RESUMO
Pleural fibrosis is characterized by severe inflammation of the pleural space and pleural reorganization. Subsequent thickening of the visceral pleura contributes to lung stiffness and impaired lung function. Pleural mesothelial cells (PMCs) can become myofibroblasts via mesothelial-mesenchymal transition (MesoMT) and contribute to pleural organization, fibrosis, and rind formation. However, the mechanisms that underlie MesoMT remain unclear. Here, we investigated the role of myocardin in the induction of MesoMT. Transforming growth factor ß (TGF-ß) and thrombin induced MesoMT and markedly upregulated the expression of myocardin, but not myocardin-related transcription factor A (MRTF-A) or MRTF-B, in human PMCs (HPMCs). TGF-ß stimulation notably induced the nuclear translocation of myocardin in HPMCs, whereas nuclear translocation of MRTF-A and MRTF-B was not observed. Several genes under the control of myocardin were upregulated in cells undergoing MesoMT, an effect that was accompanied by a dramatic cytoskeletal reorganization of HPMCs consistent with a migratory phenotype. Myocardin gene silencing blocked TGF-ß- and thrombin-induced MesoMT. Although myocardin upregulation was blocked, MRTF-A and MRTF-B were unchanged. Myocardin, α-SMA, calponin, and smooth muscle myosin were notably upregulated in the thickened pleura of carbon black/bleomycin and empyema mouse models of fibrosing pleural injury. Similar results were observed in human nonspecific pleuritis. In a TGF-ß mouse model of pleural fibrosis, PMC-specific knockout of myocardin protected against decrements in lung function. Further, TGF-ß-induced pleural thickening was abolished by PMC-specific myocardin knockout, which was accompanied by a marked reduction of myocardin, calponin, and α-SMA expression compared with floxed-myocardin controls. These novel results show that myocardin participates in the development of MesoMT in HPMCs and contributes to the pathogenesis of pleural organization and fibrosis.
Assuntos
Núcleo Celular/metabolismo , Empiema Pleural/metabolismo , Miofibroblastos/metabolismo , Proteínas Nucleares/metabolismo , Pleura/metabolismo , Transativadores/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Bleomicina/efeitos adversos , Bleomicina/farmacologia , Núcleo Celular/patologia , Modelos Animais de Doenças , Empiema Pleural/induzido quimicamente , Empiema Pleural/patologia , Feminino , Fibrose , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Miofibroblastos/patologia , Pleura/patologia , Fuligem/toxicidade , Fator de Crescimento Transformador beta/metabolismoRESUMO
Hemolytic uremic syndrome is a rare complication of invasive pneumococcal infection (pnHUS). Its pathogenesis is poorly understood, and treatment remains controversial. The emerging role of complement in various forms of HUS warrants a new look at this "old" disease. We performed a retrospective analysis of clinical and laboratory features of three sequential cases of pnHUS since 2008 associated with pneumonia/pleural empyema, two due to Streptococcus pneumoniae serotype 19 A. Profound depletion of complement C3 (and less of C4) was observed in two patients. One patient was Coombs test positive. Her red blood cells (RBCs) strongly agglutinated with blood group compatible donor serum at 0 °C, but not at 37 °C. All three patients were treated with hemodialysis, concentrated RBCs, and platelets. Patient 2 received frozen plasma for hepatic failure with coagulation factor depletion. Intravenous immunoglobulin infusion, intended to neutralize pneumococcal neuraminidase in patient 3, was associated with rapid normalization of platelets and cessation of hemolysis. Two patients recovered without sequelae or disease recurrence. Patient 2 died within 2½ days of admission due to complicating Pseudomonas aeruginosa sepsis and multiorgan failure. Our observations suggest that pnHUS can be associated with dramatic, transient complement consumption early in the course of the disease, probably via the alternative pathway. A critical review of the literature and the reported cases argue against the postulated pathological role of preformed antibodies against the neuraminidase-exposed Thomsen-Friedenreich neoantigen (T antigen) in pnHUS. The improved understanding of complement regulation and bacterial strategies of complement evasion allows to propose a testable, new pathogenetic model of pnHUS. This model shifts emphasis from the action of natural anti-T antibodies toward impaired Complement Factor H (CFH) binding and function on desialylated membranes. Removal of neuraminic acid residues converts (protected) self to non-self surfaces that supports membrane attack complex (MAC) assembly. Complement activation is potentially exacerbated by decreased CFH availability following tight CFH binding to pneumococcal evasion proteins and/or by the presence of genetic variants of complement regulator proteins. Detailed clinical and experimental investigations are warranted to better understand the role of unregulated complement activation in pnHUS. Instead of avoidance of plasma, a new, integrated model is evolving, which may include short-term therapeutic complement blockade, particularly where genetic or functional APC dysregulation is suspected, in addition to bacterial elimination and, potentially, neuraminidase neutralization.
Assuntos
Complemento C3/metabolismo , Teste de Coombs , Síndrome Hemolítico-Urêmica/metabolismo , Pneumonia Pneumocócica/metabolismo , Infecções por Pseudomonas/metabolismo , Pseudomonas aeruginosa/patogenicidade , Empiema Pleural/sangue , Empiema Pleural/complicações , Empiema Pleural/metabolismo , Empiema Pleural/urina , Evolução Fatal , Feminino , Síndrome Hemolítico-Urêmica/sangue , Síndrome Hemolítico-Urêmica/complicações , Síndrome Hemolítico-Urêmica/urina , Humanos , Lactente , Masculino , Plasma/metabolismo , Pneumonia Pneumocócica/sangue , Pneumonia Pneumocócica/complicações , Pneumonia Pneumocócica/urina , Infecções por Pseudomonas/sangue , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/urina , Pseudomonas aeruginosa/isolamento & purificação , Diálise Renal , Estudos Retrospectivos , Sepse/sangue , Sepse/complicações , Sepse/metabolismo , Sepse/microbiologia , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pneumoniae/patogenicidadeRESUMO
We report the penetration of liposomal amphotericin B into the pleural fluid of a patient with pulmonary zygomycosis and empyema. The ratio of area under the concentration-versus-time curve in pleural fluid (AUC(pleural fluid)) to that in serum (AUC(serum)) for liposomal amphotericin B over 24 h was 9.4%, with pleural fluid concentrations of 2.12 to 4.91 microg/ml. Given the relatively low level of intrapleural penetration of liposomal amphotericin B, chest tube drainage may be warranted for successful treatment of zygomycotic empyema.
Assuntos
Anfotericina B/farmacocinética , Antifúngicos/farmacocinética , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/metabolismo , Mucormicose/tratamento farmacológico , Mucormicose/metabolismo , Derrame Pleural/metabolismo , Anfotericina B/administração & dosagem , Anfotericina B/sangue , Antifúngicos/administração & dosagem , Antifúngicos/sangue , Empiema Pleural/tratamento farmacológico , Empiema Pleural/metabolismo , Feminino , Humanos , Lipossomos , Pneumopatias Fúngicas/sangue , Pessoa de Meia-Idade , Mucormicose/sangue , Derrame Pleural/tratamento farmacológicoRESUMO
IL-1ß, HMGB1, HO-1, and LDH in the pleural effusions (PE) of patients with transudative, infectious, and malignant etiologies were determined using ELISA and enzymatic assays. IL-1ß, HMGB1, HO-1, and LDH showed significant differences between the three etiologies. Post-hoc analysis revealed higher levels of HO-1 and HMGB1 in infectious versus transudative effusion. Higher levels of IL-1ß were found in infectious versus transudative or malignant effusion. The comparison of LDH levels showed significant differences. Positive correlations were found between IL-1ß, HMGB1, and LDH in infectious effusions. The samples were then divided into cancerous and non-cancerous groups, and logistic regression revealed that increasing IL-1ß levels were significantly associated with a decrease in cancer risk after adjusting for HMGB1, HO-1, and LDH. Our findings suggest that IL-1ß, HMGB1, HO-1, and LDH are expressed differently, with positive correlations between HMGB1, IL-1ß, and LDH in infectious effusions, and low IL-1ß expression in malignant effusions.
Assuntos
Proteína HMGB1/metabolismo , Heme Oxigenase-1/metabolismo , Infecções/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , L-Lactato Desidrogenase/metabolismo , Derrame Pleural/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Biomarcadores Tumorais/metabolismo , Estudos Transversais , Empiema Pleural/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural Maligno/metabolismoRESUMO
BACKGROUND: The predominance of neutrophils in pleural effusions of patients with different serious impairments of the pleural cavity organs is often found. The aim of this study was to identify the type of injury using the cytological-energy analysis of pleural effusions. METHODS: We analysed 635 samples of pleural effusions with predominance of neutrophils. We compared the values of the coefficient of energy balance (KEB), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) catalytic activities in the following subgroups of patients: with transudative effusions, purulent pneumonia, chest empyema and after chest surgery with and without purulent complications. Statistical analysis was performed using the ANOVA Kruskal-Wallis test (p < 0.05 was considered as significant). RESULTS: We found the lowest KEB values in pleural effusions of patients with chest empyema and their gradual increases in patients with purulent pneumonia and with transudative effusions. We observed the highest LDH and AST enzymes activity in patients with chest empyema and their gradual decrease in patients with purulent pneumonia and with transudative effusions. LDH and AST enzymes activity was significantly higher in pleural effusions of patients after chest surgery with purulent complications compared with non-purulent cases. CONCLUSION: The most intensive inflammation and the most extensive tissue destruction in the pleural cavity were found in patients with chest empyema. Significantly better parameters were observed in patients with purulent pneumonia. The absence of serious inflammation and the absence of tissue destruction were typical for patients with transudative effusions. Finally, our results confirmed an anticipated higher tissue destruction in patients after chest surgery. Significantly worse injury was found in surgical patients with purulent complications compared with non-purulent ones. The reviews of this paper are available via the supplemental material section.
Assuntos
Empiema Pleural/metabolismo , Metabolismo Energético , Neutrófilos/metabolismo , Derrame Pleural/metabolismo , Pneumonia/metabolismo , Complicações Pós-Operatórias/metabolismo , Aspartato Aminotransferases/análise , Biomarcadores/análise , Empiema Pleural/diagnóstico , Empiema Pleural/imunologia , Humanos , L-Lactato Desidrogenase/análise , Neutrófilos/imunologia , Derrame Pleural/diagnóstico , Derrame Pleural/imunologia , Pneumonia/diagnóstico , Pneumonia/imunologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/imunologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Torácicos/efeitos adversosRESUMO
OBJECTIVE: To study the role of fibrinolytic therapy in pediatric empyema in relation to duration of hospital stay, need for surgical intervention and survival to discharge. METHODS: Retrospective analysis of case records of children <16 y of age admitted in a tertiary care hospital during January 2013 - December 2017 with diagnosis as empyema thoracis was done. Clinico-laboratory characteristics and the primary and secondary outcomes between the group which received intrapleural urokinase (IPU) and the group which did not (non IPU), were compared. RESULTS: Of the 84 cases, 40 children received IPU. Mean duration of hospital stay in IPU group (17.51 + 4.57 d) was significantly less than non IPU group (24.32 + 10.18 d, CI -10.19 to -3.64, p < 0.001), so was the duration of intercostal drain (ICD) insertion (9.08 + 3.12 d - IPU group vs. 11.20 + 3.95 d - non IPU group, CI -3.68 to -0.50, p < 0.01). No statistically significant difference was found between the groups with regard to need for surgical intervention [IPU - 4 (10%), non IPU - 9 (20.4%), p = 0.23]. There was no mortality or adverse reaction to urokinase in either group. CONCLUSIONS: IPU holds promising results in terms of reduction of hospital stay and duration of ICD insertion. It may be the initial choice of treatment in septated empyema where surgical options are not easily available or cost-effective especially in resource limited settings.
Assuntos
Empiema Pleural/tratamento farmacológico , Empiema Pleural/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Tubos Torácicos , Criança , Pré-Escolar , Análise Custo-Benefício , Empiema Pleural/mortalidade , Empiema Pleural/cirurgia , Feminino , Hospitalização , Humanos , Tempo de Internação , Masculino , Proteínas de Membrana , Estudos Retrospectivos , ToracotomiaRESUMO
Pleural infection/empyema is common and its incidence continues to rise. Streptococcus pneumoniae is the commonest bacterial cause of empyema in children and among the commonest in adults. The mesothelium represents the first line of defense against invading microorganisms, but mesothelial cell responses to common empyema pathogens, including S. pneumoniae, have seldom been studied. We assessed mesothelial cell viability in vitro following exposure to common empyema pathogens. Clinical isolates of S. pneumoniae from 25 patients with invasive pneumococcal disease and three reference strains were tested. All potently induced death of cultured mesothelial cells (MeT-5A) in a dose- and time-dependent manner (>90% at 107 CFU/mL after 24 hours). No significant mesothelial cell killing was observed when cells were co-cultured with Staphylococcus aureus, Streptococcus sanguinis and Streptococcus milleri group bacteria. S. pneumoniae induced mesothelial cell death via secretory product(s) as cytotoxicity could be: i) reproduced using conditioned media derived from S. pneumoniae and ii) in transwell studies when the bacteria and mesothelial cells were separated. No excess cell death was seen when heat-killed S. pneumoniae were used. Pneumolysin, a cytolytic S. pneumoniae toxin, induced cell death in a time- and dose-dependent manner. S. pneumoniae lacking the pneumolysin gene (D39 ΔPLY strain) failed to kill mesothelial cells compared to wild type (D39) controls, confirming the necessity of pneumolysin in D39-induced mesothelial cell death. However, pneumolysin gene mutation in other S. pneumoniae strains (TIGR4, ST3 and ST23F) only partly abolished their cytotoxic effects, suggesting different strains may induce cell death via different mechanisms.
Assuntos
Células Epiteliais/microbiologia , Células Epiteliais/fisiologia , Pleura/microbiologia , Pleura/patologia , Streptococcus pneumoniae/patogenicidade , Proteínas de Bactérias/farmacologia , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Criança , Empiema Pleural/metabolismo , Empiema Pleural/microbiologia , Empiema Pleural/patologia , Células Epiteliais/patologia , Epitélio/microbiologia , Epitélio/patologia , Epitélio/fisiologia , Humanos , Infecções Pneumocócicas/metabolismo , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/patologia , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pneumoniae/fisiologia , Estreptolisinas/farmacologiaRESUMO
A 43-year-old male had progressive pleuritic left-sided chest tightness with shortness of breath. He had dental caries and tenderness on palpation of the left lateral chest. Complete blood count showed leucocytosis. CT scan of the chest with pulmonary emboli protocol showed multiple pulmonary nodules and nodular pleural thickening at left posterior lateral pleura. Forty-eight hours post CTPE scan, CT scan of the chest, abdomen and pelvis displayed right lower lobe consolidation and left-sided pleural effusion with superimposed compressive atelectasis. Ceftaroline intravenous was initiated, with CT-guided pigtail chest tube insertion. Pleural fluid later grew group F beta-haemolytic Streptococcus anginosus Patient improved significantly and was discharged 11 days later with intravenous ertapenem. Patients with group F beta-haemolytic streptococci should be managed aggressively with early and accurate diagnosis, antibiotics, drainage and possible surgery.
Assuntos
Cefalosporinas/administração & dosagem , Empiema Pleural/metabolismo , Infecções Estreptocócicas/diagnóstico por imagem , Administração Intravenosa , Adulto , Cefalosporinas/uso terapêutico , Tubos Torácicos , Cárie Dentária/complicações , Empiema Pleural/diagnóstico por imagem , Empiema Pleural/terapia , Humanos , Masculino , Infecções Estreptocócicas/terapia , Streptococcus anginosus/isolamento & purificação , CeftarolinaRESUMO
STUDY OBJECTIVES: We investigated pleural fluid penetration of carbapenem antibiotic agents [imipenem (IPM), panipenem (PAPM), meropenem (MEPM), and biapenem (BIPM)] using an experimental rabbit pleuritis model to clarify the usefulness of the carbapenem agents for the treatment of bacterial pleurisy or pyothorax. MEASUREMENTS AND RESULTS: Serum and pleural fluid specimens were serially collected at 5, 10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min after antibiotic administration for measurement of antibiotic levels. We investigated each agent alone as well as drug solutions containing each agent and a dehydropeptidase-I-specific inhibitor, cilastatin (CS), to remove the influence of dehydropeptidase-I-related hydrolysis. Groups of animals (n=3) received each carbapenem agent with or without CS. Serum and pleural fluid antibiotic levels were measured by high-performance liquid chromatography (HPLC). Because Cmax is not useful for evaluating the antimicrobial effects of carbapenem antibiotic agents due to their dose-dependent antimicrobial activity, we also investigated the AUC, which is correlated with the total drug levels in vivo. Among the drug solutions containing CS, MEPM/CS had the highest pleural fluid AUC0-360 (1594.8+/-510.3 microg min/ml), and the highest pleural fluid AUC0-360/plasma AUC0-360 ratio (0.79+/-0.04). BIPM/CS had the highest plasma AUC0-360 (3040.1+/-1525.9 microg min/ml). In pleural fluid AUC0-360/plasma AUC0-360 ratio MEPM/CS was significantly higher than those for the remaining agents. In pleural fluid AUC0-360 and plasma AUC0-360 there were no significant differences among these mixed solutions. CONCLUSIONS: MEPM had the most favorable pleural fluid penetration. Pleural fluid penetration should be examined in infection models and in clinical trials.
Assuntos
Líquidos Corporais/metabolismo , Carbapenêmicos/farmacocinética , Empiema Pleural/tratamento farmacológico , Cavidade Pleural/metabolismo , Pleurisia/tratamento farmacológico , Animais , Área Sob a Curva , Empiema Pleural/metabolismo , Masculino , Pleurisia/metabolismo , CoelhosRESUMO
Analysis of pleural fluid can have, on its own, a high diagnostic value. In addition to thoracocentesis, a diagnostic hypothesis based on medical history, physical examination, blood analysis and imaging tests, the diagnostic effectiveness will significantly increase in order to establish a definite or high probable diagnosis in a substantial number of patients. Differentiating transudates from exudates by the classical Light's criteria helps knowing the pathogenic mechanism resulting in pleural effusion, and it is also useful for differential diagnosis purposes. An increased N-terminal pro-brain natriuretic peptide, both in the fluid and in blood, in a due clinical context, is highly suggestive of heart failure. The presence of an increased inflammatory marker, such as C-reactive protein, together with the presence of over 50% of neutrophils is highly suggestive of parapneumonic pleural effusion. If, in these cases, the pH is<7.20, then the likelihood of complicated pleural effusion is high. There remains to be demonstrated the usefulness of other markers to differentiate complicated from uncomplicated effusions. An adenosine deaminase > 45 U/L and>50% lymphocytes is suggestive of tuberculosis. If a malignant effusion is suspected but the cytological result is negative, increased concentrations of some markers in the pleural fluid can yield high specificity values. Increased levels of mesothelin and fibruline-3 are suggestive of mesothelioma. Immunohistochemical studies can be useful to differentiate reactive mesothelial cells, mesothelioma and metastatic adenocarcinoma. An inadequate use of the information provided by the analysis of pleural fluid would results in a high rate of undiagnosed effusions, which is unacceptable in current clinical practice.
Assuntos
Líquidos Corporais/química , Derrame Pleural/diagnóstico , Toracentese , Adenocarcinoma/química , Adenocarcinoma/secundário , Adenosina Desaminase/análise , Doenças Autoimunes/complicações , Doenças Autoimunes/metabolismo , Biomarcadores , Líquidos Corporais/citologia , Proteína C-Reativa/análise , Diagnóstico Diferencial , Doenças do Sistema Digestório/complicações , Doenças do Sistema Digestório/metabolismo , Empiema Pleural/complicações , Empiema Pleural/metabolismo , Glucose/análise , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Humanos , Concentração de Íons de Hidrogênio , Mediadores da Inflamação/análise , Contagem de Leucócitos , Lipídeos/análise , Linfócitos/enzimologia , Mesotelioma/química , Mesotelioma/secundário , Peptídeos Natriuréticos/análise , Proteínas de Neoplasias/análise , Derrame Pleural/etiologia , Derrame Pleural/metabolismo , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/metabolismo , Pneumonia/complicações , Pneumonia/metabolismo , Tuberculose/complicações , Tuberculose/metabolismoRESUMO
Staphylococcus aureus necrotizing pneumonia is recognized as a toxin-mediated disease, yet the tissue-destructive events remain elusive, partly as a result of lack of mechanistic studies in human lung tissue. In this study, a three-dimensional (3D) tissue model composed of human lung epithelial cells and fibroblasts was used to delineate the role of specific staphylococcal exotoxins in tissue pathology associated with severe pneumonia. To this end, the models were exposed to the mixture of exotoxins produced by S. aureus strains isolated from patients with varying severity of lung infection, namely necrotizing pneumonia or lung empyema, or to purified toxins. The necrotizing pneumonia strains secreted high levels of α-toxin and Panton-Valentine leukocidin (PVL), and triggered high cytotoxicity, inflammation, necrosis and loss of E-cadherin from the lung epithelium. In contrast, the lung empyema strain produced moderate levels of PVL, but negligible amounts of α-toxin, and triggered limited tissue damage. α-toxin had a direct damaging effect on the epithelium, as verified using toxin-deficient mutants and pure α-toxin. Moreover, PVL contributed to pathology through the lysis of neutrophils. A combination of α-toxin and PVL resulted in the most severe epithelial injury. In addition, toxin-induced release of pro-inflammatory mediators from lung tissue models resulted in enhanced neutrophil migration. Using a collection of 31 strains from patients with staphylococcal pneumonia revealed that strains producing high levels of α-toxin and PVL were cytotoxic and associated with fatal outcome. Also, the strains that produced the highest toxin levels induced significantly greater epithelial disruption. Of importance, toxin-mediated lung epithelium destruction could be inhibited by polyspecific intravenous immunoglobulin containing antibodies against α-toxin and PVL. This study introduces a novel model system for study of staphylococcal pneumonia in a human setting. The results reveal that the combination and levels of α-toxin and PVL correlate with tissue pathology and clinical outcome associated with pneumonia.
Assuntos
Toxinas Bacterianas/metabolismo , Empiema Pleural/microbiologia , Células Epiteliais/microbiologia , Exotoxinas/metabolismo , Proteínas Hemolisinas/metabolismo , Leucocidinas/metabolismo , Pulmão/microbiologia , Pneumonia Estafilocócica/microbiologia , Staphylococcus aureus/patogenicidade , Toxinas Bacterianas/imunologia , Linhagem Celular Tumoral , Quimiotaxia , Técnicas de Cocultura , Empiema Pleural/imunologia , Empiema Pleural/metabolismo , Empiema Pleural/patologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Exotoxinas/imunologia , Fibroblastos/metabolismo , Fibroblastos/microbiologia , Fibroblastos/patologia , Proteínas Hemolisinas/imunologia , Humanos , Imunoglobulinas Intravenosas/farmacologia , Fatores Imunológicos/farmacologia , Mediadores da Inflamação/metabolismo , Leucocidinas/imunologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Necrose , Infiltração de Neutrófilos , Pneumonia Estafilocócica/tratamento farmacológico , Pneumonia Estafilocócica/imunologia , Pneumonia Estafilocócica/metabolismo , Pneumonia Estafilocócica/patologia , Staphylococcus aureus/classificação , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/imunologia , Staphylococcus aureus/metabolismo , Fatores de TempoRESUMO
STUDY OBJECTIVE: Carcinoembryonic antigen (CEA) is the most frequently used tumor marker in pleural fluid. Nevertheless, little is known about the causes of false-positive results. The aim of the study was to analyze the frequency, etiologies, and characteristics of the nonmalignant pleural effusions associated with elevated levels of CEA in pleural fluid. PATIENTS: Two hundred seventy-three consecutive patients with pleural effusions were evaluated, 91 (33%) associated with malignancy, and 182 (67%) due to benign diseases (51 transudates, 38 tuberculosis, 37 parapneumonic, 56 other). RESULTS: A level of CEA in pleural fluid above 10 ng/mL was found in 47% of pleural effusions associated with malignancy. Elevated levels of CEA were also found in 17 of the 182 (9%) nonmalignant pleural effusions: all five empyemas, one of the 23 typical parapneumonic (4%), two of the six borderline complicated (33%), and four of the eight complicated parapneumonic effusions (50%), one of the 38 tuberculous pleurisy (3%), one of the 11 hepatic transudates (9%), in the only patient with urinothorax, in the only patient with acute pancreatitis, and in one patient with postsurgery pleural effusion but with esophageal carcinoma and elevated CEA level in serum. CONCLUSIONS: Although an elevated level of CEA in pleural fluid is suggestive of malignancy, CEA can be elevated in 9% of pleurisy owing to benign diseases, especially in empyemas and in complicated parapneumonic effusions. Identifying the most frequent causes of false-positive results of CEA helps to correctly interpret the findings of this tumor marker.
Assuntos
Antígeno Carcinoembrionário/análise , Derrame Pleural/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Empiema Pleural/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/etiologia , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/metabolismo , Sensibilidade e EspecificidadeRESUMO
STUDY OBJECTIVES: We sought to determine whether pleural fluid tumor necrosis factor (TNF)-alpha is a more accurate parameter to identify nonpurulent complicated parapneumonic effusion (CPPE) than the classical chemistries, namely pH, glucose, or lactate dehydrogenase (LDH). METHODS: We studied 80 consecutive patients with parapneumonic effusions (35 with uncomplicated parapneumonic effusion [UPPE], 23 with nonpurulent CPPE, and 22 with empyema). Concentrations of standard biochemical parameters together with TNF-alpha were measured in pleural fluid, the latter by using an immunoenzymometric assay. RESULTS: Pleural TNF-alpha was significantly higher in CPPE (133.0 pg/mL) and empyema (142.2 pg/mL) than in UPPE (39.1 pg/mL). A cut-off value of 80 pg/mL for pleural TNF-alpha resulted in a sensitivity, specificity, and area under receiver operating characteristic curve (AUC) of 78%, 89%, and 0.87, respectively, for the diagnosis of nonpurulent CPPE. A multivariate analysis selected both pleural TNF-alpha > or = 80 pg/mL and LDH > or = 1,000 U/L (sensitivity, 74%; AUC = 0.86), but excluded pleural glucose < or = 60 mg/dL (sensitivity, 39%; AUC = 0.82) and pH < or = 7.20 (sensitivity, 41%; AUC = 0.78), for identifying the need for drainage. The combined sensitivity of pleural fluid TNF-alpha and LDH was found to be 91%. CONCLUSIONS: Pleural TNF-alpha may contribute to the identification of patients with nonpurulent CPPE with at least the same diagnostic accuracy, if not better, than the use of pH, glucose, or LDH.
Assuntos
Derrame Pleural/química , Pneumonia Bacteriana/complicações , Fator de Necrose Tumoral alfa/análise , Adulto , Idoso , Biomarcadores/análise , Tubos Torácicos , Drenagem , Empiema Pleural/metabolismo , Feminino , Glucose/análise , Humanos , L-Lactato Desidrogenase/análise , Masculino , Pessoa de Meia-Idade , Paracentese , Derrame Pleural/etiologia , Pneumonia Bacteriana/terapia , Curva ROC , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Defensins, also known as human neutrophil peptides, are antimicrobial peptides present in the azurophil granules of neutrophils. We measured their level in pleural effusion in various pulmonary diseases to investigate whether they could be used as a diagnostic marker in the differential diagnosis of specific pleural diseases. PATIENTS AND PARTICIPANTS: We analyzed pleural effusion samples collected from 61 patients, including 50 exudates (11 with empyema, 3 parapneumonic, 15 tuberculous, 18 neoplastic, 3 miscellaneous) and 11 transudates as controls. MEASUREMENTS: Defensins were measured by radioimmunoassay and also analyzed by reverse-phase high-performance liquid chromatography. The concentrations of interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF) in pleural effusion fluid were measured by enzyme-linked immunosorbent assay to examine the correlation between these cytokines and defensins. RESULTS: The concentration of defensins in all samples of empyema was >5,100 ng/mL and the mean concentration (13,265.8+/-1,895.2 ng/mL) in these samples was the highest among other groups. The concentration in the other 50 pleural effusion samples tested was <2,800 ng/mL. Defensins were mostly of the mature type in empyema. Pleural effusion levels of IL-8 and G-CSF in patients with empyema were also significantly higher than those in other samples. There was a significant correlation between defensins and IL-8 or G-CSF in pleural effusion fluid (r=0.762, and 0.827, respectively). CONCLUSIONS: Our results suggest that the high effusion concentrations of defensins in pleural effusion may constitute an important component of the host defense system or may have a cytotoxic role in empyema. Our results also indicate that the high levels of IL-8 and G-CSF in empyema may indirectly explain the elevated levels of defensins by increasing the number of neutrophils in the pleural space.
Assuntos
Proteínas Sanguíneas/análise , Empiema Pleural/metabolismo , Derrame Pleural/química , Biomarcadores/análise , Cromatografia Líquida de Alta Pressão , Defensinas , Diagnóstico Diferencial , Empiema Pleural/complicações , Empiema Pleural/diagnóstico , Empiema Tuberculoso/diagnóstico , Empiema Tuberculoso/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Fator Estimulador de Colônias de Granulócitos/análise , Humanos , Interleucina-8/análise , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Derrame Pleural/etiologia , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/metabolismo , Pneumonia/complicações , RadioimunoensaioRESUMO
OBJECTIVE: To determine the degree to which bioactive penicillin, metronidazole, ceftriaxone, clindamycin, vancomycin, and gentamicin penetrate into empyemic pleural fluid using our new rabbit model of empyema. METHODS: An empyema was created via the intrapleural injection of 10(8)()Pasteurella multocida bacteria into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracentesis and pleural fluid analysis, penicillin, 24,000 U/kg; metronidazole, 37 mg/kg; ceftriaxone, 30 mg/kg; clindamycin, 9 mg/kg; vancomycin, 15 mg/kg; or gentamicin, 1 mg/kg, were administered IV. Antibiotic levels in samples of pleural fluid and serum, collected serially for up to 480 min, were then determined using a bioassay. RESULTS: The degree to which the different antibiotics penetrated into the infected pleural space was highly variable. Penicillin penetrated most easily, followed by metronidazole, ceftriaxone, clindamycin, vancomycin, and gentamicin. Of the antibiotics tested, penicillin and metronidazole equilibrated the most rapidly with the infected pleural fluid. Penicillin levels remained elevated in pleural fluid even after serum levels had decreased. CONCLUSIONS: Using this rabbit model of empyema, there was marked variation in the penetration of antibiotics into the empyemic fluid. Although there are species differences between rabbit and human pleura, the variance in degree of penetration of antibiotics into the pleural space should be considered when antibiotics are selected for the treatment of patients with empyema.
Assuntos
Antibacterianos/farmacocinética , Empiema Pleural/metabolismo , Infecções por Pasteurella/metabolismo , Pasteurella multocida , Animais , Antibacterianos/administração & dosagem , Disponibilidade Biológica , Ceftriaxona/administração & dosagem , Ceftriaxona/farmacocinética , Clindamicina/administração & dosagem , Clindamicina/farmacocinética , Modelos Animais de Doenças , Empiema Pleural/tratamento farmacológico , Gentamicinas/administração & dosagem , Gentamicinas/farmacocinética , Humanos , Infusões Intravenosas , Metronidazol/administração & dosagem , Metronidazol/farmacocinética , Infecções por Pasteurella/tratamento farmacológico , Penicilinas/administração & dosagem , Penicilinas/farmacocinética , Coelhos , Vancomicina/administração & dosagem , Vancomicina/farmacocinéticaRESUMO
STUDY OBJECTIVES: To measure interleukin-1 beta (IL-1 beta) levels in pleural effusions of different etiologies and their relationship with several pleural inflammatory parameters, and to verify whether IL-1 beta can be used as diagnostic marker in the differential diagnosis of pleural diseases. MATERIAL AND METHOD: One hundred two pleural effusions were analyzed using a monoclonal antibody enzyme-linked immunosorbent assay. Pleural fluids were classified as follows: transudates (n = 28), empyema (n = 14), parapneumonic (n = 13), tuberculous (n = 19), neoplastic (n = 17), and miscellaneous effusions (n = 11). RESULTS: IL-1 beta was above 200 pg/mL in all the patients with empyema but only in three patients with other etiologies. Two of those three had parapneumonic effusions and the remaining one had a tuberculous pleurisy with a previous bacterial empyema. No significant relationships were found between pleural effusion IL-1 beta levels and the different inflammatory parameters analyzed. As a diagnostic criterion for empyema, pleural IL-1 beta concentration greater than 200 pg/mL had a sensitivity of 100%, a specificity of 96%, and a positive and negative predictive value of 0.82 and 1, respectively. CONCLUSIONS: Our data suggest that IL-1 beta has a significant role in pyogenic infections of the pleural space but not in effusions of other etiologies. It could be used as a diagnostic marker of empyema.
Assuntos
Empiema Pleural/metabolismo , Empiema Tuberculoso/metabolismo , Mediadores da Inflamação/análise , Interleucina-1/análise , Derrame Pleural Maligno/química , Derrame Pleural/química , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Criança , Pré-Escolar , Diagnóstico Diferencial , Empiema Pleural/diagnóstico , Empiema Pleural/etiologia , Empiema Tuberculoso/diagnóstico , Empiema Tuberculoso/etiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/diagnóstico , Derrame Pleural/etiologia , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/etiologia , Estatísticas não ParamétricasRESUMO
Prior attempts to create an animal model of empyema by direct inoculation of bacteria alone into the pleural space have been unsuccessful. The animals either died of overwhelming sepsis or cleared the infection from the pleural space without development of an empyema. We hypothesized that injection of bacteria with a nutrient agar into the pleural space would allow the bacteria to remain in the pleural space for an extended time period, permitting an empyema to develop. The bacterium Pasteurella multocida in brain heart infusion (BHI) agar was injected into the right hemithorax of 12 New Zealand white male rabbits. Our preliminary studies showed that the animals died in less than 7 days if they were not given parenteral antibiotics. For this reason, the rabbits were given penicillin, 200,000 U, IM, every 24 h starting 24 h after bacterial injection. Pleural fluid was sampled by thoracentesis at 12, 24, 48, 72, and 96 h after bacterial injection. Pleural fluid pH, glucose, lactate dehydrogenase (LDH), leukocyte count, and Gram's stain and culture (in one half of the animals) were obtained at each time point. Pleural biopsy specimens were obtained at autopsy after 96 h. The mean pleural fluid pH reached a nadir of 7.01 at 24 h and remained less than 7.1 throughout the experiment. The mean pleural fluid glucose level reached a nadir of 10 mg/dL at 24 h. The mean pleural fluid LDH peaked at 21,000 IU/L at 24 h and the mean pleural fluid leukocyte count peaked at 12 h with a value of 67,000 cells per cubic millimeter. Gram's stains revealed organisms and cultures were positive for growth in all animals at 12 and 24 h. Some animals had positive Gram's stains and growth on cultures up to 72 h after bacterial injection. At autopsy, all rabbits injected with bacteria had gross pus in the right pleural space and had developed a thick pleural peel. Microscopic specimens of the pleura revealed large numbers of leukocytes (primarily polymorphonuclear lymphocytes) with invasion of the adjacent lung and chest wall. In conclusion, this model more closely mimics the empyema that occurs in humans, relative to previous animal models. This model appears appropriate for additional randomized studies in which different methods for the treatment of empyema can be evaluated.
Assuntos
Modelos Animais de Doenças , Empiema Pleural/metabolismo , Infecções por Pasteurella/metabolismo , Pasteurella multocida , Derrame Pleural/química , Ágar , Animais , Biópsia , Meios de Cultura , Empiema Pleural/enzimologia , Empiema Pleural/microbiologia , Empiema Pleural/patologia , Glucose/análise , Concentração de Íons de Hidrogênio , Injeções Intramusculares , L-Lactato Desidrogenase/análise , Contagem de Leucócitos , Pulmão/microbiologia , Pulmão/patologia , Masculino , Neutrófilos/patologia , Infecções por Pasteurella/enzimologia , Infecções por Pasteurella/patologia , Pasteurella multocida/isolamento & purificação , Penicilinas/administração & dosagem , Penicilinas/uso terapêutico , Pleura/microbiologia , Pleura/patologia , Derrame Pleural/enzimologia , Derrame Pleural/microbiologia , Derrame Pleural/patologia , Coelhos , Tórax/microbiologia , Tórax/patologiaRESUMO
BACKGROUND: The roles of different drainage procedures in the management of empyema have to be redefined now that video-assisted thoracoscopic surgery (VATS) has been introduced. The debridement of fibrinopurulent stage II empyema with the use of VATS was assessed prospectively in regard to control of infection and restoration of pulmonary function. METHODS: Between January 1992 and May 1996, all patients at our institution with fibrinopurulent empyema that did not respond to chest tube drainage and antibiotic therapy were treated by debridement with the use of VATS. The patients were followed up prospectively by clinical and radiologic assessments 3 and 6 months after the operation and by spirometry 6 months after the operation. RESULTS: Video-assisted thoracoscopic surgery was initiated in 67 patients, but conversion to open decortication was required because of the finding of advanced disease in 19 patients (28%). Forty-eight patients underwent successful debridement with the use of VATS. The mean operative time was 82.1 minutes (range, 50 to 135 minutes), the mean duration of postoperative chest tube placement was 4.1 days (range, 2 to 8 days), and the mean duration of postoperative hospitalization was 12.3 days (range, 4 to 42 days). No wound infections were observed during the postoperative course. Both the 30-day mortality rate and the recurrence (ie, need for thoracotomy) rate were 4%. The mean predicted vital capacity was 84.8% +/- 14.9% and the mean predicted forced expiratory volume in 1 second was 88.6% +/- 19.2% 6 months after the operation. CONCLUSIONS: Debridement with the use of VATS is safe and efficient for stage II empyema, but open decortication should be used for more advanced disease.
Assuntos
Empiema Pleural/cirurgia , Endoscopia/métodos , Procedimentos Cirúrgicos Torácicos/métodos , Toracoscopia , Gravação em Vídeo , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Desbridamento , Empiema Pleural/metabolismo , Empiema Pleural/mortalidade , Fibrina/metabolismo , Volume Expiratório Forçado , Humanos , Lactente , Pessoa de Meia-Idade , Pleura/metabolismo , Estudos Prospectivos , Recidiva , Taxa de Sobrevida , Capacidade VitalRESUMO
Pyothorax-associated lymphoma (PAL) develops decades after receiving artificial pneumothorax for pulmonary tuberculosis. The lymphomas, develop in tissue affected by long-standing severe inflammatory process. Most cases demonstrate diffuse large B-cell lymphoma. We present a patient with T-cell phenotype-positive and B-cell phenotype-negative (CD7+, CD43+, CD19-, and CD20-) PAL. Southern blot hybridization using immunglobulin heavy chain J region (IgH) gene probe revealed a monoclonal rearrangement, and hybridization using T-cell receptor beta chain (TCR) gene probe revealed a germline configuration. This indicates that the tumor origin was of B-lymphocytes. Chromosomal abnormality of the lymphoma was complicated. It suggested that many transformations occurred. In the transformation process, probably B-cell antigens were lost, and T-cell antigens were aberrantly expressed.
Assuntos
Antígenos CD19/biossíntese , Antígenos CD7/biossíntese , Antígenos CD , Linfócitos B/metabolismo , Empiema Pleural/metabolismo , Herpesvirus Humano 4/metabolismo , Linfoma/virologia , Idoso , Anticorpos Monoclonais/metabolismo , Antígenos CD20/biossíntese , Biomarcadores Tumorais , Southern Blotting , Aberrações Cromossômicas , Humanos , Imunoglobulinas/metabolismo , Leucossialina , Ativação Linfocitária , Masculino , Hibridização de Ácido Nucleico , Fenótipo , Sialoglicoproteínas/biossíntese , Linfócitos T/metabolismoRESUMO
SETTING: Several reports have shown that tuberculous infection elicits a Th1-like immune response with increased levels of IFN-gamma. Recently, expression of CD26 on CD4+ lymphocytes has been shown to correlate with the production of Th1-like cytokines. We therefore hypothesized that CD26 expression might increase in tuberculous pleural effusion, and might thus be a possible marker for detecting tuberculous pleurisy. OBJECTIVE AND DESIGN: To test this hypothesis, we measured soluble CD26 levels in the serum and pleural fluid of patients with tuberculous pleurisy (TB; n = 13), carcinomatous pleurisy (CA, n = 17), empyema (EM, n = 6), and congestive heart failure (HF, n = 10). RESULTS: The pleural CD26 levels, but not the serum CD26 levels, in patients with tuberculous pleurisy were significantly higher than those in other groups, and were correlated with levels of adenosine deaminase and interferon-gamma in the tuberculous pleural effusion. Furthermore, when the cut-off value for p-CD26 was set at 544.5 ng/ml, the positive rate for the TB group was significantly higher than that for the CA, EM and HF groups (P < 0.05). CONCLUSION: These results suggest that elevation of soluble CD26 in pleural fluid is implicated in Th1-like immune response, and may be a useful marker for tuberculous pleurisy.