Multiple pancreatic abscesses due to Candida albicans following ERCP

The olfactory bulb of the sheep brain is hollow, the cavity (olfactory ventricle or rhinocele) is connected to the anterior horn of the lateral ventricle by a narrow channel and contains cerebrospinal fluid (c.s.f.). In an apparently healthy black-faced lamb, longitudinal sections stained Giemsa Wright showed nodules of cellular proliferation in the rhinocele wall, projecting into the cavity. Some nodules were detached from the wall and lay free in the cavity. This cellular reaction indicates that pathogens may reach the rhinocele and pass from the rhinocele into the c.s.f. of the cerebral ventricular system.     

Pacemaker endocarditis due to Candida albicans: case report and review

We describe a case of pacemaker endocarditis due to Candida albicans in a patient who responded favorably to combined surgical and antifungal therapy. Only five cases of candidal pacemaker endocarditis have been reported previously. We review these five cases and discuss the clinical presentation and therapy for this disease in comparison with candidal prosthetic valve endocarditis.     

Post-operative peritonitis due to Candida albicans. Two cases (author's transl)

Peritonitis due to Candida albicans is both rare and severe. One of the two cases reported was consecutive to subtotal pancreatectomy for necrotizing pancreatitis and the other to perforated ulcer. Genuine C. albicans peritonitis should be distinguished from ascites with superinfection. It is usually due to intra-abdominal focal infection from a perforated hollow viscus. Depending on whether the infection is systemic or localized, antifungal drugs are administered systemically or topically. The surgical treatment is that of all peritonitis and meets with the usual of re-operation in search of deep residual septic foci. Cases with extraperitoneal candidiasis have a particularly poor prognosis.     

The x-ray crystal structure of phosphomannose isomerase from Candida albicans at 1.7 angstrom resolution

Phosphomannose isomerase (PMI) catalyses the reversible isomerization of fructose-6-phosphate (F6P) and mannose-6-phosphate (M6P). Absence of PMI activity in yeasts causes cell lysis and thus the enzyme is a potential target for inhibition and may be a route to antifungal drugs. The 1.7 A crystal structure of PMI from Candida albicans shows that the enzyme has three distinct domains. The active site lies in the central domain, contains a single essential zinc atom, and forms a deep, open cavity of suitable dimensions to contain M6P or F6P The central domain is flanked by a helical domain on one side and a jelly-roll like domain on the other.     

Analysis of Candida albicans adhesion to salivary mucin

Clearance of Candida albicans from the oral cavity is thought to be mediated via specific receptor-ligand interactions between salivary constituents and the fungus. Since surfaces in the oral cavity are normally coated with a saliva-derived pellicle, specific interactions between salivary constituents and C. albicans may also contribute to adhesion of C. albicans to the oral mucosa and dental prostheses. Therefore, the purpose of this study was to identify salivary constituents to which C. albicans is capable of binding. A solid-phase overlay assay was used in which electrophoretically separated rat and human salivary constituents bound to membrane filters were incubated with radiolabelled C. albicans cells. C. albicans adhered to a single salivary component from each host. Correlation of cell-binding activity with specific monoclonal antibody (MAb)-binding activity indicated that the constituent bound by C. albicans in human saliva was low-molecular-weight mucin (MG2) and that in rat saliva was rat submandibular gland (RSMG) mucin. Further studies showed an identical cell hybridization signal and MAb colocalization by using RSMG ductal saliva and an aqueous RSMG extract in the solid-phase overlay assay. Analysis of cell binding to the aqueous extract of RSMG fractionated by anion-exchange chromatography demonstrated that C. albicans binding was restricted to an acidic subfraction of the RSMG extract, which also bound the RSMG mucin-specific MAb. The Candida-binding fraction contained predominantly RSMG mucin glycoprotein and also a noncovalently associated, chloroform-extractable material. Furthermore, we identified two strains of C. albicans which differed severalfold in the ability to bind RSMG mucin in the overlay assay. These results suggest that C. albicans binds to only a specific subfraction of RSMG mucin and that the two C. albicans strains tested differ in the ability to bind RSMG mucin subfractions.     

Cytokine response to inactivated Candida albicans in mice

Inactivated Candida albicans (CA) cells induce strong activation of natural cytotoxic effectors in mice. In the present study we examined the expression of cytokine genes involved in the immune response to CA. It has been reported that differential cytokine production by natural immune cells is important for regulating the development of specific TH response. Northern blot analysis was performed on peritoneal exudate cells (PEC) recovered from CD2F1 mice injected ip with five doses of CA (CA-5d, on Days -14, -10, -7, -3, 0 with respect to the in vitro assays at 2, 24, and 72 hr) or from mice injected ip with four doses of CA (CA-4d, on Days -14, -10, -7, -3 with respect to the in vitro assay on Day 0). On Day 0, before the fifth CA injection, PEC expressed a high level of IL-2 and a low level of IL-1 beta mRNAs while genes coding for IL-4, IL-5, IL-6, IL-10, IL-12, TNF alpha, and IFN gamma were not expressed and there was a high level of NK activity. Two hours after CA-5d a high level of IFN gamma and a low level of IL-10 mRNAs were already evident, while IL-2 and much more IL-1 beta had greatly increased. IL-6, TNF alpha, and IL-2R alpha chain mRNAs were also detectable, whereas IL-4, IL-5, and IL-12 were not expressed. IL-12 mRNA was also absent in earlier stages of the CA sensitization. Both cellularity and NK activity of peritoneal exudate had increased with respect to Day 0. At 24 hr whereas IL-2 mRNA remained high, both IL-1 beta and IFN gamma mRNAs expression had decreased. Expression of other cytokines was no longer detectable but NK activity remained high and a significant LAK activity was also induced. After 72 hr, while the IL-2 mRNA level and NK activity were still high the IL-1 beta mRNA expression had further decreased. These results indicate that CA induces a predominant production of IFN gamma and IL-2, cytokines involved in the development of TH1 response but it is unable to induce IL-12. This secondary pathway, without IL-12 involvement in the development of TH1 response, is probably the result of the ability of IL-2, IL-1 beta, and TNF alpha to synergize in inducing IFN gamma synthesis by NK cells.     

Eosinophilic lung disease associated with Candida albicans allergy

PURPOSE: We evaluate the effect of the provision of postgraduate educational material on improving practitioner knowledge base during a 3-year period. MATERIALS AND METHODS: A total of 210 urologists were provided 67 monographs in a 2-year period. They were given a pretest before and posttest 1 year after receipt of all monographs. RESULTS: There was significant improvement in posttest scores for the group as a whole. Improvement correlated with years post-training and number of monographs read. Multivariate analysis revealed the number of monographs read was the only independent predictor of outcome. CONCLUSIONS: Although the improvement in test scores was significant and did correlate with the postgraduate educational material read, it was modest. This finding raises significant concerns about the usefulness of this format for graduate medical education.     

Chronic Candida albicans otitis media in children with immunodeficiency

Biliary peritonitis is a rare but serious complication of percutaneous renal access and surgery. We present such a case and review the literature.     

Molecular and phenotypic characterization of genotypic Candida albicans subgroups and comparison with Candida dubliniensis and Candida stellatoidea

There have been increased reports of the isolation of unusual genotypic groups of Candida albicans (groups C and D) based on a well-defined genotypic method; this method uses cellular DNA digested with the EcoRI enzyme and the restriction fragment length polymorphisms (RFLPs) generated by agarose gel electrophoresis. The aim of the present study was to use additional molecular tools to characterize these unusual strains and to compare them with authentic strains of C. dubliniensis, a recently delineated species, and type I C. stellatoidea. The RFLPs of PCR products generated from the intergenic transcribed spacer (ITS) region did not differentiate among C. albicans genotypes A, B, and C and type I C. stellatoidea. However, this method did differentiate the C. albicans genotype D strains, which were identical to C. dubliniensis. The RFLPs generated by HaeIII digestion of the PCR products of the V3 region of the 25S rRNA gene (rDNA) could differentiate the same groups as RFLP analysis of the PCR amplicon of the ITS region. C. albicans genotype B isolates have been shown to have a transposable intron in the 25S rDNA, whereas genotype A isolates do not; C. dubliniensis strains also have an intron that is larger than that in genotype B C. albicans strains but that is in the same location. PCR designed to span this region resulted in a single product for C. albicans genotype A (450 bp), B (840 bp), type 1 C. stellatoidea (840 bp), and C. dubliniensis (1,080 bp), whereas the C. albicans genotype C isolates had two major products (450 and 840 bp). All C. albicans genotype D isolates gave a PCR product identical to that given by C. dubliniensis. These results indicate that those strains previously designated C. albicans genotype D are in fact C. dubliniensis, that no differences were found between type 1 C. stellatoidea and C. albicans genotype B strains, and that the C. albicans genotype C strains appear to have the transposable intron incompletely inserted throughout the ribosomal repeats in their genomes. The results of the antifungal susceptibility testing of 105 of these strains showed that, for fluconazole, strains of C. dubliniensis were significantly more susceptible than strains of each of the C. albicans genotypes (genotypes A, B, and C). The flucytosine susceptibility results indicated that strains of C. albicans genotype A were significantly less susceptible than either C. albicans genotype B or C. albicans genotype C strains. These results indicate that there is a correlation between the Candida groups and antifungal susceptibility.     

Microwave disinfection of denture base materials colonized with Candida albicans

OBJECT: Guglielmi detachable coil (GDC) technology is a valuable therapeutic alternative to the surgical treatment of ruptured or incidental intracranial aneurysms. The authors describe their technical and clinical experience in the use of the GDC technique in patients who underwent endovascular occlusion for the treatment of incidentally found intracranial aneurysms. METHODS: One hundred fifteen patients with 120 incidentally found intracranial aneurysms underwent embolization by means of the GDC endovascular technique. Ninety-one patients were females and 24 were males. Patient age ranged from 13 to 80 years. In 64 patients the incidental aneurysms were discovered when unrelated nonneurological conditions signaled the need for angiography or magnetic resonance angiography (Group 1). Twenty patients who presented with incidental aneurysms that were discovered during treatment for an acutely ruptured aneurysm underwent treatment of both types of aneurysm during the acute phase of subarachnoid hemorrhage (SAH) (Group 2). Sixteen patients with incidental aneurysms were treated during the chronic phase of SAH (Group 3). Group 4 included 15 patients who had incidental aneurysms associated with brain tumors or arteriovenous malformations. Angiographic results revealed complete or near-complete occlusion in 109 aneurysms (91%) and incomplete occlusion in five aneurysms (4%). Guglielmi detachable coil embolization was attempted unsuccessfully in six aneurysms (5%). One hundred nine patients (94.8%) remained neurologically intact or unchanged from their initial clinical status. Five patients (4.3%) deteriorated as a result of immediate procedural complications. All these complications occurred in the first 50 patients treated in the series. No clinical complications were observed in the last 65 patients. In one patient, a partially embolized aneurysm ruptured 3 years postprocedure. In Groups 1 and 3, the average length of hospitalization was 3.3 days. CONCLUSIONS: The evolution of GDC technology has proved to provide safe treatment of incidental aneurysms (a morbidity rate of 0% was achieved in the last 65 patients). The topography of the aneurysm and the clinical condition of the patient did not influence final anatomical or clinical outcomes. The GDC technology also confers a positive economic impact by decreasing hospital length of stay and by eliminating the need for postembolization intensive care.     

Reactivity of Candida albicans germ tubes with salivary secretory IgA

Salivary secretory IgA (sIgA) has been shown to react with a group of heat shock mannoproteins preferentially expressed on yeast cells grown at 37 degrees C. Since at this temperature C. albicans can induce germ tubes, we explored the role of germ tube induction on human salivary sIgA reactivity in both germinative and agerminative C. albicans strains, in an attempt to investigate whether the germ tube expressed the heat shock mannoproteins reactive with sIgA. The reactivity with sIgA of the agerminative strain, grown at 25 and 37 degrees C for different times, was measured spectrofluorometrically and was fairly constant with time. Yeast cells grown at 37 degrees C tended to be more reactive than those grown at 25 degrees C. In contrast, when compared with the yeast cells of the germinative strain grown at 25 degrees C, there was a statistically significant decrease in reactivity with sIgA during germ tube formation. Serum IgA and IgG did not show statistically significant changes in reactivity with C. albicans during germination, suggesting differences in reactivity with C. albicans cell wall antigens between mucosal and systemic humoral responses. Cell wall mannoproteins of molecular masses > 60 kDa were characterized by Western blotting as responsible for the decrease in sIgA reactivity observed in the germ tube, and the fall in sIgA reactivity was related to the release of cell wall mannoproteins into the culture medium. The release of these mannoproteins may be a mechanism whereby C. albicans avoids the action of sIgA, and it may play an important role in the post-parasite relationship in oral candidiasis.     

Serologic response to cell wall mannoproteins and proteins of Candida albicans

The cell wall of Candida albicans not only is the structure in which many biological functions essential for the fungal cells reside but also is a significant source of candidal antigens. The major cell wall components that elicit a response from the host immune system are proteins and glycoproteins, the latter being predominantly mannoproteins. Both the carbohydrate and protein moieties are able to trigger immune responses. Although cell-mediated immunity is often considered to be the most important line of defense against candidiasis, cell wall protein and glycoprotein components also elicit a potent humoral response from the host that may include some protective antibodies. Proteins and glycoproteins exposed at the most external layers of the wall structure are involved in several types of interactions of fungal cells with the exocellular environment. Thus, coating of fungal cells with host antibodies has the potential to influence profoundly the host-parasite interaction by affecting antibody-mediated functions such as opsonin-enhanced phagocytosis and blocking the binding activity of fungal adhesins for host ligands. In this review, the various members of the protein and glycoprotein fraction of the C. albicans cell wall that elicit an antibody response in vivo are examined. Although a number of proteins have been shown to stimulate an antibody response, for some of these species the response is not universal. On the other hand, some of the studies demonstrate that certain cell wall antigens and anti-cell wall antibodies may be the basis for developing specific and sensitive serologic tests for the diagnosis of candidasis, particularly the disseminated form. In addition, recent studies have focused on the potential for antibodies to cell wall protein determinants to protect the host against infection. Hence, a better understanding of the humoral response to cell wall antigens of C. albicans may provide the basis for the development of (i) effective procedures for the serodiagnosis of disseminated candidiasis and (ii) novel prophylactic (vaccination) and therapeutic strategies for the management of this type of infection.     

Iron-limited biofilms of Candida albicans and their susceptibility to amphotericin B

A perfused biofilm fermentor, which allows growth-rate control of adherent microbial populations, was used to assess whether the susceptibility of Candida albicans biofilms to antifungal agents is dependent on growth rate. Biofilms were generated under conditions of glucose limitation and were perfused with drugs at a high concentration (20 times the MIC). Amphotericin B produced a greater reduction in the number of daughter cells in biofilm eluates than ketoconazole, fluconazole, or flucytosine. Similar decreases in daughter cell counts were observed when biofilms growing at three different rates were perfused with amphotericin B. In a separate series of experiments, intact biofilms, resuspended biofilm cells, and newly formed daughter cells were removed from the fermentor and were exposed to a lower concentration of amphotericin B for 1 h. The susceptibility profiles over a range of growth rates were then compared with those obtained for planktonic cells grown at the same rates under glucose limitation in a chemostat. Intact biofilms were resistant to amphotericin B at all growth rates tested, whereas planktonic cells were resistant only at low growth rates (相似文献   

A review of infectious endocarditis due to Candida

OBJECTIVE: As fungal endocarditis is a serious disease, frequently requiring cardiac surgery, a review was made of the experience of our Departments in this pathology. DESIGN: A retrospective analysis of clinical, echocardiographic and surgical data. SETTING: Patients studied in a tertiary care Hospital with cardiac surgery available. PATIENTS: Between 1984 and 1994 there were ten cases of candida endocarditis in nine patients, four male and five female, mean age--45 +/- 12 years (31-65). INTERVENTIONS: The following parameters were analysed: clinical (predisposing factors, clinical evolution, complications, therapy and mortality), echocardiographic (presence of vegetations, abscesses, valvular regurgitations). Patients studied in other Centres and referred to our Department only for examination (echocardiograms) were excluded from this analysis. RESULTS: Eight cases in seven patients were prosthetic valve endocarditis and two native valve endocarditis. No patient was drug addicted. Seven cases of prosthetic valve endocarditis developed less than one year after surgery and another had a gynecological fungal infection as the cause of the endocarditis. Four patients had had previous endocarditis. There were four embolic events and three developed heart failure. There were three perivalvular infections, six valvular regurgitations and only one case with huge vegetations on echocardiography. Nine patients were treated with amphotericin B, in five fluocytosin was added and in four ketoconazol, which was replaced by flukonazol in one patient. Therapy was continued for at least eight weeks. Six patients were operated during the acute stage and one died. One patient was operated on late after the infection. Three patients died during the active stage. In a follow up of 5.2 +/- 4.8 years (8 months to 8 years) there was one fatal candida endocarditis relapse, one fatal candida sepsis, one non cardiac death, one patient developed a periprosthetic leak and one had recurrent systemic embolization. Abscesses/pseudoaneurysms were found in five out of seven patients submitted to surgery. CONCLUSION: Candida infective endocarditis has a bad prognosis, specially in those patients not operated early; it develops in patients with predisposing factors, which in our series were a previous infective endocarditis (four patients) and/or a prosthetic valve implantation less than one year before; it has important morbidity with multiple embolic events, perivalvular involvement, valvular regurgitation and heart failure.     

Chronic urinary tract infection due to Candida utilis

An elderly male was seen at an outpatient urology clinic over a period of 3 years with repeat urine specimens containing 10(4) to 10(5) CFU of a "Candida species, not C. albicans." The urine specimens were described as infected due to the presence of pyuria, but no antifungal therapy was administered. On two occasions, the patient presented to the emergency room and urine specimens were sent to the clinical microbiology laboratory. On both occasions, a yeast was isolated at concentrations of >10(5) CFU/ml. The organism was identified as the anamorphic yeast Candida utilis (teleomorph: Pichia jadinii) by conventional methods. Molecular methods, including karyotyping and restriction enzyme analysis, confirmed that the isolates were identical and were C. utilis. The patient developed benign prostatic hypertrophy and chronic obstructive pulmonary disease during the 3-year course. This report is the first demonstration of the isolation of the industrially important yeast C. utilis from a urinary tract infection. In the present case, the organism was associated with chronic, symptomatic disease. The significance of this unusual, low-virulence isolate from a case of urinary tract infection is discussed.     

Development of a method to detect secretory mucinolytic activity from Candida albicans

Ultrastructural examinations of sites where Candida albicans invaded the bowel wall after oral intragastric inoculation of infant mice suggested that blastoconidia are capable of progressive extracellular digestion of the intestinal mucus barrier. Microplate assay methods, based on biotin or digoxigenin-labelling systems, were therefore devised for quantitation of protease and glycosidase activities against the glycoprotein mucin. Labelled mucin was adsorbed on microplate wells, incubated with sample to be assayed for enzyme activity, and the remaining labelled mucin was quantitated by spectrophotometry. Proteolytic activity against mucin was demonstrated using concentrated culture filtrate of C. albicans strain LAM-1, grown in yeast nitrogen base medium containing mucin as sole nitrogen source. The activity was inhibited by boiling for 10 min or by incubation with the aspartyl proteinase inhibitor pepstatin A.     

Hyperlipoproteinemia enhances susceptibility to acute disseminated Candida albicans infection in low-density-lipoprotein-receptor-deficient mice

Recent studies have suggested the use of lipoproteins as an adjuvant treatment of lethal gram-negative infections. However, other important microorganisms for the etiology of sepsis, such as Candida species, grow better in lipid-rich environments. We investigated the effect of hyperlipoproteinemia on systemic candidiasis in low-density-lipoprotein-receptor-deficient (LDLR-/-) mice, in which the loss of the receptor results in a seven- to ninefold-higher plasma LDL level than that in their wild-type littermates (C57BL/6J). LDLR-/- mice died earlier, and the outgrowth of Candida albicans in the kidneys and livers of LDLR-/- mice was significantly higher compared with that of controls. After infection, circulating cytokine concentrations were significantly higher in LDLR-/- mice. In vitro, C. albicans grew better in plasma samples of LDLR-/- mice than in control plasma samples and peritoneal macrophages of LDLR-/- mice challenged with heat-killed C. albicans produced more cytokines than did those of controls. This latter phenomenon was probably due to increased binding of yeast cells to macrophages of LDLR-/- mice. These data suggest that hyperlipoproteinemia is deleterious in systemic candidiasis.     

Identification of Candida albicans types related to healthy and pathological oral mucosa

This study comprised 100 healthy dentate adults and 53 patients with either chronic erythematous oral candidosis or oral leukoplakic lesions. The presence of yeasts was determined by microscopical examination of PAS-stained smears and by culture. Biopsy material was obtained from all lesions. The isolated yeasts were identified to species level. Strain phenotypes of 147 Candida albicans isolates were determined on the basis of the ODDS & ABBOTT procedure (25, 26). Yeasts were found in the mouth of healthy dentate individuals both by culture and by smears. The identification of hyphae in healthy mucosa indicates that the presence of these structures is not an unequivocal sign of candidal infection. The results support the view that tobacco smoking may be a predisposing factor for candidal infection. Also, the results have shown an association between the occurrence of yeasts and the type of leukoplakic lesions. Finally, the strain differentiation has indicated an oral mycoflora in patients with candidal lesions disappearing after antimycotic treatment which was more homogeneous in composition than in patients with irreversible lesions; furthermore, certain strains may possess properties which may be important in the development of pathological conditions and premalignant changes.