This calls into question the applicability to the human situation of studies performed on the lower genital tract in animal models. In addition, the observed failure of HCl to substitute for lactic acid suggests the specificity of lactic acid, and not just an acidic pH, for IL-23 induction. Thus, experimental protocols as well as commercial products that attempt to acidify the vagina with acids other than lactic acid do not mimic the natural environment and may be less than ideal. The implication that lactic acid may specifically aid Cyclopamine manufacturer in immune defense

leads one to question currently held beliefs about vaginal health. Vaginal lactic acid production by both the underlying epithelium (Gross, 1961) and endogenous lactobacilli and other bacteria contribute

to the final lactic acid concentration. Individual differences in colonizing lactobacilli and other components of the vaginal flora, variations in the genetic background that influence glucose metabolism and unique Pritelivir chemical structure environmental and dietary exposures would all be expected to result in variations in lactic acid production. We postulate that the extent of lactic acid production, and not bacterial hydrogen peroxide production, is a key component of the innate immune defense mechanisms at this site. A recent investigation using gene amplification technology has revealed that the major Lactobacillus sp. in asymptomatic North American women is Lactobacillus inners, a bacterium that does not produce hydrogen peroxide (Ravel et al., 2010). Another study has demonstrated that both cervicovaginal fluid and semen block any hydrogen peroxide-induced microbicidal activity (O’Hanlon et al., 2010). Further study of larger numbers of women is clearly warranted to confirm our findings as well as to help unravel the misconceptions that now exist about vaginal bacterial flora and innate defense mechanisms

at this anatomical site. It would also be of interest to determine whether other organic acids that are structurally related to lactic acid, and that may be present in the vagina, have similar immunological C59 effects. In this regard, it has been demonstrated that lactate, but not butyrate, acetate, dichloroacetate, citrate or malate, augments lipopolysaccharide-induced IL-2 production by murine splenic T cells (Roth & Droge, 1991). In females before puberty and after menopause, vaginal lactic acid levels are much reduced and vaginal pH is elevated. Whether this contributes to a possible increased susceptibility to gram-negative bacterial infections under these conditions is not known and is worthy of investigation. In general, mucosal infection favors the induction of the Th17 subset while intravenous infection is characterized by the induction of Th1 cells (Pepper et al., 2010). This suggests that antimicrobial immunity at mucosal surfaces is preferentially geared towards IL-23 and IL-17 induction and away from the production of Th1 lymphocyte-generated IFN-γ.

0008 [.0011], z = −.71, p = .4761). Turning to interdyadic

differences (random effects, Table 2), affect and language patterns showed significant values. With respect to affect, the covariance between intercept and linear effect of age was significant (χ2[1] = 4.51, p < .05), with the variability decreasing nonlinearly toward the end of the second year of life. As regards language, significant differences between dyads were found for the intercept (σ2u0), the slopes (σ2u1), and the covariance between intercept and slopes (σ2u01) for the linear trend (respectively, χ2[1] = 4.27, p < .05; χ2[1] = 4.13, p < .05; χ2[1] = 4.21, p < .05). As shown in Figure 6, three of 10 dyads (dyads 8–10) started to increase the proportional duration of language patterns from about 14 months (65 weeks), whereas the others remained quite low until 18 months (80 weeks). buy Gefitinib Only at that age did these latter dyads begin to accelerate,

although at a slower rate than the former. Finally, the covariance effect signals that differences among dyads in the use of language become more selleck and more evident over time. Finally, intradyadic variance for the affect and language patterns showed a systematic time-dependent pattern. As to affect, the covariance between the intercept and the linear effect of age was significant (σ2e01 =.00004, χ2[1] = 3.73, p < .05), meaning that variability among sessions increased at the end of the observational period. As to language, the difference in proportional duration of these frames

among sessions was time dependent (σ2e1 = .00001, χ2[1] = 22. 56, p < .00), meaning that Phosphatidylinositol diacylglycerol-lyase this difference increased rapidly and in a nonlinear way with advancing infant age. As the covariance between the intercept and the linear component (σ2e01 =.00027, χ2[1] = 79.77, p < .00) was also significant, the sessions differed more at the end of the second year than at the beginning. Therefore, as for symmetrical patterns, language patterns also increased with a certain degree of fluctuation. This study aimed to examine mother–infant social play in the second year of life. With reference to Fogel’s (1993) model of interaction as a continuous adjustment between partners instead of a sequence of discrete acts, we focused on mother–infant interpersonal functioning during play rather than on individual behaviors. Communicative patterns were identified (Fogel, 1993) to distinguish different forms of coregulation, an intensive longitudinal design was adopted to match the developmental process as closely as possible, a multiple case study was used to make claims about the group as well as the individuals and, finally, a hierarchical linear analysis was performed to model the trajectories of different coregulation forms. We expected to find developmental transitions and individual differences.

He had been taking methotrexate (20 mg/week) for RA for 1 year, and continued until his demise. The patient had a past history of myocardial infarction, spontaneous deep vein thrombosis and pulmonary embolus. Examination revealed an afebrile, alert, cachectic man oriented to time and person but not to place. The patient displayed moderate paratonia, mild reduction of vibration sense in big toes, drifting of the left arm up and down when eyes were closed, dysdiadochokinesis and striking bilateral dysmetria in the arms and legs, left worse than right. He had an ataxic gait with marked

truncal instability and inconsistent stimulus-sensitive myoclonus. Laboratory investigations selleck kinase inhibitor were negative for click here anti-neuronal nuclear antibody 1 (ANNA-1), ANNA-2 and Purkinje cell antibodies, as well as for Lyme disease and HIV. Levels of serum gamma globulins were normal. CSF glucose, WBC and protein levels were within normal limits. The CSF was negative for JCV and BK viruses but was positive for 14-3-3 protein, raising the suspicion of CJD. Brain

MRI revealed non-enhancing white matter hyperintensities in the left cerebellar hemisphere. A repeat MRI scan 12 days later revealed “progressive vasogenic edema” suggestive of an acute progressive demyelinating disease. A CT scan of the chest, abdomen and pelvis Ergoloid was noncontributory. Due to his advanced age and the possibility of CJD, no further aggressive diagnostic procedure or treatment was undertaken. He continued to deteriorate and died at home 2 months after presentation. Standard set of neuropathology sections from all brain areas as well as samples

of grossly described abnormalities were removed for microscopic examination. The sections were processed to paraffin embedding and stained with HE, and in luxol fast blue with PAS methods. Selected sections were routinely immunostained for the following tissue antigens with commercially available primary antibodies (all from DAKO, Carpenteria, CA, USA): GFAP (polyclonal, 1:3000 dilution), ferritin (polyclonal 1:500), P53 (clone DO-7, 1:50) and neurofilament (NF, monoclonal, 1:4000, clone 2F11). Monoclonal antibodies against SV-40 T antigen (Calbiochem, 1:400) were used for initial detection of the virus. For the identification of inflammatory cells, monoclonal antibodies against CD3, CD4, CD8, CD45 and CD68 (Novocastra, Newcastle-upon-Tyne, UK; 1:50) were also applied. The streptovidin/biotin detection system (Invitrogen, Carlsbad, CA, US; “Histostatin Plus”) was used for visualization of the immune reactions and followed by a light hematoxylin counterstain. Immunohistochemistry was performed using LabVision autostainer.

Remarkably, the finding that PstS1 stimulates memory T cells specific for TT, suggests the potential exploitation of PstS1 immunomodulatory properties in other infections. Although effects on other APCs cannot be excluded, our study shows that the immunomodulatory properties of PstS1 are linked to its ability to activate DCs in vitro and in vivo. In particular, PstS1 promoted

the expression of IL-6, IL-1β, and, to a minor extent, IL-23. These cytokines were recently reported to drive a fine balance of CD4+ T-cell differentiation in the effector phase of the immune response to Candida albicans and Staphylococcus aureus [44]. Of interest, other cytokines pivotal for the homeostasis of memory T cells, such as IL-7

and IL-15 for CD8+ T cells [45], or IL-12p40 for Th1 Gemcitabine response [46], were Selleckchem JNK inhibitor not modulated by PstS1 (data not shown). The ability to stimulate DCs was peculiar to PstS1, since other immunodominant Mtb Ags such as Ag85B, Esat-6, or HBHA were unable to activate DCs (Fig. 4 and data not shown) and it was directed preferentially toward CD8α− DCs. The two major DC subsets of mouse spleen, CD8α+ and CD8α−, trigger distinct T-cell responses against pathogens. While CD8α+ DCs are thought to be specialized in antiviral response due to their unique cross-priming ability, CD8α− DCs have been involved in CD4+ T-cell immunity, particularly during bacterial infections [47]. CD8α− DCs efficiently induce CD4+ for T-cell responses through in vivo targeting of Ag via C-type lectin receptors, such as dectin-1 and DCIR-2 [30, 48]. The preferential ability of CD8α− DCs to prime CD4+ T-cell responses has been correlated with their superior capacity to process Ags via MHC class II molecules [30]. Accordingly, we report that PstS1 endowed CD8α− DCs with a strong ability to simulate CD4+ T cells. In particular, CD8α− DCs stimulated by PstS1 were found to produce much higher amounts of IL-6, IL-1β, and IL-23 with respect

to CD8α+ DCs. Moreover, PstS1-pulsed CD8α− DCs were far superior at inducing IFN-γ, IL-17, and IL-22 release by Ag85B-specific memory T cells, compared with CD8α+ DCs. The mechanisms by which PstS1 activates DCs remain to be established. Our data on DCs deficient for TLR2, the main PRR recognized by Mtb components, suggest that this receptor is dispensable. We envisage that the TLR2-independent pathway of DC maturation induced by PstS1 strongly differs from that triggered by the Mtb Ags Rv0577, Rv1196, Rv0978c, and Rv0754, which all recognize TLR2 and induce maturation of DCs leading to either Th1 or Th2 polarization, but not to IL-17 secretion by memory CD4+ T cells [14-18].

albicans following brief exposure to subtherapeutic concentrations of CG was studied. Fifty C. albicans planktonic oral isolates obtained from smokers, diabetics, asthmatics using steroid inhalers, partial denture wearers and healthy individuals were exposed to three subtherapeutic concentrations of CG (0.005%, 0.0025% and 0.00125%) for 1 h. Isolates

unexposed to CG was the control group. Thereafter the antiseptic was removed and the PAFE and phospholipase production was determined by a turbidometric method and a plate assay using an egg yolk agar medium respectively. Mean PAFE (hours) of 50 oral isolates of C. albicans following 1-h exposure to 0.005%, 0.0025% and 0.00125% CG was 6.97, 1.85 and 0.62 respectively. The phospholipase production Bortezomib of these isolates was significantly suppressed with a percentage reduction of 21.68, 18.20 and 14.04% following exposure to 0.005%, 0.0025% and 0.00125% CG respectively. Brief exposure of C. albicans isolates to subtherapeutic concentrations of CG would wield an antifungal

effect by suppressing growth and phospholipase production, thereby quelling its pathogenicity. “
“The efficacy of antifungal prophylaxis for prevention of invasive aspergillosis (IA) may depend on whether IA results from recent inhalation of spores or reactivation of latent colonisation. Compare the efficacy of liposomal Silmitasertib datasheet amphotericin B (LAmB) for prophylaxis in acute and reactivation models of IA. In the acute model, mice immunosuppressed from day 0 were challenged at day 3 with an aerosol of Aspergillus fumigatus. LAmB (15 mg kg−1) was administered at day 0 or at challenge. In the reactivation model, naïve mice exposed to A. fumigatus remained untreated until clearance of spores from the lungs, then immunosuppressed to induce reactivation. A single LAmB dose was administered at start of immunosuppression.

In the acute model, a single administration of LAmB at start of immunosuppression was not effective, but an additional administration resulted in a significant decrease in lung fungal burden (P < 0.05 vs. controls). A significant Dolichyl-phosphate-mannose-protein mannosyltransferase prophylactic efficacy was observed when LAmB was administered once at challenge (P < 0.01). In the reactivation model, a single LAmB administration at start of immunosuppression significantly reduced both reactivation rate and fungal burden vs. controls (P < 0.01). Our results show that the conditions under which IA develop and timing of administration of LAmB were determinant variables for prophylactic efficacy. "
“Malassezia species are part of the normal skin flora and are associated with a number of human and animal skin diseases.

Again, St1275 appeared to have stimulated significantly higher concentrations of IL-17 in all GIT co-cultured from buffy coat-derived PBMCs but lower concentrations or no production with CRL9850 or cord blood-derived PBMCs (Figs 1b and 2b). E. coli induced IL-10 secretion poorly from buffy coat PBMC. In contrast LAVRI-A1, B94, BL536,

ST1275 and LGG were found to stimulate high levels of IL-10 (Fig. 1b). From CRL9850 and cord blood-derived PBMCs, only LAVRI-A1, LGG, Bl536 and B94 induced significant (P < 0·05) levels of IL-10 production (Fig. 2a). Killed bacteria were able to induce substantial levels of all cytokines from buffy coat PBMC see more (Fig. 1c). Strikingly, only IL-10 was seen to be induced in significant amounts (P < 0·05) when

killed bacteria were incubated with the other cell types. PBMC incubation with LAB resulted in enhanced expression of CD25 on CD4+ T lymphocytes (Fig. 3), in line with Niers et al. SP600125 nmr [23]. To investigate whether treatment with lactobacilli or bifidobacteria lead to enhanced Th17 or Treg cell differentiation we assessed Th17/Treg populations in PBMC following 72–96 h of treatment with live or heat-killed bacteria. In all cases, following 72–96 h co-culture the number of Treg (CD4+CD25+FoxP3+) cells as a percentage of total PBMC increased substantially compared to untreated control cells, albeit to different levels [Fig. 4a(i) and a(ii)]. BL536 and B94 were found to be the most potent live strains and LAVRI-A1, B94 and St1275 the most potent heat-killed strains at inducing FoxP3 expression. The capacity of Y-27632 2HCl live or killed bacteria to induce IL-17-producing cells from PBMC was also

investigated. As shown in Fig. 4b, the number of IL-17-expressing CD3+CD4+ cells was increased substantially compared to control. Because Th17 cells typically produce IL-17 in culture, it was therefore likely that these cells were of the Th17 lineage. To confirm Th17 cell identity, extracellular marker CCR6 (CD196) and intracellular marker ROR-γt were subsequently used. The proportion of Th17 cells (CD3+CD4+CCR6+ROR-γt+) induced by live and killed bacteria was increased 2·5-fold above control [Fig. 4b(i) and b(ii)], with Bl536 being the most potent strain (P < 0·01). Interestingly, the induction of Th17 cells by the stimulation of PBMCs with E. coli or LPS were similar. Probiotic bacteria are commonly marketed to aid digestion and optimize microbial balance in the GIT. The current studies assessed the capacity of probiotic bacteria to affect the local cytokine production and regulatory cell populations among different cell types.

This study was designed to find out whether concurrent administration of alfuzosin and tadalafil to patients with LUTS due to BPH improves the beneficial effects of each drug administered alone. As the prevalence of both LUTS and ED increases with age, physicians could be in a position to

manage both of these conditions simultaneously using these drugs. After approval from the institutional ethics committee and written informed consent from all participants, men > 50 years of age and International Prostate GDC-0068 purchase Symptom Score (IPSS) ≥ 8 were randomized to receive a 12-week treatment with either alfuzosin 10 mg once daily, tadalafil 10 mg once daily, or the combination of both. The study conformed to the provisions of the Declaration of Helsinki (as revised in Edinburgh 2000). Exclusion criteria

were according to the specified contraindications of both the drugs. Patients were advised to take alfuzosin each day after the same meal and tadalafil at bed time. Patients were assessed at baseline, 6 weeks and after 12 weeks of treatment. Subjective LUTS was assessed by IPSS total, IPSS-Storage subscore (IPSS-S) and IPSS-Voiding subscore (IPSS-V). Other AZD0530 chemical structure LUTS-related measurements included maximum urinary flow rate (Q max), post-void residual urine (PVR) volume and IPSS quality of life score. Erectile function was concurrently assessed by the erectile domain score (EDS, the sum of responses to questions 1–5 and 15) of the International Index of Erectile Function (IIEF). Safety was evaluated by noting the occurrence of side-effects due to the drug therapy. To summarize the result statistically, total number or percentage was reported. Normality of the measurable data was tested by Kolmogorov Smirnov test. All three groups were compared for normally distributed data by analysis of variance (anova) followed by post Hoc test student Newman Kuel procedure for pairwise comparison.

Within the same group the variables were compared by paired t-test and variables between the groups were compared using unpaired t-test. The skewed data were analyzed for all the three groups using Kruskal–Wallis test, anova followed by Mann–Whitney test for pairwise comparison. All the classified/categorical data were analyzed for all the three groups using χ2. A P-value < 0.05 was considered as significant. A total of 75 men were randomized to receive alfuzosin 10 mg once daily (n = 25), Fenbendazole tadalafil 10 mg once daily (n = 25), or the combination of both (n = 25) for 12 weeks. The patient disposition is summarized in Figure 1. All the patients completed the study. Patient baseline clinical characteristics are shown in Table 1. Overall baseline demographics and patient characteristics were similar across the treatment groups. International Prostate Symptom Score total, IPSS-S and IPSS-V significantly improved at 6 weeks in all three treatment groups (P < 0.001) but the improvement with the combination therapy was similar to alfuzosin (P = 0.121) but greater than tadalafil (P < 0.

There was no eosinophilia and the urine sediment was bland consistent with a diagnosis of acute tubular necrosis (ATN). There was no further clinical improvement and at week 8 he underwent Fostamatinib supplier a diagnostic renal biopsy (Figs 1,2). The lung transplant biopsy showed lung parenchyma comprised of bronchopulmonary tissue and lymphovascular bundles. There was no evidence of allograft rejection, inflammation or other pathology. The renal biopsy contained 26 glomeruli and they showed mild mesangiopathic changes

and no evidence of a glomerulitis. A few glomeruli showed ischaemic obsolescence. The pathology was seen mainly in the tubules and focally in the interstitium. The tubules showed variable dilatation of the lumina and many of them were expanded by crystals, which were translucent. There were patchy areas of tubular cell degeneration, necrosis and debris in the lumen. Some tubular epithelial cells showed large vacuoles and loss of the brush border. There were focal areas of tubular atrophy and interstitial

fibrosis and mild cellular lymphocytic infiltration. Polarized microscopy showed birefringent crystals with some showing all colours of the rainbow. Some crystals were combined with calcium deposits (see Figs 1,2). Immunofluorescence microscopy showed no immunoglobulin, complement or light chain deposits. Electron microscopy showed crystals in tubular epithelial cells and in the lumen. They also showed patchy epithelial cell necrosis. The pathology features are those of an oxalate nephropathy with tubular obstruction Talazoparib price and epithelial necrosis. There are foci of tubular atrophy and interstitial fibrosis, with mild lymphocytic inflammation. The diagnosis of an acute oxalate injury was made and was felt most likely to be related

to enteric hyperoxaluria. A diagnosis of primary hyperoxaluria was unlikely, as measured urinary precursors of oxalate metabolism, Rebamipide using liquid chromatography, including urine glyoxylate, glycerate and glycolate, were not raised. There was no history of excessive ascorbic acid intake. A 24 h urine collection for oxalate showed an initial value of 367 µmol/day (normal <550 µmol/day). While within the normal range, this was in the setting of renal failure and severely reduced glomerular filtration with a low urine volume, and was likely to be a significant underestimation. Plasma oxalate was not measured. Given the absence of pretransplant renal injury or evidence for renal calculi or nephrocalcinosis, it was hypothesized that the interruption to pancreatic supplementation during his ICU stay and continuous nasogastric feeding led to lipid malabsorption with enteric calcium sequestration and increased enteric oxalate absorption with a rapid rise in serum oxalate. Severe reduction in glomerular filtration as a consequence of the vasomotor injury at the time of transplant and ATN allowed deposition of calcium oxalate crystals into sites of tissue injury, eliciting an inflammatory response and precluding reversal of tubular injury.

In brief, C. albicans, Selleckchem BYL719 strain MYA-2876 (ATCC, Manassas, VA, USA), was cultured following the Shandong Eye Institute Biosafety Code. Blastospores were harvested, washed, and suspended in a saline buffer at a concentration of 1 × 108/mL. For all experiments, at least four mice were included in one group setting for each readouts, except

for otherwise stated. For inoculation, the corneas were pierced near the center with a 30-gauge needle through to the stroma. A 33-gauge needle with a 30-degree bevel (Hamilton, Reno, NV, USA) was used to inject 1 μL of blastospore suspension (1 × 105) into the center of the cornea of only the left eye. In the sham-infection group, the same volume of saline buffer was substituted for the fungal suspension. In some experiments, 10 ng CXCL2 (Cell Sciences, Canton, MA, USA) was included with each suspension. The corneas were monitored daily (or at shorter intervals during the first day postinfection in some experiment) using a slit lamp equipped with a FDA-approved Drug Library cost digital camera, and assessed according to a 12-point scoring system [48]. Briefly, the disease was scored according to three indexes, namely area of corneal opacity, density of corneal opacity, and surface regularity, each of which

was given a grade of 0–4, with the highest score for uniform opacity in over three-quarters of the corneal area, perforation (never seen in this study), and descemetocele. At the desired time points, blood was collected from individual mice via tail venipuncture and used for ELISA measurement of cytokines. Some mice

were euthanized, MG-132 nmr and the corneas were harvested using a 2 mm diameter trephine and used for histological analysis, pathogen burden assay, or mRNA expression assay, as described below. To establish the dermatitis models, C. albicans blastospores (1 × 105) were inject into the deep dermis layers of ear skin. The injection sites were monitored daily for redness, swelling, and other clinical signs, and pictures were taken using a digital camera. Numeric scoring of the disease was not attempted. All antibodies and their usage protocols for cell depletion or cytokine neutralization are detailed in Supporting Information Table 1. Briefly, the mice were treated via intraperitoneal injection with anti-CD4, anti-CD25, anti-TCRγδ, or their respective isotype controls for three consecutive days starting from day 4 before CaK induction. Alternatively, they were treated only once with anti-IL-23p19, anti-IL-17A, anti-IFN-γ (5 h after infection), or their isotype controls. The dose for each injection was 100 μg for anti-CD4, anti-CD25, or their controls, 150 μg for anti-Ly-6G, and 200 μg for all others. The depletion rate of CD4+, CD25+, and γδ T cells was confirmed by flow cytometry to be >99%, and >95% by ELISA analysis of corneal IL-17A production at 24 h after CaK induction in BALB/c mice treated with anti-IL-23p19 or anti-IL-17A mAbs (data not shown).

, 2000; Döring & Høiby, 2004). Another example of recalcitrance to antibiotic treatment is chronic OM, which is distinguished from acute OM. Two types of chronic infection profiles are described:

OM with effusion (OME) where the effusion persists for > 3 months, or, a recurrent infection often referred to as recurrent acute OM or RAOM, www.selleckchem.com/products/VX-809.html where fluid resolves between recurrent events (Hall-Stoodley et al., 2006; Post et al., 2007). Both types are consistent with other BAI, exhibiting recurrent acute symptoms after repeated cycles of antibiotic therapy without eradication of the underlying infection. This is thought to be due to the release of planktonic bacterial cells from biofilms and their susceptibility to antibiotic treatment when microorganisms are not aggregated (Costerton et al., 1999), while the biofilm causes a persistent infection that elicits a low grade inflammatory response. Evidence that recurrent OM, in addition to OME, is a BAI was shown using both immunofluorescent methods with pathogen-specific antibodies and FISH pathogen-specific 16S rRNA gene probes to demonstrate bacterial pathogens attached to the middle ear mucosa in children having tympanostomy tube placement for the treatment of recurrent OM in addition to OME (Hall-Stoodley et al., 2006). Criteria 4 and 5 illustrate that antimicrobial

recalcitrance or evidence of greater tolerance Decitabine nmr is an important indication of BAI and may be linked to the failure of culture to identify a pathogen in fluid samples. Criterion 5 also suggests that other diagnostic guidelines are needed if BAI do not PAK6 yield culture-positive results. In CF, three additional criteria are used to diagnose biofilm infection: (1) continued isolation of P. aeruginosa from sputum for at least 6 months, (2) detection of the alginate producing mucoid phenotype of P. aeruginosa, and (3) an

increase in anti-P. aeruginosa antibodies (Pressler et al., 2006, 2009; Proesmans et al., 2006). Reliance on culture as the ‘gold standard’ of medical microbiology exclusively for the identification of bacterial pathogens as a diagnostic criterion in clinical laboratories is not clear-cut with BAI. Numerous publications indicate a discrepancy between culture and molecular diagnostic methods. In OME, culture identifies a pathogen around 25–30% of the time, while culture-independent methods such as PCR and/or FISH identify pathogens 80–100% of the time (Post et al., 1995; Hall-Stoodley et al., 2006). This discrepancy was not because of the amplification of DNA from dead bacteria (Aul et al., 1998; Dingman et al., 1998) and contrasts with acute OM where culture successfully identifies a pathogen over 90% of the time (Post et al., 1995; Rayner et al., 1998). Infectious endocarditis also has a proportion of cases (as much as one-third) that fail to grow bacteria in culture.