Pentoxifylline immunomodulation in the treatment of experimental chronic pulmonary paracoccidioidomycosis.

BACKGROUND: Pentoxifylline (PTX) is a methylxanthine compound with immunomodulatory and antifibrotic properties. The simultaneous use of PTX and antifungal therapy (itraconazole) has previously been evaluated in an experimental model of pulmonary paracoccidioidomycosis (PCM), a systemic fungal disease caused by the fungus Paracoccidioides brasiliensis (Pb) and characterized by chronic inflammation and lung fibrosis that appears even after a successful course of antifungal therapy. The results revealed prompt and statistically significant reductions in inflammation and fibrosis when compared to itraconazole alone. However, the effect of monotherapy with PTX on the host response to PCM has not been well-documented. Our aim was to determine the effect of PTX on the course of pulmonary lesions and on the local immune response. RESULTS: At the middle and end of treatment, the Pb-infected-PTX-treated mice exhibited significant reductions in lung density compared to the Pb-infected-non-treated mice as assessed by the quantification of Hounsfield units on high-resolution computed tomography (HRCT) (p <0.05 by Kruskal-Wallis test); additionally, at the end of therapy, the lung areas involved in the inflammatory reactions were only 3 vs. 22 %, respectively, by histomorphometry (p <0.05 by Mann-Whitney test), and this reduction was associated with a lower fungal burden and limited collagen increment in the pulmonary lesions. PTX treatment restored the levels of IFN-γ, MIP-1ß, and IL-3 that had been down-regulated by Pb infection. Additionally, IL-12p70, IL-10, IL-13, and eotaxin were significantly increased, whereas Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES) levels were decreased in the lungs of the Pb-infected-PTX-treated mice compared to the non-treated group. CONCLUSIONS/SIGNIFICANCE: This study showed that PTX therapy administered at an "early" stage of granulomatous inflammation controlled the progress of the PCM by diminishing the pulmonary inflammation and the fungal burden and avoiding the appearance of collagen deposits in the pulmonary lesions.

Pulmonary abnormalities in mice with paracoccidioidomycosis: a sequential study comparing high resolution computed tomography and pathologic findings.

BACKGROUND: Human paracoccidioidomycosis (PCM) is an endemic fungal disease of pulmonary origin. Follow-up of pulmonary lesions by image studies in an experimental model of PCM has not been previously attempted. This study focuses on defining patterns, topography and intensity of lung lesions in experimentally infected PCM mice by means of a comparative analysis between High Resolution Computed Tomography (HRCT) and histopathologic parameters. METHODOLOGY: Male BALB/c mice were intranasally inoculated with 3 x 10(6) Paracoccidioides brasiliensis (Pb) conidia (n = 50) or PBS (n = 50). HRCT was done every four weeks to determine pulmonary lesions, quantify lung density, reconstruct and quantify lung air structure. Lungs were also analyzed by histopathology and histomorphometry. RESULTS: Three different patterns of lesions were evidenced by hrct and histopathology, as follows: nodular-diffuse, confluent and pseudo-tumoral. The lesions were mainly located around the hilus and affected more frequently the left lung. At the 4th week post-challenge HRCT showed that 80% of the Pb-infected mice had peri-bronchial consolidations associated with a significant increase in upper lung density when compared with controls, (-263+/-25 vs. -422+/-10 HU, p<0.001). After the 8th and 12th weeks, consolidation had progressed involving also the middle regions. Histopathology revealed that consolidation as assessed by HRCT was equivalent histologically to a confluent granulomatous reaction, while nodules corresponded to individual compact granulomas. At the 16th week of infection, confluent granulomas formed pseudotumoral masses that obstructed large bronchi. Discrete focal fibrosis was visible gradually around granulomas, but this finding was only evident by histopathology. CONCLUSIONS/SIGNIFICANCE: This study demonstrated that conventional HRCT is a useful tool for evaluation and quantification of pulmonary damage occurring in experimental mouse PCM. The experimental design used decreases the need to sacrifice a large number of animals, and serves to monitor treatment efficacy by means of a more rational approach to the study of human lung disease.

Evaluación arteriográfica en el trauma vascular periférico

Se estudiaron arteriográficamente 136 pacientes con sospecha de lesión vascular periférica remitidos al servicio de radiología del Hospital Univesitario San Vicente de Paul entre abril de 1991 y junio de 1992. La mayoría fueron jóvenes con lesiones por proyectil de arma de fuego (79.4 por ciento). La indicación arteriográfica mas frecuente fue la proximidad de la herida al trayecto vascular (44.5 por ciento). El 63 por ciento de los pacientes con arteriografías positivas requirió cirugía; correspondiendo el 21 por ciento a los pacientes con proximidad de la herida al trayecto vascular y el 76 por ciento a pacientes con hallazgos mayores al ingreso. Se revisaron las complicaciones inherentes al procedimiento encontrándose sólo dos reacciones mayores al medio de contraste. No hubo complicaciones tardías. La arteriografía es un método altamente sensible (100 por ciento), específico (98.5 por ciento) y seguro en la evaluación de los pacientes con trauma vascular periférico. Dado el alto índice de falsos negativos con el exámen físico, todo paciente con proximidad de la herida al trayecto vascular debe ser avaluado con arteriografía

Papel de la galactografía en el manejo de pacientes con secreción por el pezón: comparación con citología

Se realizó galactografía y citología en 30 pacientes con secreción espontánea por el pezón. La secreción hemática fue la mas frecuente (43,3 por ciento). Los cambios fibroquísticos fueron la causa mas común de telorrea diagnosticada por los dos métodos (60 por ciento por galactografía y 56,7 por ciento por citología), los cuales coinciden para el diagnóstico de papiloma en el 50 por ciento de los casos y en el 70,6 por ciento para el diagnóstico de patología benigna no tumoral. La galactografía sigue siendo el método de elección para la evaluación de las pacientes con secreción hemática, reservandose la citología como un exámen complementario

Marcación con arpón de lesiones mamarias no palpables demostradas por mamografía: correlación radiológica e histológica

Se realizó marcación preoperatoria con arpón de 61 lesiones mamarias no palpables. Se clasificaron mamográficamente como indeterminadas probablemente benignas (I.P.B.) 39 lesiones (63 por ciento) y las 22 lesiones restantes como indeterminadas probablemente malignas. Se encontraron 12 lesiones malignas. El valor predictivo positivo de las lesiones marcadas fue del 19.7 por ciento, la sensibilidad del 83.3 por ciento, la especificidad del 75.5 por ciento, con una alta significancia estadística (p=0.0003). Podemos concluir de acuerdo a los resultados obtenidos que en el grupo de lesiones clasificadas como I.P.B. debe considerarse el empleo de otros métodos diagnósticos comlementarios o el seguimiento mamográfico periódico