RESUMO
PURPOSE: The aim of this study was to evaluate the expression profiles of the relevant selectins and PDGF in schistosomiasis-associated pulmonary hypertension. METHODOLOGY: Patients with three distinct clinical profiles were enrolled in the study: IPAH(n = 11), schistosomiasis-associated PH (Sch-PH))(n = 13), and schistosomiasis without PH (Sch) (n = 13). Healthy volunteers, were recruited as a control group(n = 13). Echocardiography was performed in all groups, and the PH patients underwent right heart catheterization. Plasma soluble adhesion molecules E- and P-Selectin, PDGF-AB, PDGF-BB were determined by ELISA. RESULTS: E-selectin was significantly increased in the IPAH group compared with the other groups [the control, Sch + PH and Sch groups) (p < 0.001) (Fig. 2)]. P-selectin was lower in Sch (20.2 + 8.9 × 103 pg/mL) as compared to the control, (43 16.8 × 103 pg/mL), IPAH (35.8 7.8 × 103 pg/mL), and Sch + PH (36.8 ± 15.7 × 103 pg/mL) (p = 0.005) groups. Serum PDGF-BB levels were higher in the control group (8.9 ± 4.8 × 103 pg/mL) compared with the IPAH (3.7 ± 2.17 × 103 pg/mL), Sch + PH (5.2 ± 3.7 × 103 pg/mL) and Sch (2.4 ± 1.7 × 103 pg/mL) groups (p < 0.05). PDGF-AB levels were also higher in the control group (25.6 ± 8.6 × 103 pg/mL), compared with the other three groups, being the Sch group the one with lower serum levels of this marker (11.4 ± 8.6 × 103 pg/mL) (p = 0.006). CONCLUSIONS: In conclusion, vascular inflammation in schistosomiasis, with or without PH, is different from IPAH suggesting distinct pathophysiological mechanisms associated with the development of pulmonary hypertension.
Assuntos
Endotélio Vascular/fisiopatologia , Hipertensão Pulmonar/sangue , Fator de Crescimento Derivado de Plaquetas/metabolismo , Esquistossomose/sangue , Selectinas/metabolismo , Adulto , Análise de Variância , Biomarcadores/metabolismo , Estudos de Casos e Controles , Endotélio Vascular/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Volume Expiratório Forçado , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/diagnóstico , Masculino , Pessoa de Meia-Idade , Valores de Referência , Medição de Risco , Esquistossomose/complicações , Esquistossomose/diagnóstico , Índice de Gravidade de Doença , Vasculite/metabolismo , Vasculite/fisiopatologiaRESUMO
BACKGROUND: The mechanisms underlying pleural inflammation and pleurodesis are poorly understood. We hypothesized that the cytokines transforming growth factor ß (TGFß1) and vascular endothelial growth factor (VEGF) play a major role in pleurodesis after intrapleural silver nitrate (SN) injection. METHOD: Forty rabbits received intrapleurally 0.5% SN alone or 0.5% SN + anti-TGFß1, anti-IL-8, or anti-VEGF. After 28 days, the animals were euthanized and macroscopic pleural adhesions, microscopic pleural fibrosis, and collagen deposition were analyzed for characterization of the degree of pleurodesis (scores 0-4). RESULTS: Scores of pleural adhesions, pleural fibrosis, total collagen, and thin collagen fibers deposition after 28 days were significantly lower for 0.5% SN + anti-TGFß1 and 0.5% SN + anti-VEGF. Significant correlations were found between macroscopic adhesion and microscopic pleural fibrosis with total collagen and thin collagen fibers. CONCLUSIONS: We conclude that both TGFß1 and VEGF, but not IL-8, mediate the pleural inflammatory response and pleurodesis induced by SN.
Assuntos
Anticorpos Monoclonais/imunologia , Pleura/imunologia , Pleura/metabolismo , Doenças Pleurais/metabolismo , Pleurodese , Fator de Crescimento Transformador beta1/imunologia , Fator de Crescimento Transformador beta1/metabolismo , Fator A de Crescimento do Endotélio Vascular/imunologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Fibrose , Inflamação , Mediadores da Inflamação , Interleucina-8/sangue , Interleucina-8/metabolismo , Doenças Pleurais/induzido quimicamente , Coelhos , Nitrato de Prata/farmacologia , Aderências Teciduais , Fator de Crescimento Transformador beta1/sangue , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
PURPOSE: This study aimed to evaluate the sleep quality and impact of thoracentesis on sleep in patients with a large pleural effusion. METHODS: Patients with large unilateral pleural effusion were evaluated by the Pittsburgh Sleep Quality Index (PSQI) questionnaire and dyspnea Borg scale. Full polysomnography (PSG) was performed on the night before and 36 h after thoracentesis. RESULTS: We studied 19 patients, 11 males and 8 females, age 55 ± 18 years and body mass index of 26 ± 5 kg/m(2). The baseline sleep quality was poor (PSQI = 9.1 ± 3.5). Thoracentesis removed 1.624 ± 796 mL of pleural fluid and resulted in a significant decrease in dyspnea Borg scale (2.3 ± 2.1 vs. 0.8 ± 0.9, p < 0.001). The PSG before and after thoracentesis showed no significant change in apnea-hypopnea index and sleep time with oxygen saturation <90%. There was a significant improvement in sleep efficiency (76% vs. 81%, p = 0.006), decrease percent sleep stage 1 (16% vs. 14%, p = 0.002), and a trend improvement in total sleep time (344 ± 92 vs. 380 ± 69 min, p = 0.056) and percentage of rapid eye movement sleep (15% vs. 20%, p = 0.053). No significant changes occurred in six patients that performed two consecutive PSG before thoracentesis. The improvement in sleep quality was not associated with the volume of pleural fluid withdrawn or changes in dyspnea. CONCLUSIONS: Patients with large pleural effusion have poor subjective and objective sleep quality that improves after thoracentesis.
Assuntos
Tubos Torácicos , Derrame Pleural/fisiopatologia , Derrame Pleural/terapia , Polissonografia , Adulto , Idoso , Drenagem , Dispneia/fisiopatologia , Dispneia/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Ventilação Pulmonar/fisiologia , Fases do Sono , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: Light's criteria are frequently used to evaluate the exudative or transudative nature of pleural effusions. However, misclassification resulting from the use of Light's criteria has been reported, especially in the setting of diuretic use in patients with heart failure (HF). The objective of this study was to evaluate the utility of B-type natriuretic peptide (BNP) measurements as a diagnostic tool for determining the cardiac aetiology of pleural effusions. METHODS: Patients with pleural effusions attributable to HF (n = 34), hepatic hydrothorax (n = 10), pleural effusions due to cancer (n = 21) and pleural effusions due to tuberculosis (n = 12) were studied. Diagnostic thoracentesis was performed for all 77 patients. Receiver operating characteristic (ROC) curves were constructed to determine the diagnostic accuracy of plasma BNP and pleural fluid BNP for the prediction of HF. RESULTS: The areas under the ROC curves were 0.987 (95% CI 0.93-0.998) for plasma BNP and 0.949 (95% CI 0.874-0.986) for pleural fluid BNP, for distinguishing between patients with pleural effusions caused by HF (n = 34) and those with pleural effusions attributable to other causes (n = 43). The cut-off concentrations with the highest diagnostic accuracy for the diagnosis of HF as the cause of pleural effusion were 132 pg/mL for plasma BNP (sensitivity 97.1%, specificity 97.4%) and 127 pg/mL for pleural fluid BNP (sensitivity 97.1%, specificity 87.8%). CONCLUSIONS: In patients with pleural effusions of suspected cardiac origin, measurements of BNP in plasma and pleural fluid may be useful for the diagnosis of HF as the underlying cause.
Assuntos
Insuficiência Cardíaca/complicações , Peptídeo Natriurético Encefálico/sangue , Derrame Pleural/sangue , Derrame Pleural/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hidrotórax/diagnóstico , Hidrotórax/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Paracentese , Derrame Pleural/etiologia , Curva ROC , Sensibilidade e Especificidade , Volume Sistólico/fisiologia , Tuberculose Pulmonar/complicaçõesRESUMO
BACKGROUND AND OBJECTIVE: Both talc and 0.5% silver nitrate have been shown to induce effective pleurodesis. However, acute adverse systemic inflammatory effects have been described with both agents. The aim of this study was to assess in rabbits the systemic effects associated with a new technique of pleurodesis using repeated low doses of 0.1% silver nitrate. METHODS: Rabbits were injected intrapleurally through a chest tube with 0.1% silver nitrate at 0, 24 and 48 h. Other groups received a single injection of 0.5% silver nitrate or 400 mg/kg of talc. Blood samples were collected at 24, 48 and 72 h, and at 7 days, and cytological and biochemical measurements were performed. After 28 days, the presence of macroscopic pleural adhesions and microscopic pleural fibrosis in the pleural cavity were evaluated. RESULTS: Both talc and 0.5% silver nitrate caused significant increases in blood neutrophils, serum LDH, IL-8, transforming growth factor-beta and CRP in comparison with control at almost all time points, whereas sequential doses of 0.1% silver nitrate only increased LDH and CRP in the first 24 h and transforming growth factor-beta at all time points. All groups showed efficient pleurodesis, with no differences in pleural adhesions or fibrosis. CONCLUSIONS: Sequential doses of 0.1% silver nitrate produced efficient pleurodesis in rabbits, with a low systemic inflammatory response in comparison with 400 mg/kg of talc or 0.5% silver nitrate.
Assuntos
Inflamação/induzido quimicamente , Inflamação/epidemiologia , Pleurodese/métodos , Nitrato de Prata/efeitos adversos , Nitrato de Prata/uso terapêutico , Animais , Proteína C-Reativa/metabolismo , Tubos Torácicos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fibrose , Inflamação/sangue , Interleucina-8/sangue , L-Lactato Desidrogenase/sangue , Leucócitos/patologia , Masculino , Neutrófilos/patologia , Pleura/patologia , Coelhos , Fatores de Risco , Nitrato de Prata/administração & dosagem , Talco/administração & dosagem , Talco/efeitos adversos , Talco/uso terapêutico , Fator de Crescimento Transformador beta/sangueRESUMO
BACKGROUND AND OBJECTIVE: Tuberculosis (TB) and cancer are two of the main causes of pleural effusions which frequently share similar clinical features and pleural fluid profiles. This study aimed to identify diagnostic models based on clinical and laboratory variables to differentiate tuberculous from malignant pleural effusions. METHODS: A retrospective study of 403 patients (200 with TB; 203 with cancer) was undertaken. Univariate analysis was used to select the clinical variables relevant to the models composition. Variables beta coefficients were used to define a numerical score which presented a practical use. The performances of the most efficient models were tested in a sample of pleural exudates (64 new cases). RESULTS: Two models are proposed for the diagnosis of effusions associated with each disease. For TB: (i) adenosine deaminase (ADA), globulins and the absence of malignant cells in the pleural fluid; and (ii) ADA, globulins and fluid appearance. For cancer: (i) patient age, fluid appearance, macrophage percentage and presence of atypical cells in the pleural fluid; and (ii) as for (i) excluding atypical cells. Application of the models to the 64 pleural effusions showed accuracy higher than 85% for all models. CONCLUSIONS: The proposed models were effective in suggesting pleural tuberculosis or cancer.
Assuntos
Técnicas de Apoio para a Decisão , Neoplasias/complicações , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/etiologia , Derrame Pleural/diagnóstico , Derrame Pleural/etiologia , Tuberculose/complicações , Adenosina Desaminase/metabolismo , Adulto , Idoso , Biópsia , Neoplasias da Mama/complicações , Diagnóstico Diferencial , Feminino , Neoplasias dos Genitais Femininos/complicações , Humanos , Neoplasias Pulmonares/complicações , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Cavidade Pleural/enzimologia , Cavidade Pleural/patologia , Derrame Pleural/patologia , Derrame Pleural Maligno/patologia , Neoplasias da Próstata/complicações , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND AND OBJECTIVE: Vascular endothelial growth factor (VEGF) is known to increase vascular permeability and promote angiogenesis. It is expressed in most types of pleural effusions. However, the exact role of VEGF in the development of pleural effusions has yet to be determined. The anti-VEGF mAb, bevacizumab, has been used in the treatment of cancer to reduce local angiogenesis and tumour progression. This study describes the acute effects of VEGF blockade on the expression of inflammatory cytokines and pleural fluid accumulation. METHODS: One hundred and twelve New Zealand rabbits received intrapleural injections of either talc or silver nitrate. In each group, half the animals received an intravenous injection of bevacizumab, 30 min before the intrapleural agent was administered. Five animals from each subgroup were sacrificed 1, 2, 3, 4 or 7 days after the procedure. Twelve rabbits were used to evaluate vascular permeability using Evans's blue dye. Pleural fluid volume and cytokines were quantified. RESULTS: Animals pretreated with anti-VEGF antibody showed significant reductions in pleural fluid volumes after talc or silver nitrate injection. IL-8 levels, vascular permeability and macroscopic pleural adhesion scores were also reduced in the groups that received bevacizumab. CONCLUSIONS: This study showed that bevacizumab interferes in the acute phase of pleural inflammation induced by silver nitrate or talc, reinforcing the role of VEGF as a key mediator in the production of pleural effusions. The results also suggest that bevacizumab should probably be avoided in patients requiring pleurodesis.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Derrame Pleural/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais Humanizados , Bevacizumab , Permeabilidade Capilar/fisiologia , Contraindicações , Modelos Animais de Doenças , Interleucina-8/metabolismo , Derrame Pleural/induzido quimicamente , Derrame Pleural/fisiopatologia , Pleurodese , Coelhos , Nitrato de Prata/efeitos adversos , Talco/efeitos adversosRESUMO
PURPOSE: Chemical pleurodesis is a therapeutic tool for the treatment of recurrent pleural effusions, mainly those of neoplastic etiology. In the past, tetracycline was the sclerosant agent of choice in clinical practice, but presently, there is no consensus about an ideal agent. The aim of this study was to evaluate the effectiveness of macrolides (azithromycin and clarithromycin) or quinolones (levofloxacin and gatifloxacin) in inducing experimental pleurodesis in rabbits. METHOD: Forty New Zealand rabbits randomized into groups of 10 received (at a total volume of 2 mL for each animal) 1 of the 4 drugs by intrapleural injection. After 28 days, the animals were euthanized and the pleural cavity was evaluated macroscopically and microscopically. RESULTS: The intensity of the macroscopic adhesions was mild in all groups. On microscopic analysis, minimal pleural fibrosis and inflammation were observed in all animals. CONCLUSION: The macrolides (azithromycin or clarithromycin) and the quinolones (levofloxacin or gatifloxacin) when injected into the normal pleural space of rabbits are not effective in promoting pleurodesis. Additional research is required to identify sclerosing agents capable of inducing pleurodesis.
Assuntos
Macrolídeos/administração & dosagem , Derrame Pleural/terapia , Pleurodese/métodos , Quinolonas/administração & dosagem , Soluções Esclerosantes/administração & dosagem , Animais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Pleurodese/normas , Coelhos , Distribuição AleatóriaRESUMO
BACKGROUND: Pleurodesis performed either by pleurectomy or pleural abrasion is recommended in the approach to primary spontaneous pneumothorax to avoid recurrence. However, the efficacy of parietal pleural abrasion in producing pleurodesis is questioned. This study aims to determine the efficacy of apical abrasion alone, abrasion plus fibrin sealant application, and pleurectomy in producing pleurodesis in rabbits. METHODS: Rabbits were subjected to video-assisted thoracic surgery alone (control) or to video-assisted thoracic surgery with apical gauze abrasion, abrasion plus fibrin sealant instillation, or apical pleurectomy. Blood samples were collected preoperatively and 48 h and 28 days postoperatively to measure total leukocytes (white blood cell count), neutrophil counts, and serum interleukin (IL)-8 levels. After 28 days the animals were sacrificed for macroscopic evaluation of the degree of apical pleurodesis and microscopic evaluation of local pleural fibrosis and collagen deposition. RESULTS: White blood cell and neutrophil counts were similar in all groups, whereas the serum IL-8 level peaked at 48 h in all groups and decreased after 28 days, except in the pleurectomy group. After 28 days the abrasion plus fibrin sealant and pleurectomy groups had significantly more pleural adhesions, pleural fibrosis, and collagen deposition than the abrasion alone group, mainly due to thick mature fibers. CONCLUSIONS: Abrasion with local fibrin sealant instillation is as effective as pleurectomy in producing pleurodesis in rabbits. Apical pleurectomy elicits a more persistent elevation of serum IL-8 levels than apical abrasion alone or abrasion plus fibrin adhesive instillation.
Assuntos
Adesivo Tecidual de Fibrina/farmacologia , Pleura/efeitos dos fármacos , Pleurodese/métodos , Pneumotórax/terapia , Adesivos Teciduais/farmacologia , Animais , Adesivo Tecidual de Fibrina/administração & dosagem , Interleucina-8/sangue , Pleura/cirurgia , Pneumotórax/sangue , Período Pós-Operatório , Coelhos , Recidiva , Cirurgia Torácica Vídeoassistida/métodos , Adesivos Teciduais/administração & dosagemRESUMO
STUDY OBJECTIVES: Several systemic effects have been described after talc pleurodesis. The aim of this study was to assess the systemic response induced by low, nonpleurodesis-inducing doses of talc and silver nitrate in an experimental model in rabbits. DESIGN: Groups of six rabbits were injected intrapleurally with talc, 100 mg/kg or 400 mg/kg, and silver nitrate, 0.1% or 0.5%. After 6, 24, or 48 h, samples of blood and pleural fluid were collected and assayed for leukocytes, percentage of neutrophils, lactate dehydrogenase, interleukin-8, and vascular endothelial growth factor (VEGF) levels. Preinjection blood samples were used as normal blood controls. MEASUREMENTS AND RESULTS: Silver nitrate 0.1% induced a more intense pleural inflammation than that produced by talc 100 mg/kg. In contrast, talc 100 mg/kg induced a more pronounced acute systemic response with higher values of WBCs and neutrophils, whereas silver nitrate 0.1% produced no significant increases in leukocytes or neutrophils. The serum interleukin-8 and VEGF levels increased in all groups, and decreased with time only in the silver nitrate 0.1% group. The highest serum VEGF levels were observed in the talc 100 mg/kg group. CONCLUSIONS: In conclusion, 0.1% silver nitrate produced an intense pleural inflammatory response with a less evident systemic response in comparison to 0.5% silver nitrate and talc 100 mg/kg or 400 mg/kg.
Assuntos
Cáusticos/administração & dosagem , Inflamação/induzido quimicamente , Pleura/efeitos dos fármacos , Pleurodese/métodos , Nitrato de Prata/administração & dosagem , Animais , Infusões Parenterais , Irritantes/administração & dosagem , Masculino , Pleura/imunologia , Derrame Pleural/induzido quimicamente , Derrame Pleural/imunologia , Coelhos , Talco/administração & dosagemRESUMO
STUDY OBJECTIVE: To determine whether the administration of antiinflammatory drugs interferes with experimental pleurodesis induced by silver nitrate or talc. STUDY DESIGN: Two groups of 30 white New Zealand rabbits were scheduled to receive an intrapleural injection of 0.5% silver nitrate or 400 mg/kg of talc. Each group was further classified into three subgroups (10 animals each), which received the following: (subgroup 1) the sclerosing agent only, (subgroup 2) the sclerosing agent plus 1 mg/kg of methylprednisolone, and (subgroup 3) the sclerosing agent plus 1.1 mg/kg of diclofenac sodium. The antiinflammatory agents were administered IM 24 h before the sclerosing agent and daily during the first week, followed by once-weekly injections until death at 28 days. At this time, the pleural cavity was macroscopically evaluated, and samples of pleura and lungs were collected for further microscopic examination. MEASUREMENTS AND RESULTS: The degree of pleural adhesions was higher after silver nitrate administration (p = 0.019). No reduction in the adhesions was observed after administering antiinflammatory drugs to this group (p > 0.05). Conversely, the adhesion score was significantly reduced after administration of both prednisolone (p = 0.028) and diclofenac (p = 0.032) to the animals that received talc. Administration of the antiinflammatory agents did not influence microscopic pleural or lung changes induced by silver nitrate or talc. CONCLUSION: These results show that the sustained systemic administration of antiinflammatory agents (steroidal or nonsteroidal) reduces the degree of pleural adhesions in animals with talc-induced pleurodesis but does not affect silver nitrate-induced pleurodesis. Extrapolation of these results to humans suggests that the use of antiinflammatory drugs should be avoided in patients with talc-induced pleurodesis and that appropriate clinical studies with silver nitrate should be conducted in patients chronically treated with these antiinflammatory agents.
Assuntos
Diclofenaco/farmacologia , Metilprednisolona/farmacologia , Doenças Pleurais/prevenção & controle , Pleurodese/métodos , Soluções Esclerosantes/farmacologia , Animais , Modelos Animais de Doenças , Feminino , Masculino , Doenças Pleurais/tratamento farmacológico , Probabilidade , Valores de Referência , Medição de Risco , Sensibilidade e Especificidade , Nitrato de Prata , Estatísticas não Paramétricas , Talco , Aderências Teciduais/prevenção & controleRESUMO
STUDY OBJECTIVE: To compare the lung damage caused by intrapleural silver nitrate (SN) with that caused by talc over a 12-month period. DESIGN: One hundred forty rabbits received an intrapleural injection of 0.5% SN or 400 mg/kg talc slurry in 2 mL saline solution. Groups of 10 rabbits were killed after 1, 2, 4, 6, 8, 10, or 12 months. The macroscopic pleurodesis, microscopic lung changes (ie, collapse, hemorrhage, and edema), and cellular infiltrates (number and proportion of cells) were graded on a scale of 0 to 4. RESULTS: The mean (+/- SEM) adhesion score after SN injection (3.3 +/- 0.1) was higher (p < 0.001) than that after talc injection (2.3 +/- 0.1). The mean alveolar collapse score was greater (p < 0.001) 1 month after SN injection (2.2 +/- 0.3) than after talc injection (0.2 +/- 0.1) and was similar from the second month on. The degree of parenchymal hemorrhage, by alveolar collapse score, (SN injection, 0.2 +/- 0.1; talc injection, 0.2 +/- 0.0) and edema (SN injection, 0.4 +/- 0.1; talc injection, 0.3 +/- 0.1) was minimal in both groups (p > 0.05). One month after the injection, the total number of inflammatory cells was greater (p < 0.001) in rabbits that had received SN injections (2.7 +/- 0.3) than in those that had received talc injections (1.2 +/- 0.1). From the second month on, cellularity decreased and became similar in both groups. The cellular profile was different, with a predominantly neutrophilic reaction after talc injection and a predominantly eosinophilic reaction after SN injection. CONCLUSIONS: Rabbits injected with intrapleural 0.5% SN had significantly higher scores for adhesions than did those that had received talc injections, with mild and reversible alveolar collapse and an eosinophilic responses, conditions showing a clear tendency to normalize with time.
Assuntos
Pulmão/efeitos dos fármacos , Pleurodese , Nitrato de Prata/efeitos adversos , Talco/efeitos adversos , Animais , Eosinófilos/patologia , Injeções Intraperitoneais , Pulmão/patologia , Neutrófilos/patologia , Alvéolos Pulmonares/patologia , Coelhos , Nitrato de Prata/administração & dosagem , Talco/administração & dosagemRESUMO
STUDY OBJECTIVE: s: To determine whether talc (TL) and silver nitrate (SN), two effective pleurodesis agents, induce a systemic inflammatory response in the acute phase of experimental pleurodesis in rabbits. DESIGN: Samples of blood and pleural fluid were collected after 6, 24, and 48 h from rabbits injected intrapleurally with 3 mL saline solution, TL (400 mg/kg), or 0.5% SN, and were assayed for WBC count, percentage of neutrophils, and levels of lactate dehydrogenase (LDH), interleukin (IL)-8, and vascular endothelial growth factor (VEGF). The pleural liquid production was compared in the three different groups. A sample of blood collected from animals preinjection was used as the control. RESULTS: At 6 h after pleural injection, the mean blood WBC count and percentage of neutrophils were significantly elevated in the TL group, whereas the mean LDH and IL-8 levels were significantly increased in the SN group. VEGF was undetectable in the preinjection serum and saline solution-injected animals, but was increased in the serum after the pleural injection of both TL and SN to a comparable degree. SN elicited a more intense acute pleural inflammation reaction than did TL, with higher WBC count and IL-8 levels found in the pleural fluid, mainly within the first 6 h. LDH and VEGF levels, and pleural liquid production were also higher for SN, and they increased with time. CONCLUSIONS: In the acute phase of pleural injection, TL induced a transient increase in blood WBC count and percentage of neutrophils, while SN induced increases in blood LDH and IL-8 levels. Both TL and SN induced significant increases in blood VEGF levels. SN induced an earlier and more intense acute pleural inflammation than TL. Pleural liquid VEGF levels were higher after SN injection and increased, as did pleural liquid production. These findings suggest that the intrapleural injection of TL and SN produce a systemic inflammatory response that may have a role in the pathogenesis of fever and ARDS, which occur with pleurodesis.
Assuntos
Mediadores da Inflamação/análise , Pleurodese/métodos , Nitrato de Prata/efeitos adversos , Talco/efeitos adversos , Doença Aguda , Animais , Modelos Animais de Doenças , Inflamação/fisiopatologia , Injeções Intralesionais , Interleucina-8/análise , Contagem de Leucócitos , Masculino , Derrame Pleural/metabolismo , Derrame Pleural/terapia , Coelhos , Distribuição Aleatória , Valores de Referência , Sensibilidade e Especificidade , Nitrato de Prata/farmacologia , Talco/farmacologia , Fator A de Crescimento do Endotélio Vascular/análiseRESUMO
OBJECTIVES: Chemical pleurodesis is an important therapeutic tool to control recurrent malignant pleural effusion. Among the various sclerosing agents, iodopovidone is considered effective and safe. However, in a recent study, ocular changes were described after iodopovidone was used in recurrent pneumothorax. The aim of the study was to evaluate the efficacy and morbidity of iodopovidone pleurodesis in an experimental model. METHODS: New Zealand rabbits were submitted to intrapleural injection of iodopovidone at concentrations of 2%, 4% and 10%. Biochemical (lactic dehydrogenase, proteins, triiodothyronine, free thyroxine, urea and creatinine) and immunological (Interleukin-8 [IL-8], VEGF and TGFß) parameters were measured in the pleural fluid and blood. After 1, 3, 7, 14 and 28 days, groups of animals were euthanized, and macro- (pleura) and microscopic (pleura and retina) analyses were performed. RESULTS: An early pleural inflammatory response with low systemic repercussion was observed without corresponding changes in thyroid or renal function. The higher concentrations (4% and 10%) correlated with greater initial exudation, and maximum pleural thickening was observed after 28 days. No changes were observed in the retinal pigment epithelium of the rabbits. CONCLUSION: Iodopovidone is considered to be an effective and safe sclerosing agent in this animal model. However, its efficacy, tolerance and safety in humans should be further evaluated.
Assuntos
Derrame Pleural Maligno/terapia , Pleurodese/métodos , Povidona-Iodo/administração & dosagem , Soluções Esclerosantes/administração & dosagem , Animais , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Modelos Animais , Pleura/efeitos dos fármacos , Povidona-Iodo/efeitos adversos , Coelhos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Soluções Esclerosantes/efeitos adversos , Fatores de TempoRESUMO
OBJECTIVES: This study aimed to evaluate a panel of proinflammatory and antiinflammatory cytokines in noncomplicated and complicated parapneumonic pleural effusions and to correlate their levels with pleural fluid biochemical parameters. METHODS: Serum and pleural effusion were collected from 60 patients with noncomplicated (n = 26) or complicated (n = 34) parapneumonic effusions and assayed for cytologic, biochemical, and proinflammatory and antiinflammatory cytokines. Student t test was used to compare serum and pleural fluid values, Spearman correlation to analyze the relationship between pleural fluid cytokines and biochemical parameters, and accuracy of pleural fluid cytokine levels to determine the optimal cutoff value for identification of complicated effusions. Corrections for multiple comparisons were applied and a P value < .05 was accepted as significant. RESULTS: Serum and pleural fluid cytokine levels of IL-8, vascular endothelial growth factor (VEGF), IL-10, and tumor necrosis factor (TNF) soluble receptor (sR) II were similar between groups. In contrast, complicated effusions had higher levels of pleural fluid IL-1ß, IL-1 receptor antagonist (ra), and TNF sRI. Negative correlations were found between pleural fluid glucose with IL-1ß and TNF sRI and positive correlations between lactic dehydrogenate (LDH) with IL-1ß, IL-8, and VEGF. Pleural fluid levels of IL-1ß, IL-1ra, and TNF sRI were more accurate than IL-8, VEGF, IL-10, and TNF sRII in discriminating complicated effusions. CONCLUSIONS: Both proinflammatory and antiinflammatory cytokine levels in pleural fluid are elevated in complicated in comparison with noncomplicated parapneumonic pleural effusions, and they correlate with both pleural fluid glucose and LDH levels. IL-1ß, IL-1ra, and TNF sRI had higher sensitivity and specificity than IL-8, VEGF, IL-10, and TNF sRII in discriminating complicated effusions.
Assuntos
Citocinas/análise , Exsudatos e Transudatos/química , Inflamação/metabolismo , Derrame Pleural/metabolismo , Biomarcadores/análise , Diagnóstico Diferencial , Humanos , Derrame Pleural/diagnóstico , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: Pleural tuberculosis is the most frequently occurring form of extra pulmonary disease in adults. In up to 40% of cases, the lung parenchyma is concomitantly involved, which can have an epidemiological impact. This study aims to evaluate the pleural and systemic inflammatory response of patients with pleural or pleuropulmonary tuberculosis. METHODS: A prospective study of 39 patients with confirmed pleural tuberculosis. After thoracentesis, a high resolution chest tomography was performed to evaluate the pulmonary involvement. Of the 39 patients, 20 exhibited only pleural effusion, and high resolution chest tomography revealed active associated-pulmonary disease in 19 patients. The total protein, lactic dehydrogenase, adenosine deaminase, vascular endothelial growth factor, interleukin-8, tumor necrosis factor-α, and transforming growth factor-ß(1) levels were quantified in the patient serum and pleural fluid. RESULTS: All of the effusions were exudates with high levels of adenosine deaminase. The levels of vascular endothelial growth factor and transforming growth factor-ß(1) were increased in the blood and pleural fluid of all of the patients with pleural tuberculosis, with no differences between the two forms of tuberculosis. The tumor necrosis factor-α levels were significantly higher in the pleural fluid of the patients with the pleuropulmonary form of tuberculosis. The interleukin-8 levels were high in the pleural fluid of all of the patients, without any differences between the forms of tuberculosis. CONCLUSION: Tumor necrosis factor-α was the single cytokine that significantly increased in the pleural fluid of the patients with pulmonary involvement. However, an overlap in the results does not permit us to suggest that cytokine is a biological marker of concomitant parenchymal involvement. Although high resolution chest tomography can be useful in identifying these patients, the investigation of fast acid bacilli and cultures for M. tuberculosis in the sputum is recommended for all patients who are diagnosed with pleural tuberculosis.
Assuntos
Biomarcadores/análise , Derrame Pleural/metabolismo , Tuberculose Pleural/metabolismo , Adenosina Desaminase/análise , Adulto , Citocinas/análise , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Exsudatos e Transudatos/química , Humanos , Pessoa de Meia-Idade , Oxirredutases/análise , Derrame Pleural/diagnóstico por imagem , Estudos Prospectivos , Radiografia , Fator de Crescimento Transformador beta1/análise , Tuberculose Pleural/diagnóstico por imagem , Tuberculose Pulmonar/metabolismo , Fator de Necrose Tumoral alfa/análise , Fator A de Crescimento do Endotélio Vascular/análise , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: Chemical pleurodesis controls recurrent malignant pleural effusion. The mechanism that determines pleural symphysis involves the action of vascular endothelial growth factor (VEGF). We assessed the influence of the anti-VEGF antibody (bevacizumab) on pleurodesis induced by talc or silver nitrate and analyzed the temporal development of pleural angiogenesis. METHODS: Sixty New Zealand rabbits received intrapleural injection (2mL) of talc (400mg/kg) or 0.5% silver nitrate. In each group, half of the animals received an intravenous injection of bevacizumab 30min before the sclerosing agent. Five animals from each group were euthanized 7, 14, or 28 days after the procedure. Adhesions and inflammation (scores: 0-4), thickness (µm), vascular density (vessels/field), and collagen fibers (µm(2)) were evaluated in the visceral pleura. RESULTS: Antibody anti-VEGF interferes in pleurodesis induced by talc or silver nitrate. Pleural inflammation was discreet with no difference between the groups, regardless the anti-VEGF treatment. Concerning the vascular density of the visceral pleura, a smaller number of neoformed vessels was noted in the animals that received bevacizumab. In the animals receiving silver nitrate, the decrement in adhesions and vascular density was associated with reduced thick and thin collagen fibers, resulting in less pleural thickness. CONCLUSION: The anti-VEGF antibody inhibits adhesions between pleural layers. Despite being an experimental study in animals with normal pleura, the results call attention to a likely lack of success in pleurodesis when VEGF blockers are used.
Assuntos
Pleura/metabolismo , Derrame Pleural Maligno/terapia , Fator A de Crescimento do Endotélio Vascular/imunologia , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Bevacizumab , Adesão Celular/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Injeções Intravenosas , Neovascularização Fisiológica , Pleura/efeitos dos fármacos , Pleura/imunologia , Pleura/patologia , Derrame Pleural Maligno/induzido quimicamente , Derrame Pleural Maligno/patologia , Derrame Pleural Maligno/fisiopatologia , Pleurodese , Coelhos , Nitrato de Prata/administração & dosagem , Talco/administração & dosagemRESUMO
OBJECTIVE: To evaluate in chest X-rays and high-resolution computed tomographies of patients with pleural tuberculosis, the incidence of parenchymal and mediastinal lung lesions suggestive of active disease. METHODS: Prospective study (2008-2009) evaluating the radiographic and tomographic abnormalities of 88 HIV-negative patients with pleural tuberculosis (unilateral effusion). The images were reviewed by 3 independent specialists, and the observed changes were classified according to previously established criteria: presence or absence of signs suggestive of disease activity, and nonspecific findings. RESULTS: Abnormal changes were observed in chest X-rays of 22 (25%) patients and in the computed tomography of 55 (63%). Images compatible with active pulmonary tuberculosis were detected by radiography in 9 (10%) patients and by tomography in 38 (43%). Only 4 (4.5%) patients had tomography images suggestive of residual disease. CONCLUSION: The present study demonstrates that pulmonary involvement is quite common in pleural tuberculosis. This finding is mainly observed in high-resolution computed tomography and has important epidemiological implications, since patients with pleural tuberculosis are significant sources of infection and disease dissemination.
Assuntos
Pulmão/diagnóstico por imagem , Doenças Pleurais/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Tuberculose Pleural/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doenças Pleurais/fisiopatologia , Estudos Prospectivos , Tuberculose Pleural/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Impairment in pulmonary capacity due to pleural effusion compromises daily activity. Removal of fluid improves symptoms, but the impact, especially on exercise capacity, has not been determined. METHODS: Twenty-five patients with unilateral pleural effusion documented by chest radiograph were included. The 6-min walk test, Borg modified dyspnea score, FVC, and FEV(1) were analyzed before and 48 h after the removal of large pleural effusions. RESULTS: The mean fluid removed was 1,564 ± 695 mL. After the procedure, values of FVC, FEV(1), and 6-min walk distance increased (P < .001), whereas dyspnea decreased (P < .001). Statistical correlations (P < .001) between 6-min walk distance and FVC (r = 0.725) and between 6-min walk distance and FEV(1) (r = 0.661) were observed. Correlations also were observed between the deltas (prethoracentesis × postthoracentesis) of the 6-min walk test and the percentage of FVC (r = 0.450) and of FEV(1) (r = 0.472) divided by the volume of fluid removed (P < .05). CONCLUSION: In addition to the improvement in lung function after thoracentesis, the benefits of fluid removal are more evident in situations of exertion, allowing better readaptation of patients to routine activities.
Assuntos
Tolerância ao Exercício/fisiologia , Paracentese , Derrame Pleural/fisiopatologia , Derrame Pleural/terapia , Caminhada/fisiologia , Adulto , Idoso , Estudos de Coortes , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espirometria , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Biochemical analysis of fluid is the primary laboratory approach in pleural effusion diagnosis. Standardization of the steps between collection and laboratorial analyses are fundamental to maintain the quality of the results. We evaluated the influence of temperature and storage time on sample stability. METHODS: Pleural fluid from 30 patients was submitted to analyses of proteins, albumin, lactic dehydrogenase (LDH), cholesterol, triglycerides, and glucose. Aliquots were stored at 21 degrees , 4 degrees , and-20 degrees C, and concentrations were determined after 1, 2, 3, 4, 7, and 14 days. LDH isoenzymes were quantified in 7 random samples. RESULTS: Due to the instability of isoenzymes 4 and 5, a decrease in LDH was observed in the first 24h in samples maintained at -20 degrees C and after 2 days when maintained at 4 degrees C. Aside from glucose, all parameters were stable for up to at least day 4 when stored at room temperature or 4 degrees C. CONCLUSIONS: Temperature and storage time are potential preanalytical errors in pleural fluid analyses, mainly if we consider the instability of glucose and LDH. The ideal procedure is to execute all the tests immediately after collection. However, most of the tests can be done in refrigerated samples, excepting LDH analysis.