MARISA DOLHNIKOFF
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
6 resultados
Resultados de Busca
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- Morphologic Aspects of Interstitial Pneumonia With Autoimmune Features(2018) NASCIMENTO, Ellen Caroline Toledo do; BALDI, Bruno Guedes; SAWAMURA, Marcio Valente Yamada; DOLHNIKOFF, MarisaContext.-Interstitial lung disease, a common complication observed in several connective tissue diseases, causes significant morbidity and mortality. Similar to individuals with connective tissue diseases, a significant subgroup of patients with clinical and serologic characteristics suggestive of autoimmunity but without confirmed specific connective tissue disease presents with associated interstitial lung disease. These patients have been classified using different controversial nomenclatures, such as undifferentiated connective tissue disease-associated interstitial lung disease, lung-dominant connective tissue disease, and autoimmune featured interstitial lung disease. The need for a better understanding and standardization of this entity, interstitial lung disease with autoimmune features, and the need for an adequate management protocol for patients resulted in the introduction of a new terminology in 2015: interstitial pneumonia with autoimmune features. This new classification requires a better comprehension of its diagnostic impact and the influence of its morphologic aspects on the prognosis of patients. Objective.-To review the diagnostic criteria for interstitial pneumonia with autoimmune features, with an emphasis on morphologic aspects. Data Sources.-The review is based on the available literature, and on pathologic, radiologic, and clinical experience. Conclusions.-The interstitial pneumonia with autoimmune features classification seems to identify a distinct subgroup of patients with different prognoses. Studies show that nonspecific interstitial pneumonia and usual interstitial pneumonia are the most prevalent morphologic patterns and show discrepant results on the impact of the usual interstitial pneumonia pattern on survival. Prospective investigations are necessary to better define this subgroup and to determine the prognosis and appropriate clinical management of these patients.
- Exercise Performed Concomitantly with Particulate Matter Exposure Inhibits Lung Injury(2018) SILVA-RENNO, Adriano; BALDIVIA, Guilherme Crisitanini; OLIVEIRA-JUNIOR, Manoel C.; BRANDAO-RANGEL, Maysa Alves Rodrigues; EL-MAFARJEH, Elias; DOLHNIKOFF, Marisa; MAUAD, Thais; BRITTO, Jose Mara; SALDIVA, Paulo Hilario Nascimento; OLIVEIRA, Luis Vicente Franco; LIGEIRO-OLIVEIRA, Ana P.; GRAUDENZ, Gustavo Silveira; VIEIRA, Rodolfo PaulaAir pollution is a growing problem worldwide, inducing and exacerbating several diseases. Among the several components of air pollutants, particulate matter (PM), especially thick (10-2.5 mu m; PM 10) and thin (2.5 mu m; PM 2.5), are breathable particles that easily can be deposited within the lungs, resulting in pulmonary and systemic inflammation. Although physical activity is strongly recommended, its effects when practiced in polluted environments are questionable. Therefore, the present study evaluated the pulmonary and systemic response of concomitant treadmill training with PM 2.5 and PM 10 exposure. Treadmill training inhibited PM 2.5- and PM 10-induced accumulation of total leukocytes (p<0.001), neutrophils (p<0.001), macrophages (p<0.001) and lymphocytes (p<0.001) in bronchoalveolar lavage (BAL), as well as the BAL levels of IL-1beta (p<0.001), CXCL1/KC (p<0.001) and TNF-alpha (p<0.001), whereas it increased IL-10 levels (p<0.05). Similar effects were observed on accumulation of polymorphonuclear (p<0.01) and mononuclear (p<0.01) cells in the lung parenchyma and in the peribronchial space. Treadmill training also inhibited PM 2.5- and PM 10-induced systemic inflammation, as observed in the number of total leukocytes (p<0.001) and in the plasma levels of IL-1beta (p<0.001), CXCL1/KC (p<0.001) and TNF-alpha (p<0.001), whereas it increased IL-10 levels (p<0.001). Treadmill training inhibits lung and systemic inflammation induced by particulate matter.
- Pulmonary interstitial emphysema in fatal asthma: case report and histopathological review(2018) MAUAD, Thais; NASCIMENTO, Felipe B. P. do; DOLHNIKOFF, Marisa; PICKA, Milena C. M.; SALDIVA, Paulo H. N.Background: Mortality related to asthma has decreased worldwide since the introduction of inhaled corticosteroid therapy in the past decades. However, there are still some asthma fatalities identified mainly in populations with less access to regular treatment. Pulmonary interstitial emphysema due to alveolar rupture has been rarely described as a complication of an acute severe asthma attack, and its identification in pathological analysis can be difficult. Previous studies reported the association of pulmonary interstitial emphysema and bronchial ductal gland ectasia in asthma. Case presentation: We present the case of a 42-year-old man that died due to a fatal asthma attack. Postmortem computed tomography revealed the unusual finding of acute Pulmonary Interstitial Emphysema, confirmed by pathological analysis. We reviewed 28 cases of fatal asthma tissue and identified the presence of pulmonary interstitial emphysema in 10% of the cases. Conclusions: Postmortem computed tomography is a useful complimentary diagnostic tool for autopsies. Pulmonary Interstitial Emphysema in acute exacerbations of asthma seems to be more frequent than reported. Alveolar hyperdistension and bronchial duct gland ectasia causing tissue rupture are possible mechanisms involved in the formation of Pulmonary Interstitial Emphysema. The clinical impact of Pulmonary Interstitial Emphysema in asthma is unknown.
- Immunohistological features related to functional impairment in lymphangioleiomyomatosis(2018) NASCIMENTO, Ellen Caroline Toledo do; BALDI, Bruno Guedes; MARIANI, Alessandro Wasum; ANNONI, Raquel; KAIRALLA, Ronaldo Adib; PIMENTA, Suzana Pinheiro; SILVA, Luiz Fernando Ferraz da; CARVALHO, Carlos Roberto Ribeiro; DOLHNIKOFF, MarisaBackground: Lymphangioleiomyomatosis (LAM) is a low-grade neoplasm characterized by the pulmonary infiltration of smooth muscle-like cells (LAM cells) and cystic destruction. Patients usually present with airway obstruction in pulmonary function tests (PFTs). Previous studies have shown correlations among histological parameters, lung function abnormalities and prognosis in LAM. We investigated the lung tissue expression of proteins related to the mTOR pathway, angiogenesis and enzymatic activity and its correlation with functional parameters in LAM patients. Methods: We analyzed morphological and functional parameters of thirty-three patients. Two groups of disease severity were identified according to FEV1 values. Lung tissue from open biopsies or lung transplants was immunostained for SMA, HMB-45, mTOR, VEGF-D, MMP-9 and D2-40. Density of cysts, density of nodules and protein expression were measured by image analysis and correlated with PFT parameters. Results: There was no difference in the expression of D2-40 between the more severe and the less severe groups. All other immunohistological parameters showed significantly higher values in the more severe group (p <= 0.002). The expression of VEGF-D, MMP-9 and mTOR in LAM cells was associated with the density of both cysts and nodules. The density of cysts and nodules as well as the expression of MMP-9 and VEGF-D were associated with the impairment of PFT parameters. Conclusions: Severe LAM represents an active phase of the disease with high expression of VEGF-D, mTOR, and MMP-9, as well as LAM cell infiltration. Our findings suggest that the tissue expression levels of VEGF-D and MMP-9 are important parameters associated with the loss of pulmonary function and could be considered as potential severity markers in open lung biopsies of LAM patients.
- Lung cancer biopsy: Can diagnosis be changed after immunohistochemistry when the H&E-Based morphology corresponds to a specific tumor subtype?(2018) BERNARDI, Fabiola Del Carlo; BERNARDI, Marcela Del Carlo; TAKAGAKI, Teresa; SIQUEIRA, Sheila Aparecida Coelho; DOLHNIKOFF, MarisaOBJECTIVES: Advancements in non-small cell lung cancer treatment based on targeted therapies have made the differentiation between adenocarcinoma and squamous cell carcinoma increasingly important. Pathologists are challenged to make the correct diagnosis in small specimens. We studied the accuracy of an immunohistochemical panel in subclassifying non-small cell lung cancer in routine small biopsies and compared the results with the diagnosis from resected lung specimens, autopsy samples or biopsied/resected metastases. METHODS: In total, 340 lung cancer biopsies were investigated for the expression of CK5, TTF1, p63 and surfactant. RESULTS: We characterized 166 adenocarcinomas and 124 squamous cell carcinomas. Overall, 85% of cases displayed binary staining (TTF1 positive/p63 negative, and vice versa). The diagnoses of ten cases with a morphology that indicated a specific tumor subtype were changed after immunohistochemistry (IHC). A second specimen was available for 71 patients, and the first diagnosis at biopsy was confirmed in 95% of these cases. Most non-small cell lung cancer cases present a binary immunohistochemical profile in small biopsies, contributing to good diagnostic accuracy with routine markers. In a small proportion of cases, the diagnosis can be changed after IHC even when the morphological aspects indicate one specific tumor subtype. CONCLUSIONS: We recommend that routine small biopsies of lung cancer without classic morphology should be subjected to a minimum immunohistochemical panel to differentiate adenocarcinoma from squamous cell carcinoma.
- Airway pathology in severe asthma is related to airflow obstruction but not symptom control(2018) FERREIRA, D. S.; CARVALHO-PINTO, R. M.; GREGORIO, M. G.; ANNONI, R.; TELES, A. M.; BUTTIGNOL, M.; ARAUJO-PAULINO, B. B.; KATAYAMA, E. H.; OLIVEIRA, B. L.; FRARI, H. S. Del; CUKIER, A.; DOLHNIKOFF, M.; STELMACH, R.; RABE, K. F.; MAUAD, T.BackgroundPatients with asthma present structural and inflammatory alterations that are believed to play a role in disease severity. However, airway remodeling and inflammation have not been extensively investigated in relation to both symptom control and airflow obstruction in severe asthmatics. We aimed to investigate several inflammatory and structural pathological features in bronchial biopsies of severe asthmatics that could be related to symptom control and airflow obstruction after standardized treatment. MethodsFifty severe asthmatics received prednisone 40 mg/d for 2 weeks and maintenance therapy with budesonide/formoterol 400/12 g twice daily + budesonide/formoterol 200/6 g as needed for 12 weeks. Endobronchial biopsies were performed at the end of 12 weeks. We performed extensive immunopathological analyses of airway tissue inflammation and remodeling features in patients stratified by asthma symptom control and by airflow obstruction. ResultsAirway tissue inflammation and remodeling were not associated with symptom control. Asthmatics with persistent airflow obstruction had greater airway smooth muscle (Asm) area with decreased periostin and transforming growth factor beta-positive cells within Asm bundles, in addition to lower numbers of chymase-positive mast cells in the submucosa compared to patients with nonpersistent obstruction. ConclusionsSymptom control in severe asthmatics was not associated with airway tissue inflammation and remodeling, although persistent airflow obstruction in these patients was associated with bronchial inflammation and airway structural changes.