Bacterial Infection Elicits Heat Shock Protein 72 Release from Pleural Mesothelial Cells

Heat shock protein 70 (HSP70) has been implicated in infection-related processes and has been found in body fluids during infection. This study aimed to determine whether pleural mesothelial cells release HSP70 in response to bacterial infection in vitro and in mouse models of serosal infection. In addition, the in vitro cytokine effects of the HSP70 isoform, Hsp72, on mesothelial cells were examined. Further, Hsp72 was measured in human pleural effusions and levels compared between non-infectious and infectious patients to determine the diagnostic accuracy of pleural fluid Hsp72 compared to traditional pleural fluid parameters. We showed that mesothelial release of Hsp72 was significantly raised when cells were treated with live and heat-killed Streptococcus pneumoniae. In mice, intraperitoneal injection of S. pneumoniae stimulated a 2-fold increase in Hsp72 levels in peritoneal lavage (p<0.01). Extracellular Hsp72 did not induce or inhibit mediator release from cultured mesothelial cells. Hsp72 levels were significantly higher in effusions of infectious origin compared to non-infectious effusions (p<0.05). The data establish that pleural mesothelial cells can release Hsp72 in response to bacterial infection and levels are raised in infectious pleural effusions. The biological role of HSP70 in pleural infection warrants exploration

Tingkat Pengetahuan Remaja Tentang Penyakit HIV/AIDS Pada Siswa/I SMA Negeri 1 Kupang Timur Tahun 2018

AIDS (Acquired Immune Deficiency Sydrom) adalah kumpulan gejala penyakit akibat menurunnya sistem kekebalan tubuh secara bertahap. HIV (Human Immunodeficiency Virus) sebagai penyebab AIDS, merupakan retrovirus yang menyerang sistem kekebalan tubuh manusia serta menghancurkan atau menggangu fungsinya. Seseorang yang terinfeksi HIV dengan mudah dapat terserang berbagai penyakit lain karena rendahnya daya tahan tubuh dan dapat mengakibatkan kematian.Jenis penelitian yang dilakukan adalah penelitian deskriptif dan populasi sampel dalam penelitian ini adalah siswa SMA Negeri 1 Kupang Timur yang berjumlah 86 orang. Dari hasil penelitian yang dilakukan di SMA Negeri 1 Kupang Timur menunjukan yang berpengetahuan baik berjumlah 42 responden dengan persentase (48,48%) dan sebagiannya berpengetahuan cukup berjumlah 35 dengan persentase (40,69%) dan juga sebagiannya lagi berpengetahuan kurang sebanyak 9 responden dengan persentase (10,46%)

A patient on RIPE therapy presenting with recurrent isoniazid-associated pleural effusions: a case report

<p>Abstract</p> <p>Introduction</p> <p>The clinical scenario of a new or worsening pleural effusion following the initiation of antituberculous therapy has been classically referred to as a 'paradoxical' pleural response, presumably explained by an immunological rebound phenomenon. Emerging evidence suggests that there also may be a role for a lupus-related reaction in the pathophysiology of this disorder.</p> <p>Case presentation</p> <p>An 84-year-old Asian man treated with isoniazid, along with rifampin, pyrazinamide and ethambutol for suspected extrapulmonary tuberculosis, presented with a recurrent pleural effusion, his third episode since the initiation of this therapy. The first effusion occurred one month after the start of treatment, without any prior evidence of pulmonary tuberculosis involvement. Follow-up testing, including thoracoscopic pleural biopsies, never confirmed tuberculosis infection. Further evaluation yielded serological evidence suggesting drug-induced lupus. No effusions recurred following the discontinuation of isoniazid, although other antituberculosis medications were continued.</p> <p>Conclusion</p> <p>The immunological rebound construct is inconsistent with the evolution of this case, which indicates rather that drug-induced lupus may explain at least some cases of new pleural effusions following the initiation of isoniazid.</p

Highly Accurate Diagnosis of Pleural Tuberculosis by Immunological Analysis of the Pleural Effusion

Pleural TB is notoriously difficult to diagnose due to its paucibacillary nature yet it is the most common cause of pleural effusions in TB endemic countries such as The Gambia. We identified both cellular and soluble biomarkers in the pleural fluid that allowed highly accurate diagnosis of pleural TB compared to peripheral blood markers. Multi-plex cytokine analysis on unstimulated pleural fluid showed that IP-10 resulted in a positive likelihood ratio (LR) of 9.6 versus 2.8 for IFN-γ; a combination of IP-10, IL-6 and IL-10 resulted in an AUC of 0.96 and positive LR of 10. A striking finding was the significantly higher proportion of PPD-specific IFN-γ+TNF-α+ cell population (PPD-IGTA) in the pleural fluid compared to peripheral blood of TB subjects. Presence of this pleural PPD-IGTA population resulted in 95% correct classification of pleural TB disease with a sensitivity of 95% and specificity of 100%. These data suggest that analysis of the site of infection provides superior diagnostic accuracy compared to peripheral blood for pleural TB, likely due to the sequestration of effector cells at this acute stage of disease

Diagnostic Accuracy of Adenosine Deaminase and Lymphocyte Proportion in Pleural Fluid for Tuberculous Pleurisy in Different Prevalence Scenarios

BACKGROUND: Tuberculous pleural effusion (TPE) is a paucibacillary manifestation of tuberculosis, so isolation of Mycobacterium tuberculosis is difficult, biomarkers being an alternative for diagnosis. Adenosine deaminase (ADA) is the most cost-effective pleural fluid marker and is routinely used in high prevalence settings, whereas its value is questioned in areas with low prevalence. The lymphocyte proportion (LP) is known to increase the specificity of ADA for this diagnosis. We analyse the diagnostic usefulness of ADA alone and the combination of ADA ≥ 40 U/l (ADA(40)) and LP ≥ 50% (LP(50)) in three different prevalence scenarios over 11 years in our area. MATERIALS AND METHODS: Biochemistry, cytology and microbiology studies from 472 consecutive pleural fluid samples were retrospectively analyzed. ADA and differential cell count were determined in all samples. We established three different prevalence periods, based on percentage of pleural effusion cases diagnosed as tuberculosis: 1998-2000 (31.3%), 2001-2004 (11.8%), and 2005-2008 (7.4%). ROC curves, dispersion diagrams and pre/post-test probability graphs were produced. TPE accounted for 73 episodes (mean prevalence: 15.5%). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for ADA(40) were 89%, 92.7%, 69.2% and 97.9%, respectively. For ADA(40)+LP(50) the specificity and PPV increased (98.3% and 90%) with hardly any decrease in the sensitivity or NPV (86.3% and 97.5%). No relevant differences were observed between the three study periods. CONCLUSIONS/SIGNIFICANCE: ADA remains useful for the diagnosis of TPE even in low-to-intermediate prevalence scenarios when combined with the lymphocyte proportion

Pleural fluid soluble triggering receptor expressed on myeloid cells-1 as a marker of bacterial infection: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>Pleural infection is a common clinical problem. Its successful treatment depends on rapid diagnosis and early initiation of antibiotics. The measurement of soluble triggering receptor expressed in myeloid cells-1 (sTREM-1) level in pleural effusions has proven to be a valuable diagnostic tool for differentiating bacterial effusions from effusions of other etiologies. Herein, we performed a meta-analysis to assess the accuracy of pleural fluid sTREM-1 in the diagnosis of bacterial infection.</p> <p>Methods</p> <p>We searched Web of Knowledge and Medline from 1990 through March 2011 for studies reporting diagnostic accuracy data regarding the use of sTREM-1 in the diagnosis of bacterial pleural effusions. Pooled sensitivity and specificity and summary measures of accuracy and Q* were calculated.</p> <p>Results</p> <p>Overall, the sensitivity of sTREM-1was 78% (95% CI: 72%-83%); the specificity was 84% (95% CI: 80%-87%); the positive likelihood ratio was 6.0 (95% CI: 3.3-10.7); and the negative likelihood ratio was 0.22 (95% CI: 0.12-0.40). The area under the SROC curve for sTREM-1 was 0.92. Statistical heterogeneity and inconsistency were found for sensitivity (p = 0.015, χ²= 15.73, I²= 61.9%), specificity (p = 0.000, χ²= 29.90, I²= 79.9%), positive likelihood ratio (p = 0.000, χ²= 33.09, I²= 81.9%), negative likelihood ratio (p = 0.008, χ²= 17.25, I²= 65.2%), and diagnostic odds ratio (p = 0.000, χ²= 28.49, I²= 78.9%). A meta-regression analysis performed showed that the Quality Assessment of Diagnostic Accuracy Studies score (p = 0.3245; RDOR, 4.34; 95% CI, 0.11 to 164.01), the Standards for Reporting of Diagnostic Accuracy score (p = 0.3331; RDOR, 1.70; 95% CI, 0.44 to 6.52), lack of blinding (p = 0.7439; RDOR, 0.60; 95% CI, 0.01 to 33.80), and whether the studies were prospective or retrospective studies (p = 0.2068; RDOR, 7.44; 95% CI, 0.18 to 301.17) did not affect the test accuracy. A funnel plot for publication bias suggested a remarkable trend of publication bias.</p> <p>Conclusions</p> <p>Our findings suggest that sTREM-1 has a good diagnostic accuracy and may provide a useful adjunctive tool for the diagnosis of bacterial pleural effusions. However, further studies are needed in order to identify any differences in the diagnostic performance of sTREM-1 of parapneumonic effusions and empyemas.</p

Does pleural fluid appearance really matter? The relationship between fluid appearance and cytology, cell counts, and chemical laboratory measurements in pleural effusions of patients with cancer

<p>Abstract</p> <p>Background</p> <p>Previous reports have suggested that the appearance of pleural effusions (i.e., the presence or absence of blood) might help to establish the etiology of the effusions. This study explores the relationship between pleural fluid appearance and the results of chemical and cytological analyses in a group of patients with recurrent symptomatic pleural effusions and a diagnosis of cancer.</p> <p>Methods</p> <p>Medical records were reviewed from all 390 patients who were diagnosed with cancer, who underwent thoracentesis before placement of an intrapleural catheter (IPC) between April 2000 and January 2006. Adequate information for data analysis was available in 365 patients. The appearance of their pleural fluid was obtained from procedure notes dictated by the pulmonologists who had performed the thoracenteses. The patients were separated into 2 groups based on fluid appearance: non-bloody and bloody. Group differences in cytology interpretation were compared by using the chi square test. Cellular counts, chemical laboratory results, and survival after index procedure were compared by using the student's t test.</p> <p>Results</p> <p>Pleural fluid cytology was positive on 82.5% of the non-bloody effusions and on 82.4% of the bloody ones. The number of red blood cells (220.5 × 10³/μL vs. 12.3 × 10³/μL) and LDH values (1914 IU/dl vs. 863 IU/dl) were statistically higher in bloody pleural effusions.</p> <p>Conclusion</p> <p>The presence or absence of blood in pleural effusions cannot predict their etiology in patients with cancer and recurrent symptomatic pleural effusions.</p

Development of an enzyme-linked immunosorbent assay for the detection of human calretinin in plasma and serum of mesothelioma patients

<p>Abstract</p> <p>Background</p> <p>Calretinin is one of the well-established immunohistochemical markers in the diagnostics of malignant mesothelioma (MM). Its utility as a diagnostic tool in human blood, however, is scarcely investigated. The aim of this study was to develop an enzyme-linked immunosorbent assay (ELISA) for human calretinin in blood and to assess its usefulness as a potential minimally invasive diagnostic marker for MM.</p> <p>Methods</p> <p>Initially, attempts were made to establish an assay using commercially available antibodies and to optimize it by including a biotin-streptavidin complex into the assay protocol. Subsequently, a novel ELISA based on polyclonal antibodies raised in rabbit immunized with human recombinant calretinin was developed. The assay performance in human serum and plasma (EDTA/heparin) and the influence of calcium concentrations on antibody recognition were studied. Stability of spiked-in calretinin in EDTA plasma under different storage conditions was also examined. In preliminary studies serum and plasma samples from 97 healthy volunteers, 35 asbestos-exposed workers, and 42 MM patients were analyzed.</p> <p>Results</p> <p>The mean detection range of the new ELISA was 0.12 to 8.97 ng/ml calretinin. The assay demonstrated markedly lower background and significantly higher sensitivity compared to the initially contrived assay that used commercial antibodies. Recovery rate experiments confirmed dependence of calretinin antibody recognition on calcium concentration. Calcium adjustment is necessary for calretinin measurement in EDTA plasma. Spiked-in calretinin revealed high stability in EDTA plasma when stored at room temperature, 4°C, or after repeated freeze/thaw cycles. Median calretinin values in healthy volunteers, asbestos workers, and MM patients were 0.20, 0.33, and 0.84 ng/ml, respectively (p < 0.0001 for healthy vs. MM, p = 0.0036 for healthy vs. asbestos-exposed, p < 0.0001 for asbestos-exposed vs. MM). Median values in patients with epithelioid and biphasic MM were similar. No influence of age, gender, smoking status, or type of medium (plasma/serum) on calretinin values was found.</p> <p>Conclusions</p> <p>The novel assay is highly sensitive and applicable to human serum and plasma. Calretinin appears to be a promising marker for the blood-based detection of MM and might complement other markers. However, further studies are required to prove its usefulness in the diagnosis of MM patients.</p

Efficacy and Safety of Tunneled Pleural Catheters in Adults with Malignant Pleural Effusions: A Systematic Review

BackgroundMalignant pleural effusions (MPE) are a frequent cause of dyspnea and discomfort at the end of cancer patients' lives. The tunneled indwelling pleural catheter (TIPC) was approved by the FDA in 1997 and has been investigated as a treatment for MPE.ObjectiveTo systematically review published data on the efficacy and safety of the TIPC for treatment of MPE.DesignWe searched the MEDLINE, EMBASE, and ISI Web of Science databases to identify studies published through October 2009 that reported outcomes in adult patients with MPE treated with a TIPC. Data were aggregated using summary statistics when outcomes were described in the same way among multiple primary studies.Main measuresSymptomatic improvement and complications associated with use of the TIPC.Key resultsNineteen studies with a total of 1,370 patients met criteria for inclusion in the review. Only one randomized study directly compared the TIPC with the current gold standard treatment, pleurodesis. All other studies were case series. Symptomatic improvement was reported in 628/657 patients (95.6%). Quality of life measurements were infrequently reported. Spontaneous pleurodesis occurred in 430/943 patients (45.6%). Serious complications were rare and included empyema in 33/1168 patients (2.8%), pneumothorax requiring a chest tube in 3/51 (5.9%), and unspecified pneumothorax in 17/439 (3.9%). Minor complications included cellulitis in 32/935 (3.4%), obstruction/clogging in 33/895 (3.7%) and unspecified malfunction of the catheter in 11/121 (9.1%). The use of the TIPC was without complication in 517/591 patients (87.5%).ConclusionsBased on low-quality evidence in the form of case series, the TIPC may improve symptoms for patients with MPE and does not appear to be associated with major complications. Prospective randomized studies comparing the TIPC to pleurodesis are needed before the TIPC can be definitively recommended as a first-line treatment of MPE