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The composition of normal pericardial fluid and its implications for diagnosing pericardial effusions.

BACKGROUND: Pericardial fluid obtained at pericardiocentesis is often subjected to biochemical and hematological analysis, and interpreted using criteria borrowed from pleural effusions. However, the validity and diagnostic yield of this approach is uncertain. Moreover, there is little data regarding the normal composition of the physiological pericardial fluid, which could serve as a reference for pathological effusions. METHODS: Pericardial fluid from 30 patients undergoing elective open heart surgery was collected. Patients were excluded if they had known pericardial disease, had systemic disorders known to be associated with pericardial disease, or if the fluid samples were hemolytic. The biochemical and hematological parameters of the fluid were determined using standard laboratory techniques, and compared with the results obtained for concurrently drawn venous blood. RESULTS: The median age of the study population was 64.5 +/- 10.6 years. Chemistry results of soluble molecules were consistent with the plasma ultrafiltrate nature of the fluid. However, fluid lactate dehydrogenase (LDH) level was unexpectedly high, averaging 2.4 times the serum level, and the mean protein level was 0.6 of the serum level. No correlation was found between comorbidities of patients and fluid characteristics. Fluids contained an average of 1430 leukocytes/muL, with a differential count that was predominated by lymphocytes (53.2 +/- 14%) and monocytes (11.6 +/- 6%). CONCLUSIONS: The composition of the physiologic pericardial fluid is remarkable for high LDH and protein content, and for predominance of lymphocytes. Thus, the biochemical criteria useful for diagnosing pleural effusions are probably not applicable for differentiating transudative from exudative pericardial effusions, and lymphocytosis should be interpreted cautiously.

Aged↗

Emergency department presentation of an unusual pleural effusion.

Pleural effusion as a manifestation of malignancy is commonly encountered in clinical practice; most are transudates or exudates of endogenous body fluids. We report a case of pleural effusion that is directly related to the inadvertent infusion of chemotherapeutic agents into the hemithorax of a patient with ovarian carcinoma. With the increasingly common use of outpatient intravenous therapy, emergency department presentations of unusual pleural effusions should be considered.

Aged↗

Collection and evaluation of equine peritoneal and pleural effusions.

This article discusses collection, slide preparation, culture technique, fluid analysis and evaluation, and cytologic evaluation of peritoneal and pleural effusions. The morphologic characteristics of various effusions are described, and the physical characteristics (volume, color, turbidity) of effusions are discussed. An algorithm for classifying effusions as transudates, modified transudates, or exudates is included, and each category is discussed.

Animals↗

[Thoraxsonography--Part 1: Chest wall and pleura].

The detection of lymph nodes and a careful interpretation of dignity is one of the main indications for chest wall sonography. Palpable unclear masses of the chest wall can undergo US guided puctures very easily. Either rib and sternum fractures are detectable very sensitively. In addition to the more sensitive detection than in normal X-ray also accompanying soft parts processes, pleural effusions and haematomas can be visualised. Despite the physical laws of ultrasound, approximately 70% of the pleural surface can be accessed by sonography. The normal parietal pleural can be visualized and delineated from circumscribed as well as diffuse pathological thickening. The normal visceral pleura is hidden by the total reflection at the surface of the aerated lung. Sonographic evidence of a pleural effusion can be obtained from 5 ml onwards and is much more sensitive than a chest X-ray, especially in supine position; false positive findings are not encountered. A more accurate estimation of the quantity of effusion can be made. Exudates are echogenic in one third of cases. Pleural thickening, nodular changes in the pleura, septa, and the formation of the quality of effusion can be made. Exual exudates, whereas transudates are always anechoic. Pleural metastases are characteristically hypoechoic and nodular-polypoid. Pleural mesotheliomas can be delineated nearly equally well on sonograms and on computed tomography. Morphological and, in particular, functional diagnosis of the diaphragm by means of sonography is both reliable and convincing.

Diagnosis, Differential↗

Expression of integrins in human cultured mesothelial cells: the roles in cell-to-extracellular matrix adhesion and inhibition by RGD-containing peptide.

Integrins play key roles in cell-to-cell and cell-to-extracellular matrix (ECM) adhesion. We investigated integrin expression on pleural mesothelial cells (PMCs) and the inhibitory effect of arginine-glycine-asparate (RGD)-containing peptide on the adhesion of PMCs to fibronectin and collagen. Using flow cytometry and immunostaining, PMCs freshly isolated from pleural effusions and one mesothelial cell line were screened for different integrins. Intact pleural tissue was evaluated by immunohistochemistry. The adhesion of Met-5A cells to fibronectin and collagen types I, III and IV was assayed with prior treatment of various concentrations of glycine-arginine-glycine aspartate-serine (GRGDS). On primary PMCs, alpha2, alpha3, alpha5, beta1, beta3 and alphavbeta3 were highly expressed (>70%); alpha1 expression was intermediate (30-70%); and alpha4 and alpha6 expressions were low (< 30%). On Met-SA cells, alpha3, alpha5, alpha6 and beta1 were highly expressed (>70%); alpha1 was intermediate (30-70%); and alpha2, alpha4, beta3 and alphavbeta3 were low (<30%). The patterns of immunostaining on pleural tissues were similar to the results of flow cytometry for primary PMCs except for beta3. There was no statistically different expression in various disease states (transudate vs. exudate, benign vs. malignant). The inhibitory effect of GRGDS peptide on Met-5A cell adhesion to all four matrix proteins was dose-dependent.

Adolescent↗

Use of cytokeratin fragments 19.1 and 19.21 (Cyfra 21-1) in the differentiation of malignant and benign pleural effusions.

BACKGROUND: Differentiation between malignant and benign pleural effusions is often difficult. Serum level of Cyfra 21-1, a marker of cytokeratin 19 fragments, has been used in the diagnosis and monitoring of epithelial tumours, especially bronchogenic carcinomas. AIM: This study is designed to establish the usefulness of effusion Cyfra 21-1 level in differentiating malignant from benign effusions. METHODS: Forty-eight malignant effusion aspirates (proven by cytology or pleural biopsy) and 34 benign samples were compared. Cyfra 21-1 concentration was measured by a solid phase sandwich radioimmunoassay (Centocur, USA). RESULTS: Cyfra 21-1 level was significantly higher in malignant effusions (geometric mean 123.6 ng/mL, 95% confidence interval [CI] 76.6-199.4) than in benign ones (geometric mean 14.3 ng/mL, 95% CI 8.5-23.9), p<0.00005. By Receiver Operating Characteristics curve analysis, the sensitivity is 77% for a specificity of 79% if the cut-off is set at 32 ng/mL. No significant difference was observed (p=0.1) in Cyfra 21-1 concentration between adenocarcinoma and mesothelioma effusions. Cyfra 21-1 level was not influenced by the effusion protein concentration (r=0.29), or by renal function as measured by serum creatinine (r=0.1). There was no significant difference between Cyfra 21-1 levels in benign exudate and transudate effusions, p=0.28. CONCLUSIONS: Cyfra 21-1 is a useful adjunct in the workup of effusions but should not replace conventional investigations as there is considerable overlap in levels between benign and malignant groups. It is unable to differentiate between subgroups of malignancies.

Biomarkers, Tumor↗

Origin of salivary hepatitis B surface antigen.

Low titers of hepatitis B surface antigen (HBsAg) is often found in mixed saliva of antigenemic individuals. In the present study the occurrence of antigen in saliva was correlated to the content of albumin, which is not synthesized by the salivary glands, but represents a leakage into the oral cavity due to hemorrhage, exudation or transudation. The presence of antigen in saliva was also correlated to the titer of antigen in serum.

Albumins↗

Comparison of different tests to diagnose feline infectious peritonitis.

Clinical data from 488 cats (1979-2000) with histopathologically confirmed feline infectious peritonitis (FIP) and 620 comparable controls were evaluated retrospectively to assess the value of several diagnostic tests frequently used in the evaluation of cats with suspected FIP. Diagnostic utility of serum albumin to globulin ratio for the diagnosis of FIP was greater than of the utility of serum total protein and gamma-globulin concentrations. Diagnostic utility of these variables was higher when performed on effusion. On effusion, positive and negative predictive values of Rivalta's test, a test that distinguishes between exudates and transudates (0.86 and 0.97), anti-coronavirus antibody detection (0.90 and 0.79), and immunofluorescence staining of coronavirus antigen in macrophages (1.00 and 0.57) were investigated. The positive and negative predictive values of presence of anti-coronavirus antibodies were 0.44 and 0.90, respectively, antibody concentrations (1:1,600) were 0.94 and 0.88. presence of immune complexes measured by a competitive enzyme-linked immunosorbent assay were 0.67 and 0.84, and detection of viral RNA by serum reverse-transcriptase polymerase chain reaction (RT-PCR) were 0.90 and 0.47. Effusion RT-PCR was performed in 6 cats; it was positive in all 5 cats with FIP and negative in the cat with another disease. Diagnostic assays on the fluid in cats with body effusion had good predictive values. Definitive diagnosis of FIP on the basis of measurement of various variables in serum was not possible. Serum tests can only be used to facilitate the decision for more invasive diagnostic methods.

Animals↗

Polymorphonuclear neutrophil leucocytes of peritoneal fluid.

Cells in the peritoneal fluid from 179 horses were examined in Giemsa stained preparations using light microscopy. Neutrophils were found in all samples whether transudative or exudative although their proportions varied enormously. They were well preserved in "normal" or sterile effusions and hardly differed morphologically from those seen on a peripheral blood film although hypersegmentation was commonly observed. In purulent effusions a reliable correlation was found between degenerative changes in neutrophils such as karyolysis and karyorrhexsis and the presence of toxin-producing microorganisms. On most occasions these degenerative changes enabled a confident judgement to be made as to whether the likelihood of a bacterial aetiology did or did not exist even in the absence of demonstrable microorganisms.

Animals↗

C-reactive protein in lymphocytic pleural effusions: a diagnostic aid in tuberculous pleuritis.

BACKGROUND: C-reactive protein (CRP) pleural fluid levels have been found to be higher in tuberculosis and parapneumonic effusions than in other causes of pleural effusion. OBJECTIVE: The aim of this study was to analyze whether CRP (a simple and inexpensive test) may be a diagnostic aid for tuberculosis in lymphocytic pleural effusions. METHODS: One hundred and forty-four patients with a lymphocytic pleural effusion (more than 50% lymphocytes in the differential white blood cell count) were included. The patients were 93 men (65%) and 51 women (35%), aged 64 +/- 18 years (mean +/- SD). The diagnoses were as follows: tuberculosis, 20; pleural effusion associated with malignancy, 69; transudates, 38; other benign exudates, 17. RESULTS: The CRP pleural fluid level was higher in tuberculous pleuritis (54 +/- 24 mg/l) than in lymphocytic effusions of other origin (21 +/- 16 mg/l; p < 0.001). High CRP levels (>or=50 mg/l) have a high specificity for tuberculosis (95%), and low levels (<30 mg/l) have a high sensitivity (95%) for excluding disease. CONCLUSIONS: CRP pleural fluid level determination is useful in the diagnostic workup of lymphocytic pleural effusions. High CRP levels are very suggestive of tuberculous pleuritis, and low CRP levels make this diagnosis unlikely.

Aged↗

Decreased heat-labile opsonic activity and complement levels associated with evidence of C3 breakdown products in infected pleural effusions.

Heat-labile opsonic activity was measured simultaneously in serum and pleural fluid of patients with transudates, infectious exudates (with positive or negative bacterial culture) and neoplastic exudates, using two different complement-dependent phagocytic tests: the killing of Staphylococcus aureus Wood 46 variant strain (K50 opsonic titers) and the assessment of ingestion rate of endotoxin-coated paraffin particles (Oil Red 0 uptake test). K50 opsonic titers were lower in culture-positive pleural effusions as compared to culture-negative (P < 0.002) or neoplastic effusions (P < 0.002). These results were corroborated by the Oil Red 0 uptake test. The data obtained with the two assays showed a significant correlation (P < 0.001). The hemolytic activity of complement (CH50) as well as the levels of C3 breakdown product, C3d, were measured in the same sera and pleural fluid samples and in an additional group of patients with pleural effusions of the same etiology. Effusions with positive cultures showed lower CH50 values (P < 0.01) and higher C3d values (P < 0.05) when compared to culture-negative pleural fluids. Finally, evidence for immune complexes in pleural effusions and sera was looked for by determination of Clq binding activity. Levels were higher in culture-positive effusions when compared to culture-negative fluids (P = 0.005).K50 opsonic titers showed a positive correlation with CH50 values (P < 0.001) for all fluids tested. Similarly Clq binding activity correlated with C3d levels in effusions of infectious origin (P = 0.05). Recovery experiments using the various bacterial species isolated from culture-positive pleural effusions showed evidence of complement inactivation upon incubation with pooled sera at concentrations of 10(7)-10(8) microorganisms/ml. These results indicate that one important reason for bacterial persistence in empyema may be decreased opsonization secondary to local consumption of complement.

Adult↗

Physiology and pathophysiology of pleural fluid turnover.

Tight control of the volume and composition of the pleural liquid is necessary to ensure an efficient mechanical coupling between lung and chest wall. Liquid enters the pleural space through the parietal pleura down a net filtering pressure gradient. Liquid removal is provided by an absorptive pressure gradient through the visceral pleura, by lymphatic drainage through the stomas of the parietal pleura, and by cellular mechanisms. Indeed, contrary to what was believed in the past, pleural mesothelial cells are metabolically active, and possess the cellular features for active transport of solutes, including vesicular transport of protein. Furthermore, the mesothelium was shown, on the basis of recent experimental evidence, both in vivo and in vitro, to be a less permeable barrier than previously believed, being provided with permeability characteristics similar to those of the microvascular endothelium. Direct assessment of the relative contribution of the different mechanisms of pleural fluid removal is difficult, due to the difficulty in measuring the relevant parameters in the appropriate areas, and to the fragility of the mesothelium. The role of the visceral pleura in pleural fluid removal under physiological conditions is supported by a number of findings and considerations. Further evidence indicates that direct lymphatic drainage through the stomas of the parietal pleura is crucial in removing particles and cells, and important in removing protein from the pleural space, but should not be the main effector of fluid removal. Its importance, however, increases markedly in the presence of increased intrapleural liquid loads. Removal of protein and liquid by transcytosis, although likely on the basis of morphological findings and suggested by recent indirect experimental evidence, still needs to be directly proven to occur in the pleura. When pleural liquid volume increases, an imbalance occurs in the forces involved in turnover, which favours fluid removal. In case of a primary abnormality of one ore more of the mechanisms of pleural liquid turnover, a pleural effusion ensues. The factors responsible for pleural effusion may be subdivided into three main categories: those changing transpleural pressure balance, those impairing lymphatic drainage, and those producing increases in mesothelial and capillary endothelial permeability. Except in the first case, pleural fluid protein concentration increases above normal: this feature underlies the classification of pleural effusions into transudative and exudative.

Humans↗

Commentary on the British Thoracic Society guidelines for the investigation of unilateral pleural effusion in adults.

The publication of guidelines for the investigation of unilateral pleural effusion in adults by the British Thoracic Society has focused attention on this subject which, although comprising only a small proportion of laboratory workload, is a fairly common clinical problem. We critically reviewed the guidance applicable to clinical biochemistry laboratories and found a number of deficiencies. In particular, the need for anaerobic sample collection for pH measurement and preservation of samples for glucose assay is not mentioned and health and safety issues related to the handling of potentially infected fluids are also not considered. There are discrepancies between recommendations in the text and in the accompanying diagnostic algorithm, which require clarification. Measurement of total protein is an essential first step in the analysis of pleural fluid and will usually distinguish transudates from exudates. Measurement of lactate dehydrogenase activity is only required when total protein results are equivocal. There are practical difficulties with measurement of fluid pH as recommended in the guidelines and there is little evidence that such measurements are valuable. Similarly, there is little evidence to support the recommendation for measurement of complement in suspected rheumatoid effusions, and the recommendation for amylase isoenzyme studies if acute pancreatitis is a possibility is not practical. The different nature of pleural fluid demands a good understanding of the handling of these samples, the limitations of the analytical methods and the subsequent result interpretation by laboratory staff. We propose a modified diagnostic algorithm reflecting our criticisms of the original. Dialogue between the laboratory and local clinicians, possibly with the production of local guidelines, informed by these recommendations, should help optimize diagnostic management of patients with pleural effusion.

Adult↗

Human pleural effusions are rich in matrix metalloproteinases.

We identified and characterized type IV collagenase and gelatinase activity in pleural fluid from 32 patients. The capacity to substantially degrade type IV collagen was demonstrated in every pleural sample. Comparable results were also noted for the degradation of a radiolabeled gelatin substrate. Gelatin gel zymography of the pleural fluids revealed two prominent zones of lysis at 66 kDa and 92 kDa. These were identified by specific polyclonal antibodies as human matrix metalloproteinases MMP-2 and MMP-9. The concentration of MMP-2 in pleural fluid, as measured by enzyme-linked immunoassay, averaged 1,622 ng/ml whereas those of MMP-9 were 210 ng/ml. Substrate degradation activity was compared in both serum and pleural fluid from three patients and found to be similar. In serum this enzymatic activity was primarily due to MMP-9 whereas in pleural fluid, the predominant gelatinase was MMP-2. This was confirmed by immunoassay that showed that MMP-2 levels were two to five times higher in pleural fluid than in serum. We conclude that substantial amounts of MMP-2 and, to a lesser degree, MMP-9 are present in pleural effusions. The bioactivity and the immunoactivity of these enzymes did not help to distinguish among pleural fluids characterized as transudates, nonmalignant exudates, or malignant exudates. The differences in the distribution of these enzymes in pleural fluid and blood suggest that their presence is not due simply to the ultrafiltration of plasma, but rather to synthesis by the resident cells at the pleural surfaces.

Biomarkers↗

Tetracycline and doxycycline inhibit pleural fluid metalloproteinases. A possible mechanism for chemical pleurodesis.

We hypothesized that inhibition of matrix-degrading metalloproteinases (MMPs) accounts for a portion of the pleural fibrosis and adhesions of tetracycline pleurodesis. MMPs recently have been described in pleural fluid from patients with both exudative and transudative effusions. Since tetracyclines are recognized inhibitors of other metalloproteinases, we investigated their inhibitory capacity in pleural fluid. High concentrations of several different tetracyclines reduced MMP activity of pleural fluid by more than 75 percent. Lower concentrations (< or = 1 mg/ml) had only modest inhibitory effects. High concentration of of tetracyclines also inhibited cell synthesis of MMPs, in vitro, but other measures of vital cell function were also impaired. We conclude that tetracyclines are effective inhibitors of MMP activity in pleural fluid and may also reduce synthesis of MMPs via non specific cell injury. These data suggest a possible mechanism to account for tetracycline pleurodesis; ie, an inhibition of MMP activity in pleural fluid.

Collagenases↗

Etiology of acute pulmonary edema during liver transplantation : a series of cases with analysis of the edema fluid.

STUDY OBJECTIVES: To describe the clinical features of a group of patients who acutely developed pulmonary edema during orthotopic liver transplantation and to determine the nature (transudate vs exudate) of the edema. DESIGN: Retrospective review of clinical records and radiographic studies. SETTING: Operating room and ICU of a tertiary-care medical center hospital. PATIENTS: End-stage liver disease patients undergoing orthotopic liver transplantation under general anesthesia. INTERVENTIONS AND MEASUREMENTS: Pulmonary edema fluid obtained from seven patients within 15 min of first appearance was analyzed for protein content and compared with the protein content of a simultaneously obtained plasma sample. Hemodynamic data, fluid administration totals, and length of postoperative intubation and ICU stay were also collected. RESULTS: Eight patients were identified. Six of the seven patients whose edema fluid was analyzed had edema fluid/plasma protein ratios > or =0.75, characteristic of increased permeability pulmonary edema (the one other patient had a ratio of 0.73). Hemodynamic monitoring at the time of onset of the edema effectively ruled out a cardiogenic etiology. One patient died intraoperatively; at autopsy, the cause of death was determined to be pulmonary fat embolization. In the other seven patients, production of edema fluid resolved within 6 h of admission to the ICU. The duration of ventilatory support ranged from 23 to 96 h, with a mean of 49 h. CONCLUSIONS: The most likely cause of the reaction is transfusion-related acute lung injury (TRALI). An incidence of TRALI that is higher than previously reported in this population indicates that other elements, such as reperfusion of the newly implanted liver, may be contributing factors.

Adult↗

Hypothyroidism and pleural effusions.

Serous effusions have been thought to be an unusual complication of hypothyroidism and most commonly have been associated with ascites, pericardial fluid and heart failure. Pleural fluid as an isolated finding in hypothyroidism is apparently rare and complete analysis of these hypothyroid-associated pleural effusions has not been described. To determine the frequency, chemical characteristics and clinical associations of hypothyroidism and pleural effusions, the medical records of 128 patients with hypothyroidism (defined by an increased serum TSH concentration) were reviewed. The majority of effusions in patients with hypothyroidism were due to other diseases. Effusions solely due to hypothyroidism appeared to be a real entity. These effusions were borderline between exudates and transudates and showed little evidence of inflammation.

Aged↗