Alexandre Todorovic Fabro

São Paulo State University, San Paulo, São Paulo, Brazil

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Publications (20)11.3 Total impact

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    ABSTRACT: OBJECTIVE: To analyze the hyaluronic acid behavior in the lamina propria of the larynx with advancing age. STUDY DESIGN: Prospective study. SETTING: UNESP-Univ Estadual Paulista, Botucatu Medical School, Brazil. SUBJECTS AND METHODS: Thirty vocal folds were obtained at necropsy from 10 adult males (30-50 years old) and 20 geriatric males (10: 60-75 years old; 10: over 76 years old). Midmembranous vocal fold sections were subjected to immunohistochemical reactions. Digital imaging software (ImageJ) was used to quantify the hyaluronic acid distribution over the lamina propria of vocal folds, from superficial to deep layers. RESULTS: Hyaluronic acid distribution was homogeneous for the larynges, at both superficial and deep layers (41.6 and 38.5, respectively). For both 30- to 50-year-old men geriatric age groups, hyaluronic acid level was lower at both layers. CONCLUSION: Hyaluronic acid level in the lamina propria of the larynx of geriatric men decreases with advancing age at both layers of the lamina.
    Otolaryngology Head and Neck Surgery 08/2014; · 1.73 Impact Factor
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    ABSTRACT: Background Myofibroblasts derived from fibroblasts in the pathogenesis of pulmonary fibrosis causes excessive and disordered deposition of matrix proteins, including collagen V, which can cause a Th17-mediated immune response and lead to apoptosis. However, whether the intrinsic ability of lung FBs to produce the matrix depends on their site-specific variations is not known. Aim To investigate the link between Th17 and collagen V that maintains pulmonary remodeling in the peripheral lung microenvironment during the late stage of experimental pulmonary fibrosis. Methods Young male mice including wild Balb/c mice (BALB, n = 10), wild C57 Black/6J mice (C57, n = 10) and IL-17 receptor A knockout mice (KO, n = 8), were sacrificed 21 days after treatment with bleomycin. Picrosirius red staining, immunohistochemistry for IL-17-related markers and “in situ” detection of apoptosis, immunofluorescence for collagen types I and V, primary cell cultures from tissue lung explants for RT-PCR and electron microscopy were used. Results The peripheral deposition of extracellular matrix components by myofibroblasts during the late stage is maintained in C57 mice compared with that in Balb mice and is not changed in the absence of IL-17 receptor A; however, the absence of IL-17 receptor A induces overexpression of type V collagen, amplifies the peripheral expression of IL-17 and IL-17-related cytokines and reduces peripheral lung fibroblast apoptosis. Conclusion A positive feedback loop between the expression patterns of collagen V and IL-17 may coordinate the maintenance of peripheral collagen I in the absence of IL-17 receptor A in fibrosis-susceptible strains in a site-specific manner.
    Immunobiology 01/2014; · 2.81 Impact Factor
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    ABSTRACT: Background Fibroblastic foci (FF) are a major histological feature of usual interstitial pneumonia (UIP) in idiopathic pulmonary fibrosis (IPF) and collagen vascular diseases (non-IPF). In addition, FF are occasionally associated with smoking-related interstitial fibrosis (SRIF). Recent studies have suggested a role for epithelial to mesenchymal transition (EMT) in pulmonary fibrogenesis. Methods Here, we investigated whether EMT was present in patients with IPF (n=19), non-IPF (n=17), and SRIF (n=16) using morphometric immunohistochemistry, electron microscopy, and confocal microscopy. All patients had received lung biopsies or lobectomies for lung cancer. Results IPF and non-IPF patients displayed restrictive lung function patterns, whereas those with SRIF presented mixed patterns. Cells within FF presented high number of alpha-smooth muscle actin (〈SMA)-staining cells; however, the foci of IPF patients showed comparatively lower number. Moreover, colocalization of thyroid transcription factor-1 (TTF1) and 〈SMA within FF showed low number of staining cells for IPF and SRIF in comparison to non-IPF (p<0.01). Nevertheless, all groups displayed colocalization of high rate of TTF1+-cells and low rate of 〈SMA+-cells within hyperplastic epithelioid cells in FF. Also, we observed areas with low proportion of TTF1+cells and 〈SMA+cells, which were present in SRIF and non-IPF more often than IPF (p<0.001). Electron microscopy revealed small breaks in the alveolar basal lamina, which allowed epithelioid cells to directly contact the collagenous matrix and fibroblasts. Three-dimensional reconstruction revealed intense 〈SMA staining within some epithelioid cells, suggesting that they had gained a mesenchymal phenotype. Conclusions These findings constitute the first report of EMT in SRIF and suggest that EMT occurs more prominently in SRIF and non-IPF than IPF.
    Respiratory Medicine. 01/2014;
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    ABSTRACT: To study in rats the effects of exposure to tobacco and alcohol on the mucosa of the tongue and pharynx. Forty adult Wistar rats were allocated into four groups of 10 animals each: GI (control), food and water "ad libitum"; GII (alcohol), 30% of ethanol diluted in drinking water and food "ad libitum"; GIII (tobacco), exposure to the smoke of 10 cigarettes/day, food and water "ad libitum"; GIV (alcohol and tobacco), simultaneous exposure to both agents. After 260 days, the animals were sacrificed. Tongue and pharynx were removed for histopathological analysis. GI had the lowest tongue and pharynx histological scores. In GII, GIII, and GIV tongue samples revealed: apical cell hyperplasia (GII: 60%, GIII: 30%, GIV: 20%), basal cell hyperplasia (GII: 60%, GIII: 40%), hyperkeratosis (GII: 70%, GIII: 30%, GIV: 30%), dysplasia (GII: 60%, GIII: 60%, GIV: 50%), and apoptosis (GII: 60%, GIII: 40%, GIV: 60%). Pharynx samples revealed: apical cell hyperplasia (GII: 40%, GIII: 30%, GIV: 70%), basal cell hyperplasia (GII: 30%, GIII: 40%, GIV: 40%), hyperkeratosis (GII: 50%, GIII: 80%, GIV: 40%), and dysplasia (GII: 50%, GIII: 80%, GIV: 50%). Carcinoma in situ was detected in both sites. Alcohol and tobacco led to significant tongue and pharyngeal lesions that ranged from benign events to severe dysplasia. These findings confirm the deleterious effects of alcohol and tobacco on the airway mucosa.
    Inhalation Toxicology 02/2012; 24(3):153-60. · 1.89 Impact Factor
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    ABSTRACT: To study the clinical, radiological, and histopathological patterns of transbronchial biopsy (TBB) used in order to confirm the diagnosis in patients with clinical suspicion of interstitial lung disease (ILD) treated at a tertiary-care university hospital. We reviewed the medical records, radiology reports, and reports of transbronchial biopsies from all patients with suspected ILD who underwent TBB between January of 1999 and December of 2006 at the Hospital das Clínicas de Botucatu, located in the city of Botucatu, Brazil. The study included 56 patients. Of those, 11 (19.6%) had a definitive diagnosis of idiopathic pulmonary fibrosis (IPF), the rate of which was significantly higher in the patients in which ILD was a possible diagnosis in comparison with those in which ILD was the prime suspect (p = 0.011), demonstrating the contribution of TBB to the diagnostic confirmation of these diseases. The histopathological examination of the biopsies revealed that 27.3% of the patients with IPF showed a pattern of organizing pneumonia, which suggests greater disease severity. The most common histological pattern was the indeterminate pattern, reflecting the peripheral characteristic of IPF. However, the fibrosis pattern showed high specificity and high negative predictive value. For CT scan patterns suggestive of IPF, the ROC curve showed that the best relationship between sensitivity and specificity occurred when five radiological alterations were present. Honeycombing was found to be strongly suggestive of IPF (p = 0.01). For ILDs, chest CT should always be performed, and TBB should be used in specific situations, according to the suspicion and distribution of lesions.
    Jornal brasileiro de pneumologia: publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia 04/2011; 37(2):168-75.
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    ABSTRACT: Reinke's edema is chronic laryngeal disease in which the superficial layer of the lamina propria is expanded by thick mucus, giving it a gelatin aspect. The disease is directly related to smoking and more frequent in women, who end up having a lower tone of voice. Its histological characteristics cannot always distinguish it from other benign lesions of the larynx for which additional histological techniques are necessary. to study the immunoexpression of fibronectin, collagen IV and laminin in Reinke's edema by immunohistochemical technique. Prospective study. histological blocks of 60 cases of surgical Reinke's edema were saved, submitted to new cross-sections and to immunohistochemical reactions for fibronectin, laminin and collagen IV by the Avidin-Biotin-Peroxidase method. Fragments of five normal vocal folds were used as control, removed during autopsy. All patients were chronic smokers and adults- 50 women and 10 men. the immunoexpression of fibronectin, collagen IV and laminin was more important in the endothelium of blood vessels (68.33%, 76.66%, 73.33%, respectively) and less relevant in the basement membrane (25.0%, 5.0% and 3.3%, respectively). the immunoexpression of fibronectin, laminin and of collagen IV in the basal membrane of Reinke's edema was not relevant, with a predominance of these antibodies in the endothelium of blood vessels.
    Brazilian journal of otorhinolaryngology 12/2009; 75(6):821-5. · 0.55 Impact Factor
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    Brazilian journal of otorhinolaryngology 12/2009; 75(6):821-825. · 0.55 Impact Factor
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    ABSTRACT: The objective of this study was to investigate the morphological and immunohistochemical characteristics of vocal fold nodules. The study design was prospective and retrospective. For the histological study, we reviewed 15 slides from the surgical cases of vocal fold nodules, in which we analyzed epithelium, basal membrane (bm), and lamina propria. For the transmission and scanning electron microscopy (TEM, SEM) studies, five new cases on vocal fold nodules were included. Immunohistochemistry study was carried out in the 15 specimens, using antifibronectin, antilaminin, and anticollagen IV antibodies. The main histological alterations were epithelial hyperplasia (73.33%), basement membrane thickening (86.66%), edema, and fibrosis (93.33%). SEM--reduction in mucous lacing and increase in the desquamating cells, without epithelial erosion. TEM--hyperplasia of the epithelium, enlargement of the intercellular junctions, which was filled by fluid, subepithelial thickening of the lamina reticularis, and break points in the basal membrane. Immunohistochemistry--we identified greater immunoexpression of fibronectin on the basal membrane, on the lamina propria, and around the vessels. Antilaminin and anticollagen IV antibodies showed higher pigmentation on the endothelium of the vessels than that on the basal membrane. In vocal fold nodules, combined assessment using light microscopy, electron microscopy, and immunohistochemistry can reveal important morphological details useful in characterizing these lesions.
    Journal of voice: official journal of the Voice Foundation 10/2009; 24(5):531-9. · 0.95 Impact Factor
  • Brazilian Journal of Otorhinolaryngology (impresso). 01/2009; 75(6).
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    Revista Brasileira de Otorrinolaringologia 01/2009; 75(1).
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    ABSTRACT: The objectives of this study were to evaluate morphologic alterations and precancerous lesions in Reinke's edema. Patients included were 54 smokers with bilateral Reinke's edema submitted to surgery in the Otolaryngology Department, Botucatu Medical School, São Paulo State University, Brazil, between 2002 and 2006. All specimens were evaluated by light microscopy and five contralateral lesions were also evaluated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The main histological alterations were edema (100%), inflammation (81.48%), basal membrane (bm) thickening (77.77%), and vessel proliferation (75.92%). Epithelium alterations were classified as grade 0 (11.11%), grade 1 (70.37%), grade 2 (14.81%), and grade 3 (3.70%). In the case included in grade 3 classification, microinvasive carcinoma was detected. SEM showed epithelial surface with some cellular desquamation, few microridges, and a polished and impermeable surface aspect. TEM showed epithelial hyperplasia, basal cells with different sizes, widening of the intercellular spaces, abnormal desmosome architecture, thickening of the bm, some electron-dense vesicles, and points of interruption. The morphological alterations presented in this study are not specific to Reinke's edema but this lesion can be the site of different grades of dysplasia and carcinoma, justifying the importance of periodic laryngeal endoscopic exams and meticulous histological analysis.
    Journal of voice: official journal of the Voice Foundation 08/2008; 23(6):721-5. · 0.95 Impact Factor
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    ABSTRACT: To evaluate the prevalence of cardiovascular events (CVE) secondary to atherosclerosis in lupus patients and correlate them to the traditional risk factors, disease duration and drug therapy used. A retrospective study was carried out based on data obtained from patients charts. Patients included were those who had a lupus diagnosis confirmed at least two years before inclusion in the study and had been followed since 1992. CVE were characterized as MI, angina pectoris and stroke non-related to lupus activity. Risk factors and drugs used for treatment were recorded. Seventy-one charts were analyzed. Patients mean age was 34.2+/-12.7 years; 68 were women and three were men; 58 were Caucasian (81.6%). Ten (14.08%) presented CVE. Patients in whom CVE were observed were older (42.7 vs. 32.8 years p=0.0021) and presented longer disease duration (10.8 vs. 7.2 years p=0.011). The traditional risk factors, daily and cumulative doses of steroids, immunosuppressive drugs and antimalarial drugs were not significant when patients with and without CVE were compared. The prevalence of CVE secondary to atherosclerosis in systemic lupus erythematosus (SLE) was 14.08%. The traditional risk factors were not associated with the development of CVE in lupus patients. Patients that presented cardiovascular events were older and presented longer disease duration. It is a premature conclusion to establish SLE as an independent risk factor for atherosclerosis development.
    Arquivos brasileiros de cardiologia 10/2006; 87(3):300-6. · 1.32 Impact Factor
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    Jornal Brasileiro De Pneumologia - J BRAS PNEUMOL. 01/2006; 32(4).
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    ABSTRACT: To increase the knowledge base regarding pulmonology research in Brazil. A retrospective, observational study of the abstracts published in the Annals of the Brazilian Pulmonology and Phthisiology Conferences held from 1986 to 2004, quantifying the institutions of origin by geographic distribution and type, as well as categorizing the abstracts by study design and topic. A total of 6467 abstracts were published. The institutions of origin were located, variously, in the Southeast (3870 abstracts), South (1309), Northeast (783), Central-West (267) and North (84). There were 94 abstracts originating from foreign institutions, especially from institutions in Portugal (56.3%) and the United States (13.8%). Most of the studies (5825) were conducted in public Brazilian institutions. There were 4234 clinical studies, 1994 case reports and 239 original research articles. A marked, progressive increase was observed in the number of clinical studies and case reports during the period evaluated. Overall, the most common themes were tuberculosis and other infections diseases (25.2%), following by oncology (11.6%), interstitial lung diseases (8.8%) and thoracic surgery (8.5%). Nevertheless, the number of abstracts on each topic varied widely from year to year. Public Brazilian institutions are the principal sources of pulmonology research in Brazil. Such research activity is concentrated in the southeastern part of the country. Case reports account for one-third of this activity. Although there was great variability in the subjects addressed, diseases that are highly prevalent in Brazil, such as tuberculosis and other infections diseases, were the most common topics.
    Jornal brasileiro de pneumologia: publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia 01/2006; 32(4):309-15.
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    Arquivos Brasileiros De Cardiologia - ARQ BRAS CARDIOL. 01/2006; 87(3).
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    ABSTRACT: INTRODUÇÃO: Tromboembolia pulmonar (TEP) é ainda uma afecção enigmática em diversos aspectos clínicos e epidemiológicos e frequentemente erroneamente diagnosticada. OBJETIVO: Descrever a prevalência e os achados anatomopatológicos de TEP em uma série de 5261 autópsias realizadas em um hospital universitário de nível terciário, correlacionar estes achados com as doenças de base e verificar a freqüência de suspeita clínica antemortem de TEP. MÉTODO: Revisão dos registros das autópsias consecutivas realizadas de 1979 a 2002 para um estudo retrospectivo. Dos prontuários e dos relatórios de autópsias dos pacientes que tiveram TEP documentada, macro e/ou microscopicamente, foram extraídos dados demográficos, doenças de base, suspeita antemortem de TEP, localização dos trombos nos pulmões e provável local de origem da TEP. RESULTADOS: A freqüência de autópsias foi de 42,0% e TEP foi encontrada em 544 pacientes, sendo a principal causa da morte (TEP fatal) em 225 casos. Doenças infecciosas (p=0,0003) foram associadas com TEP não fatal e trauma (p=0,007) com TEP fatal. A taxa de não suspeita antemortem de TEP foi 84,6% e 40,0% destes pacientes apresentaram TEP fatal. Doenças do sistema circulatório (p=0,0001), infecções (p<0,0001), doenças do sistema digestivo (p=0,0001) neoplasias (p=0,024) e trauma (p=0,005), foram associadas com TEP não suspeitada clinicamente. A provável origem da TEP mais freqüente foram os membros inferiores (48,9%). CONCLUSÃO: A taxa de não suspeita clínica antemortem de TEP foi elevada. Atenção especial deve ser dada para a possibilidade de TEP em pacientes com doenças do sistema circulatório, infecções, doenças do sistema digestivo, neoplasias e trauma.
    Jornal Brasileiro de Pneumologia 10/2004; 30(5):426-432.
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    Jornal Brasileiro De Pneumologia - J BRAS PNEUMOL. 01/2004; 30(5).
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    ALEXANDRE TODOROVIC FABRO, HYUNG BOK YOO, HELENA ABRAHÃO, THOMAZ QUELUZ
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    ABSTRACT: Objective: To increase the knowledge base regarding pulmonology research in Brazil. Methods: A retrospective, observational study of the abstracts published in the Annals of the Brazilian Pulmonology and Phthisiology Conferences held from 1986 to 2004, quantifying the institutions of origin by geographic distribution and type, as well as categorizing the abstracts by study design and topic. Results: A total of 6467 abstracts were published. The institutions of origin were located, variously, in the Southeast (3870 abstracts), South (1309), Northeast (783), Central-West (267) and North (84). There were 94 abstracts originating from foreign institutions, especially from institutions in Portugal (56.3%) and the United States (13.8%). Most of the studies (5825) were conducted in public Brazilian institutions. There were 4234 clinical studies, 1994 case reports and 239 original research articles. A marked, progressive increase was observed in the number of clinical studies and case reports during the period evaluated. Overall, the most common themes were tuberculosis and other infections diseases (25.2%), following by oncology (11.6%), interstitial lung diseases (8.8%) and thoracic surgery (8.5%). Nevertheless, the number of abstracts on each topic varied widely from year to year. Conclusion: Public Brazilian institutions are the principal sources of pulmonology research in Brazil. Such research activity is concentrated in the southeastern part of the country. Case reports account for one-third of this activity. Although there was great variability in the subjects addressed, diseases that are highly prevalent in Brazil, such as tuberculosis and other infections diseases, were the most common topics.
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    ABSTRACT: Granulomas are bilateral and pediculated lesions of the vocal apophysis. Etiologies: intubation, reflux, trauma, vocal abuse, idiopathic origin. To analyze the clinical and morphological aspects of post intubation granulomas. retrospective study of patients submitted to microsurgery for post intubation laryngeal granulomas seen at our Medical School starting in 2002. We analyzed: age, gender, indication and time of intubation, symptoms, videolaryngoscopic diagnosis and biopsy findings. Light microscopy was performed on all specimens, and electron microscopy on three of them. ten patients (7 females and 3 males), between the ages of 2 and 72 years, intubation time between 4h and 21 days. Hoarseness was a frequent symptom, starting in the first week following extubation. Histology shows mild epithelial hyperplasia, severe inflammation and vessel proliferation in the corion. Under SEM, the epithelium presented mild superficial desquamation. Under TEM, intracellular junctions showed widening with structural changes in the desmosomes. In the corion there were vessel proliferations, inflammation and fibroblasts with structural alterations. post intubation granulomas appear in any age and hoarseness is a frequent symptom. Morphological alterations occur in the corion as vessel proliferations, inflammation, and intracytoplasmatic alterations in fibroblasts suggesting cellular dysfunction and damage.
    Brazilian journal of otorhinolaryngology 75(1):116-22. · 0.55 Impact Factor
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