SUMMARY Cyclic Cushing's syndrome (CS) due to thymic carcinoid is a rare disorder. We report a case of cyclic CS due to ectopic adrenocorticotropic hormone (ACTH)-secreting atypical thymic carcinoid tumor and reviewed similar cases published in the literature. Our patient had hypercortisolemia lasting approximately one month, followed by normal cortisol secretion, with relapse one year later. Histopathology revealed an atypical ACTH-positive thymic carcinoid. Ectopic CS can be derived from atypical thymic carcinoids, which can be aggressive tumors with early relapse, suggesting that this type of tumor probably needs aggressive treatment.

ResumoObjetivo:As metaloproteinases são biomarcadores inflamatórios envolvidos na instabilidade da placa carotídea. O objetivo deste estudo foi analisar a atividade inflamatória da MMP-8 e MMP-9 plasmática e presente na placa carotídea, após administração intravenosa de hidrocortisona.Métodos:Participaram do estudo 22 pacientes portadores de estenose ≥ 70% em artéria carótida (11 sintomáticos e 11 assintomáticos), submetidos à endarterectomia de artéria carótida. Os pacientes foram divididos em dois grupos: Grupo Controle - não foi administrado hidrocortisona e Grupo 1 - foi administrado 500 mg intravenoso de hidrocortisona durante a indução anestésica. As dosagens plasmáticas de MMP-8 e MMP-9 foram efetuadas no pré-operatório (24 horas antes da endarterectomia de artéria carótida) e em 1 hora, 6 horas e 24 horas após endarterectomia de artéria carótida. Na placa carotídea foram mensurados os níveis teciduais de MMP-8 e MMP-9.Resultados:O grupo 1 exibiu elevação dos níveis séricos da MMP-8 (994,28 pg/ml e 408,54 pg/ml, respectivamente; P=0.045) e MMP-9 (106.656,34 e 42.807,69, respectivamente; P=0.014) em 1 hora após a endarterectomia de artéria carótida, em relação ao grupo controle. Os pacientes sintomáticos do grupo 1 exibiram menor concentração tecidual de MMP-8, em relação ao grupo controle (143,89 pg/ml e 1317,36, respectivamente; P=0.003). Houve correlação entre os níveis pré-operatórios de MMP-9 e as concentrações teciduais de MMP-8 (P=0.042) e MMP-9 (P=0.019) entre os pacientes sintomáticos do grupo controle.Conclusão:A hidrocortisona reduz a concentração de MMP-8 na placa carotídea, em especial nos pacientes sintomáticos. Houve associação entre a inflamação sistêmica e a tecidual.

AbstractObjective:Matrix metalloproteinases are inflammatory biomarkers involved in carotid plaque instability. Our objective was to analyze the inflammatory activity of plasma and carotid plaque MMP-8 and MMP-9 after intravenous administration of hydrocortisone.Methods:The study included 22 patients with stenosis ≥ 70% in the carotid artery (11 symptomatic and 11 asymptomatic) who underwent carotid endarterectomy. The patients were divided into two groups: Control Group - hydrocortisone was not administered, and Group 1 - 500 mg intravenous hydrocortisone was administered during anesthetic induction. Plasma levels of MMP-8 and MMP-9 were measured preoperatively (24 hours before carotid endarterectomy) and at 1 hour, 6 hours and 24 hours after carotid endarterectomy. In carotid plaque, tissue levels of MMP-8 and MMP-9 were measured.Results:Group 1 showed increased serum levels of MMP- 8 (994.28 pg/ml and 408.54 pg/ml, respectively; P=0.045) and MMP-9 (106,656.34 and 42,807.69 respectively; P=0.014) at 1 hour after carotid endarterectomy compared to the control group. Symptomatic patients in Group 1 exhibited lower tissue concentration of MMP-8 in comparison to the control group (143.89 pg/ml and 1317.36 respectively; P=0.003). There was a correlation between preoperative MMP-9 levels and tissue concentrations of MMP-8 (P=0.042) and MMP-9 (P=0.019) between symptomatic patients in the control group.Conclusion:Hydrocortisone reduces the concentration of MMP- 8 in carotid plaque, especially in symptomatic patients. There was an association between systemic and tissue inflammation.

ResumoContextoA hidrocortisona pode reduzir a concentração dos biomarcadores inflamatórios séricos e teciduais.ObjetivoAnalisar a atividade inflamatória da proteína C-reativa ultrassensível (PCR-US), do fator de necrose tumoral (FNT)-alfa e do fator de crescimento do endotélio vascular (FCEV) séricos e teciduais, mediante administração intraoperatória de hidrocortisona, após endarterectomia de artéria carótida (EAC).MétodoVinte e dois pacientes foram divididos em Grupo Controle (5 assintomáticos e 6 sintomáticos) – não foi administrada hidrocortisona – e Grupo 1 (4 assintomáticos e 7 sintomáticos) – foram administrados 500 mg intravenoso de hidrocortisona. O PCR-US, o FNT-alfa e o FCEV séricos foram dosados no pré-operatório e em 1 hora, 6 horas e 24 horas após a EAC. Na placa carotídea, mensuramos os níveis de FNT-alfa e FCEV.ResultadosO grupo 1 exibiu menor concentração sérica de FNT-alfa em 1 hora (p=0,031), 6 horas (p=0,015) e 24 horas (p=0,017) após a EAC, e menor concentração de FCEV em 1 hora (p=0,006) e 6 horas (p=0,005) após a EAC, em relação ao grupo controle. Os pacientes sintomáticos do grupo 1 exibiram menor concentração de FNT-alfa em 1 hora e 6 horas após a EAC, e menor concentração de FCEV em 1 hora após a EAC, em relação ao grupo controle. Não houve diferença estatística entre as concentrações teciduais de FNT-alfa e FCEV entre o grupo controle e o grupo 1.ConclusãoA hidrocortisona reduz as concentrações séricas pós-operatórias de FNT-alfa e FCEV, em especial nos sintomáticos; porém, não reduz os níveis teciduais destes biomarcadores.

AbstractBackgroundHydrocortisone may reduce serum and tissue concentrations of inflammatory biomarkers.ObjectiveTo analyze the inflammatory activity of serum and tissue high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) after intraoperative administration of hydrocortisone, after carotid endarterectomy (CEA).MethodTwenty-two patients were allocated to a Control Group (5 asymptomatic and 6 symptomatic patients) and were not administered hydrocortisone or to Group 1 (4 asymptomatic and 7 symptomatic patients) and were administered 500 mg intravenous hydrocortisone. Serum levels of hsCRP, TNF-α and VEGF were tested for the preoperative period and at 1 hour, 6 hours and 24 hours after CEA. Levels of TNF-α and VEGF were also measured in carotid plaques.ResultsGroup 1 exhibited lower concentrations of serum TNF-α at 1 hour (p=0.031), 6 hours (p=0.015) and 24 hours (p=0.017) after CEA and lower concentrations of serum VEGF at 1 hour (p=0.006) and 6 hours (p=0.005) after CEA, relative to controls. Symptomatic patients in group 1 exhibited lower concentrations than controls for serum TNF-α at 1 hour and 6 hours after CEA and lower concentrations than controls for serum VEGF at 1 hour after CEA. There were no statistical differences in tissue concentrations of TNF-α or VEGF between the control group and group 1.ConclusionHydrocortisone reduces postoperative concentrations of serum TNF-α and VEGF, especially in symptomatic patients; but does not reduce tissue levels of these biomarkers.

OBJECTIVE: To validate the importance of the angiotensin II receptor isotypes and the lymphatic vessels in systemic sclerosis and idiopathic pulmonary fibrosis. METHODS: We examined angiotensin II type 1 and 2 receptors and lymphatic vessels in the pulmonary tissues obtained from open lung biopsies of 30 patients with systemic sclerosis and 28 patients with idiopathic pulmonary fibrosis. Their histologic patterns included cellular and fibrotic non-specific interstitial pneumonia for systemic sclerosis and usual interstitial pneumonia for idiopathic pulmonary fibrosis. We used immunohistochemistry and histomorphometry to evaluate the number of cells in the alveolar septae and the vessels stained by these markers. Survival curves were also used. RESULTS: We found a significantly increased percentage of septal and vessel cells immunostained for the angiotensin type 1 and 2 receptors in the systemic sclerosis and idiopathic pulmonary fibrosis patients compared with the controls. A similar percentage of angiotensin 2 receptor positive vessel cells was observed in fibrotic non-specific interstitial pneumonia and usual interstitial pneumonia. A significantly increased percentage of lymphatic vessels was present in the usual interstitial pneumonia group compared with the non-specific interstitial pneumonia and control groups. A Cox regression analysis showed a high risk of death for the patients with usual interstitial pneumonia and a high percentage of vessel cells immunostained for the angiotensin 2 receptor in the lymphatic vessels. CONCLUSION: We concluded that angiotensin II receptor expression in the lung parenchyma can potentially control organ remodeling and fibrosis, which suggests that strategies aimed at preventing high angiotensin 2 receptor expression may be used as potential therapeutic target in patients with pulmonary systemic sclerosis and idiopathic pulmonary fibrosis.

OBJETIVO: Estudar a expressão de COX-1 e COX-2 em áreas pulmonares remodeladas em pacientes com esclerose sistêmica (ES) ou fibrose pulmonar idiopática (FPI) e correlacioná-la com a sobrevida desses pacientes.MÉTODOS: Examinamos espécimes de biópsia pulmonar a céu aberto de 24 pacientes com ES e de 30 pacientes com FPI, utilizando-se tecido pulmonar normal como controle. Os padrões histológicos incluíram pneumonia intersticial não específica (PINE) fibrótica em pacientes com ES e pneumonia intersticial usual (PIU) nos pacientes com FPI. Imuno-histoquímica e histomorfometria foram usadas para avaliar a expressão celular de COX-1 e COX-2 em septos alveolares, vasos e bronquíolos, sua correlação com provas de função pulmonar e seu impacto na sobrevida.RESULTADOS: A expressão de COX-1 e COX-2 em septos alveolares foi significativamente maior em FPI-PIU e ES-PINE do que no tecido controle. Não houve diferença entre FPI-PIU e ES-PINE quanto à expressão de COX-1 e COX-2. A análise multivariada baseada no modelo de regressão de Cox mostrou que os fatores associados a baixo risco de morte foram ter idade menor, valores elevados de DLCO/volume alveolar, FPI, e alta expressão de COX-1 em septos alveolares, ao passo que os fatores associados a alto risco de morte foram ter idade maior, valores baixos de DLCO/volume alveolar, ES (com PINE) e baixa expressão de COX-1 em septos alveolares.CONCLUSÕES: Nossos resultados sugerem que estratégias de prevenção de baixa síntese de COX-1 terão maior impacto sobre a ES, ao passo que as de prevenção de alta síntese de COX-2 terão maior impacto sobre a FPI. Porém, são necessários ensaios clínicos randomizados prospectivos para confirmar essa hipótese.

OBJECTIVE: To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF) patients, correlating that expression with patient survival.METHODS: We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP) in SSc patients and usual interstitial pneumonia (UIP) in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival.RESULTS: The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, IPF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NSIP), and low COX-1 expression in alveolar septa.CONCLUSIONS: Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on IPF. However, prospective randomized clinical trials are needed in order to confirm that.

OBJETIVO: Investigar os efeitos morfológicos da exposição crônica à inalação de fumaça do tabaco e o do consumo de álcool nos pulmões e no crescimento de ratos. MÉTODOS: Sessenta ratos Wistar machos foram distribuídos em quatro grupos: controle, tabaco, álcool e tabaco + álcool, e acompanhados por um período de 260 dias. No final do periodo foi realizada análise morfológica dos pulmões por microscopia óptica e eletrônica. O crescimento dos ratos foi investigado através da medição do comprimento focinho-ânus, peso corporal e índice de massa corporal. RESULTADOS: Os três grupos expostos às drogas apresentaram peso e comprimento significativamente menores que os do grupo controle. As percentagens de bronquiolite e alveolite, e o diâmetro alveolar médio foram maiores nos grupos expostos à fumaça do tabaco, mas sem significancia estatística quando comparadas ao grupo controle. A microscopia eletrônica revelou apoptose mais intensa e lesões degenerativas no grupo de fumantes, enquanto lesões degenerativas nos corpos lamelares foram mais intensas com a associação de ambas as drogas. CONCLUSÕES: Este modelo experimental mostrou alterações morfológicas observadas por microscopia eletrônica, principalmente devido à exposição ao tabaco. Tanto o alcool como o tabaco prejudicaram o crescimento dos animais, o tabaco mostrando um efeito maior sobre o comprimento e o álcool sobre o peso corporal.

PURPOSE: Investigate the morphological effects of chronic exposure to tobacco smoke inhalation and alcohol consumption on the lungs and on the growth of rats. METHODS: Sixty male Wistar rats were divided into four groups: control, tobacco, alcohol, tobacco + alcohol, for a period of study 260 days. Morphological analysis was conducted by optical and electron microscopy. Rat growth was investigated by measuring the snout-anus length, body mass index and body weight. RESULTS: The three groups exposed to the drugs presented lower growth and lower weight than the control group. The percentages of alveolitis, bronchiolitis and the mean alveolar diameter were greater, particularly in the groups exposed to tobacco smoke, but were not significantly different from the control group. Electron microscopy revealed more intense apoptotic and degenerative lesions in the smoking group, while degenerative lesions in the lamellar bodies were more intense with the association of both drugs. CONCLUSIONS: This experimental model showed morphological alterations observed by electron microscopy, principally due to tobacco smoke exposure. Alcohol and tobacco hindered the growth of rats, such that tobacco showed a greater effect on body length and alcohol on body weight.

OBJECTIVE: This study sought to identify the relationship between fibroblast telomerase expression, myofibroblasts, and telomerase-mediated regulatory signals in idiopathic pulmonary fibrosis. METHODS: Thirty-four surgical lung biopsies, which had been obtained from patients with idiopathic pulmonary fibrosis and histologically classified as usual interstitial pneumonia, were examined. Immunohistochemistry was used to evaluate fibroblast telomerase expression, myofibroblast α-smooth muscle actin expression and the tissue expression of inter leu kin-4, transforming growth factor-β, and basic fibroblast growth factor. The point-counting technique was used to quantify the expression of these markers in unaffected, collapsed, mural fibrosis, and honeycombing areas. The results were correlated to patient survival. RESULTS: Fibroblast telomerase expression and basic fibroblast growth factor tissue expression were higher in collapsed areas, whereas myofibroblast expression and interleukine-4 tissue expression were higher in areas of mural fibrosis. Transforming growth factor-β expression was higher in collapsed, mural fibrosis and honeycombing areas in comparison to unaffected areas. Positive correlations were found between basic fibroblast growth factor tissue expression and fibroblast telomerase expression and between interleukin-4 tissue expression and myofibroblast α-smooth muscle actin expression. Negative correlations were observed between interleukin-4 expression and basic fibroblast growth factor tissue expression in areas of mural fibrosis. Myofibroblast α-smooth muscle actin expression and interleukin-4 tissue expression in areas of mural fibrosis were negatively associated with patient survival. CONCLUSION: Fibroblast telomerase expression is higher in areas of early remodeling in lung tissues demonstrating typical interstitial pneumonia, whereas myofibroblast α-smooth muscle actin expression predominates in areas of late remodeling. These events seem to be regulated by basic fibroblast growth factor and interleukin-4 tissue expression, respectively.

OBJETIVO: Investigar o significado de marcadores de imunidade celular e de componentes elásticos/colágeno da matriz extracelular em estruturas granulomatosas em biópsias de pacientes com sarcoidose pulmonar ou extrapulmonar. MÉTODOS: Determinações qualitativas e quantitativas de células inflamatórias, de fibras de colágeno e de fibras elásticas em estruturas granulomatosas em biópsias cirúrgicas de 40 pacientes com sarcoidose pulmonar e extrapulmonar foram realizadas por histomorfometria, imuno-histoquímica, e técnicas de coloração com picrosirius e resorcina-fucsina de Weigert. RESULTADOS: A densidade de linfócitos, macrófagos e neutrófilos nas biópsias extrapulmonares foi significativamente maior do que nas biópsias pulmonares. Os granulomas pulmonares apresentaram uma quantidade significativamente maior de fibras de colágeno e menor densidade de fibras elásticas que os granulomas extrapulmonares. A quantidade de macrófagos nos granulomas pulmonares correlacionou-se com CVF (p < 0,05), ao passo que as quantidades de linfócitos CD3+, CD4+ e CD8+ correlacionaram-se com a relação VEF1/CVF e com CV. Houve correlações negativas entre CPT e contagem de células CD1a+ (p < 0,05) e entre DLCO e densidade de fibras colágenas/elásticas (r = -0,90; p = 0,04). CONCLUSÕES: A imunofenotipagem e o remodelamento apresentaram características diferentes nas biópsias dos pacientes com sarcoidose pulmonar e extrapulmonar. Essas diferenças correlacionaram-se com os dados clínicos e espirométricos dos pacientes, sugerindo que há duas vias envolvidas no mecanismo de depuração de antígenos, que foi mais eficaz nos pulmões e linfonodos.

OBJECTIVE: To investigate the significance of cellular immune markers, as well as that of collagen and elastic components of the extracellular matrix, within granulomatous structures in biopsies of patients with pulmonary or extrapulmonary sarcoidosis. METHODS: We carried out qualitative and quantitative evaluations of inflammatory cells, collagen fibers, and elastic fibers in granulomatous structures in surgical biopsies of 40 patients with pulmonary and extrapulmonary sarcoidosis using histomorphometry, immunohistochemistry, picrosirius red staining, and Weigert's resorcin-fuchsin staining. RESULTS: The extrapulmonary tissue biopsies presented significantly higher densities of lymphocytes, macrophages, and neutrophils than did the lung tissue biopsies. Pulmonary granulomas showed a significantly higher number of collagen fibers and a lower density of elastic fibers than did extrapulmonary granulomas. The amount of macrophages in the lung samples correlated with FVC (p < 0.05), whereas the amount of CD3+, CD4+, and CD8+ lymphocytes correlated with the FEV1/FVC ratio and VC. There were inverse correlations between TLC and the CD1a+ cell count (p < 0.05), as well as between DLCO and collagen/elastic fiber density (r = -0.90; p = 0.04). CONCLUSIONS: Immunophenotyping and remodeling both showed differences between pulmonary and extrapulmonary sarcoidosis in terms of the characteristics of the biopsy samples. These differences correlated with the clinical and spirometric data obtained for the patients, suggesting that two different pathways are involved in the mechanism of antigen clearance, which was more effective in the lungs and lymph nodes.

OBJETIVO: Este artigo objetiva descrever um modelo experimental, inédito, que mimetiza a síndrome do compartimento abdominal (SCA). MÉTODOS: Foram utilizados 20 ratos distribuídos aleatoriamente em quatro grupos. Para simular a SCA foi induzida hipertensão intra-abdominal (HIA) através da inserção de curativo cirúrgico algodoado (Zobec®) de 15x15cm (pressão intra-abdominal constante e igual a 12mmHg) associada à hipovolemia induzida através da retirada de sangue, mantendo-se a pressão arterial média (PAM) em torno de 60mmHg (HIPO). Para dissociar os efeitos da HIA daqueles induzidos pela hipovolemia per se, dois outros grupos foram analisados: aquele com somente HIA e outro com hipovolemia. O grupo Simulação (sham) foi submetido ao mesmo procedimento cirúrgico anteriormente realizado; entretanto, os níveis de pressão intra-abdominal e PAM se mantiveram iguais a 3mmHg e 90mmHg, respectivamente. RESULTADOS: Ao analisar o impacto da HIA sobre o intestino delgado, constataram-se necrose das vilosidades, congestão e infiltração neutrofílica. A hipovolemia induziu somente inflamação e edema do vilo. Entretanto, a associação de HIA e HIPO induziu, além de piora dos parâmetros supracitados, ao infarto hemorrágico. CONCLUSÃO: O presente modelo foi eficiente em induzir SCA expressa pelas repercussões encontradas no intestino delgado.

OBJECTIVE: To describe an experimental, unprecedented model that mimics the abdominal compartment syndrome (ACS). METHODS: twenty rats were randomly divided into four groups. To simulate ACS intra-abdominal hypertension (IAH) was induced by inserting cotton surgical dressing (Zobec ®), 15x15cm (intra-abdominal pressure constant and equal to 12 mmHg) associated with hypovolemia induced by withdrawing blood, keeping mean arterial pressure (MAP) around 60 mmHg (HYPO). To dissociate the effects of those IAH-induced hypovolemia per se, two other groups were analyzed: one with only with IAH and another with only hypovolemia. The simulation group (sham) underwent the same surgical procedure performed earlier, however, the levels of intra-abdominal pressure and MAP were kept in 3 mmHg and 90 mmHg, respectively. RESULTS: By analyzing the impact of IAH on the small intestine, we observed necrosis of the villi, congestion, and neutrophilic infiltration. Hypovolemia induced only inflammation and edema of the villi. However, the association of IAH and HYPO led to hemorrhagic infarction, besides worsening of the aforementioned parameters. CONCLUSION: This model was effective in inducing ACS expressed by the effects found in the small intestine.

OBJETIVO: Estudar os padrões clínicos, radiológicos e histopatológicos da biópsia transbrônquica (BTB) utilizados para a confirmação diagnóstica em pacientes com suspeita clinica de doença pulmonar intersticial (DPI) atendidos em um hospital universitário de nível terciário. MÉTODOS: Os prontuários, laudos radiológicos e de biópsias transbrônquicas de todos os pacientes com suspeita de DPI submetidos a BTB entre janeiro de 1999 e dezembro de 2006 no Hospital das Clínicas de Botucatu, localizado na cidade de Botucatu (SP), foram revisados. RESULTADOS: Foram incluídos no estudo 56 pacientes. Desses, 11 (19,6%) apresentaram o diagnóstico definitivo de fibrose pulmonar idiopática (FPI), que foi significativamente maior nos casos nos quais DPI era uma possibilidade diagnóstica em comparação com aqueles nos quais DPI era a principal suspeita (p = 0,011), demonstrando a contribuição da BTB para a definição diagnóstica dessas doenças. O exame histopatológico dessas biópsias revelou que 27,3% dos pacientes com FPI apresentavam o padrão de pneumonia organizante, o que pode sugerir doença mais avançada. O padrão histológico indeterminado foi o mais frequente, refletindo a característica periférica da FPI. Entretanto, o padrão fibrose apresentou alta especificidade e alto valor preditivo negativo. Para os padrões sugestivos de FPI em TC, a curva ROC indicou que a melhor relação entre sensibilidade e especificidade ocorreu com a presença de cinco alterações radiológicas, sendo o aspecto de favo de mel fortemente sugestivo de FPI (p = 0,01). CONCLUSÕES: Nas DPIs, a TC de tórax deve ser sempre realizada e a BTB usada em situações individualizadas, conforme a suspeita e distribuição das lesões.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: For ILDs, chest CT should always be performed, and TBB should be used in specific situations, according to the suspicion and distribution of lesions.

OBJETIVO: A granulomatose de Wegener (GW) pode causar dano nas células endoteliais e fenômenos tromboembólicos. Entretanto, poucos estudos analisaram a microcirculação pulmonar - artérias pulmonares de pequeno/médio calibre (APPMC) - em pacientes com GW. O objetivo deste estudo foi quantificar trombos de fibrina em amostras de APPMC de pacientes com GW. MÉTODOS: Analisamos 24 APPMC de seis pacientes com GW e 16 APPMC de quatro pacientes controles sem WG. Utilizamos CD34 para a marcação do endotélio em todas as amostras e microscopia confocal a laser para detectar trombos de fibrina intravasculares. Calculamos a área total do vaso, a área livre do lúmen e a área trombótica. RESULTADOS: A média da área total do vaso foi similar no grupo GW e no grupo controle (32.604 µm² vs. 32.970 µm², p = 0,8793). Trombos foram identificados em 22 das 24 APPMC (91,67%) no grupo GW, e em nenhuma do grupo controle (p < 0,0001; OR = 297 (IC95%: 13,34-6.612). A média da área trombótica foi maior no grupo GW do que no grupo controle (10.068 µm² vs. 0.000 µm², p < 0,0001). Em contraste, a média da área livre do lúmen foi menor no grupo GW que no grupo controle (6.116 µm² vs. 24.707 µm², p < 0,0001). CONCLUSÕES: A microscopia confocal a laser mostrou uma associação significante entre trombose microvascular pulmonar e GW. Isso sugere um possível papel da trombose microvascular na fisiopatologia da GW pulmonar, evocando o potencial benefício da anticoagulação na GW pulmonar. Entretanto, novos estudos são necessários para confirmar nossos achados, assim como um ensaio clínico randomizado a fim de testar o papel da anticoagulação no tratamento de pacientes com GW pulmonar.

OBJECTIVE: Wegener's granulomatosis (WG) can cause endothelial cell damage and thromboembolic events. Nevertheless, there have been few studies on the pulmonary microcirculation-small and medium-sized pulmonary arteries (SMSPA)-in patients with WG. The objective of this study was to quantify fibrin thrombi in the SMSPA of patients with WG. METHODS: We analyzed 24 SMSPA samples collected from six patients with WG and 16 SMSPA samples collected from four patients without WG. In all samples, we used the endothelial cell marker CD34 and confocal laser scanning microscopy in order to detect intravascular fibrin thrombi. We calculated the total vessel area, the free lumen area, and the thrombotic area. RESULTS: The mean total vessel area was similar in the WG and control groups (32,604 µm² vs. 32,970 µm², p = 0.8793). Thrombi were present in 22 (91.67%) of the 24 WG group samples and in none of the control group samples (p < 0.0001; OR = 297; 95% CI: 13.34-6,612). The mean thrombotic area was greater in the WG group samples than in the control group samples (10,068 µm² vs. 0.000 µm²; p < 0.0001). In contrast, the mean free lumen area was smaller in the WG group samples than in the control group samples (6,116 µm² vs. 24,707 µm²; p < 0.0001). CONCLUSIONS: Confocal laser scanning microscopy revealed a significant association between pulmonary microvascular thrombosis and WG. This suggests a possible role of microvascular thrombosis in the pathophysiology of pulmonary WG, evoking the potential benefits of anticoagulation therapy in pulmonary WG. However, further studies are needed in order to confirm our findings, and randomized clinical trials should be conducted in order to test the role of anticoagulation therapy in the treatment of patients with pulmonary WG.

OBJETIVO: Comparar os níveis séricos de CA19-9 e CEA e a expressão tecidual do CA19-9 e relacioná-los com os aspectos morfológicos do carcinoma colorretal. MÉTODOS: Quarenta e cinco pacientes com carcinoma colorretal foram operados com coleta de CEA e CA19-9 séricos pré-operatórios. Valores séricos de CEA = 5,0ng/mL e de CA19-9 = 37UI/mL foram considerados aumentados. A avaliação da imunoexpressão do CA19-9 no tecido neoplásico foi realizada por meio de estudo imunoistoquímico com anticorpo monoclonal anti-CA19-9. A intensidade de expressão do CA19-9 no tecido neoplásico foi semiquantificada em leve(+/+++), moderada(++/+++), intensa(+++/+++) e ausente. RESULTADOS: Os valores do CA19-9 sérico foram progressivamente maiores conforme o aumento da expressão do CA19-9 no tecido neoplásico, porém sem significância (p=0,06). O aumento do nível sérico do CA19-9 foi acompanhado de elevação significante (p<0,001) do nível sérico do CEA. O nível sérico do CA19-9, a imunoexpressão tecidual do CA19-9 e o nível sérico do CEA não apresentaram associação significante com características morfológicas do carcinoma colorretal. CONCLUSÃO: As expressões sérica e tissular do CA19-9 demonstraram relação diretamente proporcional entre si, enquanto que os aspectos morfológicos da neoplasia não tiveram influência no CEA e CA19-9 séricos ou na imunoexpressão do CA19-9 tissular.

OBJECTIVE: To compare sera levels of CEA and CA19-9 and tissular expression of the CA19-9 and to correlate these with morphological features of the colorectal carcinoma. METHODS: Forty five patients with colorectal carcinoma underwent surgical treatment following measurement of pre-operative levels of CA19-9 and CEA. Sera levels of CEA = 5.0ng/ml and CA19-9 = 37UI were deemed high values. Evaluation of CA19-9 immunoexpression in neoplastic tissue was carried through by means of immunohistochemical study with monoclonal antibody anti-CA19-9. The intensity of expression of CA19-9 in neoplastic areas was semi-quantified in each area of tumor differentiation into mild(+/+++), moderate(++/+++), intense(+++/+++) or absent. RESULTS: Sera CA19-9 values were progressively higher in the presence of elevated CA19-9 immunoexpression in colorectal carcinoma tissue, although not significant (p=0.06). Increased sera CA19-9 levels were found to be associated with significantly elevated (p<0.001) sera CEA levels. Levels of sera CA19-9, tissular immunoexpression of CA19-9 and sera levels of CEA presented no significant association with morphological features of the colorectal carcinoma. CONCLUSION: Sera and tissular levels of the CA19-9 marker exhibited, each other, a directly proportional relationship. The morphological features of the neoplasia had no influence on sera CEA or CA19-9 levels or tissular immunoexpression of CA19-9.

OBJECTIVE: The importance of type V collagen and its relationships with other types of collagen and with vascular and epithelial apoptosis were studied in a model of chemical carcinogenesis in the mouse lung. METHODS: Two groups of male Balb/c mice were studied: a) animals that received two intraperitoneal doses of 3 g/kg urethane carcinogen (urethane group = 24); and b) animals submitted to a sham procedure, comparable to the test group (control group = 7). Both groups were sacrificed after 120 days. In situ detection of apoptosis, immunohistochemistry, immunofluorescence and histomorphometry were used to evaluate the fraction occupied by the tumor, vascular and epithelial apoptosis, and type V, III and I collagen fibers in the lung parenchyma from both groups. RESULTS: The lung parenchyma from the urethane group showed low fractions of vascular and epithelial apoptosis as well as reduced type V collagen fibers when compared to the control group. A significant direct association was found between type V and III collagen fibers and epithelial apoptosis, type V collagen fibers and vascular apoptosis, and type V and type I collagen fibers. CONCLUSION: The results show that a direct link between low amounts of type V collagen and decreased cell apoptosis may favor cancer cell growth in the mouse lung after chemical carcinogenesis, suggesting that strategies aimed at preventing decreased type V collagen synthesis or local responses to reduced apoptosis may have a greater impact in lung cancer control.

BACKGROUND: Cases of H1N1 and other pulmonary infections evolve to acute respiratory failure and death when co-infections or lung injury predominate over the immune response, thus requiring early diagnosis to improve treatment. OBJECTIVE: To perform a detailed histopathological analysis of the open lung biopsy specimens from five patients with ARDS with confirmed H1N1. METHODS: Lung specimens underwent microbiologic analysis, and examination by optical and electron microscopy. Immunophenotyping was used to characterize macrophages, natural killer, T and B cells, and expression of cytokines and iNOS. RESULTS: The pathological features observed were necrotizing bronchiolitis, diffuse alveolar damage, alveolar hemorrhage and abnormal immune response. Ultrastructural analysis showed viral-like particles in all cases. CONCLUSIONS: Viral-like particles can be successfully demonstrated in lung tissue by ultrastructural examination, without confirmation of the virus by RT-PCR on nasopharyngeal aspirates. Bronchioles and epithelium, rather than endothelium, are probably the primary target of infection, and diffuse alveolar damage the consequence of the effect of airways obliteration and dysfunction on innate immunity, suggesting that treatment should be focused on epithelial repair.

CONTEXTO: O adenocarcinoma da junção esôfago-gástrica tem um comportamento agressivo e o estádio TNM não é sempre suficiente para categorizar o paciente de acordo com a evolução do mesmo. OBJETIVO: Avaliar a imunoexpressão do p53, ciclina D1 e Bcl-2 em pacientes com adenocarcinoma da junção esôfago-gástrica sem esôfago de Barrett e comparar com as características clínicas e sobrevida. MÉTODOS: Cortes histológicos de 75 adenocarcinomas da esôfago-gástrica ressecados de 1991 a 2003 foram analisados por imunoistoquímica para o p53, ciclina D1 e Bcl-2, usando-se o método da estreptavidina-biotina-peroxidase. O tempo médio de seguimento foi de 60 meses, DP=61,5 (variando de 4 a 273 meses). RESULTADOS: Cinquenta (66,7%) dos tumores eram do tipo intestinal e 25 (33,3%) eram difusos. Verificou-se infiltração vascular, linfonodal e perineural em 16%, 80% e 68% dos pacientes, respectivamente. O estádio TNM foi IA em 4 (5,3%), II em 15 (20%), IIIA em 15 (20%), IIIB em 15 (20%) e IV em 16 (21,3%). A análise imunoistoquímica foi positiva para p53, ciclina D1 e Bcl-2 em 68%, 18,7% e 100, respectivamente. Não houve associação entre a imunoexpressão e invasão vascular ou perineural, características clinicopatológicas e sobrevida geral. CONCLUSÃO: Nesta população selecionada, não houve associação entre os imunomarcadores, p53, ciclina D1 e Bcl-2 e os dados clinicopatológicos e a sobrevida geral dos pacientes.

CONTEXT: Esophagogastric junction adenocarcinoma has an aggressive behavior, and TNM (UICC) staging is not always accurate enough to categorize patient's outcome. OBJECTIVES: To evaluated p53, cyclin D1 and Bcl-2 immunoexpressions in esophagogastric junction adenocarcinoma patients, without Barrett's esophagus, and to compared to clinicopathological characteristics and survival rate. METHODS: Tissue sections from 75 esophagogastric junction adenocarcinomas resected from 1991 to 2003 were analyzed by immunohistochemistry for p53, cyclin D1 and Bcl-2 using streptavidin-biotin-peroxidase method. The mean follow-up time was 60 months SD = 61.5 (varying from 4 to 273 months). RESULTS: Fifty (66.7%) of the tumors were intestinal type and 25 (33.3%) were diffuse. Vascular, lymph node and perineural infiltration were verified in 16%, 80% and 68% of the patients, respectively. The patients were distributed according to the TNM staging in IA in 4 (5.3%), IB in 10 (13.3%), II in 15 (20%), IIA in 15 (20%), IIIB in 15 (20%) and IV in 16 (21.3%). Immunohistochemical analysis was positive for p53, cyclin D1 and bcl-2 in 68%, 18.7% and 100%, respectively. There was no association between immunoexpression and vascular and/or perineural invasions, clinicopathological characteristics and patients' survival rate. CONCLUSION: In this selected population, there was no association between the immunomarkers, p53, cyclin D1 and bcl-2 and clinicopathological data and/or overall survival.