Thesis (M.S.)--Case Western Reserve University, 2008. / [School of Medicine] Department of Clinical Research. Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

We describe the case of a patient with documented temporal arteritis, who presented two years into her course with acute digital ischemia, presumed secondary to small vessel vasculitis. To our knowledge, this complication of temporal arteritis has not been previously reported.

Polyomavirus nephropathy is a disease that predominates in renal transplant patients due to the immunosuppressive treatment for the maintenance of the renal graft. The current prevalence of this disease ranges between 1-14%. The suspicion of the disease comes from the presence of decoy cells in urine samples and the gold standard for the diagnosis is the presence of viral inclusions in the renal biopsy. In this case report, we describe a patient with a renal transplant secondary to Takayasu arteritis who presented renal failure evidenced by progressive elevation of serum creatinine. The renal biopsy showed viral inclusions, confirming the diagnosis. / La nefropatía por poliomavirus es una enfermedad que predomina en los pacientes con trasplante renal por el tratamiento inmunosupresor para manutención del injerto renal. La prevalencia actual de esta enfermedad oscila entre el 1 y el 14%. La sospecha de la enfermedad se da por la presencia de decoy cells en el examen de orina y el diagnóstico, mediante el hallazgo de inclusiones virales en la biopsia renal. Se describe el caso de un paciente con trasplante renal secundario a arteritis de Takayasu, que presenta disfunción renal evidenciada por elevación progresiva de creatinina sérica, por lo que se le realiza una biopsia renal en donde se observaron inclusiones nucleares virales que permitieron concluir el diagnóstico / Revisión por pares

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Made available in DSpace on 2014-06-11T19:23:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-04-27Bitstream added on 2014-06-13T19:48:05Z : No. of bitstreams: 1 braga_prc_me_botfmvz.pdf: 1253627 bytes, checksum: 841018a463fea183c2e1b5ae5a1e9c0a (MD5) / Universidade Estadual Paulista (UNESP) / O presente estudo investigou a ocorrência de anticorpos contra o vírus da arterite eqüina, utilizando a técnica de soroneutralização viral em 1.400 eqüinos criados nas Mesorregiões Macro Metropolitana Paulista e Campinas, pertencentes a 42 municípios do estado de São Paulo (SP), Brasil entre os meses de janeiro de 2007 a dezembro de 2008. Do total das amostras, 80 (5,71%) apresentaram anticorpos para o vírus (títulos entre 4 e 4096). Dentre os 42 municípios amostrados, 15 (35,7%) apresentaram pelo menos um animal sororeagente. Foram analisadas 238 propriedades das quais 41 apresentaram ao menos um animal sororeagente. A ocorrência de animais reagentes foi maior em cavalos destinados ao esporte, particularmente das raças de Salto e Quarto de Milha e foi semelhante entre machos e fêmeas. A ocorrência também foi maior em animais acima de 24 meses de idade. Os resultados obtidos sugerem a circulação do vírus nos criatórios amostrados e alertam para o impacto econômico- sanitário da doença para a eqüideocultura do estado de São Paulo / This study investigate the occurence of arteritis virus antibodies using virus neutralization teste in 1,400 equines from Campinas and Macro Metropolitan Paulista Mesoregions which belong to the 42 cities located on State of Sao Paulo, Brazil between january of 2007 until december of 2008. All the samples, 80 (5.71%) showed antibodies to equine arteritis virus (titers ranging from 4 to 4096). Among the 42 cities, 15 (35.7%) presented at least one positive animal to equine arteritis virus. Were studied 238 farms, and from these 41 showed at least one soropositive animal. The prevalence was higher in sport horses like Jumping Horses, Quarter Horses and was similar between females and males. The seropositive ocurrence was higher in animals above 24 months of age. These results suggest the circulation of virus among horse population in farms sampled and alert to sanitary and economical importance of this disease for the Sao Paulo State equine husbandry

Introduction: There are no validated strategies in the teaching of ultrasound as a diagnostic tool in undergraduate medicine students. Given the role that ultrasound plays in the diagnostic capacity of any clinician is currently undeniable, a teaching method is proposed based on the demonstration of the association between the histopathology of a large vessel vasculitis and the characteristic ultrasound finding, known as the «halo sign». Methods: The teaching strategy was imparted by means of a 10-minute video presentation. Twenty-one final-year students from a single medical school participated in a concordance study and a validation test, identifying images corresponding to the halo sign in 120 different cases. The overall sensitivity, specificity and likelihood ratio of the students were also determined. Results: The overall concordance test had a kappa coefficient of 0.749 (SD: 0.11). The kappa concordance was 0.76 with dynamic images, and 0.84 with cross-sectional slices. The overall sensitivity was 89.7%, and the positive predictive value was 92.3%. The likelihood ratio achieved was 7.28. Conclusions: It has been shown that the application of this pedagogical method is useful in teaching the identification of an ultrasound sign to medical students. This study also suggests conditions that could be useful to improve between-observer agreement in both teaching scenarios and multiple observer scientific studies. / Revisión por pares

Giant Cell arteritis (GCA) is a systemic inflammatory disease that affects arteries of medium- and large size. Symptoms of GCA such as headache and fever usually promptly improve with treatment of glucocorticoids. Apart from advanced age, female sex and Northern-European descent, risk factors for GCA are unknown. Most studies have found that life expectancy for patients with GCA is not reduced compared with the general population and studies on cardiovascular disease in GCA have provided conflicting results. Data for the studies of this thesis are drawn from the Reykjavik Study (RS) that is a general population-based cohort study with continuous surveillance for coronary heart disease and vital status. Subjects born in 1907–1934 and living in Reykjavik, Iceland or adjacent communities in 1966 were invited for study visit from 1967-1994. Information on cardiovascular risk factors were collected at study visit. Diagnosis of GCA for this study was based on re-examination of all temporal arteries biopsies (TAB) from members of the RS cohort; however, information was also obtained from the original pathology report. Of 19,360 subjects included in the RS, 194 developed GCA during the follow-up period. Body mass index was inversely associated with the occurrence of GCA. Among men, but not women, hypertension was associated and smoking inversely associated with the occurrence of GCA. Among women, but not men, GCA was associated with coronary heart disease. Subjects with GCA had approximately 50% increase in mortality risk compared with the general population. Increase mortality was mainly observed among GCA patients based on the diagnosis of re-examination of TAB; however, no such an association was found if diagnosis of GCA was made based on the original pathology report. Those subjects were likely not clinically diagnosed with GCA, signaling that treatment for GCA might be beneficial with respect to mortality risk.

La etiología de la arteritis de células gigantes (ACG) es desconocida y sus aspectos etiopatogénicos están poco estudiados.Objetivos. 1. Estudiar la presencia de parvovirus B19 y los virus herpes en las arterias temporales positivas y negativas para la ACG. 2. Estudiar la asociación entre la expresión de metaloproteinasa-2 (MMP-2) y 9 (MMP-9) y el resultado de la biopsia de la arteria temporal (BAT), qué células las expresan y su localización. 3. Analizar si la presencia de estas MMP o los virus se relaciona con las alteraciones histológicas y con las variables clínico-epidemiológicas de los pacientes. 4. Conocer cuáles son los factores predictores del resultado de la BAT. Material y métodos. Se incluyeron todas las BAT valorables realizadas de forma consecutiva en el Hospital Universitari Vall d'Hebron por sospecha clínica de ACG entre Enero de 1997 y Marzo del 2002. Como criterios anatomopatológicos se utilizaron los del ACR. La presencia de ADN vírico se determinó mediante reacción en cadena de la polimerasa. Se realizaron nuevas tinciones de hematoxilina-eosina, de fibras elásticas y tricrómicro de Masson. Los macrófagos CD68, la MMP-2 y la MMP-9 se detectaron mediante inmunohistoquímica. De las historias clínicas se obtuvieron datos clínicos y epidemiológicos. Para el ajuste multivariable se utilizó la regresión logística múltiple.Resultados. En el período en estudio se encontraron 147 BAT válidas, 50 (35%) positivas para ACG y 97 (66%) negativas. Se recuperó la historia clínica de 125 pacientes, 46 (36,8%) con BAT (+) y 79 (63,2%) BAT (-). No se encontró presencia de ADN de los virus estudiados en ninguna de las BAT. La MMP-9 se expresaba con más frecuencia en BAT positivas que negativas para ACG (OR=2,93 p=0,005). Para la MMP-2 la diferencia no fue estadísticamente significativa (p=0,08). Ambas MMP se expresaban en macrófagos de la íntima y de la media cercanos a la lámina elástica interna, en células gigantes y en células con apariencia de músculo liso de la media y de la íntima. Le expresión de MMP-2 se relacionó de forma inversa con la afectación exclusiva de la adventicia (p=0,047) y de forma positiva con la fiebre (p=0,025). La MMP-9 se relacionó de forma positiva con: hiperplasia intimal (0,037), degeneración lámina elástica (0,0001), disminución de la luz (0,008), hipercolesterolemia (0,032), hiperestesia craneal (0,009). Ajustando por variables que podrían influir en el resultado de la biopsia, (edad, género, tiempo de evolución de los síntomas hasta la BAT, tratamiento previo con glucocorticoides y año de realización de la biopsia), se mantuvieron los resultados entre la expresión de MMP-2 y MMP-9. El engrosamiento de la arteria temporal, la disminución de su pulso y la pérdida de peso se asociaron de forma independiente con el resultado de la biopsia, ajustando por edad, género, días de evolución, tratamiento previo, año de realización, cefalea, hiperestesia craneal, claudicación mandibular, alteraciones visuales y VSG.Conclusiones. Ninguno de los virus estudiados parece estar implicado en la etiopatogenia de la ACG. La MMP-9, al contrario de la MMP-2, parece tener un papel en dicha etiopatogenia. La MMP-9 se asocia con hipercolesterolemia y la MMP-2 con la fiebre. El engrosamiento, la disminución de la luz de la arteria temporal y la pérdida de peso se han encontrado asociadas a una elevada probabilidad de resultado positivo de la biopsia en los enfermos estudiados. / The etiology of giant cell arteritis (GCA) is unknown and their etiopathogenic aspects have been little studied.Aims. 1. To study the presence of parvovirus B19 and herpes viruses in positive and negative temporal artery biopsies (TAB) for GCA. 2. To study the association between metalloproteinase-2 (MMP-2) and 9 (MMP-9) expression and TAB result, the type of cells expressing them and their location. 3. To analyse if the presence of these MMP or the viruses is related to histologic findings and to clinical-epidemiological variables of the patients. 4. To identify predictive factors of TAB result. Material and methods. All the valid TAB consecutively performed in Hospital Universitari Vall d'Hebron because of clinical suspicion of GCA between January 1997 and March 2002. ACR anatomopathological criteria were used. The presence of viral DNA was determined by means of polymerase chaín reaction. New hematoxilin-eosin, elastic fibers and Masson's trichromic stainings were performed. CD68 macrophages, MMP-2 and MMP-9 were detected by immunohistochemistry. Clinical and epidemiological data were obtained from clinical files. The multiple logistic regression was used for multivariable analysis. Results. During the study period, 147 valid TAB were found, 50 (35%) positive and 97 (66%) negative for GCA. Clinical files of 125 patients were retrieved, 46 (36.8%) with positive TAB and 79 (63.2%) with negative TAB. DNA of the viruses studied was not found in any of the TAB. MMP-9 was more frequently expressed in positive than in negative TAB for GCA (OR=2.93; p=0.005). The difference was not statistically significant for MMP-2 (p=0.08). Both MMP were expressed in macrophages of the intima and the media near internal elastic lamina, in giant cells and in cells of the media and the intima resembling smooth muscle cells. The expression of MMP-2 was inversely related to the isolated involvement of the adventitia (p=0.047) and positively to fever (p=0.025). MMP-9 was positively related to: intimal hyperplasia (0.037), elastic lamina degeneration (0.0001), luminal narrowing (0.008), hypercholesterolemia (0.032), scalp tenderness (0.009). Controlling for variables which could influence the biopsy result (age, gender, evolution of symptoms before TAB, previous glucocorticoids treatment and year of biopsy performance), the results between MMP-2 and MMP-9 expression remained unaltered. Temporal artery thickening, pulse decrease and weight loss were independently associated with biopsy result, controlling for age, gender, days of evolution of symptoms, previous treatment, year of biopsy performance, headache, scalp tenderness, jaw claudication, visual disturbances and erythrocyte sedimentation rate.Conclusions. None of the viruses studied seems to be involved in GCA etiopathogenesis. MMP-9, in contrast to MMP-2, seems to play an etiopathogenic role in GCA. MMP-9 is associated with hypercholesterolemia and MMP-2 with fever. Temporal artery thickening and luminal narrowing and weight loss are associated with a high probability of positive biopsy result in the patients studied.

Resumo: O presente estudo investigou a ocorrência de anticorpos contra o vírus da arterite eqüina, utilizando a técnica de soroneutralização viral em 1.400 eqüinos criados nas Mesorregiões Macro Metropolitana Paulista e Campinas, pertencentes a 42 municípios do estado de São Paulo (SP), Brasil entre os meses de janeiro de 2007 a dezembro de 2008. Do total das amostras, 80 (5,71%) apresentaram anticorpos para o vírus (títulos entre 4 e 4096). Dentre os 42 municípios amostrados, 15 (35,7%) apresentaram pelo menos um animal sororeagente. Foram analisadas 238 propriedades das quais 41 apresentaram ao menos um animal sororeagente. A ocorrência de animais reagentes foi maior em cavalos destinados ao esporte, particularmente das raças de Salto e Quarto de Milha e foi semelhante entre machos e fêmeas. A ocorrência também foi maior em animais acima de 24 meses de idade. Os resultados obtidos sugerem a circulação do vírus nos criatórios amostrados e alertam para o impacto econômico- sanitário da doença para a eqüideocultura do estado de São Paulo / Abstract: This study investigate the occurence of arteritis virus antibodies using virus neutralization teste in 1,400 equines from Campinas and Macro Metropolitan Paulista Mesoregions which belong to the 42 cities located on State of Sao Paulo, Brazil between january of 2007 until december of 2008. All the samples, 80 (5.71%) showed antibodies to equine arteritis virus (titers ranging from 4 to 4096). Among the 42 cities, 15 (35.7%) presented at least one positive animal to equine arteritis virus. Were studied 238 farms, and from these 41 showed at least one soropositive animal. The prevalence was higher in sport horses like Jumping Horses, Quarter Horses and was similar between females and males. The seropositive ocurrence was higher in animals above 24 months of age. These results suggest the circulation of virus among horse population in farms sampled and alert to sanitary and economical importance of this disease for the Sao Paulo State equine husbandry / Orientador: Alexandre Secorun Borges / Coorientador: Márcio Garcia Ribeiro / Banca: Wilson Roberto Fernandes / Banca: João Pessoa Araújo Junior / Mestre