This process ensures the preservation of the benefits of randomization and avoids the introduction of bias during analysis. As-treated analysis may sometimes be used to test the robustness of findings but should rarely be used to replace the

use of intention-to-treat analysis. In the study by Akt inhibitor Suki et al.,1 as almost half of the study participants discontinued the study for a range of reasons such as non-compliance, loss to follow-up and adverse events, it was particularly important to include this proportion in the analyses so as to prevent overestimation of the treatment effect. Based on the results presented in the article, you are confident that the study has undertaken analyses according to the original randomization of participants, Alectinib clinical trial that is, by intention-to-treat. Questions: What were the results? What was the size and precision of the effect? When considering the results of a study, an assessment of the precision is essential. The exact ‘true’ effect of an intervention is never known. However, it is possible to estimate this effect.

When we consider the precision of a study, we are considering the proximity of an estimate to the ‘true’ effect. The interval, enclosed by the extremes at which the estimate may possibly lie, is known as the 95% confidence intervals (CIs). By accepting the 95% CI, one is accepting that the true effect lies within that range 95% of the time, in other words, the estimate will lie outside the interval 5% of the time. The precision of a study ultimately depends on the number of events, and therefore its sample size. As a general rule of thumb, the larger the proportion of participants who experience the outcome, the greater the precision, that is, total number of events drives the power of the study whilst the sample size and event rate determines Decitabine the total number of events. A larger sample size will produce more outcomes

and therefore narrower CIs, allowing one to be more confident that the estimate is closer to the true effect. The results of a study can be expressed in a number of different ways and it is important to understand and interpret the significance of such results. Some examples include differences in a continuous factor (e.g. effects of sevelamer on serum phosphate levels), a dichotomous outcome (e.g. relative risk of hyperphosphataemia or risk of cardiovascular events) or as time-to-event analyses, comparing the length of time taken for a particular event of interest to occur between the two groups, thus providing additional information and statistical power.8 The results of time-to-event analyses are often expressed by hazard ratios.9 Perhaps the most important method for presenting the results of dichotomous outcomes is the absolute risk difference, which describes the proportion of individuals prevented from having an event, and can be used to calculate numbers needed to treat.

16 Korean National Health and Nutrition Examination Survey (KNHNES) data revealed that the age-adjusted prevalence of MS increased significantly from 24.9% in 1998, 29.2% in 2001, and 30.4% in 2005 to 31.3% in 2007.17 Among the five components of MS, the AZD6244 research buy level of low HDL-cholesterol increased the most, by 13.8% over 10 years. Next was abdominal obesity, which increased by 8.7%, then hypertriglyceridemia, which increased by 4.9%. Lipid abnormality and abdominal obesity were major factors in increasing prevalence of MS in Koreans over 10 years, reflecting a Westernized diet pattern and sedentary lifestyle. In addition, obesity, which is the major factor in the development of

MS has become

a common problem in both children and adults. Hildrum et al.18 conducted a large Norwegian population-based study and found that the prevalence of MS was highly age-dependent. This was evident especially in women, with a sevenfold increase in prevalence from age groups 20–29 years to 80–89 years. In Korea, Kim et al.19 analyzed data from the third Korean National Health and Nutrition Examination Survey (KNHNES III). The prevalence of MS was 6.4 (95% CI 4.5–8.4) and 22.3 (95% CI 20.8–23.8) in adolescents and adults, respectively. Prevalence was lower in women and all age groups showed a significant gender difference, except for the 50–59 year age group; men had a higher prevalence than women for all age groups 10–49. STK38 selleckchem A rapid increase was observed in the 30–59 age group in both genders, (8.8 and 19.1% aged in the 30s; 16.5 and 29.7% aged in the 40s; and 36.4 and 39.1% aged in the 50s for women and men, respectively). Women had a higher prevalence in the 60-year and above age group. They also found that the obesity was closely correlated with a high risk of MS. There have been some data about the correlation between MS and benign prostatic hyperplasia (BPH). Well-known lifestyle factors, such as the consumption of food such

as meat and fat, are widely known high-risk factors of BPH. Recent epidemiological studies have revealed that, to a large extent, lifestyle factors associated with metabolism—including obesity, blood glucose, exercise, and diet—also contribute substantially to the development of these conditions.20 The clinical pathophysiologic background of MS is compounding; leading to neurological or vascular damages to the lower urinary tract (Fig. 1). These observations are important because they suggest the existence of modifiable pathways for BPH and LUTS that offer novel targets for prevention and treatment. Factors that increase or decrease the risk for BPH are also factors that increase or decrease the risk for MS (Table 1). BPH is the most common prostate disease in middle-aged and elderly men, and the risk of developing BPH increases with advancing age.

Total hospital admission rate was 1.48 per patient year with hospital days totalling 8.54 days per patient year. The three most common reasons for first admission were cardiac (33%), infection (18%) and gastrointestinal (12%). Predictors of future selleckchem hospitalization included the first dialysis occurring in hospital (hazard ratios (HR) 2.1, 95% CI 1.4–3.3, P = 0.0005) and the use of a CVC at first haemodialysis (HR 2.6, CI 1.6–4.4, P < 0.0001). Hospitalizations are common in older incident haemodialysis patients. Access preparation and overall burden of illness leading to the initial hospitalization appear to play a role. Identification of additional factors

associated with hospitalization will allow for focused interventions to reduce hospitalization rates and increase the value of care. “
“Aim:  SM22α (transgelin) has been focused upon as a player in the process of phenotypic changes of types of cells. The SM22α expression in the rat anti-glomerular basement membrane (GBM) nephritis model and differences from an established Ku 0059436 phenotypic marker

for the myofibroblast, α-smooth muscle actin (αSMA), were investigated. Methods:  The rat kidney tissues were processed for histological studies, immunohistochemical and immunoelectronmicroscopy analyses on days 0, 7, 28, 42 and 56 after injection of rabbit anti-GBM serum for the disease induction. Results:  Immunohistochemistry with anti-SM22α antibodies (Ab) revealed that kidneys of the nephritic rats on day 7 expressed SM22α in podocytes, crescentic cells and epithelial cells of Bowman’s capsule. After 28 days, SM22α was also expressed in peritubular interstitial cells. Double immunofluorescence with anti-SM22α Ab and anti-αSMA Ab showed

that SM22α was preferentially expressed in podocytes, whereas αSMA was positive in mesangial cells on day 7. After day 28, both molecules became positive in peritubular interstitial cells. Conclusion:  SM22α was expressed in epithelial cells Selleckchem Vorinostat of inflamed glomeruli in the early phase, and then also in peritubular interstitial cells in the later phase of anti-GBM nephritis model. SM22α presented unique kinetics of expression distinct from αSMA. “
“Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis with various histological and clinical phenotypes. N-acetylgalactosamine (GalNAc) exposure plays a pivotal role in the pathogenesis of IgAN. The aim of the current study is to investigate whether GalNAc exposure of serum IgA1 was associated with clinical and pathological manifestation of IgAN. Sera from 199 patients with biopsy proved IgAN were collected. Clinical and pathological manifestations were collected. Biotinylated Helix aspersa were used in ELISA to examine GalNAc exposure on IgA1 molecules. Patients were divided into two groups according to the GalNAc exposure rate less or more than 0.4.

Samples for soluble factors (e.g. cytokines) can be recovered undiluted or diluted. Diluted samples are obtained by washing the vaginal tract in a cervicovaginal lavage (CVL). Samples can be diluted with normal saline (pH range from 4.5 to 5.5) or by phosphate-buffered saline (PBS, pH 7.4). Depending on volume of samples needed for testing, researchers have used 3, 5 and 10 mL washes; however, each volume will

result in different recovered volume depending on clinician technique and secretions already in the vaginal vault (i.e. vaginal discharge) GSK1120212 supplier (see below, ‘Issues with measuring soluble factors’). Saline is favored over PBS in field settings to avoid the extra step to prepare PBS and 10 mL has been used mostly in clinical trials. Undiluted specimens are recovered by swabs, sponges (Weck-Cell), wicks, spears and brushes by a clinician.11,12 If a sample is obtained undiluted, an optional dilution step can be added to extract material from sampling devices or to increase the final volume. Selleckchem JAK inhibitor Both undiluted (swab) and diluted samples can be self-collected by the participant. Though clinician sampling has the advantage of being standardized, the development of new devices for self-collection is ongoing with an aim to improve participant acceptability as well as sample between clinic visits (samples can be dropped off, or returned by post to a centralized laboratory).13,14 Examples of undiluted self-sampling

methods include a vaginal cup, an aspirator or a swab. Lavages, with new self-sampling devices, have also been tested in clinical trial settings.15,16 Many soluble factors (e.g. inflammatory cytokines) have short half-lives and will break down quickly. It is important that samples are put immediately into cool boxes and stored at −80°C as soon as possible. Also, it may be necessary

to add a protease inhibitor cocktail to inhibit the breakdown of these proteins. Samples must be shipped to a central laboratory on dry ice. In addition, blood will also be an alternate source of soluble factors, and blood contamination by sampling trauma or menstruation must be recorded and the results taken into account for the analysis. Hemastix® NADPH-cytochrome-c2 reductase can be used to measure blood in CVLs prior to centrifuge. Antigen-presenting cells and T lymphocytes are useful for assessing vaginal cellular immunity. Cervical or vaginal cells can be obtained, surface antigens stained and then tested by flow cytometry.17 In research settings, these cells are mostly isolated with brushes, but other methods such as endocervical aspiration, a cell pellet from a lavage, a scraping of the cervix, and endocervical swabs have been used to obtain cells. In addition, biopsies are useful for investigating several cell layers; however, the invasive character of a biopsy makes it often not acceptable in a clinical trial setting when a large number of participants are enrolled or in at risk populations where causing a breach in the vaginal barrier could increase risk of HIV transmission.

Sustained suppression of the B cell compartment can lead to impairment of T cell responses, resulting in a prolonged immunosuppressive

state with an increased risk of vertical transmission of cytomegalovirus (CMV) infection from mother to fetus [112]. Pan-specific depletion of B cells can deplete autoantibodies as well as protective natural antibodies and regulatory B cell subsets [5]. Therefore, it is clear that carefully planned clinical trials are needed to evaluate learn more the full benefits and harms of rituximab in pregnancy before it can be recommended for wider use in pregnancy. The evidence presented in this review has clearly highlighted the important role of B cells in shaping pregnancy outcomes that have implications for long-term Selleck Dabrafenib human health. Despite this, there are still limited data detailing the changes in the human B cell compartment, and the role of B cell subsets in pregnancy outcomes is poorly studied. This is due to the limited

number of B cell markers used in earlier studies to describe changes in B cell subsets during pregnancy. Recent advances in B cell biology indicate clearly that these markers alone are not adequate in describing their full functions in human pregnancy. Further efforts should be dedicated to delineate the contribution of these B cell subsets in the maintenance of a healthy pregnancy as well as their roles in pregnancy complications. In light of the potential benefits of rituximab in depleting autoreactive B cells and the emerging safety profile of rituximab in pregnancy, it is anticipated that B cell depletion therapies will eventually be trialled in obstetric complications that involve autoantibodies such as APS, SLE or ITP. It is reasonable to expect that rituximab will make some advances in the treatment of refractory conditions in pregnancy and provide a viable option that spares the use of high doses of chemotherapeutics

and steroids in high-risk pregnancy to reduce risk of fetal toxicity [115], and thereby allows the pregnancy a better chance to develop to full term. Future pilot studies into the Glycogen branching enzyme safety and efficacy of rituximab in pregnant patient cohorts are needed to provide a rational basis for larger studies. Although B cell depletion has demonstrated clinical benefits for maternal conditions in high-risk pregnancies, its potential benefits and risks for neonatal outcomes have not yet been investigated fully. It remains to be determined whether or not B cell depletion can improve neonatal outcomes on preterm birth, low birth weights, congenital malformations and their associated long-term health consequences.

By creating RND efflux pump mutants and transcriptional fusions, Gillis et al. (2005) showed that the mexAB-oprM and mexCD-oprJ RND efflux pumps are required for the formation of azithromycin-resistant P. aeruginosa biofilms. Also, the various efflux pumps showed different expression patterns: while mexA was expressed continuously throughout

the biofilm regardless NVP-LDE225 of the presence of azithromycin, mexC was expressed only in biofilms (but not in planktonic cells) in the presence of azithromycin and expression levels appeared to be the highest in the central parts of the biofilm [it should be noted that in an earlier study, the expression of mexAB-oprM and mexCD-oprJ was found to be the highest at the biofilm substratum, and not the center (de Kievit et al., 2001)]. Interestingly, genes PA0105,

PA0106 and PA0108 (encoding cytochrome c oxidase subunits) were significantly downregulated in response to azithromycin treatment, suggesting that Selleck Roxadustat there may be a coupling between electron transport and susceptibility to macrolides as already observed for tobramycin (Whiteley et al., 2001) (Table 2). When P. aeruginosa PA14 biofilms formed on cystic fibrosis-derived airway epithelial cells are treated with 500 μg mL−1 tobramycin (approximately half of the minimum bactericidal concentration under these conditions) for 30 min, 338 transcripts were upregulated and 500 were downregulated (Anderson et al., 2008). Tobramycin treatment reduced the virulence of the bacteria toward the epithelial cells and several virulence-related genes were downregulated. Conversely, several genes involved in alginate biosynthesis were upregulated (algU, mucA, algZ), but as core alg biosynthetic genes were not upregulated, it is uncertain whether this leads to increased alginate production. The transcript levels for most resistance-related genes were only slightly altered (PA1541, mexB, mexR) or remained unchanged, suggesting that the expression of other, yet unknown, find more factors

is important for resistance under these conditions. Comparing the data reported in the various studies revealed that very few differentially expressed genes are common between the different studies (Table 2). Analysis of the expression data reported by Whiteley et al. (2001) and Bagge et al. (2004) revealed that only PA2703 (encoding a hypothetical protein) and PA3819 (encoding a hypothetical membrane protein) are overexpressed as a result of both tobramycin and imipenem treatment (Table 2). The only two genes that were upregulated by imipenem (Bagge et al., 2004) and tobramycin (cystic fibrosis-derived airway epithelial cell model, Anderson et al., 2008) (PA5261 and PA5162) are both involved in alginate biosynthesis. Also, when a treatment with imipenem (Bagge et al., 2004) is compared with treatment with azithromycin (Gillis et al.

Non-T-cell activation linker (NTAL), a linker protein of the signalosome that contains Gab2, is expressed as a 25-kDa protein in BMMC 30. Since activation of Lyn kinase induces tyrosine phosphorylation of NTAL in mast cells 31, we examined tyrosine phosphorylation of NTAL. Like pp25, tyrosine phosphorylation of NTAL by adenosine was significantly reduced in αβFFFγ2 mast cells

(Fig. 7D). We examined whether adenosine enhances FcεRI-mediated tyrosine phosphorylation of NTAL in BMMC. As expected, tyrosine phosphorylation of NTAL was significantly increased upon adenosine loading (Fig. 8A). Furthermore, we observed that adenosine augments FcεRI-dependent tyrosine phosphorylation of FcRβ in BMMC (Fig. 8B). Low-dose allergen can trigger bronchoconstriction and airway inflammation in asthmatics and various factors are considered to be involved in this hyper-responsiveness to allergen 32–35. Adenosine has been recognized as one of the important factors related click here to airway hyper-responsiveness and allergic inflammation in allergic asthma. Our findings in the present study suggest one of the principal mechanisms for airway hyper-responsiveness to allergen in allergic asthma, namely, exacerbation RGFP966 order factors, such as adenosine, that

occur concurrently with low-dose allergen can increase the FcεRI-mediated degranulation response. Murine mast cells express various GPCR including adenosine receptors. Like adenosine, prostaglandin E2, macrophage inflammatory protein-1α, and RANTES themselves fail to induce degranulation, but potentiate the FcεRI-mediated degranulation response 5, 8, 36. Although augmentation of the degranulation response by these GPCR agonists is sensitive to pertussis toxin, contribution of PI3K to this augmentation differs among agonists. As demonstrated in Fig. 1, FcεRI-mediated degranulation was synergistically increased by adenosine. Furthermore, up-regulation of FcεRI expression by monomeric IgE further increased this degranulation response. Our experiments employing a chemical inhibitor wortmannin revealed that PI3K plays crucial roles

in both stimuli. In contrast, Kuehn et al. reported that wortmannin had little effects on degranulation response induced by antigen and prostaglandin E2 36. Therefore, it is collectively suggested that PI3K activity is not necessarily Thymidylate synthase required for all cases of degranulation responses synergistically elicited by costimulation of FcεRI and GPCR. In line with previous studies 13, 14, [Ca2+]i mobilization was enhanced in mast cells upon costimulation of low-dose antigen and adenosine. Treatment of mast cells with wortmannin significantly decreased the enhanced [Ca2+]i mobilization (Fig. 2D). However, a fraction of calcium response, insensitive to the PI3K inhibitor, was observed. We believe that the level of [Ca2+]i mobilization may be insufficient to support degranulation response when activation of PI3K is pharmacologically suppressed.

Despite ongoing nephrotic range proteinuria (most recently a urine protein to creatinine ratio of 467 mg/mmol), renal function has since remained stable

at 2 years post transplant with a serum creatinine of 130 μmol/L. In patients with ESKD caused by MCGN who have received a renal allograft, rMCGN occurs in approximately 40%, with15% losing their graft due to recurrent disease.[1] In a series of 29 patients with rMCGN, all recurred within 14 months of transplantation with the majority (83%) recurring within 6 months. Interestingly, in 7 of these 29 patients, the diagnosis was made on protocol biopsies or on indication biopsies without a clinical suspicion of recurrent disease. In the absence of proven effective treatment, it is unknown whether an earlier diagnosis by way of protocol biopsy would lead to improved outcomes.[2] In

the same study, the authors made the observation that patients www.selleckchem.com/products/SB-203580.html receiving transplants from living donors had a trend toward higher rates of recurrence compared with those receiving kidneys from deceased selleck screening library donors (P = 0.06).[2] A subsequent study in a different cohort of patients however did not find this association.[3] The other predictors of recurrences include hypocomplementaemia, a feature noted in our patient, and the presence of a serum monoclonal protein.[2, 3] Recently, there has been a move to classify MCGN based on the pattern of immunostaining into immune-complex-mediated or complement-mediated.[4] Immune-complex mediated processes Mannose-binding protein-associated serine protease trigger the activation of complement via the classical pathway resulting in glomerular endothelial damage. Renal biopsies of these patients typically demonstrate both immunoglobulin and complement staining. In contrast, complement-mediated MCGN is thought to be secondary

to dysregulated complement activation without significant immunoglobulin deposition. This hypothesis is supported by the finding that MCGN is associated with genetic polymorphisms in genes encoding complement regulatory factors.[5] At this stage however, there is no evidence to suggest which type is more likely to recur after transplantation. It is unclear why only 40% of patients develop recurrent disease. The suggestion that recurrence rates are higher among living related donor transplants and among those with evidence of complement activation suggests a complex interplay between circulating factors as well as pre-disposition of the kidney tissue to immune-complex or complement mediated damage.[2] In our case, the disease progressed much more quickly in her live-related transplant compared with the subsequent deceased donor transplant. Another possible factor may be differences in baseline immunosuppression with our patient having used cyclosporine maintenance for her first graft and tacrolimus for her second graft.

Another explanation is the presence of soluble forms of B7-H3 and TLT-2. Indeed, secretion of a soluble form of human B7-H3 has been reported in patients with cancer16 and we have also observed a soluble form of TLT-2 in culture supernatants of TLT-2-transduced cells (M.H., unpublished observation). Excess molecule expression in the transduced cells may produce a soluble

form and neutralize the mAb action. Additionally, the presence of an opposite function from an unknown B7-H3 receptor may have neutralized the co-stimulatory action of the B7-H3–TLT-2 pathway. Unfortunately, we could not induce agonistic signals by ligation of TLT-2 using immobilized anti-TLT-2 mAbs. This causes further difficulty for the direct analyses of TLT-2 function in selleck products T cells. Further studies are needed to clarify the direct interaction of TLT-2 with B7-H3 in T-cell responses. Most reports describing the role of B7-H3 in humans suggest regulatory roles selleck chemical for tumour-associated B7-H3,18,19,21,22 and all murine tumour B7-H3-transduction experiments, including our study, demonstrate positive co-stimulatory functions for tumour-associated B7-H3.24–27 However, a number of mouse studies using various assay systems in vitro and disease models in vivo still support the regulatory role of B7-H3.13–15,46,47 The discrepancy in B7-H3 function is not simply explained by the different forms of B7-H3 found in humans and mice. Further studies to clarify the real function(s)

of B7-H3 will be required before developing cancer immunotherapy targeting B7-H3. We thank BCKDHA T. Kitamura (University of Tokyo, Tokyo, Japan) for kindly providing the retrovirus vector and the packaging cell line Plat-E, Dr W. R. Heath for OT-I mice, and A. Yoshino and S. Miyakoshi for cell sorting. This

study was supported by a Grant-In-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to M.A.) and grants from the Japan Society for the Promotion of Science (to M.H. and M.A.). The authors declare no conflict of interests. Figure S1. Expression of cell surface antigens on parental and B7-H3-transduced tumor cell lines. B7-H3-transduced tumor cells were generated as described in the Materials and Methods. Parental and B7-H3-transduced P815, EL4, J558L, SCCVII, B16 and E.G7 cells were stained with FITC-anti-B7-H3, FITC-anti-MHC class I, PE-anti-CD54, PE-anti-CD80, and PE-anti-CD86 mAbs or with the appropriate fluorochrome-conjugated control immunoglobulin. Data are displayed as histograms (4-decade logarithm scales) with the control histograms nearest the ordinate (shaded). Figure S2. Expression of TLT-2 on CD4+ and CD8+ T cells. Splenocytes from BALB/c mice were stimulated with anti-CD3 mAb (10 μg/ml) for 6 and 24 h. Freshly isolated and activated splenocytes were stained with PerCP-Cy5.5-anti-CD4, PE-anti-CD8, and biotinylated anti-TLT-2 mAbs or with the appropriate isotype control Ig, followed by APC-streptavidin.

We have demonstrated that early vaccination (at 7 days of life) with a live gE-deleted ADV vaccine, in the presence of high levels of MDA could be effective, but that the intensity and duration of the recall proliferative T-cell response depended on the moment of the second vaccination. Humoral as well cellular responses were most similar to results obtained in the group vaccinated following the manufacturer’s recommendation when the second vaccination was performed at 12 weeks of life. Future studies are required to evaluate the protective effects of vaccination with this protocol. Vaccination of pigs as young

as 7 days of age, from a practical point of view, could be more convenient for herd personnel. This work is supported by Project no. NN 308 275934 funded by Ministry MK-2206 order of Science and Higher

Education. The NIA-3 ADV strain was kindly provided by Dr Andrzej Lipowski from NVRI Pulawy. “
“The conventional acid fast Dabrafenib purchase bacilli (AFB) smear and Mycobacterium tuberculosis (M.tb) culture of pleural effusion and tuberculin skin test (TST) in tuberculous pleurisy are unable to meet clinical needs because of their low sensitivities and specificities. To evaluate the diagnostic accuracies of QuantiFERON TB Gold In-Tube test (QFT-GIT) and nested-PCR in tuberculous pleurisy, we conducted a cross-sectional study in regions of China with a high tuberculosis (TB) epidemic. Seventy-eight participants were enrolled: 58 TB patients with diagnosis of confirmed or probable tuberculous pleurisy and 20 non-TB patients with a diagnosis of other non-TB diseases. The positive rates of AFB smear and M.tb culture in the pleural effusion were 5.8% (2/42) and 10.6% (5/47), respectively. The sensitivity and specificity of QFT-GIT were 93.1% (54/58) and 90.0% (18/20), whereas those of TST were 68.5% (37/54) and 86.7% (13/15), respectively; the sensitivity of QFT-GIT was significantly higher Cyclin-dependent kinase 3 than TST (P = 0.013). The sensitivity and specificity of M.tb-specific nested-PCR in pleural effusion were 94.8% (55/58) and 90.0% (18/20), respectively, with a turnaround

time of 7 h. Furthermore, combined QFT-GIT and nested-PCR detection improves the specificity to 100% with a sensitivity of up to 90.0%. This combination of immunoassay and molecular detection holds promise for the clinical diagnosis of tuberculous pleurisy. Tuberculous pleurisy is the most common extrapulmonary tuberculosis (TB), accounting for c. 10–20% of all tuberculous patients and c. 10–30% of disease causing pleural effusions (Porcel, 2009). The conventional acid fast bacilli (AFB) smear and Mycobacterium tuberculosis (M.tb) culture in pleural effusion are unable to meet clinical needs because of their low sensitivities (Light, 2007). There is an overriding need for the development of highly sensitive, specific and rapid tools to aid in the diagnosis of tuberculous pleurisy.