the treated group.

OBJECTIVES: Congenital heart disease or CHD is a condition that affects 8 out of every 1,000 newborns. Every year more than 35,000 newborns are diagnosed with a congenital heart disease in the United States. Neonates and children with congenital heart disease are at increased risk for thrombotic events, especially those with a single ventricle physiology. The objective of this study was to assess the incidence and to identify the predictors of thrombosis in neonates and children with surgical and non-surgical heart diseases. METHODS: We performed a retrospective analysis of the Health Care and Cost Use Project Kid’s Inpatient Database. Neonates and children with a congenital heart disease were identified using the international classification of disease, 9th revision, clinical modification (ICD-9 CM) diagnostic codes, and grouped into two sub-categories of surgical heart and non-surgical heart diseases. These groups were further divided into four types of lesions: septal defects, single ventricle physiology, right ventricle outflow tract obstruction, and left ventricle outflow tract obstruction. Demographic characteristics, the presence of co-morbidities, the incidence of any thrombotic events, mortality rate, and the presence of additional complications such as acute kidney injury, sepsis, neurologic complications, the need for extracorporeal membrane oxygenation or ventricular assist device were also collected using ICD-9 CM codes. After propensity-matched analysis, neonates and children with a surgical congenital heart disease were compared with those with a non-surgical heart disease. We used uni- and multivariable logistic regression analysis to identify the predictors associated with the incidence of thrombotic events in both sub-group. RESULTS: In children with surgical heart disease, the incidence of thrombosis was 3.90%, compared with 2.13% in children with non-surgical heart disease. Furthermore, those with single ventricle physiology (surgical 2.13%; non-surgical 3.41%) or right ventricle outflow tract obstruction (surgical 1.54%; non-surgical 1.66) had the highest incidence of thrombosis. In addition to demographic characteristics (e.g. age) and the type of congenital heart disease, we observed that extracorporeal membrane oxygenation (ECMO) or ventricular assist device(VAD), the presence acute kidney injury, sepsis, and coagulopathy were strong predictors for the development of thrombotic events. CONCLUSIONS: Children with both surgical and non-surgical heart disease have an increased risk for thrombotic events, but those with a single ventricle physiology or a right ventricle outflow tract obstruction had a further increased risk.

Cancer and thrombosis are common co-occurrences in healthcare today. Cancer is the second leading cause of death in the United States with thrombosis being the second leading killer of cancer patients behind tumor progression. Cancer patients as a whole are 4 to 7 times more likely to develop thrombosis and 20%-30% of all first-time thrombosis diagnoses are cancer-related. Risk assessment and treatment options have much room for improvement. The lack of success for conventional antithrombotic prophylaxis suggests that hyperthrombosis in cancer works through a discrete pathway. A discovery by our group in recent years correlated the increased activity of Aryl hydrocarbon receptor (AHR) in the body to increase thrombotic phenotypes in patients with chronic kidney disease. Another group had published a manuscript about Kynurenine (Kyn), an activating ligand of the receptor that was produced by tumor cells to promote tumor growth through an AHR pathway (Opitz 2011). The link between the findings of these two groups could show that Kyn—AHR pathway is causing the increase in thrombosis in cancer patients. We used an animal model of thrombosis in cancer and created a new variation of it to test the Kyn—AHR pathway. We hypothesized that cancerous animals would show an increase in thrombosis and increased levels of AHR and Kyn along with downstream elements such as Tissue Factor (TF). Cancer was induced on nude mice via xenograft injection of cancer cells and 4-5 weeks of incubation to allow the tumors to proliferate. After the incubation period, mice underwent inferior vena cava (IVC) ligation, and were then euthanized 48 hours later. Two types of cancer were tested: HT-29 colon adenocarcinoma and A549 non small cell lung adenocarcinoma. There were 4 animal groups: mice that were injected with cancer cells and operated on, mice that were injected with cancer cells but not operated on, mice that were not injected but were operated on, and mice that did not receive neither the injections or the operation. After euthanasia, blood, tumors, and major organs were harvested to assess markers and pathways of thrombosis associated with cancer. We were able to successfully grow xenograft tumors in the nude mice. The HT-29 tumors grew very aggressively while A549 tumors experienced a small latent period before starting to proliferate. Animals with HT-29 and A549 xenograft tumors displayed greater thrombosis, measured by the weight of the blood clot formed in the IVC due to ligation (p=0.04 and p=0.05, respectively). HT-29 also displayed significant increases in Kyn, AHR activity, indoxyl sulfate (IS), and showed increased staining of tissue factor with immunohistochemistry. A549 did not have significant p-values in these experiments, but did show upward trends in all categories besides IS sera levels. In summary, we developed a new animal model of thrombosis in colon adenocarcinoma and showed significant increases in thrombosis as well as multiple markers of thrombosis. This is an exciting and complex way to study thrombosis in cancer in an in vivo approach with opportunities for future therapeutic testing. / 2020-07-03T00:00:00Z

Orientador: Hamilton Almeida Rollo / Coorientador: Kátia Luz Torres Silva / Banca: Winston Bonetti Yoshida / Banca: Fernando Luiz Westphal / Banca: Cleinaldo de Almeida Costa / Banca: Juscimar Carneiro Nunes / Resumo: A trombose venosa profunda (TVP) é doença frequente e importante causa de morbidade e mortalidade, apresentando complicações potencialmente fatais como o tromboembolismo pulmonar. A dificuldade no diagnóstico é um dos aspectos mais problemáticos. Por se tratar de uma doença com sintomas e sinais inespecíficos, a realização de exames complementares é mandatória para o diagnóstico de certeza e início da terapia anticoagulante. Avaliar a eficácia do protocolo de Wells et al. (2003) e do Dímero-D (DD) como métodos diagnósticos para TVP em comparação ao mapeamento dúplex (MD) e analisar alterações da Proteína C Reativa (PCR) comparando ao DD. Foram selecionados 203 pacientes com sintomas e sinais sugestivos de TVP, atendidos no setor de emergência de dois prontos-socorros de referência em Manaus/AM, durante o período de 13 meses. Após serem submetidos a anamnese e exame físico geral para preenchimento da ficha de avaliação e do protocolo de Wells et al e coleta de material para dosagem de DD e PCR, os pacientes foram submetidos ao MD para confirmação ou exclusão da TVP.Dos 203 pacientes estudados, 133 (65,5%) tiveram o diagnóstico de TVP confirmado por MD e os outros 70 (34,5%), o MD Resumo não foi compatível com TVP. No grupo com TVP, 75 (56,4%) eram do sexo feminino e 58 (43,6%) eram do sexo masculino. A média de idade foi de 51,7 (± 17,5) anos. No grupo sem TVP, 36 (51,4%) eram do sexo feminino e 34 (48,6%) eram do sexo masculino. A média de idade foi de 51,8 (±16,2) anos. Não houve diferenças significativas entre sexo e idade nos grupos (p = 0,500 e p = 0,987, respectivamente). A sensibilidade encontrada para o protocolo de Wells foi de 100% (IC 95%: 99,6 - 100,0) e a especificidade foi de 72,9% (IC 95%: 61,7 - 84,0). O Valor Preditivo Positivo (VPP) foi de 87,5% (IC 95%: 81,9 - 93,1) e o Valor Preditivo Negativo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Deep vein thrombosis (DVT) is common and important cause of morbidity and mortality, presenting potentially fatal complications such as pulmonary thromboembolism. Diagnosis is one of the most problematic aspects. As disease signs and symptoms are non-specific, complementary exams must be performed to confirm diagnosis and start of anticoagulant treatment. to evaluate the efficacy of the Wells et al. protocol (2003) and D Dimer test (DD) as diagnostic methods for DVT compared to Duplex Mapping (DM) and analyse changes in C-reactive protein (CRP) compared to DD. We selected 203 patients with signs and symptoms suggesting DVT, seen in two reference emergency units in Manaus/AM, Brazil over 13 months. After being submitted to anamnesis and general physical examination to fill out the Wells et al. evaluation protocol card and collection of material for DD and CRP measurements, patients were submitted to DM to confirm or exclude DVT. From the 203 patients studied, 133 (65.5%) had DVT diagnosis confirmed by DM and in the other 70 (345%), DM was not compatible with DVT. In the DVT group, 75 (56.4%) were female and 58 (43.6%) masculine. Mean age was 51.7 ± 17.5 years. In the without DVT group, 36 (51.4%) were female and 34 (48.6%) masculine. Mean age was 51.8 ± 16.2 years. Abstract There were no significant differences between gender and age in the groups (p = 0.500 and p = 0.987, respectively). Wells protocol sensitivity was found to be 100% (IC 95%: 99.6 - 100.0) and specificity was 72.9% (IC 95%: 61.7 - 84.0). Positive Predictive Value (PPV) was 87.5% (IC 95%: 81.9 - 93.1) and Negative Predictive Value (VPN) was 100% (IC 95%: 99.0 - 100.0). DD sensitivity was 100% (IC 95%: 99.6 - 100.0) and specificity was 98.6% (IC 95%: 95.1 - 100.0). PPV was 99.3% (IC 95%: 97.4 - 100.0) and NPV was 100.0% (IC 95%: 99.3 - 100.0)... (Complete abstract click electronic access below) / Doutor

Orientador: Carlos Alberto Hussni / Coorientador: Regina Moura / Banca: Marcos Jun Watanabe / Banca: Luiz Emiliano Cisneros Alvarez / Banca: Regina Kiomi Takahira / Banca: Marcone Lima Sobreira / Resumo: A trombose jugular nos equinos ocorre comumente em situações iatrogênicas, secundárias a quadros de endotoxemia e coagulação vascular disseminada, podendo levar ao óbito. A profilaxia com agentes antitrombóticos tem reduzido a gravidade dos casos. No entanto, em situações em que há cronicidade do quadro, com intensa aderência do trombo ao vaso, a terapêutica alopática pode ser insatisfatória sendo necessária a intervenção cirúrgica. O objetivo deste trabalho é avaliar a aplicabilidade da trombectomia com Anel de Vollmar e observar a ação da passagem do Cateter de Fogarty através de trombos aderidos - crônicos. Foram utilizados 10 equinos hígidos divididos em dois grupos de cinco animais cada, sendo estes tratados com anel de Vollmar e Cateter de Fogarty (GVF) e somente com o Cateter de Fogarty (GF), após 13 dias da indução de trombose jugular unilateral direita. Durante vinte e oito dias (D0-27), os animais foram avaliados em momentos específicos, quanto aos parâmetros físicos, termográficos, laboratoriais, ultrassonográficos e venográficos, compreendendo quatro períodos de avaliação: o momento pré-indução à tromboflebite (MPIT); período de indução da tromboflebite (MIT), que teve 72 horas de duração; o período de tromboflebite (MT), onde os animais foram avaliados por dez dias; e avaliados em grupos divididos (GF x GVF) após a aplicação das técnicas de correção de trombose, o período pós-operatório (MPT). Dados quantitativos foram comparados seguindo media e desvio padrão. As análises laboratoriais foram avaliadas pela comparação dos dados de momento e tratamento, pela análise de variância. Já os dados ultrassonográficos, foram avaliados em duas etapas, sendo a comparação de momento e segmento e momento e tratamento. Em ambas as análises, valores de significância inferiores a p<0,05 foram submetidos ao teste de Tukey. Através da análise... / Abstract: The jugular thrombosis in horses commonly occurs in iatrogenic situations secondary to endotoxemia, and disseminated intravascular coagulation, which may lead to death. Prophylactic treatment with antithrombotic agents has reduced the severity of the cases. However, in situations where there chronic cases, with intense adhesion of thrombus to the vessel, drug therapy may be unsatisfactory and surgical intervention is required. The objective of this study is to evaluate the applicability of thrombectomy with Vollmar ring and watch the action of the passage of the Fogarty catheter through adhered thrombi. 10 healthy horses were used and divided into two groups of five animals each, treated with Vollmar ring and Fogarty catheter (GVF) and only with the Fogarty catheter (GF), after 13 days from unilateral right jugular vein thrombosis induction. During twenty-eight days (D0-28), the animals were evaluated at specific times, as the physical parameters, thermography, laboratory, ultrasound and phlebography, comprising four evaluation periods: the pre-induction of thrombophlebitis time (MPIT); Induction period of thrombophlebitis (MIT), which is 72 hours duration; thrombophlebitis the period (MT), where the animals was evaluated for ten days; and evaluated in divided groups (GF x GVF) after application of thrombosis correction techniques, the postoperative period (MPT). Quantitative data were compared following mean and standard deviation. Laboratory tests were evaluated by comparing the treatments by analysis of variance ANOVA. Already sonographic data were evaluated in two phases, the comparison point and segment and treatments. In both analyzes, significance values below p <0.05 were submitted to Tukey test. By analyzing the data, we observed laboratory findings and similar physiological parameters between the groups, no escape from physiological patterns or present differences than expected by the use of ... / Doutor

Síndrome de Turner é causada por alterações no cromossomo X. Afeta de 1:2000 a 1:3000 recém-nascidas femininas. Apesar de ser uma doença genética, aspectos como crescimento deficiente e insuficiência ovariana são de interesse da Endocrinologia. Manifestações clínicas importantes também incluem malformações cardíacas, linfáticas e renais e estão implicadas em maior morbidade da doença. Muito embora já tenha sido descrita há quase 80 anos, novos aspectos genéticos relacionados à etiopatogenia da doença vem sendo descritos. As abordagens terapêuticas relativas aos tratamentos hormonais têm sido discutidas e novos diagnósticos clínicos, incluindo alterações cardíacas, hepáticas e casos de trombose vem sendo descritos recentemente. / Turner Syndrome is caused by X chromosome anomalies. It affects 1:2000 to 1:3000 live born females. Some aspects of the syndrome such as growth failure and ovarian failure are of interest to the Endocrinologist. Other important features of this disorder include cardiac, lymphatic and renal malformations, the cause of high morbidity. Although recognized and described for almost 80 years, new genetic information has been added to update the understanding of the etiopathogenesis of the disorder. Hormone therapies and novel clinical findings, cardiac, hepatic and thrombotic, recently described, are reviewed.