Insights From the Histopathologic Analysis of Acquired and Genetic Thoracic Aortic Aneurysms and Dissections.

OBJECTIVE: The purpose of this study was to apply contemporary consensus criteria developed by the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology to the evaluation of aortic pathology, with the expectation that the additional pathologic information may enhance the understanding and management of aortic diseases. METHODS: A scoring system was applied to ascending aortic specimens from 42 patients with heritable thoracic aortic disease and known genetic variations and from 86 patients from a single year, including patients with known genetic variations (n = 12) and patients with sporadic disease (n = 74). RESULTS: The various types of lesions of medial degeneration and the overall severity of medial degeneration overlapped considerably between those patients with heritable disease and those with sporadic disease; however, patients with heritable thoracic aortic disease had significantly more overall medial degeneration (P = .004) and higher levels of elastic fiber fragmentation (P = .03) and mucoid extracellular matrix accumulation (P = .04) than patients with sporadic thoracic aortic disease. Heritable thoracic aortic disease with known genetic variation was more prevalent in women than in men (27.2% vs 9.8%; P = .04), and women had more severe medial degeneration than men (P = .04). Medial degeneration scores were significantly lower for patients with bicuspid aortic valves than for patients with tricuspid aortic valves (P = .03). CONCLUSION: The study's findings indicate considerable overlap in the pattern, extent, and severity of medial degeneration between sporadic and hereditary types of thoracic aortic disease. This finding suggests that histopathologic medial degeneration represents the final common outcome of diverse pathogenetic factors and mechanisms.

Diagnostic methodology in labelled leukocyte scan for prosthetic / non-prosthetic osteoarticular infection: Visual or semi-quantitative analysis? One- or two-day protocol?

OBJECTIVE: as scarce literature on the topic is available, we aimed to compare diagnostic utility of semi-quantitative versus visual analysis in labelled white blood cell scintigraphy (WBCS) for osteoarticular infection. One-day and two-day protocols were assessed, particularly in orthopaedic devices. MATERIAL AND METHODS: prospective study of 79 consecutive patients with suspected osteoarticular infection. In all patients, WBCS were performed at 30min, 4h, 8h and 24h. Images were analysed by grouping in two protocols: one-day-protocol (experts evaluated 30min, 4h and 8h planar images) and two-day-protocol (experts evaluated 30min, 4h and 24h planar images). Planar images were interpreted qualitative and semiquantitatively and also were compared grouping patients with and without orthopaedic devices. To find which cut-off value of the percentage variation could predict of osteoarticular infection, multiple cut-off values were calculated in both protocols from the Youden index. Three blinded readers analysed the images. RESULTS: Comparing final diagnosis visual analysis of the one-day-protocol provided better results with sensitivity of 95.5%, specificity of 93% and diagnostic accuracy of 93.7% (p<001) than the two-day-protocol with values of 86.4%, 94.7% and 92.4%, respectively (p<001). For semi-quantitative analysis, the one-day-protocol also obtained better results with sensitivity of 72.7%, specificity of 78.9% and accuracy of 77.2% (p<001) than two-day-protocol (no significant results; p=0.14), especially in the group of patients with orthopaedic devices (sensitivity of 100%, specificity of 79.5% and accuracy of 82.7%; p<001). CONCLUSIONS: most accurate approach in the diagnosis of osteoarticular infection corresponded to visual analysis in one-day-protocol that showed greater sensitivity and specificity than semi-quantitative analysis. Semi-quantitative analysis only could be useful when visual analysis is doubtful. In patients with joint prostheses, an increase in percentage variation above 9% obtained maximum sensitivity and negative predictive value.

Utility of 8 h and time decay-corrected acquisition scintigraphy with in-vitro labeled white blood cells for the diagnosis of osteoarticular infection.

INTRODUCTION: Except in the spine, labeled white-blood cell scintigraphy (WBCS) with image acquisition up to 24 h is the nuclear medicine test of choice for diagnosing osteoarticular infection. However, distinguishing between inflammation and infection is a challenge. OBJECTIVES: The first aim of this study was to verify earlier research studies that used 4 and 24 h time decay-corrected acquisition (TDCA) to differentiate infection from inflammation. The second aim was to analyze whether 8 h acquisition (1-day protocol) yielded similar results as 20-24 h acquisition. PATIENTS AND METHODS: This was an observational study of 94 patients (22-86 years, 52 women) with suspected osteoarticular infection referred to nuclear medicine to confirm infection. WBCS and TDCA images were obtained at 30 min, 4 h, and 8 h after injection of the labeled leukocytes, with collection times of 5, 8, and 12 min, respectively. Scintigrams were classified into three protocols: protocol 1: experts read only 30 min and 4 h images; protocol 2: experts read the whole set of images (30 min, 4 h, and 8 h) with different pixel intensities (each image normalized to its own maximum activity); protocol 3: experts read the whole set of images with the same pixel intensity. Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated. In patients with orthopedic implants, the interobserver reproducibility for visual analysis was calculated using the κ index. RESULTS: Infection was confirmed in 26 cases. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and κ results were as follows: protocol 1: 92.3, 50.0, 41.4, 94.4, 61.7%, 0.79; protocol 2: 92.3, 94.1, 85.7, 97.0, 93.6%, 0.80; protocol 3: 96.2, 97.1, 92.6, 98.5, 96.8%, 0.77. CONCLUSION: TDCA acquisition of WBCS at 8 h (1-day protocol) enables a faster diagnosis than 24 h acquisition. The use of TDCA with the same pixel intensity in all images enables an accurate diagnostic of osteoarticular infection, with a considerable interobserver agreement for all protocols.

Morphologic changes in the aortic wall media after support with a continuous-flow left ventricular assist device.

BACKGROUND: Continuous-flow left ventricular assist devices (LVADs) provide durable, reliable, energy-efficient long-term support. However, the biologic effects of continuous flow are not completely known. Therefore, we examined aortic wall morphology in patients with heart failure before and after prolonged circulatory support with a continuous-flow LVAD. METHODS: After applying a partial aortic occlusion vascular clamp in the lower half of the ascending aorta, we removed samples of aortic wall tissue and then attached the outflow graft of the pump. Samples were obtained from 11 patients (9 men and 2 women, mean age 65 ± 7 years) with severe heart failure at the time of LVAD implantation. We obtained matched specimens at explantation after heart transplantation (n = 5) or autopsy (n = 6). These specimens were removed from the distal ascending aorta, remote from the aortic anastomotic site. Tissue sections were stained with hematoxylin and eosin, Movat's pentachrome and Masson's trichrome. Smooth muscle actin immunohistochemistry was performed on all sections. To evaluate the morphology of the aortic wall media, we quantitatively graded tissue sections for medial thickness, medial degenerative changes, smooth muscle cell (SMC) disorientation and depletion, elastic fiber fragmentation and depletion, medial fibrosis and atherosclerotic changes. RESULTS: The mean duration of support was 140 ± 136 days (range 87 to 580 days). The histologic evaluation and comparison of specimens obtained before and after LVAD support showed significantly increased foci of medial degeneration, SMC depletion, elastic fiber fragmentation, medial fibrosis and atherosclerotic changes after LVAD support. Mean medial thickness was not significantly different after LVAD support. We observed similar changes between samples obtained at transplantation and those obtained at autopsy. CONCLUSIONS: After continuous-flow LVAD support, the morphology of the aortic wall media was altered in all of our patients. The clinical relevance of these findings is unknown.

Inmunologia de la gestacion / Inmune reaction of pregnancy

Dado que el feto presenta una diferencia de 50 por ciento en antigenicidad relacionada con el HLA de la madre gestante, sería de esperar una reacción inmunológica específica de rechazo, con muerte y expulsión del feto. Sin embargo, ello no ocurre, pues se presenta un fenómeno de tolerancia inmune de la madre hacia el feto. Se ha comprobado que la madre produce una serie de factores inmunosupresores que evitan ese rechazo, pero que actúan únicamente a nivel del útero y no a nivel sistémico pues generaría tendencia grave a infecciones

Matrix metalloproteinases and their tissue inhibitors in the lesions of cardiac and pulmonary sarcoidosis: an immunohistochemical study.

The pathogenesis of the tissue damage and fibrosis in sarcoidosis is poorly understood. The matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) must be considered in this regard, because they control the lysis of connective tissue components. Immunohistochemical studies (peroxidase and dual labeling for confocal microscopy) of reactivity for MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, and the 4 membrane-type-MMPs were made on tissues from patients with cardiac (n = 4) and pulmonary (n = 5) sarcoidosis. The granulomas were histochemically similar in both organs. The multinucleated giant cells (MGCs) showed moderate reactivity for MMP-1 and MMP-9 and variable reactivity for MMP-2 and MMP-3; in addition, they showed colocalization of MT-1-MMP, which activates MMP-2. The reactivity of epithelioid cells (ECs) was moderate for MMP-2 and mild for other MMPs. Macrophages showed weaker reactivity for MMPs than did MGCs and ECs. All 3 types of cells showed very low reactivity for TIMPs. Staining for type IV collagen showed focal damage to the basement membranes of cardiac myocytes and pulmonary alveoli near the granulomas. The cells in sarcoid granulomas contain an abundance of MMPs and a paucity of TIMPs. The MGCs also contain MT-1-MMP and thus can activate MMP-2 in the granulomas. The MMPs can cause damage to adjacent cardiac myocytes and pulmonary alveoli, leading to the interstitial fibrosis produced by sarcoidosis.

De miocarditis a miocarditis. Utilidad de la biopsia endomiocardica / From myocarditis to myocardiophaty

La miocarditis es un proceso inflamatorio, generalmente de origen viral, en el cual se desencadena una respuesta autoinmune que puede progresar a la cronicidad, con desarrollo de cardiomiopatía dilatada. La biopsia endomiocárdica es importante para definir el manejo, establecer el grado de actividad y la presencia de indicadores de progresión. Permite también evaluar los resultados del tratamiento. Los estudios de inmunohistoquímica y biología molecular en las biopsias son útiles para definir la etiología y evaluar marcadores de severidad. Constituyen el fundamento de numerosos estudios que contribuirán a esclarecer la patogénesis y a optimizar el tratamiento de la miocarditis

Desensibilizacion de pacientes alergicos por via sublingual-oral. Primera parte / Desensitization of allergic patients by sublingual-oral. I part

Se trataron 30 pacientes con diferentes tipos de enfermedades alérgicas empleando la inmunoterapia por vía sublingual-oral. Los resultados obtenidos permiten observar una respuesta de remisión temprana de signos y síntomas de la enfermedad tratada, en un período máximo de 6 meses de tratamiento. En ningún caso se produjo una reacción de tipo anafiláctico o un efecto colateral que pusiera en peligro la vida del paciente o que obligara a suspender el tratamiento. Todos los pacientes que siguieron la desensibilización, según lo indicado, mejoraron. En un período de observación después de terminado el tratamiento un paciente presentó recaída leve de su enfermedad (asma bronquial), para esto, fue necesario hacer un refuerzo de la inmunoterapia por un mes adicional con antígeno puro, lográndose los resultados deseados. Se considera que los resultados obtenidos son ventajosos con relación a la inmunoterapia parenteral en lo que respecta a tiempo empleado, prontitud en la respuesta de tolerancia, ausencia de respuestas anafilácticas, facilidad de administración por el mismo paciente, atraumático y muy económico, con base en los cual los investigadores recomiendan esta terapia como muy efectiva y segura para el paciente

Biopsia endomiocardica: patron de oro para el diagnostico del rechazo agudo en el trasplante cardiaco / Endomyocardial biopsy

El trasplante cardíaco es la alternativa terapéutica para la falla cardíaca refractaria al tratamiento farmacológico. El manejo de los inmunosupresores y el seguimiento de los pacientes trasplantados se basa en la biopsia endomiocárdica, la cual constituye el patrón de oro para el diagnóstico del rechazo agudo. Permite la valoración de los resultados del tratamiento, así como el diagnóstico de isquemia, infecciones oportunistas y neoplasias post-trasplante. En el rechazo crónico, la biopsia detecta estadios avanzados con lesiones isquémicas y compromiso de las arterias coronarias intramiocárdicas

Estado del arte en inmunologia de mucosas / Review of literature on mucosal immunology

El presente estudio evalúa la positividad de las pruebas cutáneas a diferentes aeroalérgenos en 27 hombres y 73 mujeres de 15 a 55 años de edad, con historia clínica sugestiva de asma y/o rinoconjuntivitis alérgica, atendidos en la Consulta Externa de Alergia e Inmunopatología del Hospital de Clínicas de la Facultad de Medicina de la Universidad de San Pablo, Brasil. Fue utilizada la prueba de puntura por ser mundialmente reconocido dada su excelente reproductibilidad y baja incidencia de efectos colaterales. Se utilizaron doce extractos patronizados, purificados y concentrados con alergenos de Dermatophagoides pteronyssinus, Dermatophagoides farinae, Cladosporum herbarum, Alternaria tenuis, Aspergillus fumigatus, epitelio de gato y perro, Lolium perenne, Thyrophagus putrescentiae, Euroglyphus mainei, Blomia tropicalis y Blatella germánica. Se encuentra como resultado que los alergenos de mayor prevalencia en las condiciones ambientales y meteorológicas específicas de la ciudad de San Pablo, Brasil fueron: Dermatophagoides pteronyssinus 78.7 por ciento, Dermatophagoides farinae 61.2 por ciento y Blomia tropicalis 50 por ciento