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1.  Pleural effusion: An unusual cause and association 
Filaria has a wide spectrum of presentation. We hereby present a case of Filarial pleural effusion that is a rarity in itself. Filarial lung involvement is usually in the form of tropical pulmonary eosinophilia with pulmonary infiltrates and peripheral eosinophilia, unlike our case where isolated pleural effusion of Filarial etiology was detected. Microfilaria has been isolated from Pleural fluid in very few cases, and ours was one such. Of late, there have been many incidental detections of Filarial parasites from varied anatomical sites in association with malignancy. Even in our case, we had one such unusual association.
PMCID: PMC3669559  PMID: 23741100
Filariasis; malignancy; pleural effusion
2.  Bancroftian filarial pleural effusion. 
Postgraduate Medical Journal  1993;69(817):869-870.
This paper describes a case of filarial pleural effusion, the fifth such to be reported. Microfilariae of Wuchereria bancrofti were detected in the pleural fluid on cytological examination. There was a prompt and complete response to treatment with diethylcarbamazine. There were, however, no symptoms and signs of tropical pulmonary eosinophilia nor any peripheral eosinophilia.
PMCID: PMC2399909  PMID: 8290434
3.  Pneumothorax, pneumomediastinum and subcutaneous emphysema following closed percutaneous pleural biopsy: a case report 
Cases Journal  2008;1:274.
Minimally invasive investigations, such as pleural fluid cytological assessment and closed percutaneous pleural biopsy, are often performed first in the investigation of suspected malignant pleural effusions. Malignant pleural effusions can be diagnosed with pleural fluid cytology alone in most cases; however, closed pleural biopsy is performed to increase the diagnostic yield when pleural fluid cytology is negative. This additional yield is at the expense of increased complication rates. We report a 64-year old man with a negative pleural fluid cytology but suspected malignant pleural effusion who underwent a closed pleural biopsy, which was complicated by pneumothorax, pneumomediastinum and severe subcutaneous emphysema. Pulmonary laceration by the pleural biopsy needle is the most likely aetiology of these complications. Our case report highlights an infrequent but significant complication of closed percutaneous pleural biopsy.
PMCID: PMC2584077  PMID: 18950521
4.  Pleural fluid ferritin concentrations in human disease. 
Journal of Clinical Pathology  1985;38(7):818-824.
The concentration of ferritin was measured in the pleural fluid of 108 patients with pleural effusions. In all groups of patients the ferritin concentration was higher in pleural fluid than in serum. The greatest differences, with up to 100 times more ferritin in the pleural fluid, were found for patients with rheumatoid pleurisy, malignant effusions, and empyema. In patients with non-malignant inflammatory pleural effusions the concentration of ferritin in pleural fluid correlated significantly with other pleural fluid indices of inflammation: there was a positive correlation with lactate dehydrogenase activity and a negative correlation with concentrations of glucose and complement components C3 and C4. Ferritin was detected immunocytochemically only in the macrophages found among the pleural fluid cells. Our study shows that large amounts of ferritin accumulate locally in the pleural cavity in certain types of pleural inflammation. The accumulation is probably partly the result of increased local reticuloendothelial system activity. Determination of the concentration of ferritin in pleural fluid may provide corroborative information for differential diagnosis and may further our understanding of the pathogenetic events that lead to the perpetuation of inflammatory activity in pleural effusions.
PMCID: PMC499311  PMID: 4019803
5.  Role of pleural biopsy in etiological diagnosis of pleural effusion 
Pleural effusion remains the most common manifestation of pleural pathology. Sometimes it is difficult to differentiate between tubercular and malignant pleural effusion in spite of routine biochemical and cytological examination of pleural fluid.
This study aims to evaluate the role of pleural biopsy to determine the etiology of pleural effusion and to correlate it with the biochemical and cytological parameters of pleural fluid.
Settings and Design:
Seventy two consecutive patients of pleural effusion were selected from the out patient and indoor department of a tertiary hospital of Kolkata. It was a prospective and observational study conducted over a period of one year.
Materials and Methods:
Biochemical, cytological and microbiological evaluation of pleural fluid was done in all cases. Those with exudative pleural effusions underwent pleural biopsy by Abram’s needle. Subsequently, the etiology of effusion was determined.
Malignancy was the most common etiology, followed by tuberculosis. Pleural biopsy was done in 72 patients. Pleural tissue was obtained in 62 cases. Malignancy was diagnosed in 24, tuberculosis in 20 and non-specific inflammation in 18, on histopathological examination. Out of 20 histological proven tuberculosis cases adenosine de-aminase (ADA) was more than 70 u/l in 11 cases.
In our study, malignancy is more common than tuberculosis, particularly in elderly. When thoracoscope is not available, pleural fluid cytology and pleural biopsy can give definite diagnosis. Pleural fluid ADA ≥ 70 u/l is almost diagnostic of tuberculosis, where pleural biopsy is not recommended.
PMCID: PMC2988168  PMID: 21139714
Malignancy; pleural biopsy; pleural effusion; tuberculosis
6.  Pleural Fluid Cholesterol in Differentiating Exudative and Transudative Pleural Effusion 
Pulmonary Medicine  2013;2013:135036.
Objectives. To study the diagnostic value of pleural fluid cholesterol in differentiating transudative and exudative pleural effusion. To compare pleural fluid cholesterol level for exudates with Light's criteria. Design. Cross sectional descriptive study. Settings. Medical wards of Tribhuvan University Teaching Hospital. Methods. Sixty two cases of pleural effusion with definite clinical diagnosis admitted in TUTH were taken and classified as transudates (19) and exudates (43). The parameters pleural fluid protein/serum protein ratio (pfP/sP), pleural fluid LDH/ serum LDH ratio, pleural fluid LDH (pfLDH) and pleural fluid cholesterol (pCHOL) were compared with clinical diagnosis with regard to their usefulness for distinguishing between pleural exudates and transudates. Results. The pCHOL values determined were 1.92 ± 0.75 for exudates, 0.53 ± 0.28 for transudates, the differences between the transudates and others are statistically significant (P < 0.0001). It is seen that pfP/sP ratio has a sensitivity of 81.4% and specificity of 82.6%; pfLDH/sLDH ratio has a sensitivity of 86% and specificity of 94.7% and pCHOL with sensitivity of 97.7% and specificity of 100% for differentiating exudative and transudative PE. Conclusion. The determination of pCHOL is of great value for distinguishing between pleural exudates and transudates and should be included in routine laboratory analysis of pleural effusion.
PMCID: PMC3556870  PMID: 23365740
7.  Diagnostic value of ex vivo pleural fluid interferon-gamma versus adapted whole-blood quantiferon-TB gold in tube assays in tuberculous pleural effusion 
Annals of Thoracic Medicine  2012;7(4):220-225.
Noninvasive diagnosis of pleural tuberculosis (TB) remains a challenge due to the paucibacillary nature of the disease. As Mycobacterium tuberculosis (MTB)-specific T cells are recruited into pleural space in TB effusion; their indirect detection may provide useful clinical information.
Evaluation of pleural fluid interferon (INF)-γ levels vs Quantiferon–TB Gold In tube assay (QFT- IT) in blood and its adapted variants, using pleural fluid or isolated pleural fluid cells in the diagnosis of pleural TB.
Thirty-eight patients with pleural effusion of unknown etiology presented at Assiut University Hospital, Egypt, were recruited. Blood and pleural fluid were collected at presentation for INF-γ assays. Ex vivo pleural fluid INF-γ levels, QFT-IT in blood and its adapted variants were compared with final diagnosis as confirmed by other tools including blind and/or thoracoscopic pleural biopsy.
The final clinical diagnosis was TB in 20 (53%), malignancy in 10 (26%), and effusion due to other causes in eight patients (21%). Ex vivo pleural fluid INF-γ levels accurately identified TB in all patients and were superior to the QFT-IT assays using blood or pleural fluid (70 and 78% sensitivity, with 60 and 83% specificity, respectively). QFT-IT assay applied to isolated pleural fluid cells had 100% sensitivity and 72% specificity. The optimal cut-off obtained with ROC analysis was 0.73 for TB Gold assay in blood assay, 0.82 IU/ml for the cultured pleural fluid assay, and 0.94 for isolated pleural cells assay.
The ex vivo pleural fluid INF-γ level is an accurate marker for the diagnosis of pleural TB. QFT- IT assay in peripheral blood or its adapted versions of the assay using pleural fluid and/or washed pleural fluid cells had no diagnostic advantage over pleural fluid INF-γ in the diagnosis of pleural TB.
PMCID: PMC3506102  PMID: 23189099
Diagnosis; interferon-γ; interferon-γ release assays; quantiferon–TB gold in tube assay; tuberculous effusion
8.  Assessment of the N-PCR Assay in Diagnosis of Pleural Tuberculosis: Detection of M.tuberculosis in Pleural Fluid and Sputum Collected in Tandem 
PLoS ONE  2010;5(4):e10220.
The nonspecific clinical presentation and paucibacillary nature of tuberculous pleuritis remains a challenge for diagnosis. Diagnosis of tuberculous pleural effusion depends on the demonstration of the presence of tubercle bacilli in the sputum, pleural fluid, or pleural biopsy specimen, or demonstration of granuloma in pleura by histological examination. We examined the clinical utility of the diagnosis of pleural tuberculosis using the in house N-PCR assay, AFB smear microscopy and culture. Besides pleural fluid the inclusion of sputum in the efficacy of diagnosis of pleural tuberculosis was scrutinized.
Methodology/Principal Findings
Pleural fluid and sputum samples of 58 tuberculous and 42 non-tuberculous pleural effusion patients were processed for AFB smear microscopy, culture and the N-PCR assay. Mycobacteria were detected exclusively in tuberculous pleural effusion samples. None of the non-tuberculous pleural effusion samples were positive for mycobacteria. Comparative analysis showed that the N-PCR assay had the highest sensitivity. Inclusion of sputum along with pleural fluid increased N-PCR sensitivity from 51.7 to 70.6% (p<0.0001).This improved sensitivity was reflected in AFB smear microscopy and isolation by culture. The sensitivity enhanced on inclusion of sputum from 3.4 (p = 0.50) to 10.3% (p = 0.038) for AFB smear microscopy and for isolation of mycobacteria from 10.3(p = 0.03) to 22.4% (p = 0.0005). Thirteen isolates were obtained from 58 pleural tuberculosis patients. Eleven mycobacterial isolates were identified as M.tuberculosis and two as M.fortuitum and M.chelonae. Complete concordance was seen between the biochemical identification of isolates and the N-PCR identification of mycobacterial species prior to isolation.
To the best of our knowledge this is the first PCR based report on utility of sputum for diagnosis of pleural tuberculosis. The present study demonstrates that a combination of pleural fluid with sputum sample and N-PCR improved the diagnosis of pleural tuberculosis.
PMCID: PMC2856669  PMID: 20419090
9.  Closed Pleural Biopsy is Still Useful in the Evaluation of Malignant Pleural Effusion 
Pleural fluid cytology for malignant cells is the easiest way to diagnose malignant pleural effusion with good sensitivity and specificity. With the introduction of medical thoracoscopy, the use of closed pleural biopsy for the diagnosis of cytology negative malignant pleural effusion is gradually decreasing. However use of thoracoscopy is limited due to its high cost and procedure related complications.
The aim was to assess the usefulness of closed pleural biopsy in the diagnosis of malignant pleural effusion.
Materials and Methods:
Sixty-six patients of pleural effusion associated with malignancy were selected from the patients admitted in the chest ward of a tertiary care hospital over a period of 1 year. Pleural fluid aspiration for cytology and closed pleural biopsy were done in all the patients.
Out of 66 patients, 46 (69%) patients showed malignant cells in pleural fluid cytology examination. Cytology was positive in 35 (52%), 10 (15%), and 1 (1.5%) patients in the first, second, and third samples respectively. Closed pleural biopsy was positive in 32 (48%) patients. Among them, 22 also had positive cytology. Additional 10 cytology negative patients were diagnosed by pleural biopsy. Cytology–histology concordance was seen in 12 patients. Definite histological diagnosis could be achieved in five patients with indeterminate cytology. Pleural biopsy was not associated with any major postoperative complication.
Closed pleural biopsy can improve the diagnostic ability in cytology negative malignant pleural effusion. Closed pleural biopsy has still a place in evaluation of malignant pleural effusion especially in a resource-limited country like India.
PMCID: PMC3425262  PMID: 22923920
Closed pleural biopsy; malignant pleural effusion; pleural fluid cytology
10.  Neurone-specific enolase levels in pleural effusions in patients with rheumatoid arthritis. 
Thorax  1996;51(1):92-94.
BACKGROUND: High pleural fluid levels of neurone-specific enolase (NSE) have been reported, not only in patients with small cell lung cancer but also in those with chronic inflammatory diseases. METHODS: NSE concentrations were determined in pleural fluid and serum from 342 patients with pleural effusions including 17 with rheumatoid arthritis. RESULTS: The median NSE concentration in pleural fluid was higher in rheumatoid effusions than in any other condition studied. The median pleural fluid:serum NSE ratio was highest in patients with rheumatoid arthritis (11.6) and about unity in all other diseases including small cell lung cancer (0.9). In patients with rheumatoid arthritis pleural fluid concentrations of NSE correlated inversely with pleural fluid glucose concentrations and the pH of the pleural fluid. CONCLUSIONS: A high pleural fluid:serum NSE ratio was found consistently in pleural effusions from patients with rheumatoid disease.
PMCID: PMC472809  PMID: 8658380
11.  Chlamydia trachomatis in hydrocele fluid. 
Genitourinary Medicine  1997;73(6):503-505.
OBJECTIVE: To determine the presence of Chlamydia trachomatis in hydrocele fluid. METHODS: 90 male patients with hydrocele of tunica vaginalis from an endemic area for bancroftian filariasis were investigated for the presence of Chlamydia trachomatis in their hydrocele fluids. C trachomatis antigen detection tests-a direct immunofluorescence assay and an enzyme immunoassay along with polymerase chain reaction assay for amplification of a 517 bp fragment of C trachomatis endogenous plasmid-were used in this study. The patients were also tested for the presence of microfilaria in their hydrocele fluids and night blood. Histopathological examination was carried out to detect adult filarial worm in tunica vaginalis testes. RESULTS: Eight (8.88%) patients had chlamydia antigen in the hydrocele fluids; C trachomatis plasmid sequences could be amplified from five of these. Seven (7.77%) patients had microfilaria in the hydrocele fluids, three of them having adult worm in tunica vaginalis. CONCLUSION: C trachomatis infection might be associated with hydrocele in some of these patients.
PMCID: PMC1195934  PMID: 9582470
12.  Alkaline phosphatase: Distinguishing between tuberculous and nontuberculous pleural effusion 
To evaluate the value of pleural fluid alkaline phosphatase and pleural fluid/serum alkaline phosphatase ratio for the purpose of differentiating tuberculous from nontuberculous pleural effusion.
Materials and Methods:
A total of 60 indoor patients, admitted to our hospital, having pleural effusion and suffering from varying etiologies, were included in this study. According to the final diagnosis, these 60 patients were divided into two groups: Tuberculous (30) and nontuberculous (30) pleural effusion.
The mean pleural alkaline phosphatase and pleural fluid/serum alkaline phosphatase ratio was significantly higher in tuberculous compared to nontuberculous pleural effusion. (P < 0.0001). In receiver operating characteristic curve analysis, sensitivity and specificity values were 90% and 80% for a cut-off value of 71 IU/L for pleural alkaline phosphatase activity; and were 90% and 86.66% for a cut-off value of 0.51 for pleural fluid/serum alkaline phosphatase ratio.
From this study it is concluded that alkaline phosphatase activity remains a useful test in differentiation of tuberculous from nontuberculous pleural effusion.
PMCID: PMC2862511  PMID: 20442841
Alkaline phosphatase; differentiation; pleural effusion; tuberculosis
13.  Tumor necrosis factor alpha and high sensitivity C-reactive protein in diagnosis of exudative pleural effusion 
Differentiation between exudative and transudative pleural effusions is the initial step in assessment of pleural effusion. The aim of this study was to determine whether high sensitivity C-reactive protein (hsCRP) and tumor necrosis factor α (TNFα) are diagnostic utilities for exudative pleural effusion.
This experimental study assessed 79 patients with pleural effusion who underwent diagnostic evaluations at Imam Reza hospital, Mashhad, Iran in 2009-2010. The complete biochemical analysis of pleural fluid, pleural fluid culture, and pathological examination of pleural fluid and tissue were performed. Moreover, hsCRP and TNFα concentrations were measured in pleural fluid samples. The data was analyzed by student's t-test and Mann-Whitney test.
According to Light's criteria, 50 patients (63.30%) had exudative effusions while 29 subjects (36.70%) had transudative effusion. The pleural fluid concentrations of hsCRP and TNFα were significantly higher in the exudative group than the transudative group (p < 0.05). At a cutoff value of 5 mg/L for hsCRP, the results showed 94% sensitivity and 96.6% specificity. Regarding TNFα, a cutoff value of 12.9 ng/dl represented 96% sensitivity and 93% specificity.
HsCRP and TNFα levels may be considered as beneficial diagnostic factors for detecting exudative effusion in patients with pleural effusion.
PMCID: PMC3430056  PMID: 22973340
Pleural Effusion; Exudative; Transudative; HsCRP; TNFα
14.  C1q enhancement of antibody-dependent granulocyte-mediated killing of nonphagocytosable targets in vitro. 
Journal of Clinical Investigation  1988;82(3):945-949.
A possible role for C1q in antibody-dependent granulocyte-mediated killing of nonphagocytosable targets was investigated utilizing IgG-dependent granulocyte cytotoxicity directed against microfilariae of Dirofilaria immitis. Granulocyte-mediated killing of microfilariae is enhanced by addition of fresh serum. Lack of C4 did not significantly reduce the observed increase in cytotoxicity. The addition of highly purified monomeric human Clq (0.2 microgram/ml) in the presence of immune IgG resulted in a two- to fivefold enhancement of killing (P less than 0.025). C1q enhancement of killing occurred in the absence of fluid-phase IgG, but killing was significantly less than when both fluid-phase IgG and C1q were present. The effect of C1q was inhibited by the addition of solubilized type I collagen (44-92% inhibition of killing, P less than 0.05). Significant 125I-Clq binding to microfilariae occurred only in the presence of immune IgG. In addition, C1q in concentrations ranging from 0.5 to 2.0 micrograms/ml resulted in a dose-dependent increase in binding of 125I-immune IgG to microfilariae. Finally, when purified C1q was added to preopsonized, washed microfilariae, granulocyte production of superoxide was increased from 0.25 +/- 0.07 to 0.68 +/- 0.07 nm/10(6) cells.10 min (P less than 0.01). These results describe a novel functional role for C1q in enhancement of antibody-dependent cellular cytotoxicity towards nonphagocytosable targets.
PMCID: PMC303606  PMID: 2843577
15.  Cell Origins and Diagnostic Accuracy of Interleukin 27 in Pleural Effusions 
PLoS ONE  2012;7(7):e40450.
The objective of the present study was to investigate the presence of interleukin (IL)-27 in pleural effusions and to evaluate the diagnostic significance of pleural IL-27. The concentrations of IL-27 were determined in pleural fluids and sera from 68 patients with tuberculous pleural effusion, 63 malignant pleural effusion, 22 infectious pleural effusion, and 21 transudative pleural effusion. Flow cytometry was used to identify which pleural cell types expressed IL-27. It was found that the concentrations of pleural IL-27 in tuberculous group were significantly higher than those in malignant, infectious, and transudative groups, respectively. Pleural CD4+ T cells, CD8+ T cells, NK cells, NKT cells, B cells, monocytes, macrophages, and mesothelial cells might be the cell sources for IL-27. IL-27 levels could be used for diagnostic purpose for tuberculous pleural effusion, with the cut off value of 1,007 ng/L, IL-27 had a sensitivity of 92.7% and specificity of 99.1% for differential diagnosing tuberculous pleural effusion from non-tuberculous pleural effusions. Therefore, compared to non-tuberculous pleural effusions, IL-27 appeared to be increased in tuberculous pleural effusion. IL-27 in pleural fluid is a sensitive and specific biomarker for the differential diagnosing tuberculous pleural effusion from pleural effusions with the other causes.
PMCID: PMC3392223  PMID: 22792330
16.  Myelomatous effusion with poor response to chemotherapy. 
Journal of Korean Medical Science  2000;15(2):243-246.
While pleural effusion in multiple myeloma is relatively infrequent, myelomatous pleural effusion is extremely rare. We experienced a 61-year-old woman with IgD-lambda multiple myeloma and pleural effusion. The diagnosis was made originally by pleural biopsy, pleural fluid cytology and immunoelectropheresis of pleural fluid. Transient improvement of the pleural effusion was observed after administration of combination chemotherapy of vincristine, melphalan, cyclophosphamide, prednisone (VMCP)/vincristine, cyclophosphamide, adriamycin, prednisone (VCAP). Two months later, myelomatous pleural effusion recurred and no response to salvage therapy was observed. We reviewed the clinical feature of this case and literature concerning myelomatous pleural effusion.
PMCID: PMC3054621  PMID: 10803706
17.  Evaluation of real-time PCR of patient pleural effusion for diagnosis of tuberculosis 
BMC Research Notes  2011;4:279.
Pleural tuberculosis (TB) diagnosis often requires invasive procedures such as pleural biopsy. The aim of this study was to evaluate the role of real-time polymerase chain reaction (PCR) for the IS6110 sequence of M. tuberculosis in pleural fluid specimens as a rapid and non-invasive test for pleural TB diagnosis.
For this cross-sectional study, 150 consecutive patients with pleural effusion diagnosed by chest radiography, who were referred for diagnostic thoracocentesis and pleural biopsy and met eligibility criteria, had a pleural fluid specimen submitted for real-time PCR testing. Overall, 98 patients had pleural TB and 52 had pleural effusion secondary to other disease. TB diagnosis was obtained using acid-fast bacilli (AFB) smear or culture for mycobacteria and/or histopathologic examination in 94 cases and by clinical findings in 4 cases. Sensitivity, specificity, positive and negative predictive values of PCR testing for pleural TB diagnosis were 42.8% (95% CI 38.4 - 44.8), 94.2% (95% CI 85.8 - 98.0), 93.3% (95% CI 83.6 - 97.7), and 48.5% (95% CI 44.2 - 50.4), respectively. The real-time PCR test improved TB detection from 30.6% to 42.9% when compared to AFB smear and culture methods performed on pleural fluid specimens, although the best sensitivity was achieved by combining the results of culture and histopathology of pleural tissue specimens.
The real-time PCR test of pleural fluid specimens is a useful and non-invasive additional assay for fast diagnosis of pleural TB.
PMCID: PMC3224496  PMID: 21819571
18.  The clinical utility of pleural YKL-40 levels in diagnosing pleural effusions 
Journal of Thoracic Disease  2013;5(5):634-640.
Background and objective
Recent evidence suggests that YKL-40 is a relatively new biomarker of inflammation and it is involved in the pathogenesis of several pulmonary diseases. Details of serum and pleural YKL-40 in pleural effusions however, remain unknown. We aimed to assess whether serum and pleural YKL-40 is an accurate biomarker of pleural effusions.
This clinical study was prospective, observational and cross-sectional. The concentrations of serum and pleural fluid YKL-40 and conventional pleural marker levels were measured in 80 subjects with pleural effusions, including 23 transudates caused by congestive heart failure (CHF), and 57 exudates including 23 parapneumonic, 22 malignant and 12 tuberculous pleural effusions (TBPEs).
Median pleural fluid YKL-40 levels were higher in exudates than in transudates (219.4 and 205.9 ng/mL, respectively, P<0.001). High pleural YKL-40 levels, with a cutoff value of >215 ng/mL, yielded a 73% sensitivity, 73% specificity, likelihood ratio 2.8 for diagnosing exudate, with an area under the curve of 0.770 [95% confidence intervals (CI): 0.657-0.884]. Pleural YKL-40/serum YKL-40 ratio >1.5 yielded a 75% sensitivity, 72% specificity and likelihood ratio 2.6 for diagnosing TBPE, with an area under the curve of 0.825 (95% CI: 0.710-0.940).
High concentrations of pleural YKL-40 level may help to differentiate exudate from transudate and a high pleural YKL-40/serum YKL-40 ratio may be helpful in seperating TBPE from non-tuberculous effusions.
PMCID: PMC3815719  PMID: 24255777
Exudate; pleural effusion; transudate; tuberculosis; YKL-40
19.  Pleural fluid cell-free DNA integrity index to identify cytologically negative malignant pleural effusions including mesotheliomas 
BMC Cancer  2012;12:428.
The diagnosis of malignant pleural effusions (MPE) is often clinically challenging, especially if the cytology is negative for malignancy. DNA integrity index has been reported to be a marker of malignancy. The aim of this study was to evaluate the utility of pleural fluid DNA integrity index in the diagnosis of MPE.
We studied 75 pleural fluid and matched serum samples from consecutive subjects. Pleural fluid and serum ALU DNA repeats [115bp, 247bp and 247bp/115bp ratio (DNA integrity index)] were assessed by real-time quantitative PCR. Pleural fluid and serum mesothelin levels were quantified using ELISA.
Based on clinico-pathological evaluation, 52 subjects had MPE (including 16 mesotheliomas) and 23 had benign effusions. Pleural fluid DNA integrity index was higher in MPE compared with benign effusions (1.2 vs. 0.8; p<0.001). Cytology had a sensitivity of 55% in diagnosing MPE. If cytology and pleural fluid DNA integrity index were considered together, they exhibited 81% sensitivity and 87% specificity in distinguishing benign and malignant effusions. In cytology-negative pleural effusions (35 MPE and 28 benign effusions), elevated pleural fluid DNA integrity index had an 81% positive predictive value in detecting MPEs. In the detection of mesothelioma, at a specificity of 90%, pleural fluid DNA integrity index had similar sensitivity to pleural fluid and serum mesothelin (75% each respectively).
Pleural fluid DNA integrity index is a promising diagnostic biomarker for identification of MPEs, including mesothelioma. This biomarker may be particularly useful in cases of MPE where pleural aspirate cytology is negative, and could guide the decision to undertake more invasive definitive testing. A prospective validation study is being undertaken to validate our findings and test the clinical utility of this biomarker for altering clinical practice.
PMCID: PMC3495778  PMID: 23009708
Malignant pleural effusions; Mesothelioma; Lung cancer; DNA integrity index; Mesothelin
20.  Factors affecting pleural fluid adenosine deaminase level and the implication on the diagnosis of tuberculous pleural effusion: a retrospective cohort study 
BMC Infectious Diseases  2013;13:546.
Adenosine deaminase (ADA) is useful in the diagnosis of tuberculous pleural effusion (TPE). This study aims to determine the factors affecting pleural fluid ADA levels and to establish the optimal ADA levels for diagnosis of TPE for different age groups.
This was a retrospective study from January 2007 to October 2011. One hundred and sixty patients who had pleural fluid ADA performed for investigation of pleural effusion were analyzed. Variables examined included demographics, pleural fluid characteristics and peripheral blood counts. The ADA cut-offs according to age were selected using the receiver operating characteristic (ROC) curve.
The mean pleural fluid ADA was significantly higher in the TPE group (100 ± 35 IU/L) compared to non TPE patients (30 ± 37 IU/L). There was significant correlation between pleural fluid ADA and age, pleural fluid protein, LDH, and fluid absolute lymphocyte count. The strongest correlation was seen with age (r = −0.621). For patients ≤ 55 years old the ROC for ADA had area under curve (AUC) of 0.887. A pleural fluid ADA of 72 IU/L had sensitivity of 95.1%, specificity of 87.5%, positive predictive value (PPV) of 95.1% and negative predictive value (NPV) of 87.5% for the diagnosis of TPE. For patients > 55 years old the AUC is 0.959. ADA of 26 IU/L had a sensitivity of 94.7%, specificity of 80.4%, PPV of 62% and NPV of 97.8%.
There is a significant negative correlation between pleural fluid ADA and age. For older patients, a lower ADA cut-off should be used to exclude TPE.
PMCID: PMC3835552  PMID: 24238276
Adenosine deaminase; Tuberculosis; Pleural effusion; Biological markers
21.  Interferon gamma for diagnosing tuberculous pleural effusions 
Thorax  1999;54(10):921-924.
BACKGROUND—A study was undertaken to evaluate the diagnostic value of pleural fluid concentrations of interferon gamma (IFN-γ) as a marker of tuberculosis.
METHODS—Patients admitted to King Chulalongkorn Memorial Hospital between April 1997 and January 1998 with a lymphocytic exudative pleural effusion were enrolled into the study. The pleural fluids were examined for cytology, staining for acid fast bacilli, and mycobacterial culture. Pathological examination and mycobacterial culture were performed on each pleural biopsy specimen. The diagnosis of tuberculosis was made when one of the following criteria was met: (1) Mycobacterium tuberculosis was isolated from either the pleural fluid or pleural tissue; (2) granulomas were demonstrated in the pleural tissue which stained positive for acid fast bacilli (AFB); or (3) in the presence of granulomas negative on staining for AFB in pleural tissue there was a response to antituberculous treatment on follow up. All pleural fluid samples were stored at -70°C and the IFN-γ level was measured by immunoassay. Analysis was made using sensitivity, specificity, and likelihood ratio for a positive test result. The best cut off point was determined by the highest likelihood ratio and receiver operating characteristic curve.
RESULTS—A total of 66 patients were enrolled and tuberculosis was confirmed in 39 of them. The diagnoses in the non-tuberculous group included malignancy (15), paramalignancy (11), and chronic pleuritis secondary to infective endocarditis (1). The mean (SE) IFN-γ level in the pleural fluid was significantly higher in the tuberculous group than in the non-tuberculous group (1493.3 (131.3) pg/ml versus 80.1 (50.4) pg/ml, p<0.001). The overlap between the two groups was minimal. At the cut off value of 240 pg/ml the sensitivity was 94.9% (95% CI 86.6 to 100), the specificity was 96.3% (95% CI 89.2 to 100), and the likelihood ratio for a positive test result was 25.6.
CONCLUSIONS—The pleural fluid concentration of IFN-γ is a good and useful diagnostic marker of tuberculosis presenting as a lymphocytic exudative pleural effusion.

PMCID: PMC1745364  PMID: 10491456
22.  Interferon-Gamma Release Assay Performance of Pleural Fluid and Peripheral Blood in Pleural Tuberculosis 
PLoS ONE  2013;8(12):e83857.
The diagnosis of pleural tuberculosis (TB) remains to be difficult. Interferon-gamma release assay (IGRA) is a promising method for diagnosing TB in low TB burden countries. The release of interferon-gamma (IFN-γ) by T lymphocytes increases at a localized site of infection with Mycobacterium tuberculosis antigen. This study aimed to examine the clinical accuracy of T-SPOT.TB on pleural fluid and peripheral blood for the diagnosis of pleural TB in high TB burden country.
168 subjects with pleural effusion were enrolled prospectively and examined with T-SPOT.TB on pleural fluid and peripheral blood samples simultaneously.
The receiver operating characteristic (ROC) curve and cut-off value of pleural fluid T-SPOT.TB was established according to spot forming cells (SFC) between culture/biopsy-confirmed pleural TB group and no pleural TB group. The sensitivity of pleural fluid T-SPOT.TB and peripheral blood T-SPOT.TB was similar (96.3% and 92.7%, respectively) (P= 0.691). In contrast, the specificity of pleural fluid T-SPOT.TB (94.5%) was significantly higher than that of peripheral blood T-SPOT.TB (76.1%) (P=0.002). 2% (2/98) of pleural fluid T-SPOT.TB results were indeterminate.
The diagnostic accuracy of peripheral blood T-SPOT.TB is low in high TB burden countries due to latent tuberculosis infection. Pleural fluid T-SPOT.TB is a relatively useful and supplementary test to explore pleural TB in high TB burden countries, but its diagnostic accuracy needs to be validated in further large scale research.
PMCID: PMC3873962  PMID: 24386296
23.  A possible case of spontaneous Loa loa encephalopathy associated with a glomerulopathy 
Filaria Journal  2006;5:6.
It is well known that renal and neurological complications may occur after antifilarial treatment of patients infected with Loa loa. Conversely, spontaneous cases of visceral complications of loiasis have been rarely reported. A 31-year-old Congolese male patient who had not received any antifilarial drug developed oedema of the lower limbs, and then transient swellings of upper limbs. Two months after, he developed troubles of consciousness within several hours. At hospital, the patient was comatose with mild signs of localization. Laboratory tests and an abdominal echography revealed a chronic renal failure due to a glomerulopathy. Three weeks after admission, Loa microfilariae were found in the cerebrospinal fluid, and a calibrated blood smear revealed a Loa microfilaraemia of 74,200 microfilariae per ml. The level of consciousness of the patient improved spontaneously, without any specific treatment, but several days after becoming completely lucid, the patient died suddenly, from an undetermined cause. Unfortunately, no biopsy or autopsy could be performed. The role of Loa loa in the development of the renal and neurological troubles of this patient is questionable. But the fact that such troubles, which are known complications of Loa infection, were found concomitantly in a person harbouring a very high microfilarial load suggests that they might have been caused by the filarial parasite. In areas endemic for loiasis, examinations for a Loa infection should be systematically performed in patients presenting an encephalopathy or a glomerulopathy.
PMCID: PMC1471781  PMID: 16686951
24.  Influence of the softness of the parietal pleura on respiratory sliding mechanisms 
The pleural surfaces of the lung and chest wall slide against each other with low friction. Normal load support can be effected either by a combination of quasi-static fluid pressure and solid-solid contacts of relatively stiff asperities, or by shear-induced hydrodynamic pressures in the pleural fluid layer. To distinguish between these mechanisms, we measured surface topography and spatial distribution of stiffness of rat parietal pleura using atomic force microscopy. The topography of the pleural surface has unevenness at length scales smaller than the thickness of pleural fluid, similar to mesothelial cell diameters. The estimated maximum normal contact pressure that could be borne by asperities of the soft pleura is much less than that required to support a substantial difference between pleural fluid pressure and the pleural surface pressure. These results suggest that during sliding motion, unevenness of the pleural surface is smoothed by local hydrodynamic pressure, preventing any significant contribution of solid-solid contacts.
PMCID: PMC3157327  PMID: 21473935
Parietal pleura; AFM; Elastohydrodynamic lubrication; Rat; Topography
Journal of Clinical Pathology  1960;13(5):425-431.
The diagnosis of bronchopulmonary carcinoma was either corroborated or arrived at in 13 out of a total of 26 cases by pleural biopsy. Taken as a whole, pleural biopsy is inferior to repeated examination of the pleural exudate for neoplastic cells. In individual observations, however, the former can be found positive at a time when neither the pleural fluid nor any other material provide a diagnostic clue.
In an instance of primary pleural growth (mesothelioma) its nature was recognizable in the pleural biopsy material.
Pleural biopsy can correctly lead to the diagnostic exclusion of growth in favour of tuberculosis.
Pleural biopsy can be suggestive of the rheumatic aetiology of changes.
A pleural biopsy positive for carcinoma can be obtained on both sides.
All stages, from early submesothelial deposition of individual neoplastic cells to the dense infiltration of the subserous connective and fat tissue, were observed.
PMCID: PMC480112  PMID: 13732035

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