laminaran and Mycoses

With the high mortality rate associated with invasive fungal infections, methods for timely detection and diagnosis are necessary for appropriate and effective treatment. Testing for 1,3-β-D-glucan, a cell wall component of many medically important fungi, can be a useful adjunct in diagnosing such infections. The Fungitell assay (Associates of Cape Cod, East Falmouth, Massachusetts) is a US Food and Drug Administration-approved laboratory test that quantitatively measures 1,3-β-D-glucan levels and is widely available for clinical use as a relatively noninvasive method to aid in detecting the presence of invasive fungal infections. Numerous studies have evaluated its performance in clinical settings, and results have, overall, been favorable. It is not without its drawbacks, however, and the test must be interpreted and applied with care. Ordering practices are also widely variable among clinicians, and official guidelines have not been readily available. We present the details of this test and aim to propose evidence-based guidance for its use.

Topics: beta-Glucans; Humans; Microbiological Techniques; Mycoses; Sensitivity and Specificity

The serum 1,3-beta-D-glucan (BG) assay aids in the early diagnosis of invasive fungal diseases (IFDs) and has been approved for their diagnosis. However, reports on the screening performance of BG are scarce. We performed a meta-analysis of data extracted from only prospective cohort studies to evaluate the screening performance of the BG assay in the diagnosis of IFDs. We specifically searched 4 databases (the PubMed, Web of Science, Elsevier, and Cochrane Collaboration databases) according to EORTC-MSG criteria. A total of 1068 patients in 11 studies were analyzed. Deeks' funnel plot asymmetry test suggested a low likelihood of publication bias for the included studies (p = 0.055). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve, with 95% confidence intervals, were 0.75(0.63,0.84), 0.87(0.81,0.92), 5.85(3.96,8.63), 0.30(0.20,0.45), 19.53(11.16,34.18), and 0.89(0.86,0.91), respectively. The findings of this meta-analysis suggest that the BG assay is a useful screening tool with high sensitivity and specificity for discriminating between patients with and without IFDs. In clinical practice, BG assay results should be evaluated together with clinical and microbiological findings.

Topics: beta-Glucans; Humans; Mycoses; Prospective Studies; Sensitivity and Specificity

Fungal infections are of great relevance in surgical intensive care and Candida species represent the predominant part of fungal pathogens. Invasive aspergillosis is also relevant especially in patients with chronic pulmonary diseases. It is crucial for therapy success to begin adequate antifungal treatment at an early stage of the disease. Risk stratification of individual patient symptoms is essential for therapy timing. In case of suspected or proven candida infection, fluconazole is the agent of choice when the patient is clinically stable and no azoles have been administrated in advance and the local epidemiology makes azol resistance unlikely. For clinically instable patients with organ dysfunction the echinocandins serve as primary therapy because of their broad spectrum and reasonable safety profile. Due to a relevant proportion of azole resistant Candida species, susceptibility testing should be done routinely. Depending on the species detected de-escalating to an azole is feasible if organ dysfunctions have resolved. An invasive aspergillosis is primarily treated with voriconazole.

Topics: Adjuvants, Immunologic; Antifungal Agents; Azoles; beta-Glucans; Candidiasis; Critical Care; Cryptococcosis; Echinocandins; Galactose; Humans; Mannans; Mucus; Mycoses; Polyenes; Reverse Transcriptase Polymerase Chain Reaction; Risk Assessment; Tomography, X-Ray Computed

In the last few years, major advances in the treatment of transplant recipients, with hemato-oncological diseases or admitted to the intensive care unit, has been accompanied by an increase in classical fungal infections and by the emergence of uncommon fungal infections. Despite the development of new diagnostic techniques such as galactomannan detection and the availability of new antifungal agents, these opportunistic infections continue to pose a diagnostic challenge, prolong length of hospital stay, and increase costs. In addition, mortality from these infections is high. The present chapter provides a brief review of the epidemiology of these infections, diagnostic advances, and the new antifungal agents that have been developed in the last few years.

Topics: Anidulafungin; Antifungal Agents; Aspergillosis; beta-Glucans; Candidiasis; Clinical Trials as Topic; Critical Care; Diabetes Complications; Disease Susceptibility; Echinocandins; Fungemia; Galactose; Hematologic Diseases; Humans; Immunocompromised Host; Mannans; Meta-Analysis as Topic; Mycoses; Neoplasms; Opportunistic Infections

Measurement of (1-->3)-beta-D-glucan for invasive fungal infection is used practically in Japan. The problem of false positive results due to the frequent occurrence of non-specific reaction in alkaline treatment, chromogenic automated kinetic assay to measure (1-->3)-beta-D-glucan had been recognized in Japan. But this important problem was resolved in July 2005 by improvement made in the pretreatment reagent in a (1-->3)-beta-D-glucan measurement kit. In this manuscript, we describe the process of improvement of this kit and its clinical usefulness.

Topics: beta-Glucans; Biomarkers; Clinical Chemistry Tests; False Positive Reactions; Humans; Mycoses; Predictive Value of Tests; Reagent Kits, Diagnostic; Sensitivity and Specificity

The echinocandins are a new and unique class of antifungal agents that act on the fungal cell wall by way of noncompetitive inhibition of the synthesis of 1,3-beta-glucans. All agents of this class are of parenteral formulation, with no oral preparations available. Caspofungin (Cancidas) was the first approved echinocandin, followed recently by micafungin (Mycamine) and anidulafungin (Eraxis). The precise role of the echinocandins in the antifungal armamentarium is still unfolding. Caspofungin is approved for the treatment of candidal esophagitis and candidemia, salvage therapy of Aspergillus infections and for empirical therapy of febrile neutropenia. Micafungin is likewise approved for candidal esophagitis, in addition to antifungal prophylaxis for hematopoietic stem cell transplant recipients. Anidulafungin is also approved for treatment of candidal esophagitis, as well as therapy of candidemia. There has been anecdotal use of these agents to treat less common fungal pathogens, as well as limited use as a component of combination antifungal therapy. The echinocandins are an important addition to the antifungal armamentarium in the treatment of fungal infections in both immunocompromised patients and those with normal immunity.

Topics: Anidulafungin; Animals; Antifungal Agents; beta-Glucans; Caspofungin; Echinocandins; Fungal Proteins; Humans; Lipopeptides; Lipoproteins; Micafungin; Mycoses; Peptides, Cyclic

Topics: beta-Glucans; Biomarkers; Cellulose; Deferoxamine; Glucans; Humans; Membranes, Artificial; Mycoses; Peritoneal Dialysis, Continuous Ambulatory; Reagent Kits, Diagnostic

Topics: Amphotericin B; Antifungal Agents; beta-Glucans; Biomarkers; Disease Progression; Fatal Outcome; Fluconazole; Glucans; Humans; Immunocompromised Host; Male; Middle Aged; Mycoses; Otorhinolaryngologic Diseases; Risk Factors

Early diagnosis and treatment for an immunocompromised patient with a deep-seated mycosis are very important for the prognosis of the patient. Several methods of serodiagnosis for deep-seated mycosis have been developed and are clinically available. Detection of (1,3)-beta-D-glucan from serum samples of a patient can be evaluated with high sensitivity and specificity. Antigens detection test for fungi is another useful method for this serodiagnosis. A novel sandwich ELISA to detect galactomannan has higher sensitivity than the latex agglutination test. The cryptococcus capsular antigen detection technique is also very useful for patients with cryptococcosis. Thus, serodiagnosis for deep-seated mycosis appears to be a useful tool for treatment of immunocompromised patients.

Topics: Antigens, Fungal; beta-Glucans; Biomarkers; Glucans; Humans; Immunocompromised Host; Mycoses; Sensitivity and Specificity; Serologic Tests

The dramatic increase in nosocomial invasive mycoses over the past two decades has led to increased interest in the area of antifungal development. Unfortunately, the infusion of new diagnostic technology into the clinical mycology laboratory has lagged behind. Although newer, automated, continuous-monitoring blood culture systems are as sensitive as the older, manual "gold standard" system, the recovery of fungi from blood, as well as other clinical specimens, remains an insensitive marker for invasive fungal infection. Antigen assays for the rapid diagnosis of invasive fungal infections are in development, and galactomannan and glucan are two such promising antigens. Glucan may be present in the blood of patients with infection secondary to a wide variety of fungal pathogens, including Candida, Aspergillus, Fusarium, Saccharomyces, Trichosporon and Acremonium species. Early data suggest galactomannan may be present in the blood in detectable levels very early in the course of invasive aspergillosis. The galactomannan assay currently undergoing evaluations may actually be positive prior to the clinical suspicion for infection and may be useful in monitoring therapeutic response as well; however, the etiology of false-positive results following cytotoxic chemotherapy still has to be elucidated. PCR assays are also being developed in the research laboratory, however, the PCR assays will require a significant amount of adaptation and validation before they are ready for clinical care. Well-planned studies to evaluate the performance characteristics as well as appropriate clinical and cost-effective application of these new tests are needed.

Topics: Antigens, Fungal; Aspergillosis; beta-Glucans; Biotechnology; Candidiasis; Centrifugation; Culture Media; Enzyme-Linked Immunosorbent Assay; Fungemia; Glucans; Humans; Immunocompromised Host; Mannans; Medical Laboratory Science; Membrane Glycoproteins; Mycoses; Polymerase Chain Reaction

Liver transplantation is one of the transplant fields where invasive mycosis is frequently encountered. The diagnosis of fungal infection in this population is often very difficult due to the fact that the liver itself is a key organ for immune defence for infection and due to immunosuppressive state of the patient. Although the majority of fungal infection is caused by Candida, Aspergillus infection is gradually increasing and mortality following invasive infection, often multifactorial, reaches to 70%. A characteristic feature of the infection in liver transplant recipients is the high incidence of preceding occult infection, often from the pretransplant period. Although the specificity is not satisfactory, peritransplant screening culture for fungi is a good prognostic parameter. Plasma beta-D-glucan is also very useful in the decision for preemptive treatment, although its plasma level is potentially affected by the reticuloendothelial system of the grafted liver. Referring to these parameters, avoidance of excessive antibiotics and/or immunosuppressants, maintenance of graft function, and a high index of suspicion are always necessary.

Topics: beta-Glucans; Biomarkers; Fungi; Glucans; Humans; Immunocompromised Host; Immunosuppressive Agents; Liver Transplantation; Mycoses

Invasive deep mycoses following bone marrow and solid-organ transplantation remain a major cause of morbidity and mortality. Species of Candida and Aspergillus account for more than 80% of these mycoses. Because these infections are often difficult to diagnose and treat successfully, antifungal prophylaxis is recommended in high-risk patients. Fluconazole is useful in patients who are at risk of invasive candidiasis, including bone marrow transplants, liver and pancreatic transplants. Although invasive aspergillosis is frequent in patients with bone marrow, lung and heart transplantation, no established methods have been available for its prophylaxis. Recently, efforts to improve the efficiency of diagnostic tests have been directed toward the detection of fungal components or metabolites. The requirements for clinical use (monitoring) are as follows: capability of early diagnosis, quantitative measurement, and easy sampling and simple assay procedure. The detection of plasma (1-3)-beta-D-glucan (BDG), a characteristic cell wall component of almost all fungi, is widely used in Japan. Twenty-seven episodes of fungemia were observed in our hematology ward and all were positive with BDG. Positive results were observed before the documentation of fungemia in 14 patients (51.9%). Although the positive rate of BDG also was 100% in 17 patients with invasive aspergillosis, it rose slightly at an early stage of the disease in 13 patients (76.5%). The determination of plasma BDG appears useful in the monitoring of deep fungal infection, but its usefulness for early diagnosis remains to be determined. The utility of detection of Aspergillus galactomannan by ELISA and fungal DNA by polymerase chain reaction are also discussed.

Topics: Animals; Antifungal Agents; Antigens, Fungal; beta-Glucans; Biomarkers; Galactose; Glucans; Humans; Mannans; Monitoring, Physiologic; Mycoses; Organ Transplantation; Polymerase Chain Reaction; Postoperative Complications

Candidemia is still a major source of high morbidity and mortality in severely disease patients. However, the etiology and risk factor is still unknown.. To evaluate the risk factor of fungal infection in intensive care patients.. 505 patients who stayed in the intensive care unit of the Critical Care Center, Kyorin University more than 10 days between May 1, 1997 to June 31, 1998 were studied. They were divided into 7 groups: 1) trauma (injury severity score<10), 2) burn (burn index<10), 3) cerebro-vascular disease (unconsciousness15), were in a coma, and had severe injury of lung parenchyme with chest AIS 3 or higher. In these serious patients, it is necessary to make a rapid diagnosis and treatment based on the surveillance culture and serological examination of sputum and urine for occult fungal infection.

Topics: Antifungal Agents; beta-Glucans; Biomarkers; Fungi; Glucans; Humans; Immunocompromised Host; Intensive Care Units; Length of Stay; Mycoses; Respiration, Artificial; Risk; Severity of Illness Index

Plasma (1-->3)-beta-D-glucan determination has been developed for the diagnosis of fungemia and deep mycosis to make up for the low yield of blood culture. This method uses Factor G, a coagulation enzyme of the horseshoe crab that is highly sensitive to this glucan. Since (1 -->3)-beta-D-glucan is a characteristic fungal cell-wall constituent which is common to virtually all fungi, the method aims to screen fungal infections as a whole. This is advantageous today when new fungi are appearing one after another as a causative agent of opportunistic deep fungal infections. Plasma (1-->3)-beta-D-glucan concentrations in 60 normal individuals were less than 10pg/ml. With a cutoff value at 20pg/ml, the sensitivity of the test was 90%, and the specificity was 100%. No cases of fungal colonization showed values above the cutoff level. In addition to invasive candidiasis, aspergillosis, and cryptococcosis, trichosporonosis was also found positive with the test. Glucanemia was not associated with primary cryptococcosis, probably because the growth of the organism is checked by the competent immunity in these afebrile patients. Levels of plasma (1-->3)-beta-D-glucan were variable in aspergilloma, indicating that the disease is essentially a colonization, but that (1-->3)-beta-D-glucan may appear in the blood when cavitary walls are invaded, depending on the integrity of local or systemic immunity. In addition to being useful for diagnosis, the test is also helpful in initiating early treatment of deep mycosis with improved survival.

Topics: beta-Glucans; Clinical Trials as Topic; Glucans; Humans; Multicenter Studies as Topic; Mycoses; Sensitivity and Specificity

Fungal infections are increasingly common and, in certain vulnerable patients, can be serious and even life threatening. The fungal cell wall, a structure with no mammalian counterpart, presents an attractive therapeutic target. Inhibitors of the synthesis of one cell-wall component, beta-(1,3)-glucan, are currently under development as antifungal and antipneumocystis agents.

Topics: Antifungal Agents; beta-Glucans; Carbohydrate Sequence; Cell Wall; Chitin; Chitin Synthase; Glucans; Glucosyltransferases; Molecular Sequence Data; Mycoses

The purpose of this study was to evaluate a preemptive approach with serum 1,3-beta-d-glucan (BDG) as a marker for treatment stratification of systemic antifungal (AF) therapy in patients with clinical suspected invasive fungal infections (IFI) at intensive care units (ICU), and the impact of surgical procedures. A total of 66 ICU patients with clinical suspected IFI were included in this retrospective analysis. Serum BDG testing was performed prior to initiation of AF treatment and in addition to routine diagnostic measures. Based on the BDG results the initial clinical decision whether or not to start systemic AF therapy was re-evaluated. Impact of surgical procedures on clinical utility of serum BDG was evaluated in a sub-group of 25 patients who had undergone surgical procedures prior to BDG evaluation. BDG test results led to discontinuation of AF therapy in 13 patients, and initiation of AF therapy in seven patients. In 46 patients the clinical decision was confirmed by BDG. The majority of suspected, probable and proven IFI cases (10/13, 77%) was predicted by the test. BDG testing turned out positive in 9/25 (36%) of patients that had undergone recent surgery and levels correlated with clinical findings. Serum BDG evaluation seems to be a promising tool to guide AF therapy in ICU patients even after recent surgical procedures.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Aspergillus; beta-Glucans; Candida; Female; Humans; Intensive Care Units; Male; Middle Aged; Mycoses; Retrospective Studies; Young Adult

The prevalence of fungal infection (FI) in developing countries is high, but the diagnosis of FI is still challenging to determine, so it is needed evaluation of biomarkers other than microbiological culture, because the culture has low sensitivity, high cost, not available in every laboratory and needs a long time. The detection of human galactomannan Aspergillus antigen (GAL) and 1,3-beta-D-glucan (BDG) on the fungal cell wall could be the promising biomarkers for fungal infection. Neutropenia, lymphopenia and CD4T cells in the immunocompromised patients are essential factors, but these cell associations with BDG and GAL levels have not been evaluated yet. The study aimed to evaluate GAL and BDG for detecting fungal infection and their association with total leucocyte count, neutrophil, monocyte, lymphocyte and CD4T cells.. A cross-sectional study was conducted among 86 patient with suspected FI. Fungal infection established using EORTC/MSG criteria. Serology test performed using ELISA. Leucocyte cells were measured using a haematology autoanalyser, and CD4T cells were analysed using BD FACSPresto. Statistical analysis obtained using Spearman's correlation coefficient, ROC curve analysis and 2 × 2 contingency table.. Serum Galactomannan and BDG had a significant correlation with CD4T cells and total lymphocyte count (p < 0.05). The cut-off OD GAL >0.3 had sensitivity 54.6%, specificity 87.5% and AUC 0.71; meanwhile, the BDG cut-off >115.78 pg/ mL had sensitivity 71.2%, specificity 52.4% and AUC 0.63 for detecting fungal infection.. The immunocompromised patients can undergo GAL for determining the diagnose of FI. The lower the CD4T cells and total lymphocyte count, the higher the GAL and BDG serum levels.

Topics: Adolescent; Adult; Aged; Antigens, Fungal; Aspergillus; beta-Glucans; Cross-Sectional Studies; Female; Follow-Up Studies; Galactose; Humans; Immunocompromised Host; Male; Mannans; Middle Aged; Mycoses; Prognosis; Young Adult

The presence of (1 → 3)-β-D-glucan in human plasma is a marker for fungal infections. Currently, the Limulus amebocyte lysate (LAL)-based assay is widely used for the quantification of plasma (1 → 3)-β-D-glucan. However, it has limitations in clinical use, such as an unstable supply of natural resources, complicated manufacturing process, and low-throughput of the reagents. Alternative assays exploiting specific antibodies against (1 → 3)-β-D-glucan have been developed to overcome these challenges. However, these methods are associated with low sensitivity and poorly correlate with the data obtained by the LAL-based assay. The aim of this study is to develop a novel enzyme immunoassay that is as sensitive and accurate in determining plasma (1 → 3)-β-D-glucan levels as compared to that obtained with the LAL-based assay. We generated specific monoclonal antibodies against (1 → 3)-β-D-glucan that recognizes four-unit glucose oligomers with (1 → 3)-β-D-linkages, and constructed a sandwich enzyme-linked immunosorbent assay (ELISA) using these antibodies. The newly developed ELISA showed proportional increase in absorbance with the volume of (1 → 3)-β-D-glucan added. The limit of detection of the assay was 4 pg/ml of plasma (1 → 3)-β-D-glucan that was equivalent to the LAL-based assay and the working range was 4-500 pg/ml. The intra-assay coefficient of variation was 2.2-5.4% using three different concentrations of plasma samples. We observed strong correlation (R = 0.941, slope = 0.986) between the measurements obtained by our ELISA and Fungitec G test ES Nissui, a commonly used LAL-based assay, using 26 types of plasma samples. This could be attributed to the epitopes of the antibodies. Both antibodies could inhibit the LAL-based assay, suggesting that the antibodies recognize the identical regions in β-D-glucan, thereby inactivating factor G, an initiation zymogen for coagulation cascade, in the LAL-based assay. Thus, the ELISA developed in this study can detect fungal infections in clinical settings with similar efficiency as the LAL-based assay. This assay is characterized by good performance, stable supply of materials, and simple manufacturing process and is more suitable for the high-throughput diagnosis of fungal infections.

Topics: Antibodies, Monoclonal; Antibody Affinity; Antibody Specificity; beta-Glucans; Biomarkers; Enzyme-Linked Immunosorbent Assay; Epitopes; Humans; Limulus Test; Mycoses; Predictive Value of Tests; Reproducibility of Results

Molecular changes associated with response to powdery mildew (PM) caused by

Topics: Down-Regulation; Energy Metabolism; Gene Expression Regulation, Plant; Genotype; Glucans; Mycoses; Photosynthesis; Plant Diseases; Plant Growth Regulators; Plant Leaves; Transcription, Genetic; Transcriptome; Vitis

Topics: Aspergillosis; beta-Glucans; Candidiasis; Humans; Mycoses; Plasma; Pneumonia, Pneumocystis; Reagent Kits, Diagnostic; Sensitivity and Specificity; Serologic Tests; Serum

1,3-ß-D-glucan (BDG) is increasingly used to diagnose invasive fungal infections (IFI), although false positive results are a concern. To evaluate the potential interaction of blood products with the BDG assay, human albumin (HA), fresh frozen plasma (FFP), undiluted platelet transfusion (UPT) and packed red blood cells (PRBC) were tested for their BDG content using two different b-D-glucan tests. UPTs tested negative, FFP, PBRC and HA tested positive for BDG. In serial dilution, BDG concentration correlated with blood product concentration. To investigate the clinical impact of blood product transfusions, we measured BDG levels before and after the transfusion in three patients (2 PRBC, 1 HA). In the patients receiving PRBC transfusions, BDG values increased from 13 and 17 pg ml(-1) to 183 and 361 pg ml(-1), the HA transfusion increased the serum level from 42 to 58 pg ml(-1). BDG concentrations measured in blood products can be used to predict false positive BDG results.

Topics: beta-Glucans; Blood Component Transfusion; Blood Platelets; Erythrocytes; False Positive Reactions; Humans; Mycoses; Plasma; Serum Albumin

Topics: beta-Glucans; Humans; Mycoses

The diagnosis of neonatal invasive fungal disease (IFD) is difficult and often delayed. The platelet parameters and (1, 3)-β-D-Glucan (BG) may be useful for diagnosing IFD, but their diagnostic performance are not well characterized in neonates. We studied 63 preterm infants with IFD, 160 preterm infants without sepsis (preterm control), and 41 preterm infants with bacterial sepsis. Platelet parameters at the first day of onset of IFD and at the fourteenth day after antifungal treatment were evaluated. Serum BG was measured. Platelet count (PC), plateletcrit (PCT), and platelet distribution width (PDW) values were significantly lower, and mean platelet volume (MPV) values significantly higher in the IFD versus preterm control infants. PC and PCT values were much lower in infants with IFD versus bacterial sepsis, and there were significant differences in BG value between the two groups. After 14 days of antifungal treatment, significant elevations in PC, PCT, PDW and reductions in MPV levels in IFD group were observed. Receiver operating characteristic (ROC) curves showed that PC and PCT were strong predictors of IFD. The PC and PCT cut-offs for predicting IFD were 119.5 (sensitivity 78%, specificity 95%) and 0.21 (sensitivity 83%, specificity 85%), respectively. There were significant differences in PC and PCT levels between deceased and survived patients. The PC and PCT cut-offs for predicting deceased IFD were 39 (sensitivity 62%, specificity 86%) and 0.04 (sensitivity 50%, specificity 95%), respectively. The sensitivity in diagnosing IFD by a BG cutoff of ≥10 pg/ml was 68.3% and specificity was 75.6%. PC and PCT levels in the BG ≥400 pg/ml group were significantly lower compared to the BG<400 pg/ml group. Platelet parameters and BG could be useful biomarkers for the diagnosis and prognosis of neonatal IFD.

Topics: beta-Glucans; Biomarkers; Blood Platelets; Case-Control Studies; Female; Fluconazole; Humans; Infant, Newborn; Infant, Premature; Male; Mean Platelet Volume; Mycoses; Platelet Count; Prognosis; ROC Curve; Sensitivity and Specificity; Sepsis

Using 415 residual blood samples subjected to (1→3) -β-D-glucan assay, we studied the correlation of measurement results between Fungitec G Test MKII "Nissui" (Nissui Pharmaceutical Co., Ltd., Tokyo) and its predecessor, Fungitec G Test MK (Seikagaku Corporation, Tokyo), which is now out of production. Their major difference is that MK II uses reagents derived from blood cells of Limulus polyphemus, the American horseshoe crab, whereas MK used those of Tachypleus tridentatus, an Asian horseshoe crab. Passing-Bablok analysis showed a linear regression with nearly one-to-one correspondence (slope=1.065, intercept=-0.287) between the two test kits over the regular range of measurements (4.0 pg/ml -500 pg/ml ). This was also true when data were subdivided and analyzed in the low to medium (≦150 pg/ml ) and in the low range (≦50 pg/ml ). There were several cases, however, that showed a wide discrepancy between the pair of measurements. This discrepancy is believed to be due in part to the difference between Limulus and Tachypleus in their reactivity to β-glucans with diverse side chains. Despite of this, the even distribution on either side of the regression line of those samples that are associated with deep fungal infection and the abrupt disappearance of such samples below 20 pg/ml attest that MK II "Nissui" is an acceptable successor of MK.

Topics: Animals; beta-Glucans; Biomarkers; Horseshoe Crabs; Humans; Japan; Microbiological Techniques; Mycoses; Reagent Kits, Diagnostic; Sensitivity and Specificity; Serologic Tests

Beta-glucan is a major component of fungal cell walls and shows various immunopharmacological activities including antitumor activity. Previously, we detected anti-beta-glucan antibody in human sera. Anti-beta-glucan antibody participates in the immune response to fungal cell wall beta-glucan. Patients on dialysis are at high risk of infection including fungal infections. We examined the plasma beta-glucan level and the titer of anti-beta-glucan antibody in dialysis patients. We measured plasma beta-1,3-glucan concentrations with the limulus G test and anti-beta-glucan antibody titers by ELISA with Candida beta-glucan-coated plates. We also examined the influence of the period of dialysis and the kind of dialysis membrane. The patients were positive for beta-1,3-glucan in their plasma. The anti-beta-glucan antibody titer was lower in the dialysis patients than in healthy volunteers. Long-term dialysis patients showed lower anti-beta-glucan antibody titers than short-term dialysis patients. No significant difference was found between the kinds of dialysis membrane. The titer of anti-beta-glucan antibody as recognition molecule of beta-glucan was low in dialysis patients compared with healthy volunteers. This is likely to be one factor explaining the sensitivity to infection of the dialysis patients. An appropriate application of culinary-medicinal mushroom such as Agaricus brasiliensis has potential for the prevention of fungal infection in dialysis patients.

Topics: Agaricus; Aged; Antibodies, Fungal; Aspergillus niger; beta-Glucans; Candida; Candida albicans; Cell Wall; Female; Humans; Kidney Failure, Chronic; Limulus Test; Male; Middle Aged; Mycoses; Renal Dialysis

We have evaluated the contribution of the 1,3-beta-d-glucan (BG) assay for the screening of invasive fungal infections (IFIs) in patients with haematological malignancies. Serum samples from patients at risk of IFI were collected twice a week and retrospectively tested using the BG assay. BG screening was performed on 1143 samples from 91 patients during 104 anticancer treatment cycles. Proven and probable cases of IFI occurred in 9 (8.7 %) treatment cycles. Depending on the criterion of positivity used (1x >60 pg ml(-1), 1x >80 pg ml(-1), 2x >60 pg ml(-1) or 2x >80 pg ml(-1)) the sensitivity and specificity were 89, 89, 67 and 44 %, and 20, 48, 33 and 56 %, respectively. Although the test was marked as positive in 82, 68, 54 and 45 % of all the treatment cycles, in the majority of cases, these positivities were probably false. The major limit of the BG test was an extremely low positive predictive value (10 to 12 %). We have analysed mucositis, candida colonization, bacteraemia, use of antimicrobials, erythrocyte and thrombocyte filtered blood products, collecting tubes or sampling via venous catheters. Even though no factor is a major source of BG, it could at least partially influence BG assay performance. Thus, BG detection has a limited usefulness as a screening method for IFIs in patients with haematological malignancies.

Topics: Antineoplastic Agents; beta-Glucans; Female; Hematologic Neoplasms; Humans; Immunoassay; Immunocompromised Host; Male; Mycoses; Opportunistic Infections; Predictive Value of Tests; Sensitivity and Specificity

Topics: beta-Glucans; Child; Child, Preschool; Female; Humans; Infant; Male; Mycoses; Nephrotic Syndrome

Topics: Animals; beta-Glucans; Humans; Immunologic Factors; Mycoses

Blood (1 --> 3)-beta-D-glucan (betaG) measurement is widely used as an effective sero-diagnostic method for deep-seated mycosis. Antitumor betaG (lentinan, schizophyllan) administration is known as one of the false-positive factors of blood betaG measurement. To understand the influence of administered betaG preparation to betaG measurement in blood, we compared the interfering effect of betaG administration in different betaG measuring methods.. betaG concentration in plasma was measured by three different methods.. betaG concentration was measured in plasma of 18 samples of 7 cases with betaG administration and 86 samples without betaG administration. The period after last betaG administration was three days to three years.. In the cases for which betaG was administered, blood betaG level drastically increased using the method which employs alkaline pretreatment. Even in the cases for which betaG was administered three years previously; betaG value measured by alkaline pretreatment was significantly high. Thus, interference of betaG administration in blood betaG measurement continued for years after the last administration.. Disparity in betaG values measured by different methods for betaG administered cases is due to differences among sample pretreatment methods. Conformation of administered betaG seemed to be transformed into a sensitive form to factor G by alkaline pretreatment. Especially in the case of the alkaline pretreatment method, betaG administration disturbance was much stronger than for dilution-heating pretreatment. Therefore, in suspected cases, it is important to pay attention to betaG administration during the previous few years.

Topics: Aged; beta-Glucans; Colorimetry; Female; Glucans; Humans; Male; Middle Aged; Mycoses; Nephelometry and Turbidimetry; Reagent Kits, Diagnostic; Time Factors

We investigated the detection of non-specific reactions in the measurement of plasma (1-->3)-beta-D-glucan (beta-glucan) and countermeasures against them using alkaline treatment, chromogenic automated kinetic assay (alkaline-kinetic assay). In this study, we reexamined the values of beta-glucan using the alkaline-kinetic assay with and without laminaran oligosaccharides (LO) as a kind of beta-glucan that blocks the Limulus reaction. The materials for this study were 584 plasma samples in which beta-glucan had been measured. These were taken from 232 patients in Kawasaki Medical School Hospital between January 2002 and March 2002. Non-specific reactions were judged by a calculated value under a LO additive condition. Determination as to whether or not the each time course of the Limulus reaction was influenced by a non-specific reaction was also studied by applying a non-specific reaction index set up independently. Non-specific reactions were recognized in 51.9% of the samples (81/156). The amount of non-specific reaction was 9.9 pg/ml or less in major samples. On the other hand, when the cut off value of the index for detection of non-specific reactions was set at 0.5, the sensitivity was 88.9% and specificity was 73.7%. The positive and negative predictive values were 93.5% and 60.9% respectively. Non-specific reactions can be approximately distinguished by applying the non-specific reaction index. By so doing, unnecessary initiation of anti fugal therapy in response to non-specific reactions can be avoided. Further prospective and radical studies of non-specific reactions in the alkaline-kinetic assay are necessary.

Topics: Adult; Aged; Aged, 80 and over; beta-Glucans; Chromogenic Compounds; Clinical Chemistry Tests; Female; Glucans; Humans; Limulus Test; Male; Middle Aged; Mycoses; Predictive Value of Tests; Reagent Kits, Diagnostic; Sensitivity and Specificity

Topics: beta-Glucans; Chromogenic Compounds; Evaluation Studies as Topic; Female; Glucans; Humans; Limulus Test; Male; Middle Aged; Mycoses; Reagent Kits, Diagnostic

beta-Glucan Test MARUHA for high sensitive diagnosis of deep mycosis which was developed recently detects (1-->3)-beta-D-glucan, a component of the cell wall. The performance of beta-Glucan Test MARUHA is evaluated in this report. Although existing methods to detect (1-->3)-beta-D-glucan have trouble with sulfa drugs, hemolysis, and immunoglobulin G (IgG), these problems were overcome by the beta-Glucan Test MARUHA: No effect was observed for beta-Glucan Test MARUHA at lower than 200 micrograms/ml, 500 mg/dl, and 6,000 mg/dl of sulfa drugs, hemoglobin, and IgG, respectively. The effect of drugs administrated on the measurement value of beta-glucan Test MARUHA was checked at several concentrations. However, almost no effect of drugs, such as, 5 kinds of antifungals, 8 kinds of antibiotics, a kind of antibacterial, 2 kinds of infusions, and a kind of contrast media was observed at the practical concentrations.

Topics: beta-Glucans; Biomarkers; Evaluation Studies as Topic; Glucans; Humans; Mycoses; Reagent Kits, Diagnostic; Sensitivity and Specificity

Using Amebocyte lysate of horseshoe crab to measure (1-->3)-beta-D-glucan specifically, a component of the cell wall, several kinds of diagnostic methods for deep mycosis are in practical use in Japan. However, the most important problem is that the judgment of positive or negative is method dependent. To elucidate the cause of the problem, each measurement value of the identical sample by four methods, beta-Glucan Test Maruha (MARUHA), beta-Glucan Test Wako (WAKO). FUNGITEC G Test (FUNGITEC-G) and FUNGITEC G Test MK (FUNGITEC-MK) was compared with the clinical data using 119 cases and 289 tests. Each case was divided into three groups; proven fungal infection, probable fungal infection and non-fungal infection. The negative cases for all the methods tested in the groups of proven fungal infection and probable fungal infection were allergic bronchopulmonary aspergillosis and cryptococcosis, and that for all the methods tested except FUNGITEC-MK method in the group was pulmonary aspergilloma. It seems that these cases cannot be detected correctly by only measuring (1-->3)-beta-D-glucan. On the other hand, the ratio of false positive, positive for non-fungal infection group was high in the case of FUNGITEC-MK. About 23% against the total case was positive for FUNGITEC-MK method, but negative for MARUHA, WAKO, and FUNGITEC-G methods. Although the difference of the sensitivity among four methods was not observed, the specificity, the diagnostic efficiency, and the positive predictive value of FUNGITEC-MK method were remarkably lower than those of the other methods due to false positive measurement. In conclusion, MARUHA, WAKO and FUNGITEC-G except FUNGITEC-MK is not method dependent. It is suggested that FUNGITEC-MK detects non-specific reaction resulted in false positive.

Topics: beta-Glucans; Glucans; Humans; Mycoses; Reagent Kits, Diagnostic; Sensitivity and Specificity

The level of (1-->3)-beta-D-glucan in blood is a diagnostic index of fungal infection because it is released from the fungal cell wall. However, high levels of plasma (1-->3)-beta-D-glucan in patients administered blood components may give false positive results. High levels of (1-->3)-beta-D-glucan have been detected in blood components. We suspected that (1-->3)-beta-D-glucan from cellulose filters had been eluted into blood components by filtration in the manufacturing process. To investigate the contamination of blood components by (1-->3)-beta-D-glucan from cellulose filters, in vitro experiments were performed by using six cellulose filters and a nylon filter. Human serum albumin (HSA) solution (100 ml) was flowed through each filter after rinsing with 100 ml of distilled water, and (1-->3)-beta-D-glucan in each fraction was determined by Fungitec G test MK. The concentration of (1-->3)-beta-D-glucan eluted from cellulose filters in 100-ml distilled water fractions ranged from 6 to 207 pg/ml, and that of HSA fractions ranged from 33 to 20,784 pg/ml. These data showed that remarkably higher (1-->3)-beta-D-glucan levels were detected in HSA fractions flowed through cellulose filters in spite of advance rinsing with 100 ml of distilled water. In the case of a nylon filter, (1-->3)-beta-D-glucan was not eluted in either fraction. These results indicate that (1-->3)-beta-D-glucan contamination in blood components is caused by filtration with cellulose filters in the manufacturing process.

Topics: beta-Glucans; Blood Chemical Analysis; Cellulose; False Positive Reactions; Filtration; Glucans; Humans; In Vitro Techniques; Manufactured Materials; Membranes, Artificial; Mycoses

The desert locust Schistocerca gregaria behaviorally thermoregulates in order to try and maintain a favoured "set point" body temperature. Locusts infected with the deuteromycete fungal pathogen Metarhizium anisopliae var acridumchoose a significantly elevated temperature. This "behavioral fever" greatly delays the progress of mycosis. We have confirmed this phenomenon and shown that desert locusts also fever when infected with the bacterial pathogen Serratia marcescens. Elevation in the prefered environmental temperature occurs also upon injection with laminarin and lipopolysaccharide (microbial cell wall components). Since such treatments also stimulate the immune system it would appear that "behavioral fever" is probably a feature of the immune response. The eicosanoid biosynthesis inhibitor dexamethasone prevented laminarin invoked fever. This effect was reversable by arachidonic acid. Therefore in common with the febrile response in mammals behavioral fever in insects may be mediated locally by circulating eicosanoids.

Topics: Animals; Body Temperature Regulation; Dexamethasone; Eicosanoids; Fever; Glucans; Grasshoppers; Male; Mitosporic Fungi; Mycoses; Polysaccharides; Serratia Infections; Serratia marcescens; Time Factors

The false-positive elevation of plasma (1-->3)-beta-D-glucan level, a serodiagnostic test for deep-seated mycosis, is suspected in patients administered with blood components.. (1-->3)-beta-D-Glucan and endotoxin levels in blood components consisting of 12 albumins, 8 immunoglobulins, and 3 blood coagulation factors were measured by fungal infection tests (Fungitec G-test, Seikagaku Co.; the Wako WB003 test, Wako Pure Chemical Industries; and the Endospec ES test, Seikagaku Co.). In vitro release of (1-->3)-beta-D-glucan from the depth-type filters made by cellulose membrane to process blood components was analyzed through an in vitro filtration process as a source of (1-->3)-beta-D-glucan in blood components.. The amounts of (1-->3)-beta-D-glucan in blood components ranged from 0 to 7510 pg per mL in the Fungitec G-test, with wide variations among brands. The positive rates over 20 pg per mL were 75 percent in albumin solutions, 40 percent in blood coagulation factors, and 63 percent in immunoglobulin solutions. (1-->3)-beta-D-Glucan levels released from the five depth filters ranged from 5 to 2516 pg per mL. The (1-->3)-beta-D-glucan level in filtration fluid was decreased by rinsing with distilled water, but rebounded again during the albumin filtration process.. Depth filters are considered the source of (1-->3)-beta-D-glucan content in some blood components.

Topics: Artifacts; Bacterial Proteins; beta-Glucans; Biomarkers; Blood Coagulation Factors; Blood Component Transfusion; Blood Proteins; Cell Wall; Cellulose; Endotoxins; False Positive Reactions; Filtration; Fungi; Glucans; Glycoside Hydrolases; Humans; Immunoglobulins; Membranes, Artificial; Mycoses; Reagent Kits, Diagnostic; Serum Albumin; Solubility; Solutions

Determination of the blood (1-->3)-beta-D-glucan (beta-DG) concentration is a sensitive marker to detect the presence of deep mycosis and fungal infections. Although cellulose material is known to contain beta-DG, the influence of a cellulose dialyzer membrane on the blood beta-DG level remains to be elucidated. In this study, we determined the plasma beta-DG levels in dialysis outpatients using either a modified regenerated cellulose (MRC) or a synthetic polysulfone (PS) membrane for more than 3 months. Plasma beta-DG levels were extremely high in patients using the MRC (2,778 +/- 549 pg/ml, n = 9) but not the PS membrane (18.8 +/- 3.7 pg/ml, n = 8) compared to normal ranges (<20 pg/ml). A single dialysis session using the MRC membrane further increased blood beta-DG values to 5,561 +/- 722 pg/ml (p < 0.01). After changing the membranes from MRC to PS, the blood beta-DG levels gradually decreased and reached 29.6 +/- 6.0 pg/ml at 6 months. In contrast, the PS membrane did not affect plasma beta-DG levels after a single dialysis session (16.0 +/- 3.9 pg/ml) or 4 months later (24.0 +/- 4.9 pg/ml). These findings suggested that a cellulose membrane could influence the measurement of blood beta-DG concentrations in the long-term. Careful assessment is required to diagnose the presence of fungal infection in HD patients using a cellulose membrane.

Topics: Aged; beta-Glucans; Biocompatible Materials; Cellulose; False Positive Reactions; Glucans; Humans; Kidney Failure, Chronic; Membranes, Artificial; Middle Aged; Mycoses; Polymers; Renal Dialysis; Sulfones

The measurement of serum (1-3)-beta-D-glucan (beta-glucan) in cases with deep seated mycosis is a useful diagnostic method. Beta-glucan has usually been measured using two different methods: by an alkali treatment, chromogenic automated kinetic assay (chromogenic assay), and by detergent dilution and heating methods, kinetic turbidimetric assay (turbidimetric assay). However, there are often large discrepancies in the beta-glucan values measured by these two methods. In this study, we reexamined the values of beta-glucan obtained by the two techniques, using 343 serum samples from 146 patients who had been treated in Kawasaki Medical School between January 1999 and May 1999, and then analyzed the reasons for the differences. Serum beta-glucan results measured were evaluated by segregating them into three clinical categories: cases with proven deep mycosis, cases with probable deep mycosis and cases without deep mycosis. In addition, the beta-glucan in the samples was suppressed by carboxy-methylated curdlan (CM-curdlan), and then was remeasured to find a non-specific reaction. Although a certain correlation was found between the serum beta-glucan results measured by the two methods, the values measured by the chromogenic assay were, in general, higher than those measured by the turbidimetric assay. There were also many samples in the cases without deep mycosis that showed positive values with the chromogenic assay, but not with the turbidimetric assay. With the turbidimetric assay, the addition of CM-curdlan suppressed the values of beta-glucan in all samples; however, when measured by the chromogenic assay the values in many samples remained high. These results suggest that a non-specific reaction which did not include beta-glucan was detected by the chromogenic assay. Further studies are needed to evaluate the characteristics and comparable usefulness of the two assays.

Topics: Adult; Aged; Aged, 80 and over; beta-Glucans; Biomarkers; Colorimetry; Female; Glucans; Humans; Male; Middle Aged; Mycoses; Nephelometry and Turbidimetry; Reagent Kits, Diagnostic; Sensitivity and Specificity

The clinical features of invasive deep mycosis in the critical care center was studied and the usefulness for determinations of plasma (1-->3)-beta-D-glucan, one of the major structural components of fungi, in making the diagnosis of deep mycosis was evaluated in comparison with that of blood culture and candida antigen titer using CAND-tec kit. A total of 92 febrile patients (mean age = 54.5 yr., M/F = 70/22) in our critical care center were enrolled in this study. Seventeen out of the 92 febrile patients (18.5%) were those with deep mycosis. In the deep mycosis group, there were 10 patients with fungal panperitonitis, 5 with fungaemia, one with candidal pneumonia and one with candidal empyema. A total of 52 blood samples were obtained from 17 patients with deep mycosis. Forty five out of the 52 blood samples (86.5%) were positive for serum (1-->3)-beta-D-glucan while only 10 were culture-positive. In contrast, six (15.0%) out of the 40 blood samples were obtained from 17 patients with deep mycosis were positive for candida antigen by CAND-tec kit. In the critical care center, deep mycosis is a common infection and determination of serum concentration of (1-->3)-beta-D-glucan is found to be a very useful examination in screening of deep mycosis with high sensitivity and specificity.

Topics: Antigens, Fungal; beta-Glucans; Candida; Emergency Medical Services; Female; Glucans; Humans; Male; Middle Aged; Mycoses; Sensitivity and Specificity

The present multicentre clinical study was conducted to assess the clinical utility of a new diagnostic method for deep mycosis in which (1-->3)-beta-D-glucan, a fungal cell wall component existing in plasma, was quantitatively measured by the kinetic turbidimetric Limulus test (WB003). Plasma (1-->3)-beta-D-glucan concentrations were 0.57 +/- 0.10 microgram/l in 92 healthy subjects and 0.62 +/- 0.32 microgram/l in 26 patients with non-mycotic diseases (disease control group). In comparison with these healthy subjects and patients with non-mycotic diseases, patients with mycosis had significantly higher plasma (1-->3)-beta-D-glucan concentrations: 19.63 +/- 73.28 micrograms/l in 12 patients with candidaemia, 11.28 +/- 21.42 micrograms/l in 7 patients with urinary Candida infection, 4.84 +/- 12.71 micrograms/l in 5 patients with pulmonary candidiasis, and 12.21 +/- 31.31 micrograms/l in 4 patients with invasive pulmonary aspergillosis. On the statistical analysis of these data, a cut-off value was set at 1.0 microgram/l. Using this cut-off value, 3 patients with pulmonary cryptococcosis and 4 patients (4/6) with pulmonary aspergilloma were all negative with low plasma (1-->3-beta-D-glucan levels. The test WB003 provided equivalent or higher efficiency of diagnosis of candidiasis and aspergillosis, in comparison with commercially available antigen detection kits, demonstrating its utility as a diagnostic reagent. It may also be useful in assessing therapeutic effectiveness when used periodically after treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aspergillosis; beta-Glucans; Candidiasis; Cryptococcosis; Diagnostic Errors; Evaluation Studies as Topic; Female; Fungemia; Glucans; Humans; Kinetics; Limulus Test; Lung Diseases, Fungal; Male; Middle Aged; Mycoses; Nephelometry and Turbidimetry; Time Factors; Urinary Tract Infections

The Measurement of serum (1-->3)-beta-D-glucan (beta-glucan) has been considered to be useful in the early diagnosis of deep mycosis. In this study, we investigated the clinical significance of beta-glucan in pleural effusion or liquor from patients with various conditions. beta-glucan was measured in 29 samples of pleural effusion from 27 patients (male: 17, female: 10 median age: 62.1). Two patients undergoing hemodialysis treatment were excluded from the study of normal range of beta-glucan in these samples. beta-glucan was also measured in 39 samples of liquor from 23 inpatients (male: 15, female: 8 median age: 48.4) with certain neurological disorders. In these cases, only two patients had deep mycosis. beta-glucan in the pleural effusion from a patient with Aspergillus pyothorax showed an extremely high value of more than 1100 pg/ml. Slight elevation of beta-glucan was observed in the spinal fluid from a patient with cryptococal, meningitis. In the other cases with no mycotic infection or any factor influencing the value of beta-glucan, beta-glucan in pleural effusion and spinal fluid were generally lower than the normal range of serum samples. However, there is false positive elevation of beta-glucan in pleural effusion. The above results indicated that measurement of beta-glucan in pleural effusion or spinal fluid may be useful for the diagnosis of mycotic infection as the cause of pleuritis or meningitis.

Topics: Adult; Aged; Aged, 80 and over; beta-Glucans; Biomarkers; Female; Glucans; Humans; Male; Middle Aged; Mycoses; Pleural Effusion

(1-->3)-beta-D-glucan is a characteristic fungal cell-wall constituent. To assess the clinical usefulness of this glucan in screening for invasive fungal infection or fungal febrile episodes, we measured the plasma concentration at the time of routine blood culture in 202 febrile episodes by means of factor G, a horseshoe-crab coagulation enzyme that is extremely sensitive to this polysaccharide. With a plasma cut-off value of 20 pg/mL, 37 of 41 episodes of definite fungal infections (confirmed at necropsy or by microbiology) had positive results (sensitivity 90%). All of 59 episodes of non-fungal infections, tumour fever, or collagen diseases had concentrations below the cut-off value (specificity 100%). Of 102 episodes of fever of unknown origin, 26 had plasma glucan concentrations of more than 20 pg/mL. With those 102 cases taken as non-fungal infections, the positive predictive value of the test was estimated as 59% (37/63), the negative predictive value as 97% (135/139), and the efficiency as 85% (172/202). The positive predictive value should improve if there were a sensitive gold standard that could discriminate fungal from non-fungal infections. Causative fungi included candida, aspergillus, cryptococcus, and trichosporon. Determination of plasma (1-->3)-beta-D-glucan with factor G is a highly sensitive and specific test for invasive deep mycosis and fungal febrile episodes, and will substantially benefit immunocompromised patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aspergillosis; beta-Glucans; Blood Coagulation Factors; Candidiasis; Child; Child, Preschool; Female; Fever; Fungemia; Glucans; Humans; Male; Middle Aged; Mycoses; Sensitivity and Specificity; Serine Endopeptidases

Efficacy of fluconazole (FLCZ), an anti-fungal agent of triazole derivatives, was evaluated in patients with systemic mycoses and suspected mycoses associated with hematologic malignancies including leukemia, myelodysplastic syndrome and malignant lymphoma. Plasma beta-D-glycan levels, the differences between the levels determined toxicolor test and in endospecy test, were also investigated. Fourteen patients with systemic mycoses and 31 patients with suspected mycotic infections were treated with intravenous administration of FLCZ at a daily dose of 400 mg. Excellent to good responses were observed in 4 of the 14 patients (28.6%) with definitive diagnosis of mycosis, and in 18 of the 31 patients (58.1%) with suspected fungal infections, with an overall efficacy rate of 48.9% (22/45). Levels of plasma beta-D-glycan correlated well with efficacies of FLCZ in 19 of 30 patients. In several cases, however, plasma beta-D-glucan levels were low during the entire course of treatment. Even in 10 cases of definite mycosis, 4 cases showed low levels of plasma beta-D-glucan (below 15 pg/ml by repeated determinations). The results indicate that FLCZ is an effective agent for the treatment of severe systemic fungal infections in patients with hematologic disorders. Deep seated mycosis cannot be ruled out even when its plasma levels of beta-D-glucan are low.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; beta-Glucans; Biomarkers; Drug Evaluation; Female; Fluconazole; Glucans; Humans; Leukemia; Lymphoma; Male; Middle Aged; Mycoses

An assessment has been made regarding usefulness of measuring beta-D-glucan (beta-glucan) as fungal serodiagnosis in 50 cases of fungal infection with hematological diseases. Further, an assessment has been made regarding relation between hematological findings and therapeutic effect by administering miconazole, an antifungal agent (MCZ: Florid, clinically to the subjects. Positivity of beta-glucan (beta-glucan > or = 10 pg/ml) was observed in 54.5% (24/44), and the effective rate of MCZ in the positive cases was 75.0% (18/24). In the cases in whom fungus was detected, beta-glucan-positive rate was 50.0% (8/16), and MCZ-effective rate in beta-glucan-positive cases was 62.5% (5/8). The total effective rate of MCZ was 80% (40/50). Side effects were observed in 3 cases, but continual administration of MCZ was possible in all of the 3 cases. By the assessment regarding the relation between hematological findings and therapeutic effect of MCZ, it was found that the effective rates in the cases who underwent a transition with neutrophil and lymphocyte counts less than 500/microliters during the period of MCZ administration were 64.7% (11/17) and 50% (5/10), respectively, and large effects were observed in the cases who underwent a transition with the neutrophil and lymphocyte counts more than 500/microliters was 86.7% (19/22) and 91.7% (22/24), respectively. These results suggested that lymphocytes rather than neutrophils had an important role in the morbidity of fungal infection. It was noteworthy that MCZ was effective for the treatment of deep seated mycosis and significant effective rate was obtained in the group of patients who had neutrophils and lymphocytes less than 500/microliters.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; beta-Glucans; Child; Female; Glucans; Hematologic Diseases; Humans; Male; Miconazole; Middle Aged; Mycoses; Serologic Tests

The number of deep mycosis has been increasing because of increases in immunocompromised hosts and in fungal colonization associated with increasing use of broad-spectrum antibacterial antibiotics. Based on these phenomenon, a simple test method for an early diagnosis of deep mycosis is urgently desired. We therefore investigated the usefulness of assaying a fungal cell component, (1-->3)-beta-D-glucan (beta-glucan). The amount of beta-glucan was obtained from the difference between the amounts determined using Toxicolor and Endospecy, and the serum levels of more than 10 pg/ml were considered positive signs for beta-glucan. The following results were obtained: We found that beta-glucan was positive in 75% of the patients who had been definitely diagnosed to have mycosis, and in 58.3% of the patients strongly suspected of mycosis. The numbers of beta-glucan positive patients' in these 2 groups of patients were significantly different from that in those without mycosis (14.7%, P < 0.05). Thus a usefulness of beta-glucan measurement for the diagnosis of mycosis was demonstrated. However, beta-glucan was sometimes negative even in patients with fungemia at an early phase of the disease and turned positive several days later. Even in a patient with definite lung mycosis, who had a latent circumscribed lesion (afebrile and CRP-negative), beta-glucan was also negative. From these findings, one should be aware that the beta-glucan test produces false negatives even in patients with definite mycosis and that the test should be repeated during the course of the disease.

Topics: Aged; beta-Glucans; Female; Glucans; Hematologic Diseases; Humans; Immunocompromised Host; Limulus Test; Male; Middle Aged; Mycoses

We present additional evidence that plasma from patients with deep-seated mycoses contains (1-->3)-beta-D-glucan. Digestion of such samples with endo-(1-->3)-beta-D-glucanase completely abolished the ability of the plasma to activate factor-G, a horseshoe crab coagulation enzyme that is extremely sensitive to this polysaccharide. Measurement of plasma (1-->3)-beta-D-glucan is a promising method for the diagnosis of deep-seated mycoses and for monitoring the response of these infections to antifungal therapy.

Topics: Amino Acid Sequence; beta-Glucans; Biomarkers; Glucan Endo-1,3-beta-D-Glucosidase; Glucans; Humans; Male; Middle Aged; Molecular Sequence Data; Mycoses

Topics: Antifungal Agents; Antigens, Fungal; beta-Glucans; Candida; Catheterization, Central Venous; Fluorescein Angiography; Fungi; Glucans; Humans; Latex Fixation Tests; Mycoses; Risk Factors

In order to correctly diagnose and treat severe postoperative infections, it may be critical to detect and differentiate between endotoxin derived from Gram-negative bacteria and/or beta-glucan derived from fungi. In addition to the chromogenic assay, the turbidimetric kinetic assay has been performed for the quantification of endotoxin in plasma using Limulus amebocyte lysate as previously reported. However, it is also known that beta-glucan triggers the coagulation of Limulus amebocyte lysate. In the present study, the differentiation of beta-glucan from endotoxin and its clinical application were studied. Endotoxin was able to be inactivated in plasma using one-tenth dilution by 10 per cent ethanol or distilled water, followed by heating at 100 degrees C for 120 min, without affecting the activity of coexisting beta-glucan. The treated sample was then subjected to the turbidimetric kinetic assay using Toxinometer ET-201. Using this method, as little as 30 pg/ml of beta-glucan in the plasma may be assayed separately, with the amount of circulating beta-glucan in the plasma of normal subjects being less than 50 pg/ml. On the other hand, in patients with a fungal infection, the amount of beta-glucan in their plasma was elevated significantly. Clinically, beta-glucanemia may often occur in severe postoperative infection even if fungi are not detected.

Topics: beta-Glucans; Candidiasis; Endotoxins; Escherichia coli Infections; Glucans; Humans; Mycoses; Pseudomonas aeruginosa; Pseudomonas Infections; Reference Values; Salmonella Infections; Surgical Wound Infection