Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma.

Herein, we aimed at identifying global transcriptome microRNA (miRNA) changes and miRNA target genes in lung adenocarcinoma. Samples were selected as training (N = 24) and independent validation (N = 34) sets. Tissues were microdissected to obtain >90% tumor or normal lung cells, subjected to miRNA transcriptome sequencing and TaqMan quantitative PCR validation. We further integrated our data with published miRNA and mRNA expression datasets across 1,491 lung adenocarcinoma and 455 normal lung samples. We identified known and novel, significantly over- and under-expressed (p ≤ 0.01 and FDR≤0.1) miRNAs in lung adenocarcinoma compared to normal lung tissue: let-7a, miR-10a, miR-15b, miR-23b, miR-26a, miR-26b, miR-29a, miR-30e, miR-99a, miR-146b, miR-181b, miR-181c, miR-421, miR-181a, miR-574 and miR-1247. Validated miRNAs included let-7a-2, let-7a-3, miR-15b, miR-21, miR-155 and miR-200b; higher levels of miR-21 expression were associated with lower patient survival (p = 0.042). We identified a regulatory network including miR-15b and miR-155, and transcription factors with prognostic value in lung cancer. Our findings may contribute to the development of treatment strategies in lung adenocarcinoma.

Paracoccidioidomycosis in patients with lymphoma and review of published literature.

This paper describes four new cases of lymphomas, two Hodgkin lymphomas and two non-Hodgkin lymphomas in patients with paracoccidioidomycosis. All had mycosis diagnosed before lymphomas with Paracoccidioides brasiliensis demonstrated in several lymph nodes, as seen in the disseminated form of the disease. When lymphoma was diagnosed, one patient was under regular paracoccidioidomycosis treatment and in clinic-serological remission for this disease, another was under regular treatment but with clinic-serological mycosis activity, one had abandoned paracoccidioidomycosis treatment 6 years earlier, and the other had not yet received any kind of antifungal drugs. Three patients received treatment for lymphomas with one remaining in remission until now, one achieving tumor remission which relapsed years later, and one having only residual lymphoma in bone marrow for a decade but clinically well. All three experienced paracoccidioidomycosis clinical remission, however, serology became negative just in one. Similar previously described cases were reviewed: five Hodgkin lymphomas, three non-Hodgkin lymphomas, and one described only as "lymphoma" without specifying type; a summary of their findings is presented. Finally, there is also a brief discussion on the possible pathophysiological mechanisms involved in the concomitance of these two disorders.

Lung morphology and growth of rats exposed to tobacco smoke and alcohol.

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.

Lung morphology and growth of rats exposed to tobacco smoke and alcohol / Estudo morfológico dos pulmões e crescimento de ratos expostos à fumaça do cigarro e ao álcool

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.

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.

Effects of inhaled nitric oxide on oxidative stress and histopathological and inflammatory lung injury in a saline-lavaged rabbit model of acute lung injury.

BACKGROUND: Conventional mechanical ventilation (CMV) is fundamental in acute respiratory distress syndrome (ARDS) treatment. Inhaled nitric oxide (INO), an adjunctive therapy, has been used with ventilation in an attempt to improve oxygenation and reduce lung injury. OBJECTIVE: To analyze the early effects of low INO dose on oxygenation, oxidative stress, inflammatory, and histopathological lung injury in a rabbit model of acute lung injury (ALI). METHODS: This was a prospective, controlled, in vivo animal laboratory study. Forty rabbits were instrumented and ventilated at F(IO(2)) 1.0. ALI was induced by tracheal infusion of warm saline (30 mL/kg, 38°C) and lung oxidative stress was assessed by total antioxidant performance (TAP) assay. Animals were assigned to groups: control group (no. = 10, low tidal volume [V(T)] = 6 mL/kg, PEEP = 5 cm H(2)O), ALI without INO (no-INO group, no. = 10, low V(T) = 6 mL/kg, PEEP = 10 cm H(2)O), ALI plus INO (INO group, no. = 10, low V(T) = 6 mL/kg, PEEP = 10 cm H(2)O, INO = 5 ppm). Plateau pressure was limited to 30 cm H(2)O in all groups. Ten non-instrumented animals (healthy group) were studied for TAP assay. Ventilatory and hemodynamic parameters were recorded every 30 min for 4 hours. RESULTS: After lung injury, the instrumented groups were worse than the control group for P(aO(2)) (control group 438 ± 87 mm Hg, no-INO group 80 ± 13 mm Hg, INO group 81 ± 24 mm Hg, P < .001). The INO group showed decreased lung inflammation by leukocyte count in lung lavage fluid (no-INO group 4.8 ± 1.64, control group 0.16 ± 0.15, INO group 0.96 ± 0.35 polymorphonuclear cells × 10(6)/bronchoalveolar lavage fluid/lung, P < .001), decreased histopathological injury score (no-INO group 5 [range 1-16], INO group 2 [range 0-5], control group 0 [range 0-3], P < .001), and better lung protection against oxidative injury than the no-INO group (healthy group 68 ± 8.7, control group 66.4 ± 6.8, INO group 56.3 ± 5.1, no-INO group 45.9 ± 3.4 percent protection/g protein, P < .001). CONCLUSIONS: INO attenuates oxidative stress and histopathological and inflammatory lung injury in a saline-lavaged rabbit ALI model.

Morphological findings in the tracheal epithelium of dogs exposed to the inhalation of poorly conditioned gases under use of an endotracheal tube or laryngeal mask airway / Alterações morfológicas no epitélio traqueal de cães expostos à inalação de gases pouco condicionados, sob ventilação com tubo traqueal ou máscara laríngea

PURPOSE: To study morphological findings in the tracheal epithelium of dogs exposed to the inhalation of poorly conditioned gases under use of an endotracheal tube (ET) or laryngeal mask airway (LMA). METHODS: Twelve dogs randomly were allocated to two groups: ET group (n-6) and LMA group (n-6), anaesthetized and mechanically ventilated, without CO2 reabsorption. Haemodynamic and ventilatory parameters, tympanic temperature, temperature, relative and absolute humidity of the ambient and inhaled gases were analyzed during three hours. The animals were submitted to euthanasia and biopsies were carried out along the tracheal segment to morphological study. Three healthy dogs were used to morphological control. RESULTS: Inhaled gas temperature was maintained between 24ºC and 26ºC, relative humidity between 10 percent and 12 percent, and absolute humidity between 2 - 3 mg H2O.L-1 with no significant differences between groups. In both groups, histological analysis showed epithelial inflammation and congestion in the corion and scanning electron microscopy showed ciliary grouping and disorganization. Transmission electron microscopy showed higher alterations in ET group than LMA group as widening of cell junctions, ciliary disorientation, cytoplasmic vacuolization, nuclear abnormalities, picnosis and chromatin condensation. CONCLUSION: LMA determined less pronounced changes in the tracheal epithelium in dogs exposed to the inhalation of poorly conditioned gases.

OBJETIVO: Avaliar as alterações morfológicas no epitélio traqueal de cães expostos à inalação de gases pouco condicionados, sob ventilação com tubo traqueal (TT) ou máscara laríngea (ML). MÉTODOS: Doze cães adultos foram divididos aleatoriamente em dois grupos: grupo TT (n-6) e grupo ML (n-6), submetidos à anestesia venosa e ventilação mecânica, em sistema sem reabsorção de CO2. Foram registrados parâmetros hemodinâmicos e ventilatórios, temperatura timpânica, temperatura, umidade relativa e absoluta do ar ambiente e dos gases inalados durante 3 horas. Ao término do experimento, os animais foram submetidos a eutanásia e realizadas biópsias ao longo do segmento traqueal para estudo morfológico. Três cães saudáveis foram utilizados para controle morfológico. RESULTADOS: A temperatura dos gases inalados manteve-se entre 24ºC e 26ºC, a umidade relativa entre 10 por cento e 12 por cento, e umidade absoluta entre 2 -3 mg H2O.L-1 sem diferença significativa entre os grupos. Em ambos os grupos a análise histológica evidenciou processo inflamatório epitelial e congestão no córion, e a microscopia eletrônica de varredura mostrou agrupamento e desorganização ciliar. A microscopia eletrônica de transmissão detectou maiores alterações no grupo TT do que no ML, como alargamento das junções intercelulares, desorientação ciliar, vacuolização citoplasmática, alterações nucleares como pcinose e condensação da cromatina. CONCLUSÃO: A máscara laríngea determinou alterações menos pronunciadas no epitélio traqueal de cães expostos à inalação de gases pouco condicionados.

High-frequency oscillatory ventilation attenuates oxidative lung injury in a rabbit model of acute lung injury.

Mechanical ventilation (MV) can induce lung oxidative stress, which plays an important role in pulmonary injury. This study compared protective conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFOV) for oxygenation, oxidative stress, inflammatory and histopathological lung injury in a rabbit model of acute lung injury (ALI). Rabbits (n = 30) were ventilated at FiO(2) 1.0. Lung injury was induced by tracheal saline infusion (30 mL/kg, 38°C). Animals were randomly assigned to: (a) sham control (CG: tidal volume [V(T)] 6 mL/kg, positive end expiratory pressure [PEEP] 5 cmH(2)O, respiratory rate [RR] 40 ipm); (b) ALI + CMV (CMVG: V(T) 6 mL/kg, PEEP 10 cmH(2)O, RR 40 ipm); or (c) ALI + HFOV (HFG: mean airway pressure [Paw] 14 cmH(2)O, RR 10 Hz) groups. Lung oxidative stress was assessed by total antioxidant performance assay, inflammatory response by the number of polymorphonuclear leukocytes/bronchoalveolar lavage fluid/lung and pulmonary histological damage was quantified by a score. Ventilatory and hemodynamic parameters were recorded every 30 min. Both ALI groups showed worse oxygenation after lung injury induction. After four hours of ventilation, HFG showed better oxygenation (partial pressure of oxygen [PaO(2)] - CG: 465.9 ± 30.5 = HFG: 399.1 ± 98.2 > CMVG: 232.7 ± 104 mmHg, P < 0.05) and inflammatory responses (CMVG: 4.27 ± 1.50 > HFG: 0.33 ± 0.20 = CG: 0.16 ± 0.15; polymorphonuclear cells/bronchoalveolar lavage fluid/lung, P < 0.05), less histopathological injury score (CMVG: 5 [1-16] > HFG: 1 [0-5] > CG: 0 [0-3]; P < 0.05), and lower lung oxidative stress than CMVG (CG: 59.4 ± 4.52 = HFG: 69.0 ± 4.99 > CMVG: 47.6 ± 2.58% protection/g protein, P < 0.05). This study showed that HFOV had an important protective role in ALI. It improved oxygenation, reduced inflammatory process and histopathological damage, and attenuated oxidative lung injury compared with protective CMV under these experimental conditions considering the study limitations.

Morphological findings in the tracheal epithelium of dogs exposed to the inhalation of poorly conditioned gases under use of an endotracheal tube or laryngeal mask airway.

PURPOSE: To study morphological findings in the tracheal epithelium of dogs exposed to the inhalation of poorly conditioned gases under use of an endotracheal tube (ET) or laryngeal mask airway (LMA). METHODS: Twelve dogs randomly were allocated to two groups: ET group (n-6) and LMA group (n-6), anaesthetized and mechanically ventilated, without CO(2) reabsorption. Haemodynamic and ventilatory parameters, tympanic temperature, temperature, relative and absolute humidity of the ambient and inhaled gases were analyzed during three hours. The animals were submitted to euthanasia and biopsies were carried out along the tracheal segment to morphological study. Three healthy dogs were used to morphological control. RESULTS: Inhaled gas temperature was maintained between 24ºC and 26ºC, relative humidity between 10% and 12%, and absolute humidity between 2 - 3 mg H(2)O.L(-1) with no significant differences between groups. In both groups, histological analysis showed epithelial inflammation and congestion in the corion and scanning electron microscopy showed ciliary grouping and disorganization. Transmission electron microscopy showed higher alterations in ET group than LMA group as widening of cell junctions, ciliary disorientation, cytoplasmic vacuolization, nuclear abnormalities, picnosis and chromatin condensation. CONCLUSION: LMA determined less pronounced changes in the tracheal epithelium in dogs exposed to the inhalation of poorly conditioned gases.

Evaluation of the use of transbronchial biopsy in patients with clinical suspicion of interstitial lung disease.

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.

Avaliação da utilização de biópsia transbrônquica em pacientes com suspeita clínica de doença pulmonar intersticial / Evaluation of the use of transbronchial biopsy in patients with clinical suspicion of interstitial lung disease

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 por cento) 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 por cento 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 percent) 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 percent 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.

Vocal polyps: clinical, morphological, and immunohistochemical aspects.

OBJECTIVES: To study the clinical, morphological, and immunohistochemical characteristics of vocal polyps. STUDY DESIGN: Prospective and retrospective. METHODS: Clinical study: 76 medical charts from patients with polyps were reviewed. Histology study: in 42 slides from surgical specimens, the following were analyzed: epithelium, basal membrane, and lamina propria. In the transmission and scanning electron microscopy (TEM and SEM) studies, eight new cases of polyps were included. An immunohistochemical study was carried out in the 42 specimens, using antibody antifibronectin, antilaminin, and anticollagen IV. RESULTS: Genders--43% males and 57% females; age range--between 21 and 40 years (36.85%); and between 41 and 60 years of age (51.31%); smoking and drinking-reported by 39 and 15 patients, respectively; associated symptoms-vocal abuse (61%), gastroesophageal (47%), and nasosinusal symptoms (32%); occupation--teachers (24.0%) and maids (18.0%). Histology--epithelial hyperplasia (31.71%), hyperkeratosis, (14.28%), edema (100%), vessel proliferation (92.86%), and congestion (83.33%). SEM--reduction in mucous lacing and increase in desquamating cells. TEM--hyperplastic epithelium, enlargement of the intercellular junctions, dense subepithelial network of collagen and basal membrane with adhesion loss. Immunohistochemistry--greater immunoexpression of fibronectin, laminin, and collagen IV around the vessels. CONCLUSIONS: In vocal polyps, the morphological analyses show lamina propria with edema, vessel proliferation and inflammation, basement membrane with adhesion loss in some areas and dense network of subepithelial collagen. Immunohistochemistry techniques identify pigmentation of the antibodies anti-fibronectin, anti-laminin, and anti-collagen IV in the endothelium of blood vessels.

Vocal fold nodules: morphological and immunohistochemical investigations.

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.

Curso de reumatologia: aula 1: significado clínico do FAN anticorpos antinucleares / Course of rheumatology: class 1: clinical significance of antinuclear antibodies ANA

A utilização de células HEp-2 na detecção dos anticorpos antinucleares (FAN-HEp-2) constituiu-se em grande avanço metodológico. Como consequência, o teste tornou-se muito sensível, porém com diminuição da especificidade, fato comprovado pelo crescente número de exames positivos em indivíduos sabidamente hígidos. O objetivo deste artigo é fazer uma abordagem sobre os pontos importantes, para correta valorização dos achados do teste de FAN, que possa auxiliar o clínico na exata identificação de pacientes com doenças autoimunes, particularmente o lúpus eritematoso sistêmico. Os autores discutem a importância do título e do padrão na interpretação de um FAN positivo. Discutem também os possíveis significados do teste positivo em pacientes sem evidências objetivas de doenças imunológicas.

Antinuclear antibody (ANA) tests are frequently used to screen patients for chronic inflammatory diseases such as lupus erythematosus (SLE). However, the methodological advances have brought up a considerable improvement in the test's sensitivity and consequently a decrease in its specificity. This has resulted in an increasing number of positive tests in apparently healthy subjects. The present article brigs an approach on the most important points to be considered in the analyses and evaluation of an ANA test, like titer and immunofluorescence pattern of a positive test. Those points are importants parameters in the evaluation of the significance of a positive ANA-HEp-2 test that might help the identification of patients with autoimmune disease. Also, it is important to consider the possible and alternative significance of a positive ANA test in patients without objective evidence of autoimmune diseases.

Traqueobroncopatia osteocondroplástica em portador de tumor de Klatskin: relato de caso e revisão da literatura / Tracheopathia osteochondroplastica in a patient with Klatskin tumor: a case report and review of the literature

A traqueopatia osteocondroplástica (TO) é uma desordem idiopática, incomum, caracterizada pela presença de nódulos osteocartilaginosos na submucosa das vias aéreas, causando rigidez e estreitamento da árvore respiratória. Afeta principalmente homens acima dos 50 anos com manifestações clínicas devidas à obstrução e/ou a infecções locais. Sua patogênese é desconhecida. Relatamos um caso de TO encontrada acidentalmente em autopsia de mulher com 73 anos de idade, que apresentava carcinoma ductal biliar extra hepático (tumor de Klatskin).

Tracheopathia osteochondroplastica (TO) is an unusual idiopathic disorder, characterized by osteocartilaginous nodules in the submucosa of the respiratory airway, which causes rigidity and narrowing of the respiratory tree. It affects mainly men over 50 and clinical manifestations are due to obstruction and/or local infections. The pathogenesis is uncertain. We report a case of TO found incidentally in an autopsy of a 73 year-old woman, who had an extrahepatic biliary ductal carcinoma (Klatskin tumor).

Lung cancer: histology, staging, treatment and survival.

OBJECTIVE: To analyze principal histological types of lung cancer, as well as the staging, treatment and survival of lung cancer patients. METHODS: This was a retrospective study based on the analysis of medical charts of patients treated at the Botucatu School of Medicine Hospital das Clínicas over a six-year period. RESULTS: From January of 2000 to January of 2006, 240 patients with lung cancer, most (64%) of whom were male, were treated. The most common histological type was squamous cell carcinoma (37.5%), followed by adenocarcinoma (30%), neuroendocrine carcinoma (19.6%) and large cell carcinoma (6.6%). Only 131 patients (54.6%) were treated. Of those, 52 patients (39.7%) received only chemotherapy, 32 (24.4%) were treated with chemotherapy combined with radiotherapy, and 47 (35.9%) were submitted to surgery alone or surgery accompanied by chemotherapy, with or without radiotherapy. Only 27 patients (20.6%) were submitted to surgery alone. Concerning staging, 34.4% presented stage IV at the time of diagnosis, 20.6% presented stage IIIB, 16.8% presented stage IIIA, and the remaining 28.2% were classified as stage I or II. Five-year survival was 65% for those in stage I and 25% for those in the remaining stages. CONCLUSIONS: Of the various histological types, the most common was squamous cell carcinoma and the least common was large cell carcinoma. Most cases presented advanced stages at the moment of diagnosis, and less than 30% of the cases presented early stages. This accounts for the low survival rate and the small number of patients submitted to surgical treatment alone, the majority being submitted to chemotherapy alone.

Câncer de pulmão: histologia, estádio, tratamento e sobrevida / Lung cancer: histology, staging, treatment and survival

OBJETIVO: Analisar os principais tipos histológicos, estádio, tratamento e sobrevida dos portadores de câncer de pulmão. MÉTODOS: Estudo retrospectivo a partir da análise dos prontuários de pacientes acompanhados no Hospital das Clínicas da Faculdade de Medicina de Botucatu, num período de seis anos. RESULTADOS: De janeiro de 2000 a janeiro de 2006, foram acompanhados 240 doentes com câncer de pulmão, com predominância do sexo masculino (64 por cento). O tipo histológico mais freqüente foi o carcinoma escamoso (37,5 por cento), seguido pelo adenocarcinoma (30 por cento), carcinoma neuroendócrino (19,6 por cento) e carcinoma de grandes células (6,6 por cento). Apenas 131 pacientes (54,6 por cento) foram tratados. Destes, 52 pacientes (39,7 por cento) foram submetidos à quimioterapia exclusiva, 32 (24,4 por cento) realizaram quimioterapia associada à radioterapia e 47 (35,9 por cento) foram submetidos à cirurgia associada ou não à quimioterapia exclusiva e/ou radioterapia. Somente 27 pacientes (20,6 por cento) foram submetidos à cirurgia exclusiva.Em relação ao estadiamento, 34,4 por cento apresentavam, no momento do diagnóstico, estádio IV, 20,6 por cento estádio IIIB, 16,8 por cento estádio IIIA e os outros 28,2 por cento pertenciam aos estádios I e II. A sobrevida em cinco anos foi de 65 por cento para o estádio I e 25 por cento para os estádios remanescentes. CONCLUSÕES: O tipo histológico predominante foi o carcinoma escamoso e o de menor freqüência foi o carcinoma de grandes células. A maioria se encontrava em estádio avançado ao diagnóstico, estando nos estádios iniciais menos de 30 por cento dos casos. Isto justifica a baixa sobrevida e a pequena quantidade de pacientes submetidos ao tratamento cirúrgico exclusivo, em comparação à maioria que foi submetida à quimioterapia exclusiva.

OBJECTIVE: To analyze principal histological types of lung cancer, as well as the staging, treatment and survival of lung cancer patients. METHODS: This was a retrospective study based on the analysis of medical charts of patients treated at the Botucatu School of Medicine Hospital das Clínicas over a six-year period. RESULTS: From January of 2000 to January of 2006, 240 patients with lung cancer, most (64 percent) of whom were male, were treated. The most common histological type was squamous cell carcinoma (37.5 percent), followed by adenocarcinoma (30 percent), neuroendocrine carcinoma (19.6 percent) and large cell carcinoma (6.6 percent). Only 131 patients (54.6 percent) were treated. Of those, 52 patients (39.7 percent) received only chemotherapy, 32 (24.4 percent) were treated with chemotherapy combined with radiotherapy, and 47 (35.9 percent) were submitted to surgery alone or surgery accompanied by chemotherapy, with or without radiotherapy. Only 27 patients (20.6 percent) were submitted to surgery alone. Concerning staging, 34.4 percent presented stage IV at the time of diagnosis, 20.6 percent presented stage IIIB, 16.8 percent presented stage IIIA, and the remaining 28.2 percent were classified as stage I or II. Five-year survival was 65 percent for those in stage I and 25 percent for those in the remaining stages. CONCLUSIONS: Of the various histological types, the most common was squamous cell carcinoma and the least common was large cell carcinoma. Most cases presented advanced stages at the moment of diagnosis, and less than 30 percent of the cases presented early stages. This accounts for the low survival rate and the small number of patients submitted to surgical treatment alone, the majority being submitted to chemotherapy alone.

Tuberculose em necropsias realizadas no Serviço de Anatomia Patológica da Faculdade de Medicina de Botucatu / Tuberculosis in necropsies performed at the Department of Pathology of Botucatu Medical School

Entre 6.316 necropsias realizadas, no período de 1969 a 2000, no Departamento de Patologia da Faculdade de Medicina de Botucatu da Universidade Estadual Paulista (FMB/UNESP), foram encontradas 240 necropsias com diagnóstico de tuberculose, sendo 117 registradas como doença principal (grupo tuberculose/doença principal) e 123, como doença associada (grupo tuberculose/doença associada). No grupo tuberculose/doença principal, 100 por cento apresentavam tuberculose ativa, com 80 ocorrências em homens e 37 em mulheres e média de idade de 47,7 anos. Caquexia (37,2 por cento) e cor pulmonale (23,7 por cento) foram as co-morbidades mais prevalentes nesse grupo. Os pulmões estavam comprometidos em 95,7 por cento dos casos, seguido pelos linfonodos (38,9 por cento) e pleuras (27,1 por cento). Os padrões morfológicos das lesões pulmonares foram: 1. miliar, 58,4 por cento; 2. cavernas, 56,6 por cento; 3. fibrose, 41,5 por cento; 4. bronquiectasias, 26,5 por cento; 5. enfisema, 19,4 por cento; e 6. cistos, 1,7 por cento. Cavernas foram observadas em diferentes áreas, com discreto predomínio no pulmão direito, sendo a localização apical preferencial (100 por cento) e quase sempre bilaterais (94 por cento). Lesões miliares, bronquiectasias e fibrose estavam distribuídas, de forma difusa e aleatória, nos pulmões. No grupo tuberculose/doença associada também houve predomínio de homens (70,8 por cento). Nesses casos, a AIDS e o alcoolismo crônico foram as doenças principais mais freqüentes, representando 22 por cento e 16,3 por cento, respectivamente. Os pulmões estavam acometidos em 85,2 por cento dessas necropsias (100 por cento nos casos de AIDS), seguidos pelos linfonodos (31,9 por cento) e baço (28,6 por cento). Nossos dados corroboram a importância da necropsia no estudo e no conhecimento da tuberculose, fornecendo subsídios para uma melhor abordagem clínica e epidemiológica dessa doença em nossa região.

Among 6,316 necropsies performed in the period 1969-2000 at the Department of Pathology of Botucatu Medical School UNESP, 240 were of tuberculosis. Among them, 117 were registered as the principal disease (tuberculosis/principal disease group) and 123, as associated to another disease (tuberculosis/associated disease group). In the tuberculosis-principal disease group, 100 percent had active tuberculosis, 80 patients were male and 37 were female, with mean age of 47.7 years. Cachexia (37.2 percent) and cor pulmonale (23.7 percent) were the most prevalent comorbities in this group. The lungs were affected in 95.7 percent of the cases, followed by lymph nodes (38.9 percent) and pleura (27.1 percent). The morphology and frequency of pulmonary lesions were: 1. miliar: 58.4 percent; 2. caverns, 56.6 percent; 3. fibrosis, 41.5 percent; 4. bronchiectasias, 26.5 percent; 5. emphysema, 19.4 percent and 6. cysts, 1.7 percent. Caverns were observed in different areas of both lungs, with discreet predominance in the right lung, were located mainly in the apices (100 percent), and the great majority (94 percent) was bilateral. The others lesions were distributed randomly in both lungs. In the tuberculosis/associated disease group, 70.8 percent was male, and the two most frequent principal diseases were AIDS (22.1 percent) and alcoholism (16.3 percent). Also, the lung was the most affected organ (85.2 percent), followed by lymph nodes (31.9 percent) and spleen (28.6 percent). In 100 percent of AIDS there were pulmonary lesions. This study in necropsies reinforces epidemiological data that tuberculosis is an important disease, and, also, constitutes an invaluable tool to gather information for a better understanding of the pathology and the epidemiology of tuberculosis in our region.

Condroma pulmonar isolado: caso incompleto da tríade de Carney? / Isolated pulmonary chondroma: a case of incomplete Carney triad?

Um homem, de 45 anos, com infecções pulmonares de repetição havia quatro anos apresentou-se com tosse, secreção amarelada, escarros hemópticos e dor torácica não pleural. A tomografia revelou nódulo calcificado ocluindo brônquio lobar inferior direito. Realizada bilobectomia inferior e média, o exame histopatológico revelou condroma endobrônquico, bem circunscrito. O condroma pulmonar é um tumor raro, em geral associado à tríade de Carney (condroma, leiomiossarcoma gástrico e paraganglioma extra-adrenal), sendo o menos freqüente dos três componentes. No presente caso, os outros dois componentes não foram observados. Podem, entretanto, se manifestar tardiamente, sendo, assim, necessário seguimento clínico em longo prazo do paciente.

A importância da contra-imunoeletroforese na detecção de antígenos nucleares extraíveis para o diagnóstico de doenças reumáticas sistêmicas / The importance of counterimmunoelectrophoresis in the detection of extractable nuclear antigens for the diagnosis of systemic rheumatic diseases

Os antígenos nucleares extraíveis (ENAs) são encontrados no soro da maioria dos pacientes com doença reumática sistêmica. Os principais ENAs estudados são SS-A/Ro, SS-B/La, RNP, Sm, Scl-70 e Jo-1. Objetivou-se neste trabalho: a) padronizar a técnica de contra-imunoeletroforese (CIE) para a detecção de ENAs; b) padronizar o substrato antigênico (ENAs) para a CIE a partir de baço de cão; c) comparar os resultados da CIE com as técnicas de imunofluorescência indireta (IFI) e Elisa para esses antígenos. Para tal foram estudados 40 soros de pacientes com doença reumática sistêmica confirmada por exames clínico e laboratorial (sorológico e biópsia). Como controle negativo foram utilizados dez soros de doadores de sangue normais, e, como controles positivos, seis soros-padrão anti-Ro, anti-La, anti-RNP, anti-Sm, anti-Scl-70, anti-Jo-1, para caracterizar os antígenos presentes no extrato de baço. Neste último foram detectados vários ENAs, exceto RNP e Scl-70. A técnica de CIE apresentou boas sensibilidade (70 por cento) e especificidade (100 por cento) em relação às outras técnicas (IFI e Elisa). A titulação dos soros pela CIE revelou positividade até diluições de 1:16 em 32,5 por cento dos casos. Concluímos que a CIE e os antígenos extraídos de baço de cão podem ser utilizados na rotina laboratorial para triagem destes ENAs, com a vantagem, em relação à IFI, de poderem ser titulados.