These new findings demonstrate a critical role for Cox-2 in the terminal differentiation of human B lymphocytes to antibody-secreting plasma cells. The use of NSAIDs may adversely influence the efficacy of vaccines, especially in the immunocompromised, elderly and when vaccines are weakly

immunogenic. Generation of antibody is a goal of vaccination and is essential for effective immune responses against pathogens. Transcription factors, including Blimp-1 and Xbp-1, BIBW2992 in vitro regulate the terminal differentiation of B lymphocytes to plasma cells, which are responsible for antibody production. Blimp-1, a transcriptional repressor, is necessary for plasma cell differentiation, as well as for maintenance of the plasma cell phenotype.1–3 Mice deficient in Blimp-1 fail to produce antibodies against both T-independent and T-dependent antigens, indicating that Blimp-1 is required for antibody production.3–5 Blimp-1 represses Palbociclib ic50 genes such as Pax5, c-myc and Bcl-6 that are important for the function of mature B cells.2,6 Expression of Blimp-1 is necessary for the expression of Xbp-1, a transcriptional activator that prepares a plasma cell to become

an antibody-secreting factory.2,7 Xbp-1 controls the expression of proteins that are responsible for increased cell volume, protein synthesis, protein folding and enlarged endoplasmic reticulum, all important for plasma cell function.7,8 Cyclooxygenases are enzymes that regulate inflammation, at least in part, through the production of lipid mediators called eicosanoids. The constitutively expressed isoform cyclooxygenase-1 (Cox-1) maintains homeostatic levels of eicosanoids, while the inducible isoform Cox-2 is responsible for elevated mediator production, so controlling inflammation. It was previously thought that only tissue structural cells expressed Cox-2. However, Cox-2 can be expressed by immune cells including T cells, macrophages and B cells.9,10

Human B cells express Cox-2 after exposure to provoking agents such as CpG 4-Aminobutyrate aminotransferase DNA, CD40 ligand and B-cell receptor (BCR) engagement.11,12 This was further confirmed by Hanten et al.,13 who demonstrated that activation of human B cells with ligands of Toll-like receptors 7 and 9 increased Cox-2 transcript levels. Cox-2 activity in B cells is important for optimal antibody production.12,14 We previously demonstrated that Cox-2-deficient mice have impaired antibody responses to human papillomavirus-16 virus-like particles.15 Cox-2 inhibitor-treated mice also showed reduced B-cell responses to T-dependent antigens, including tetanus and diphtheria toxin.16 The purpose of the present study was to determine whether the reduction in total immunoglobulin G (IgG) levels caused by Cox-2 inhibition influenced all human IgG isotypes and whether or not CD38+ antibody-secreting cells were influenced.

5 and E11.5 due to defects in placental vascularization, highlighting its role in placental vascular development [5]. Placentas of PPARγ-null mice are with an unsettled balance of pro- and anti-angiogenic factors, that is, increased proangiogenic factor proliferin and decreased anti-angiogenic factor proliferin-related protein.

This has been confirmed with “gain of function” studies because the PPARγ activator rosiglitazone Roscovitine inhibits placental angiogenesis via regulating PRP and VEGF expression [90]. To this end, it is speculating that the critical PPARγ dimerization partner RXR may also have a role in placental angiogenesis because RXR-null mice show a similar phenotype to PPARγ [119]. Mammalian embryogenesis Small molecule library mouse and placental development

are believed to take place under constant low-O2 relative to ambient O2 [54]. For example, in a human placenta the intervillous space O2 is as low as ~2% at ≤8–10 weeks of gestation at a time when placental vasculature forms; at the end of the first trimester this level rises threefold to ~8% when maternal blood is delivered into the placenta from the uterine spiral arteries; thereafter, O2 level gradually declines to ~6% at the end of the third trimester [102, 84], possibly due to the substantial increased demand of fetus. At the end of the third trimester, the O2 level in the human fetus is even lower, ~2.2% O2 (range 1.9–3.1%) and ~3.7% O2 (range 2.3–5.1%) in the umbilical artery and vein, respectively [102]. Low O2 or hypoxia is known to stimulate the expression of numerous hypoxia-responsive genes via HIF-1β, DNA Methyltransferas inhibitor also known as Arnt heterodimerization with

HIF-1α [32]. HIF-1β mediates hypoxia-induced transcription of many angiogenic genes in the placenta, including VEGF [41]. Thus, one would expect that HIF should play a critical role in placental angiogenesis. Surprisingly, vascular defect is likely to be secondary to the primary trophoblast defect in the Arnt-null mice [2]. This is because placentas of Arnt-null mice display greatly reduced size in the spongiotrophoblast and labyrinth layers but with increased numbers of giant trophoblast cells, suggesting that HIF-1β is critical for determining the fate of the trophoblasts [63]. The MAPK pathways are evolutionarily conserved signal transduction cascades that are implicated in control of different and even opposite cellular responses including proliferation, differentiation, and cell death. In vertebrates, multiple isoforms of MAPK have been identified and categorized into three subfamilies, that is, the ERKs, p38MAPK, and the JNKs or stress-activated protein kinases. The MAPK signaling is important for transmitting extracellular signals including growth factors, hormones, and chemokines into the intracellular targets for nearly all fundamental cellular processes. The p38MAPK comprises four members, including p38α/MAPK14, p38β/MAPK11, p38γ/MAPK12, and p38δ/MAPK13 [14].

e., interpreting infants’ interests and goals and adapting her/his own behavior accordingly (Bornstein, 1989; Conner & Cross, 2003; Kochanska & Aksan, 2004). Following Fogel’s theory (1993), our interest was in how mothers and children jointly contribute to the interaction. Therefore, unlike Bakeman selleck compound and Adamson’s (1984), Adamson and Bakeman’s (1985), and Bakeman and Gottman’s (1986) (more recently, see Bigelow, Maclean, & Proctor, 2004) studies on social

play and unlike most research on social interaction (a recent example is Kochanska & Aksan, 2004), we chose the dyad as the unit of analysis rather than the individual (the infant or the mother). Accordingly, we coded that unit as a single entity, using an instrument which has been designed for the purpose of observing interaction per se, i.e., the Relational Coding System (Fogel & Lyra, 1997). Based on a corollary of Fogel’s (1993) relational theory, which posits that the Nutlin-3 mouse organized patterns of behavior are to be found in the whole system of communication rather than in one of its components, this instrument captures the ways in which the partners adjust to each other continuously while interacting. Different patterns of coregulation are identified that correspond to the nature of this adjustment: unilateral, when only one partner is paying attention to the other while the other is engaged in something else; asymmetrical, when there is a joint

focus of attention but only one partner is elaborating on the activity while the other only observes; and symmetrical, where both partners adapt to each other and together come up with innovative ways to take

part in an activity. Unlike previous studies that used the Relational Coding System to examine the first few months of life (Hsu & Fogel, 2001; Lavelli, 2005), our study focuses on a later period, from 10 to 24 months of age. It therefore contributes to extending the analysis of interpersonal coregulation from face-to-face interaction to mother–infant–object interaction. We also partly modified the original coding system according to the developmental changes in the content of interaction shown by previous studies. They found that in the first half of the second year of life infants use affective expressions (Bakeman Sorafenib manufacturer & Adamson, 1984) or manipulative actions (Bakeman & Adamson, 1984; Camaioni et al., 2003) to interact with their mother during social play; later, with the advancement of representational skills, infants begin to produce linguistic expressions related to shared activity, such as protowords and words (Adamson et al., 2004; Camaioni et al., 2003). To account for these possible changes during the observed period, we divided symmetrical coregulation into three subcategories, which, in line with the above results, aimed at coding episodes in which affect, action or language is shared. We expected to find a developmental sequence in the predominant patterns shared by the dyads to achieve coregulation.

coli) were dissolved in sterile, endotoxin-free water to obtain concentrations of from 0.1 mg/mL

to 10 pg/mL, and mixed with an equal amount of LAL (E-Toxate, Sigma). After 1 hr of incubation at 37°C (in a water bath), gelation was determined by inverting the test tubes once. The human myelomonocytic cell line THP-1 (from the European Collection of Cell Cultures, Cat No. 88081201) was cultured in RPMI 1640 medium Temozolomide purchase supplemented with 2 mM L-glutamine, 10% FBS (Sigma), and 1% antibiotic-antimycotic solution (Sigma). The culture was maintained at 37°C in a humidified atmosphere containing 5% CO2. A mature macrophage-like state was induced by treating the THP-1 cells with PMA (Sigma). Release of NO, measured as its end product, nitrite, was assessed using Griess reagent (35). Briefly, THP-1 cells were stimulated with the LPS preparations (0.01 μg/mL) for 24 hr. The culture supernatant (100 μL) was mixed with 100 μL of Griess reagent for 10 min, then the absorbance at 570 nm was measured using a microplate reader

(Molecular Devices, Sunnyvale, CA, USA) and computer software (Softmax). THP-1 cells were plated on 24-well tissue culture plates (Nunc, Roskilde, Denmark) at a density of 5 × 105 cells/mL (1 mL in each well) and cultured in RPMI 1640 cell culture medium supplemented with 2mM L-glutamine, 10% FBS, antibiotics, and 50 ng/mL PMA for 72 hr. Differentiated, plastic-adherent cells were washed twice with cold Dulbecco’s PBS (Sigma) Erlotinib concentration Chorioepithelioma and incubated with a fresh culture medium without PMA. The medium was then changed every 24 hr for another 3 days. Cytokine induction was performed on the fourth day after removal of PMA. The medium was replaced by fresh RPMI 1640 medium supplemented with 2% FBS and LPSs from the examined strains or standard LPS from Salmonella enterica sv. Typhimurium. The LPSs were diluted in RPMI 1640 cell

culture medium and added at concentrations of 0.01 μg/mL and 1 μg/mL. After 24 hr of incubation at 37°C in a humidified atmosphere containing 5% CO2, supernatants were collected, centrifuged, and stored at −80°C until cytokine assay. The concentrations of IL-1β, IL-6, and TNF in the supernatants were measured by ELISA using kits from Bender MedSystems, GmbH (Vienna, Austria) according to the manufacturer’s protocols. The detection limits were 0.32 pg/mL for IL-1β, 0.92 pg/mL for IL-6, and 3.83 pg/mL for TNF. For each experiment, the mean of three wells ± SD was expressed. Analyses were performed with GraphPad Prism 5 software. Statistical significances were determined by Student’s t-test and set at P < 0.05 or P < 0.01. The LPS preparations were isolated using standard hot phenol/water extraction. The majority of LPSs from B. sp. (Lupinus), B. japonicum, B. yuanmingense, M. huakuii, and A. lipoferum strains were found in the water phase, whereas LPSs from B. elkanii and B. liaoningense were extracted into the phenol phase. SDS-PAGE analysis revealed a high degree of heterogeneity for all the examined LPSs (Fig.

Moreover, our results offered a mechanistic explanation for pre-BCR autoreactivity by suggesting recognition and binding between neighboring pre-BCR molecules. Here, we investigate the hypothesis that autoreactivity is critically required for the positive selection of precursor B cells in vivo and that the central role of the pre-BCR

is the initiation of selection signals that can be replaced by signals from autoreactive selleck products BCRs. Based on our observations on the functional similarity between pre-BCRs and self-reactive BCRs in vitro, we hypothesized that if the pre-BCR was a specialized autoreactive receptor, then expressing an autoreactive BCR should overcome the developmental block in pre-BCR-deficient mice. To test this, we crossed 3-83Igi mice, in which the HC (3-83Hi) and LC (3-83κi) variable gene segments of the autoreactive BCR 3-83 are knocked into the IgH and Igκ loci respectively, with λ5-deficient mice 6, 10, 13. The 3-8 3 BCR recognizes MHC class I proteins of different haplotypes with different affinities, with H-2Kb being strongly recognized, whereas the binding affinity to H-2Kd ranked as the lowest 14–16. Thus, the 3-83 BCR is strongly autoreactive on the H-2b background and should rescue pre-BCR deficiency when selleck combined with

H-2b but not with H-2d. Indeed, flow cytometric analysis of bone marrow cells showed that autoreactive B cells (3-83Hi/3-83κi on the H-2b background) overcame the early developmental block in λ5-deficient mice (Figs. 1A and B, S1A). In contrast, O-methylated flavonoid on the H-2d background lacking the specific auto-antigen, the 3-83 BCR failed to efficiently rescue B-cell development. The majority of the B lineage

cells in the bone marrow were pro-B cells, which, similar to λ5-deficient cells bearing WT Ig genes, express the early marker CD43 (Fig. 1A and B). In agreement with the rescue of B-cell development in the bone marrow, λ5-deficient mice expressing the 3-83 BCR on the H-2b background showed normal proportions of B cells in the spleen and restored B-cell numbers. On the H-2d background, however, B-cell numbers were significantly reduced, suggesting that 3-83 BCR expression alone is not sufficient to rescue B-cell development (Fig. 1C–E). Together, the above results suggest that an autoreactive BCR efficiently initiates B-cell development and rescues an otherwise severe developmental block caused by pre-BCR deficiency. To further investigate the ability of autoreactive BCRs to drive early B-cell development, we injected HSCs from λ5-deficient 3-83Hi/3-83κi mice into immune deficient Rag-2/γC−/− mice 17. The cells were mixed in various proportions with WT HSCs to test the capacity of autoreactive B cells to compete with WT cells (Fig. 2A).

9,15–18 Further studies are needed to increase our understanding of the roles of eosinophils and IL-5 in inflammatory responses and other diseases in which hypereosinophilia occurs. The differential migration of eosinophils versus neutrophils to thyroids of IFN-γ−/− and WT mice during the development of G-EAT offers a unique opportunity to examine the role of eosinophil trafficking to sites of inflammation and to investigate the potential role of these

cells in the induction and resolution of inflammation. Neutralization of IL-5 markedly inhibited migration of eosinophils to thyroids of IFN-γ−/− mice during development of G-EAT. However, IL-5 neutralization had no effect on the severity or rate of resolution of inflammation in G-EAT, suggesting that eosinophil migration has no apparent pathogenic role in G-EAT. WT and IFN-γ−/− DBA/1 mice were produced learn more in our animal facilities at the University of Missouri as previously described.6–8 Both male and female mice (6–10 weeks old) were used. G-EAT was induced as previously described.1,5 Briefly, mice were injected intravenously

(i.v.) twice at 10-day intervals with 150 μg of MTg3 and 15 μg of lipopolysaccharide (LPS) (Escherichia coli 011:B4; Sigma Chemical Co., St Louis, MO). Seven days later, donor spleen cells were re-stimulated in vitro Selleck Tanespimycin with 25 μg/ml MTg and 5 ng/ml IL-12.1 Cells were harvested after 72 hr and washed twice, and 3·5 × 107 cells were transferred i.v. to 500-Rad irradiated

syngeneic recipients. Anti-IL-5 was purified from culture supernatants of the anti-IL-5-producing hybridoma TRFK-5 (provided by Dr Robert Coffman, DNAX Research Institute, Palo Alto, CA, USA) using protein G. IFN-γ−/− recipients of IFN-γ−/− donor cells were given 300 μg of anti-IL-5 intraperitoneally (i.p.) or rat immunoglobulin G (control IgG) every 4 days beginning on the www.selleck.co.jp/products/AG-014699.html day of cell transfer until euthanasia. WT recipients of WT donor cells were used for comparison. Thyroids were removed from groups of five or six recipient mice 20 days (peak of disease) or 40–50 days (fibrosis versus resolution) after cell transfer.1–6 Thyroids were fixed in formalin, sectioned and stained with haematoxylin and eosin (H&E), and scored quantitatively for G-EAT severity (the extent of inflammatory cell infiltration and thyroid follicle destruction) using a scale of 1+ to 5+, as described previously.6 1+ thyroiditis is defined as an infiltrate of at least 125 cells in one or several foci; 2+ is 10–20 foci of cellular infiltration involving up to 25% of the gland; 3+ indicates that 25–50% of the gland is infiltrated; 4+ indicates that > 50% of the gland is destroyed by infiltrating inflammatory cells; and 5+ indicates virtually complete destruction of the thyroid with few or no remaining follicles. Thyroid lesions were also evaluated qualitatively.

Pseudallescheria boydii and S. aurantiacum were the this website second most found species in symptomatic patients; but interestingly P. boydii is rare in samples from the environment and therefore over-represented in clinical samples.11 Immunocompromised persons generally bear an increased risk for infections with Pseudallescheria and Scedosporium.2,12,13 In immunocompetent individuals, two entry routes for Pseudallescheria and Scedosporium are relevant: first, the aspiration of contaminated water followed by a comatose period14,15 as a result of a near-drowning event; second, a traumatic inoculation of infectious material.16

As soon as the central nervous system (CNS) is affected by fungal invasion, case fatality is high for both immunocompromised and immunocompetent patients.17,18 In an animal model, infection by P. apiosperma or P. boydii killed 20% of immunocompetent mice and even 100% of immunosuppressed animals. Similarly, S. dehoogii caused the death of even 70% of the immunocompetent mice.19 This high fatality rate highlights the urgent need to clarify the pathogenic mechanisms and subsequently to develop new therapeutic approaches. Two prerequisites enable the invading fungus to survive in the infected host and thus represent Staurosporine ic50 interesting targets for antifungal intervention: the capacity to gain nutrients from the host, and the effective execution of immune

evasion processes. The production and secretion of proteases could encounter both challenges. Digestion of proteins into peptides or free amino acids allows the acquisition of nutrients such as nitrogen and carbon out of proteins, as well as the sourcing of iron by degradation of

transferrin that binds free iron in blood and bodily fluids.20,21 Furthermore, secreted fungal proteases might target complement proteins which represent a major immune shield in the CNS.22,23 Whereas microglia and astrocytes have to undergo a long-standing multistep activation process before exerting antimicrobial activities in the brain, the complement cascade can start within seconds Adenosine triphosphate after contact with immune complexes (classical pathway), of microbial carbohydrates (lectin pathway) or activator surfaces (alternative pathway) (Fig. 1). The broad spectrum of antimicrobial functions not only include cell lysis of many invading pathogens via formation of the membrane attack complex (MAC), but also the deposition of complement fragments on microbial surfaces (opsonisation) to target them for phagocytosis. Additional complement effects are the attraction of phagocytes to the site of infection and the activation of different cell types via intracellular signal transduction pathways.23 The spectrum of secreted proteases depends on the genetic background of the fungi as well as on the regulatory mechanisms driven by the available nutrients in the environment.

Owen et al. designed and implemented a predialysis clinical pathway, which led to improved outcomes with late referrals (GFR <10 mL/min) falling from 29% to 6%.61 As a consequence, median time to

initiation of dialysis improved from <1 to 14 months and permanent access at the time of initial dialysis increased from 24% to 83%. Paris et al. studied 1137 patients from 15 centres starting dialysis.62 Early referral was defined as >2 months before initiation of dialysis. Eighty-six per cent of these had permanent access and 44% commenced with peritoneal dialysis. Units with structured predialysis H 89 chemical structure education programmes had higher rates overall of permanent access (66.3% vs 48.2%) and more patients on peritoneal dialysis (40% vs 22%). Peña et al. investigated 178 patients who started haemodialysis and survived at least 3 months.63 Patients with acute kidney injury were excluded. Early referral was defined as >4 months before dialysis commencement (139 early and 39 late). Late referral was associated with a worse clinical and metabolic state and was an independent risk factor for mortality in the first 2 years. Roderick et al. in a retrospective study of 361 patients identified 124 (35%) as late referrals (<4 months before starting dialysis).64 Of these, 84 were referred <1 month before starting dialysis. There was evidence

of CKD in all late referrals. Late referrals were older with more comorbidities, worse biochemistry, less permanent access, were more likely to start on haemodialysis rather than predialysis and

had a higher rate of hospitalization (P = 0.001) and death at 6 months (P = 0.002). Roubicek et al. in AZD2014 molecular weight a study of 270 patients defined 177 as early referral (>16 weeks before the start of dialysis) and 93 as late (<16 weeks).65 The late referral group had higher short-term morbidity (emergency dialysis, acute pulmonary oedema, severe hypertension, use of temporary vascular access and duration of hospitalization). However, in this retrospective study, survival at 3 months, 12 months and 5 years was the same for the two groups. Sabath et al. studied 163 patients commencing predialysis with 94 defined as early referrals (>3 months before CYTH4 first dialysis) and 69 as late referrals (<3 months).66 Early referral patients had a shorter duration of hospitalization in the first 6 months, fewer emergency catheter placements and better biochemistry and haemoglobin. Schwenger et al. reviewed 280 patients. Of these, 137 were late referral (<17 weeks prior to starting dialysis) and 143 early referral (>17 weeks prior). The median time of referral was 17 weeks.67 Late referred patients had a higher incidence of temporary vascular access and increased mortality at 12 months (34.2% vs 5.5%). In a subsequent paper, Schwenger et al. from Heidelberg68 reported on a group of 254 consecutive patients with late referral defined as less than 8 weeks before initiation of dialysis.

While dialysis may offer a better quality and quantity of life compared with conservative management, this may not always be the case; hence the patient is entitled to be well-informed of all options and potential outcomes before embarking on such therapy. They should be assured of adequate symptom control and palliative care whichever

option is selected. No randomized controlled trials have been conducted in this area and only a small number of observational studies provide guidance; thus predicting which find more patients will have poor outcomes is problematic. Those undertaking dialysis may benefit from being fully aware of their choices between active and conservative treatment should their functional status seriously deteriorate and this should be shared with caregivers. This clarifies treatment pathways and reduces Autophagy Compound Library price the ambiguity surrounding decision making. If conservative therapy or withdrawal from dialysis

is chosen, each should be supported by palliative care. The objective of this review is to summarize published studies and evidence-based guidelines, core curricula, position statements, standards and tools in palliative care in end-stage kidney disease. The role of palliative care in end-stage kidney disease (ESKD) is well developed in the UK, USA, Italy and Canada.1–9 Palliative care in ESKD is important in the contexts of conservative therapy (choosing a non-dialysis pathway), withdrawal of therapy and in symptom control. Advanced care directives and end-of-life decisions overarch these pathways. There is a recognized need for education regarding provision of palliative care in

dialysis patients.10 However, there is no clear pathway to palliative care,11 considerable variation in the provision of palliative care services for ESKD patients12 Cobimetinib and little evidence upon which to develop standards of renal palliative care in ESKD.13 There has been an increase in the elderly accepted onto dialysis in Australia. In 2004, 244 (445 per million population) new patients were accepted on dialysis in the 75–79 year age group. This increased to 277 (504 per million) in 2008. In the 80–84 year age group 103 (267 per million) started dialysis in 2004, which increased to 187 (442 per million) in 2008 and in the >85 year group 32 (107 per million) started dialysis in 2004, which increased to 58 (159 per million) in 2008.14 Despite this, the Caring for Australasians with Renal Impairment (CARI) Guidelines do not address palliative care.15 In addition, many elderly assessed for dialysis either do not progress16 or die before they would have required dialysis therapy.17 We will review the existing literature on palliative care provision in ESKD in the contexts of conservative therapy and withdrawal from dialysis. The available observational, retrospective and case studies are summarized in Table 1.

According to a large survey on bloodstream infections in the US,1C. glabrata CH5424802 mouse and C. krusei are associated with higher mortality rates (>50%) than C. albicans, while C. parapsilosis is associated with a lower rate (28%). However, this analysis was not adjusted for patient factors. An interesting potential contributor to the comparatively high mortality of C. glabrata infections was identified by Fernandez et al. [29] who analysed the time to blood culture positivity in patients diagnosed with candidaemia. Mean time to yeast detection was 35 h for C. albicans vs. 80 h for C. glabrata. Mean time to appropriate therapy for C. albicans isolates was 43 h compared to 98 h for C. glabrata. In the

context of data highlighting the importance

of adequate therapy at an early stage of IC discussed below, this amount of delay may well result in substantially higher mortality in patients with Candida sepsis because of difference in time to yeast detection in C. glabrata vs. C. albicans.1 In the ICU setting, diagnosis of IC and candidaemia in particular remains difficult, uncertain and often delayed. This relates to the fact that the clinical signs and symptoms are usually uncharacteristic and pathogen detection mainly relies on detection of the fungi in blood culture. www.selleckchem.com/products/midostaurin-pkc412.html This remains a notoriously slow procedure with limited sensitivity. The detection rates of blood cultures are in the 50% range and time to detection may reach several days. Taur et al. [30] report a median duration of 33 h to positivity. The blood volume inoculated per culture bottle is certainly a critical factor and should be at least 10 ml according to current guidelines. Moreover, it should be noted that C. glabrata may require anaerobic media for optimal growth31 and that patients very recently exposed to antifungals

or on prophylaxis may have negative cultures despite ongoing bloodstream infection. Therefore, serological testing for Candida antigens and/or antibodies has been investigated for its diagnostic value. The beta-glucan test detecting (1-3)-beta-d-glucan, much a polysaccharide contained in the cell walls of various fungi, has been shown in a multicentre clinical evaluation in patients with proven candidaemia to yield sensitivities of 60–100% depending on species and cut-off value.32 Interestingly, the performance of the assay was not significantly affected by antifungal therapy. However, it is unknown whether positive beta-glucan tests reliably predate blood culture positivity. Medical materials and devices containing cellulose may lead to false-positive results. Routine use of this test clearly requires further prospective studies. Other tests e.g. based on the detection of highly immunogenic mannose-based fungal cell wall polymers or antibodies directed against germ tubes of C.