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Concentrations of C-reactive protein in effusions in dogs.

The concentration of C-reactive protein (CRP) was measured in effusions from 50 dogs to assess the potential for measuring this protein to differentiate body cavity fluids. The effusions were classified as either transudates, modified transudates or exudates according to their total protein concentration, total nucleated cell count, cytological findings and aetiology, and the concentration of CRP was determined by a time-resolved immunofluorometric assay. There were significant differences between the concentrations of CRP in the three types of effusion; the highest concentrations were observed in the exudates (4.47 to 54.59 microg/ml), the lowest were in the transudates (0.0094 to 7.87 microg/ml), and the modified transudates contained intermediate concentrations of CRP (0.045 to 10.78 microg/ml). A cut-off value of 4 microg/ml had a sensitivity of 100 per cent and a specificity of 94.4 per cent for differentiating transudates from exudates, and a cut-off value of 11 microg/ml had a sensitivity of 88.2 per cent and a specificity of 100 per cent for distinguishing modified transudates from exudates. However, a cut-off value of 1 microg/ml had a lower sensitivity (80 per cent) and an unacceptably low specificity (66.7 per cent) for differentiating transudates from modified transudates.

Animals↗

Pleural diseases.

In the United States, approximately one million patients each year develop a pleural effusion. Pleural effusions have classically been divided into transudative and exudative pleural effusions. A transudative pleural effusion occurs when the systemic factors influencing pleural fluid formation and reabsorption are altered so that pleural fluid accumulates; an exudative pleural effusion occurs when the local factors influencing pleural fluid formation and reabsorption are altered, allowing accumulation of pleural fluid. The leading causes of transudative pleural effusions are left ventricular failure and cirrhosis with ascites. The leading causes of exudative pleural effusions are pneumonia, malignancy, and pulmonary embolization. Transudative pleural effusions can be differentiated from exudative pleural effusions by measurement of the pleural fluid protein and lactic dehydrogenase (LDH) levels. The ratio of the pleural fluid protein to the serum protein is less than 0.5, the ratio of the pleural fluid LDH to the serum LDH is less than 0.6, and the absolute value of the pleural fluid LDH level is less than two thirds of the upper normal limit for serum with transudative pleural effusions while at least one of these criteria is not met with exudative effusions. Most patients who have a pleural effusion with congestive heart failure have left ventricular failure. It is believed that the transudation of the pulmonary interstitial fluid across the visceral pleura overwhelms the capacity of the lymphatics to remove the fluid. Most patients with cirrhosis who have a pleural effusion also have ascites. It is also believed that the pleural effusions form when fluid moves directly from the peritoneal cavity into the pleural cavity through pores in the diaphragm. Approximately 40% of patients with pneumonia will have a pleural effusion. If these patients have a significant amount of pleural fluid, a diagnostic thoracentesis should be performed. Chest tubes should be inserted if the pleural fluid is gross pus, if the Gram stain of the pleural fluid is positive, if the pleural fluid glucose level is below 40 mg/dl, or if the pleural fluid pH level is less than 7.00. If drainage with the chest tubes is unsatisfactory, either streptokinase or urokinase should be injected intrapleurally. If drainage is still unsatisfactory, a decortication should be considered. The three leading malignancies that have an associated pleural effusion are breast carcinoma, lung carcinoma, lymphomas and leukemias. The diagnosis of pleural malignancy is made most commonly with pleural fluid cytology; in recent years immunohistochemical tests have proved invaluable in differentiating benign from malignant pleural effusions.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗

Diagnostic value of cholesterol in pleural effusions.

The separation of pleural effusions into transudates and exudates is the first task the physician must solve in evaluating a pleural effusion for management. Many criteria have been established, but without a definite efficacy of any of them. Cholesterol is an easy, effective, relatively cheap determination to differentiate transudates from exudates. In our prospective study of 40 patients, cholesterol best separated transudates from exudates. A pleural fluid cholesterol value of 60 mg/dl or above has sensitivity, specificity, PPV, NPV and efficacy of 100%, 93%, 96%, 92%, and 95.5% respectively. Pleural fluid to serum cholesterol ratio of 0.3 or higher has sensitivity, specificity, PPV, NPV and efficacy of 96%, 93%, 96%, 92%, and 95% respectively. P. CHOL and P/S CHOL ratio has a misclassification rate of 2.5% each. When both were combined all cases are clearly separated into transudates and exudates.

Adult↗

Evaluating pleural effusions. How should you go about finding the cause?

Although many pulmonary and systemic diseases are known to cause pleural effusions, analysis of the pleural fluid pinpoints the cause in most cases. Distinguishing pleural transudates from exudates is an important step. Transudate effusions are caused by a small, well-defined group of illnesses (e.g., cirrhosis, congestive heart failure). Exudative effusions, on the other hand, are associated with a wide variety of causes, including pneumonia, malignancy, TB, drug-induced reactions, and many others. Some effusions remain unexplained despite extensive tests. Surgical approaches may be appropriate for some of these patients, but the risks must be carefully weighed against the benefits.

Diagnosis, Differential↗

Significance of pleural fluid cholesterol and beta-2 microglobulin levels for the differentiation of pleural effusions in childhood.

We studied 60 children, ages 3-15 years, with pleural effusions to determine the usefulness of different criteria for the separation of transudates from exudates. Twenty of these effusions were classified as transudates and 40 as exudates. Pleural cholesterol (P chol), pleural/serum cholesterol ratio (P/S chol), and pleural/serum beta 2 microglobulin (P/S beta 2 m) were determined to characterize pleural effusions and were compared with Light's criteria (pleural/serum protein ratio, pleural LDH, pleural/serum LDH ratio). With a threshold of 0.3, the sensitivity and specificity of P/S chol for diagnosis of exudates were 95 and 90%, respectively. With a threshold of 1.3, the sensitivity of P/S beta 2 m was 77.5%, and its specificity was 95%. Our findings indicate that determination of P chol and P/S chol, as well as Light's criteria, is of value for characterizing pleural effusions in childhood, but the measurement of P/S beta 2 m is less sensitive in distinguishing transudates from exudates and it should not be used routinely.

Adolescent↗

Cholesterol in pleural effusions. A diagnostic aid.

In this prospective study of 70 patients with pleural effusion, the underlying disease could be identified in 62 cases. By predefined criteria, 31 of these effusions were classified as transudates and 31 as exudates. Pleural fluid protein content, LDH activity and cholesterol level were measured to investigate their utility in differentiating the exudates from the transudates. Protein and LDH levels, and their pleural fluid-to-serum ratios, resulted in erroneous classification of 11 to 15 percent of the effusions. Mean cholesterol level in malignant effusions was 94 mg/dl, 76 mg/dl in inflammatory effusions and 30 mg/dl in the transudates. Using a dividing line of 60 mg/dl to separate the exudates from the transudates, only 5 percent were incorrectly classified. Elevated cholesterol levels in exudates seem to be independent of the serum levels. Our findings indicate that the pleural fluid cholesterol level is a simple and cost-effective aid in differentiating exudative from transudative pleural effusions.

Cholesterol↗

Influence of diuretics on the concentration of proteins and other components of pleural transudates in patients with heart failure.

PURPOSE: Diuretic therapy increases the total protein and lactate dehydrogenase concentrations in pleural fluid in patients with transudates due to heart failure, but the effect of diuresis on other substances in pleural fluid constituents is not known. SUBJECTS AND METHODS: Twenty-one patients with transudative pleural effusions due to congestive heart failure were prospectively studied. Repeated diagnostic thoracentesis (mean +/- SD = 3 +/- 1; range, 2 to 6) was performed until the effusions were radiographically unapparent (5 +/- 2 days). Thirty-one patients with congestive heart failure who underwent only a single thoracentesis after diuretic therapy served as controls. We measured the concentrations of various components of pleural effusions in the serum and in the pleural fluid, and determined the serum-pleural fluid gradient (serum concentration minus pleural fluid concentration) and ratio (serum concentration divided by pleural fluid concentration). RESULTS: The pleural concentrations of most components increased significantly (P <0.001) from the initial specimen to the final specimen: total protein, from 23 +/- 7 g/L to 33 +/- 9 g/L; albumin, from 13 +/- 4 g/L to 18 +/- 6 g/L; lactate dehydrogenase, from 177 +/- 62 U/L to 288 +/- 90 U/L; cholesterol, from 31 +/- 16 mg/dL to 52 +/- 22 mg/dL; and cholinesterase, from 1,304 +/- 616 U/L to 1,884 +/- 674 U/L. Expressed as percentage change, the increases in the serum-pleural fluid gradients for albumin (12% +/- 22%) and total protein (11% +/- 12%) were significantly less than the increases in their concentrations in pleural fluid (albumin, 47% +/- 49%; total protein, 48% +/- 40%) or in their pleural fluid/serum ratios (albumin, 27% +/- 29%; total protein, 38% +/- 34%). CONCLUSIONS: The concentrations of the biochemical components commonly measured in pleural fluid increase progressively during diuretic therapy. Calculation of the serum-pleural fluid gradients for protein and albumin may be the most useful way to distinguish transudates from exudates in patients with congestive heart failure who have undergone diuresis.

Aged↗

Quantitative analysis of pleural fluid cell-free DNA as a tool for the classification of pleural effusions.

BACKGROUND: Recently, much interest has been focused on the quantification of DNA in miscellaneous body fluids. In this study, the application is extended to classifying pleural effusions by measuring cell-free DNA in pleural fluid. METHODS: We recruited 50 consecutive patients with pleural effusions with informed consent. Pleural fluids were centrifuged at 13000 g, with supernatants aliquoted for extraction and analysis of beta-globin DNA sequence by quantitative real-time PCR. Serum and pleural fluid biochemistries were performed to classify pleural effusions using the modified criteria of Light et al. (Ann Intern Med 1972;77:507-13). The ROC curve was plotted to determine the cutoff DNA concentration for classifying pleural fluids as transudates or exudates. Indicators of diagnostic accuracy were calculated for both pleural fluid DNA and modified criteria of Light et al., using the discharge, microbiologic, and histologic diagnoses as the reference standard. RESULTS: The area under the ROC curve was 0.95 [95% confidence interval (CI), 0.84-0.99]. At 509 genome-equivalents/mL, pleural fluid DNA alone correctly classified 46 of 50 pleural effusions with 91% sensitivity (95% CI, 76-98%), 88% specificity (95% CI, 64-98%), and positive and negative likelihood ratios of 7.7 (95% CI, 3.1-19.5) and 0.10 (95% CI, 0.04-0.27), respectively. With the modified criteria of Light et al., 43 of 50 pleural effusions were correctly classified with 97% sensitivity (95% CI, 91-100%) and 67% specificity (95% CI, 45-89%). There were significant correlations between cell-free DNA and both lactate dehydrogenase and total protein in pleural fluid, suggesting their common origin. CONCLUSIONS: Pleural fluid DNA concentrations are markedly increased in exudative effusions, making it a potential new tool to evaluate the etiologic causes of pleural effusions.

Adolescent↗

The value of cells in the pleural fluid in the differential diagnosis.

Fifty samples of pleural fluid, collected from consecutive patients in a thoracic clinic who had diagnostic thoracentesis, were studied prospectively. Pleural fluid protein was of value in differentiating transudates from exudates. Pleural fluid red cell counts, white blood cell counts, and differential white blood cell counts have no specificity and no usefulness in the differential diagnosis of the origin of the effusion. Pleural fluid cytology was positive in 60% of all the malignancies studied in this series; for the group with metastatic breast carcinoma, there was a 78% positive pleural fluid cytology. Differential white cell counts revealed tumor cells in 45% of malignant effusions. In our experience, the finding of tumor cells is the only useful finding in differential cell counts of the pleural fluid.

Blood Cells↗

Isolated pleural fluid lactic dehydrogenase level: a cost effective way of characterizing pleural effusions.

BACKGROUND: Characterization of pleural effusion into an exudate or transudate is usually the first step in diagnostic evaluation. Light's criteria have been universally accepted as gold standard in this regard. We wanted to see the utility of isolated pleural fluid lactic dehydrogenase level (representing one of Light's classical criteria) in characterizing pleural effusion in our setting. We also wanted to compare the accuracy of commonly used conventional criteria with Light's criteria of isolated pleural fluid lactic dehydrogenase. METHODS: Patients who underwent diagnostic thoracentesis for one-year period were studied. Characterization of pleural effusions using biochemical criteria including pleural fluid protein, lactic dehydrogenase level (LDH), red blood cell (RBC) count and white blood cell (WBC) count were identified and compared with predetermined clinical criteria (gold standard). For each biochemical criteria sensitivity, specificity, positive predictive value and negative predictive value were calculated. RESULTS: Sixty-two patients underwent diagnostic thoracentesis. Sixteen were excluded, as they did not fulfill predetermined clinical criteria. Eight patients had transudative effusion vs. 38 exudates. LDH was found to be the most sensitive (97.2%) while WBC > 1000/mm3 was the most specific (100%) of all the criteria looked at. The overall accuracy was highest for Light's criteria of isolated LDH > 200 IU/litre (95.6%) followed by pleural fluid protein, WBC count and RBC count. CONCLUSION: We conclude that isolated pleural fluid LDH, as a representative of classical Light's criteria, is the most accurate criteria for characterizing pleural effusions. Due to its low accuracy isolated pleural fluid protein should not be ordered routinely. This approach may result into potential cost savings in our economically restraint society.

Clinical Enzyme Tests↗

Diagnostic procedures for pleural disease.

Using a systematic approach based upon findings obtained from the patient's history, physical examination, routine laboratory studies, and chest roentgenograms, the clinician will establish the presence and location of pleural effusion in the majority of cases. The selective use of tests based upon the clinician's initial diagnostic impressions will allow accurate separation of transudative from exudative effusions; exudative effusions will be diagnosed in over 85 per cent of patients. There remain many unanswered questions regarding the diagnosis of pleural effusion. Prospective studies are needed to establish diagnostic algorithms that minimize under- and overutilization of tests. The introduction of Medicare Prospective Reimbursement under Diagnosis-Related Groups (DRGs) on October 1, 1983, may provide the appropriate incentives to hospitals and clinicians to carry out these important studies.

Amylases↗

Transudative ascites with a high protein content. Case reports.

The case reports of 2 patients with constrictive pericarditis and 1 patient with the Budd-Chiari syndrome are used to show that high-protein ascites may occur in the absence of disease of the peritoneum. Protein content should not be the only factor assessed in differentiating between transudative and exudative ascites.

Adult↗

Thoracentesis in clinical practice.

Thoracentesis is a commonly performed procedure indicated for diagnostic and therapeutic purposes. Removal of pleural fluid should be performed by experienced operators and, when attempted by physicians-in-training, close supervision by credentialed individuals is necessary. Diagnostic thoracentesis is most valuable in separating exudates from transudates. Analysis of the exudative fluid has the highest yield when infection and malignancy is likely. Pneumothorax is the most common major complication and can be minimized by the use of small-gauge needles (no. 21 or no. 22) when a small amount of fluid is removed (35 to 50 ml). Patients who may pose difficulties (e.g., those receiving ventilator support) appear to have no greater morbidity with thoracentesis than those patients not ventilator dependent. Ultrasound may be of value to decrease morbidity when small or loculated volumes of fluid are present. Therapeutic thoracentesis offers relief of symptoms of dyspnea, but caution is particularly needed because large needles and large volumes of fluid removed may increase morbidity.

Biopsy↗

Comparison of biochemical parameters in pleural effusion.

A comparison of various biochemical parameters used in differentiation of nature of pleural effusion in transudate and exudate was done in 84 patient of pleural effusion. Pleural fluid (P) cholesterol and bilirubin which have gained an importance in recent years were compared with pleural fluid protein, LDH, P/S protein, P/S LDH and Light's criteria. It was seen that Light's criteria is still the best in differentiation. Sensitivity of individual test was nearly same for Pl. protein (94.11%), P/S Protein (94.11%), Pl. LDH (95.5%), P/S LDH (92.75%). Pl cholesterol (88.3%) and P/S cholesterol (91.42%) had slightly lower sensitivity. Pl. Protein and P/S LDH had 100% specificity. Lights criteria had 100% specificity and sensitivity % of cases misclassified by various criteria were Pl Protein 5.95%, P/S protein 5.95%, PLDH 4.76%, P/S LDH 4.76% P. Cholesterol 13% and P/S Cholesterol 9.52% Measurement of Bilirubin did not provide any correlation in classifying the effusion and thus did not hold any value.

Bilirubin↗

Multilevel likelihood ratios for identifying exudative pleural effusions(*).

STUDY OBJECTIVES: To determine multilevel likelihood ratios for pleural fluid tests that are commonly used to discriminate between exudative and transudative pleural effusions. DESIGN: Meta-analysis of patient-level data. PATIENT DATA: Selected studies included patients with diagnoses of exudative or transudative pleural effusions who underwent thoracentesis and laboratory analysis of their pleural fluid. MEASUREMENTS AND METHODS: Studies were identified by searching MEDLINE and related bibliographies. Data were obtained for 1,448 patients from seven primary investigators or extracted from dot plots in published reports. Likelihood ratios were calculated from extracted data stratified across ranges of test result values. RESULTS: Sufficient data were available to calculate multilevel likelihood ratios for the elements of Light's criteria (pleural fluid lactate dehydrogenase [LDH], ratio of pleural fluid to serum LDH, and ratio of pleural fluid to serum protein), pleural fluid protein, ratio of pleural fluid to serum cholesterol, pleural fluid cholesterol, and gradient of pleural fluid to serum albumin. Each of these tests provided levels of likelihood ratios through the most clinically relevant range (0 to 10). CONCLUSION: Multilevel likelihood ratios combined with a clinician's estimation of the pretest probability of an exudative effusion improve the diagnostic accuracy of discriminating between exudative and transudative pleural effusions. Likelihood ratios avoid the use of confusing terms, such as "pseudoexudates," that derive from the use of single cutoff points for pleural fluid tests.

Diagnosis, Differential↗

Use of acute phase proteins in pleural effusion discrimination.

The differentiation between exudates and transudates is fundamental when investigating the cause of pleural effusions. Acute-phase proteins could be potentially useful markers in this discrimination. In the attempt to define diagnostic criteria for the differentiation of pleural exudates from transudates, we measured alpha 1 acid glycoprotein, C-reactive protein, haptoglobin, ceruloplasmin and transferrin in pleural effusions and serum in patients with pleural effusions of various etiologoies. We measured the concentrations of the above proteins in the serum and pleural fluid of 80 (54 exudate, 26 transudate) consecutive patients by immunoturbidometrical methods. Pleural effusion acute phase proteins were elevated in the patients with exudate compared to patients with transudate (p< 0.001 for all). In receiver operator characteristic analysis showed that pleural fluid ceruloplasmin levels and the ratio pleural fluid/serum transferrin were superior to the others. Using the optimum cut-off point of 0.16 g/L pleural fluid ceruloplasmin achieves a sensitivity of 92% with a specificity of 85%. In addition to, the optimum cut-off point for pleural fluid/serum transferrin ratio was 0.4 with sensitivity and specificity of 92% and 80%. When using together these parameters sensitivity and specificity were increased (95%, 85%). In differential diagnosis, none of these proteins were significantly different in subgroups of pleural exudate. We conclude that when using together ceruloplasmin levels in pleural fluid and the ratio of pleural to serum transferrin have a high sensitivity and specificity in discrimination of exudative pleural effusions.

Acute-Phase Proteins↗

[Alpha 1-antitrypsin in the blood and pleural effusion fluid].

Alpha-1 antitrypsin levels were determined in 27 pleural effusion liquids classified as transudates and exudates in accordance with the clinical and laboratory data, and in their respective blood samples. Absolute values proved insufficient to distinguish transudates from exudates, though they were capable of signifying and replacing the relative protein value. The relation between liquid: serum alpha-1 AT ratio and the liquid: serum proteins ratio was direct and highly significant. Along with the liquid: serum LAD and liquid: serum proteins ratios, the liquid: serum alpha-1 AT ratio enables transudates and exudates to be differentiated with certainty.

Adult↗