J Ethnopharmacol, 2001 Nov, 78(1), 103 - 7 Antimicrobial activity of plants used in traditional medicine of San Juan province, Argentine; Feresin GE et al.; Eighteen extracts from Acaena magellanica, Baccharis grisebachii, Ephedra breana, Oxalis erythrorhiza, Pachylaena atriplicifolia and Satureja parvifolia were assessed for antimicrobial activity against bacteria and fungi with the agar dilution method . The hexane (H) and dichloromethane (DCM) extracts of B . grisebachii and O . erythrorhiza showed the broadest spectrum of action against fungi, inhibiting all of the tested dermatophytes with MICs ranging from < or =25 to < or =1000 microg/ml . Trichophyton rubrum was the most susceptible species and Cryptococcus neoformans was inhibited only by the DCM extract of B . grisebachii with MIC of 600 microg/ml . Regarding the antibacterial activity, H and DCM extracts of B . grisebachii as well as the DCM of O . erythrorhiza, were active on methicillin-resistant and methicillin-sensitive Staphylococcus aureus with MIC from < or =125 to < or =500 microg/ml . The DCM extract of B . grisebacchii was more active against methicillin-resistant than methicillin-sensitive strains. Expert Opin Pharmacother, 2001 Aug, 2(8), 1259 - 68 Treatment of acute cryptococcal disease; Apisarnthanarak A et al.; Successful treatment outcome for cryptococcal disease has been available since the introduction of the polyene antifungal, amphotericin B . Over the past 15-20 years, treatment of acute cryptococcal disease has dramatically improved . Several therapeutic strategies have been introduced which improve overall outcome of therapy and help decrease the duration of treatment . Not surprisingly, most data now exists on the treatment of AIDS-associated cryptococcal disease, especially cryptococcal meningitis . Currently, amphotericin B with or without flucytosine is regarded as the best initial therapy for patients with meningitis or more severe illness, although, the azoles and other formulations of amphotericin B can considered in other situations . The choice of treatment for cryptococcal disease depends on both the anatomic sites of involvement and the host's immune status, all of which will be addressed in this article. Expert Opin Pharmacother, 2001 Aug, 2(8), 1211 - 26 Genitourinary fungal infections: a therapeutic conundrum; Wise GJ; Fungi cause 8% of nosocomial infections . This is caused, in part, by the increasing pool of immunocompromised patients . Elderly, transplant and HIV patients, as well as premature infants, have become prime candidates for invasive fungal infections . The widespread use of broad spectrum antibiotics plays a role . Utilisation of appropriate antifungal treatment modalities requires an understanding of the pathogenesis of infection . This is a challenging problem as fungi can cause different clinical manifestations that depend on the type of fungal species and patient response to the infection . Although Candida spp . are the most frequent pathogen, other species such as Aspergillus and Cryptococcus have become major pathogens . Environmental fungi which include Blastomyces, Coccidioides and Histoplasma have become more aggressive in the vulnerable patient . The genitourinary system can be a source or target of disseminated fungal infection . Diagnosis depends on clinical awareness, utilisation of appropriate diagnostic modalities, imaging modalities and a thorough clinical assessment . The treatment of primary (Blastomyces, Coccidioides, Histoplasma) infection generally requires amphotericin B (AmpB) . The opportunistic infections (Aspergillus, Cryptococcus and Candida) may respond to the triazoles although AmpB remains the 'gold standard' . Infections caused by Candida spp . represents the greatest challenge to the clinician . The presence of Candida spp . in the urine may indicate colonisation or infection . Untreated, Candida can remain as a 'saprophyte' or develop ascending infection, sepsis or death . The prophylactic use of fluconazole may in itself result in resistant infection, hence the 'conundrum'. J Vet Diagn Invest, 2001 Sep, 13(5), 439 - 42 PCR detection of the Cryptococcus neoformans CAPS9 gene from a biopsy specimen from a case of feline cryptococcosis; Kano R et al.; A polymerase chain reaction assay was developed to detect Cryptococcus neoformans in biopsy samples . The assay detects the CAP59 gene of Cryptococcus neoformans and was used to substantiate cutaneous cryptococcosis in a 5-year-old cat submitted to the Veterinary Medicine Center at the University of Tokyo. J Clin Microbiol, 2001 Oct, 39(10), 3505 - 11 Rapid identification of dimorphic and yeast-like fungal pathogens using specific DNA probes; Lindsley MD et al.; Specific oligonucleotide probes were developed to identify medically important fungi that display yeast-like morphology in vivo . Universal fungal primers ITS1 and ITS4, directed to the conserved regions of ribosomal DNA, were used to amplify DNA from Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis, Paracoccidioides brasiliensis, Penicillium marneffei, Sporothrix schenckii, Cryptococcus neoformans, five Candida species, and Pneumocystis carinii . Specific oligonucleotide probes to identify these fungi, as well as a probe to detect all dimorphic, systemic pathogens, were developed . PCR amplicons were detected colorimetrically in an enzyme immunoassay format . The dimorphic probe hybridized with DNA from H . capsulatum, B . dermatitidis, C . immitis, P . brasiliensis, and P . marneffei but not with DNA from nondimorphic fungi . Specific probes for H . capsulatum, B . dermatitidis, C . immitis, P . brasiliensis, P . marneffei, S . schenckii, C . neoformans, and P . carinii hybridized with homologous but not heterologous DNA . Minor cross-reactivity was observed for the B . dermititidis probe used against C . immitis DNA and for the H . capsulatum probe used against Candida albicans DNA . However, the C . immitis probe did not cross-react with B . dermititidis DNA, nor did the dimorphic probe hybridize with C . albicans DNA . Therefore, these fungi could be differentiated by a process of elimination . In conclusion, probes developed to yeast-like pathogens were found to be highly specific and should prove to be useful in differentiating these organisms in the clinical setting. J Clin Microbiol, 2001 Oct, 39(10), 3466 - 71 Rapid identification of yeasts in positive blood cultures by a multiplex PCR method; Chang HC et al.; Yeasts are emerging as important etiological agents of nosocomial bloodstream infections . A multiplex PCR method was developed to rapidly identify clinically important yeasts that cause fungemia . The method amplified the internal transcribed spacer 1 (ITS1) region between the 18S and 5.8S rRNA genes and a specific DNA fragment within the ITS2 region of Candida albicans . With this method, C . albicans produced two amplicons, whereas other species produced only one . Through sequence analysis, the precise lengths of the PCR products were found to be as follows: C . glabrata (482 or 483 bp), C . guilliermondii (248 bp), C . parapsilosis (229 bp), C . albicans (218 or 219 and 110 bp), C . tropicalis (218 bp), Cryptococcus neoformans (201 bp), and C . krusei (182 bp) . The PCR products could be effectively separated by disk polyacrylamide gel electrophoresis . The method was used to test 249 positive blood cultures (255 isolates), from which the following species (strain number) were isolated: C . albicans (128), C . tropicalis (51), C . glabrata (28), C . parapsilosis (23), C . neoformans (9), C . krusei (5), C . guilliermondii (3), and other, minor species (8) . The test sensitivity of the method was 96.9% (247 of 255 isolates) . The eight minor species were either misidentified (one strain) or not identified (seven strains) . From the time at which a positive bottle was found, the multiplex PCR could be completed within 8 h; the present method is simpler than any previously reported molecular method for the identification of blood yeasts. Ann Pharmacother, 2001 Sep, 35(9), 1037 - 41 Amphotericin B-induced seizures in a patient with AIDS; Aruna AS et al.; OBJECTIVE: To report a case of multiple episodes of seizure activity in an AIDS patent following amphotericin B infusion . CASE SUMMARY: A 46-year-old African-American man experienced recurrent grand mal seizures during intravenous infusion of amphotericin B, then petit mal seizures as the infusion was stopped and the drug concentrations decreased with time . The patients concurrent medications included didanosine, hydroxyzine, promethazine, hydrocortisone, and prochlorperazine . Despite administration of phenytoin and lorazepam, the seizures persisted and occurred only during amphotercin B administration . DISCUSSION: AIDS and cryptococcal meningitis, both of which the patient had, can potentially cause seizures . The patient had a history of alcohol abuse; alcohol intake as well as withdrawal can also cause seizures . Didanosine also has a potential for inducing seizures . However, these other potential causes of seizure were ruled out . The time course of events suggested that amphotericin B was the cause of the seizures in this AIDS patient . CONCLUSIONS: Amphotericin B seems to be the probable cause of the seizures . To date, only three cases of seizures associated with amphotericin B have been reported in the literature, but healthcare providers should be aware of the potential for this rare adverse effect. Laryngoscope, 2001 Aug, 111(8), 1338 - 42 Sinusitis complicated by meningitis: current management; Younis RT et al.; OBJECTIVES: Meningitis is the most common intracranial complication of sinusitis . We review the incidence, current management, outcomes, and complications of this serious infection . Our study also examines the evolving roles of endoscopic sinus surgery and other new therapeutic and diagnostic modalities in our armamentarium . STUDY DESIGN: A retrospective chart review was performed at a tertiary academic medical center of all patients diagnosed with sinusitis with complications between January 1985 and December 1999 . METHODS: The patients were divided into two main groups: intracranial versus orbital complications . Meningitis was the most common intracranial complication . Data on patients with sinusitis and meningitis were collected and analyzed . RESULTS: Intracranial complications were present in 39 of 82 patients whereas orbital complications were noted in 43 patients . Twenty-one of the 39 intracranial complications were meningitis . The most common computed tomography finding in adults (54%) was sphenoid sinusitis . All patients with AIDS (6 of 21) had unique cryptococcus meningitis . In patients without AIDS, the most common organism was Streptococcus pneumoniae (10 of 21) . The most common sequela was seizure disorder (4 of 21) . Endoscopic sinus surgery was performed on 7 of 21 patients . One patient with AIDS who had sinusitis and meningitis died . CONCLUSIONS: Meningitis as a complication of sinusitis may still pose a serious threat . Although outcomes are encouraging, sequelae such as seizure disorders and hearing loss are common complications . The introduction of high-resolution computed tomography scans and magnetic resonance imaging and the availability of wide-spectrum antibiotics have improved our management significantly. Curr Opin Investig Drugs, 2001 Apr, 2(4), 488 - 95 Nystatin LF (Aronex/Abbott); Arikan S et al.; Nystatin LF (Nyotran) is a liposomal, intravenous nystatin formulation under development by Aronex, under license from the MD Anderson Cancer Research Center, as a systemic antifungal agent against strains including Aspergillus and Candida . Like amphotericin, nystatin is a polyene derivative that binds to ergosterol, a fungal cell membrane component, creating a pore in the membrane and thus killing the cell . Nystatin is an established antifungal agent, but is restricted to topical use as it is ineffective orally and severely toxic when administered iv {187583}, {187589} . It has demonstrated good, broad in vitro antifungal activity against clinically relevant filamentous fungi {319465}, including fungi resistant to fluconazole and amphotericin B products {264505}, {2869821, {287790}, 1289522} . The company is also conducting a phase III trial to evaluate its efficacy against cryptococcal meningitis {305531}, {334156} . Aronex filed for approval of nystatin LF in Spain in December 1997 {272986} and expected to file an NDA in the US by the end of 1999 1311208}, {342003} . However, in an effort to ensure that its US and European filings contained data from the phase III cryptococcal meningitis trial in its entirety, Aronex's marketing partner requested that all the 70-day data be gathered prior to unblinding this study . The filing had initially been based on interim data at the 14- and 21-day endpoint 1344887} . In September 2000, the company anticipated an NDA filing in the US in the fourth quarter of 2001 1382861}, 1387947} . In December 1997, Aronex, together with Grupo Ferrer Internacional, filed an MAA in Spain seeking approval for Nyotran for the treatment of systemic fungal infections . Aronex intended to follow the filing with additional filings in other European countries 1272986} . In 1997, a commercialization agreement was signed with Ferrer for Spain and Portugal, with Aronex intending to form other such partnerships throughout Europe and Asia 1248346} . In November 1998, Aronex signed a licensing collaboration with Abbott Laboratories for the worldwide rights to nystatin LF {305531}. J Immunol, 2001 Oct 1, 167(7), 3988 - 95 Potent inhibition of neutrophil migration by cryptococcal mannoprotein-4-induced desensitization; Coenjaerts FE et al.; Cryptococcal capsular Ags induce the production of proinflammatory cytokines in patients with cryptococcal meningitis . Despite this, their cerebrospinal fluid typically contains few neutrophils . Capsular glucuronoxylomannan is generally considered to mediate the inhibition of neutrophil extravasation . In the current study, culture supernatant harvested from the nonglucuronoxylomannan-producing strain CAP67 was found to be as potent as supernatant from wild-type strains in preventing migration . We identified capsular mannoprotein (MP)-4 as the causative agent . Purified MP-4 inhibited migration of neutrophils toward platelet-activating factor, IL-8, and fMLP, probably via a mechanism involving chemoattractant receptor cross-desensitization, as suggested by its direct chemotactic activity . Supporting this hypothesis, MP-4 elicited Ca(2+) transients that were inhibited by preincubation with either fMLP, IL-8, or C5a, but not platelet-activating factor, and vice versa . Moreover, MP-4 strongly decreased the neutrophil surface expression of L-selectin and induced shedding of TNF receptors p55/p75, whereas CD11b/18 increased . Finally, MP-4 was clearly detectable in both serum and cerebrospinal fluid of patients suffering from cryptococcal meningitis . These findings identify MP-4 as a novel capsular Ag prematurely activating neutrophils and desensitizing them toward a chemoattractant challenge. Chemotherapy, 2001 Sep-Oct, 47(5), 377 - 80 Effect of ravuconazole, a new triazole antifungal, in a rat intraabdominal abscess model; Mikamo H et al.; BACKGROUND: Ravuconazole (BMS-207147) is a long-lasting triazole antifungal agent active against a broad spectrum of fungal pathogens including non-albicans Candida, Aspergillus, Cryptococcus and key dermatophytic fungi . METHODS: The efficacy of ravuconazole was evaluated using an experimental intraabdominal abscess model in rats caused by Candida albicans (E81022) . Two hundred milligrams of cyclophosphamide per kilogram was injected intraperitoneally into 40 rats . Four days (96 h) after the injection of cyclophosphamide, a mixture of C . albicans and autoclaved rat cecal contents {C . albicans 1.7 x 10(8) colony-forming units/rat} was inoculated into the peritoneal cavity . The rats were divided into four groups: ravuconazole treated, fluconazole treated, itraconazole treated and untreated . Each antifungal was given orally at a dose of 10 mg/kg twice a day for 5 days . On the day after the last administration, the rats were dissected and the viable fungi in the abscesses were determined . The number of C . albicans in each abscess was determined by a quantitative culture technique . RESULTS: Ravuconazole inhibited abscess formation and significantly decreased the viable cell counts in abscesses in comparison with the untreated group . It's efficacy was at least equivalent to fluconazole and itraconazole against this pathogen . The rank order of potency (inhibition) was ravuconazole > itraconazole > fluconazole . CONCLUSION: Taking into consideration the antifungal spectrum of ravuconazole, which includes non-albicans Candida as well as C . albicans and Aspergillus, it is suggested that ravuconazole would be a good agent for the treatment of fungal peritonitis . J Med Assoc Thai, 2001 May, 84(5), 688 - 92 Transthoracic aspiration cytology for the diagnosis of thoracic infection; Tangthangtham A et al.; The article describes the use and results of transthoracic aspiration cytology for diagnosis of thoracic infection in a Thai referral chest center . We reviewed 60 cytologic samples, initially diagnosed as thoracic infection or inflammation among a total of 532 percutaneous transthoracic needle aspirations obtained from patients with clinical suspicion of malignancy in a period of 6 years . Follow-up clinical data were collected and correlated with cytologic diagnosis . We found specific microorganisms in 8 samples (13.33%) . These included 4 cases of actinomycosis, 3 cases of cryptococcosis and a case of aspergillosis . Granulomatous inflammation was found in 12 samples (20.00%) . Among these patients, 10 cases were verified as having tuberculosis . The remaining 40 samples (66.67%) revealed acute inflammatory exudate with no specific microorganism . Follow-up clinical data confirmed or assumed infection in 27 cases . Therefore, in patients with thoracic infection who presented with clinical suspicion of malignancy, from our experience, aspiration cytology revealed adequate morphology for accurate diagnosis which resulted in prompt specific treatment and better prognosis. Antimicrob Agents Chemother, 2001 Oct, 45(10), 2862 - 4 In vitro activities of posaconazole (Sch 56592) compared with those of itraconazole and fluconazole against 3,685 clinical isolates of Candida spp . and Cryptococcus neoformans; Pfaller MA et al.; Posaconazole is a new investigational triazole with broad-spectrum antifungal activity . The in vitro activities of posaconazole were compared with those of itraconazole and fluconazole against 3,685 isolates of Candida spp . (3,312 isolates) and C . neoformans (373 isolates) obtained from over 70 different medical centers worldwide . The MICs of the antifungal drugs were determined by broth microdilution tests performed according to the National Committee for Clinical Laboratory Standards method using RPMI 1640 as the test medium . Posaconazole was very active against all Candida spp . (MIC at which 90% of the isolates were inhibited {MIC(90)}, 0.5 microg/ml; 97% of MICs were < or =1 microg/ml) and C . neoformans (MIC(90), 0.5 microg/ml; 100% of MICs were < or =1 microg/ml) . Candida albicans was the most susceptible species of Candida (MIC(90), 0.06 microg/ml), and Candida glabrata was the least susceptible (MIC(90), 4 microg/ml) . Posaconazole was more active than itraconazole and fluconazole against all Candida spp . and C . neoformans . These results provide further evidence for the spectrum and potency of posaconazole against a large and geographically diverse collection of clinically important fungal pathogens. Phytochemistry, 2001 Oct, 58(3), 475 - 80 Dihydroagarofuran alkaloid and triterpenes from Maytenus heterophylla and Maytenus arbutifolia; Orabi KY et al.; The antimicrobially active EtOH extracts of Maytenus heterophylla yielded a new dihydroagarofuran alkaloid,1beta-acetoxy-9alpha-benzoyloxy-2beta,6alpha-dinicotinoyloxy-beta-dihydroagarofuran, together with the known compounds beta-amyrin, maytenfolic acid, 3alpha-hydroxy-2-oxofriedelane-20alpha-carboxylic acid, lup-20(29)-ene-1beta,3beta-diol, (-)-4'-methylepigallocatechin, and (-)-epicatechin . In addition, beta-amyrin, (-)-epicatechin and (-)-4'-methylepigallocatechin were isolated from Maytenus arbutifolia . The structure elucidation of the isolated compounds was based primarily on 1D and 2D NMR analyses, including HMQC, HMBC, and NOESY correlations . Maytenfolic acid showed moderate antimicrobial activity by inhibiting the growth of Candida albicans, Cryptococcus neoformans, Staphylococcus aureus and Pseudomonas aeruginosa. Med Mycol, 2001 Aug, 39(4), 379 - 81 Colonization of a voice prosthesis by Cryptococcus neoformans; Bauters TG et al.; Tracheoesophageal voice prostheses in laryngectomized patients commonly deteriorate due to the presence of yeasts, particularly Candida species . We describe the first case of colonization of such a device by Cryptococcus neoformans in a patient with a history of glottic carcinoma . The isolate showed an identical genomic pattern with C . neoformans from pigeon excreta in the patient's environment. Med Mycol, 2001 Aug, 39(4), 353 - 7 Melanization of Cryptococcus neoformans reduces its susceptibility to the antimicrobial effects of silver nitrate; Garcia-Rivera J et al.; Cryptococcus neoformans is a human pathogenic fungus that is frequently found in avian feces and Eucalyptus trees . There is evidence that C . neoformans can make a melanin-like pigment in pigeon excreta, a major natural environmental niche . Silver nitrate, AgNO3, is a highly toxic compound for bacteria and fungi . In this study we investigated the effects of melanin production by C . neoformans on the susceptibility of this fungus to AgNO3 . C . neoformans was grown in media with and without the melanin precursor, L-dopa, for various times and susceptibility to AgNO3 was determined by measuring percentage of survival after incubation in AgNO3 . There was an inverse association between time allowed for melanization and susceptibility to Ag+ . Addition of melanin particles to a suspension of non-melanized C . neoformans cells reduced their susceptibility to AgNO3, consistent with metal ion chelation by melanin . Binding of Ag+ to melanin particles was demonstrated by atomic absorption spectroscopy . The results indicate that melanization of C . neoformans reduces susceptibility to a toxic heavy metal . This suggests a role for melanin in environmental protection against heavy metal toxicity. Mycopathologia, 2001, 151(2), 63 - 9 Decaying wood in tree trunk hollows as a natural substrate for Cryptococcus neoformans and other yeast-like fungi of clinical interest; Randhawa HS et al.; The occurrence of Cryptococcus neoformans var . neoformans and other yeast-like fungi of clinical interest in decaying wood inside tree trunk hollows, bark and other plant materials is reported . The var . neoformans was isolated from 3 of 45 (6.6%) wood and one of 390 Eucalyptus bark samples . Two of the positive wood samples came from a tree trunk hollow of Butea monosperma (Family: Papilionaceae) growing in Roshan Ara Garden, Old Delhi whereas the third was from a trunk hollow of Tamarindus indica (Family: Papilionaceae) growing outside of Talkatora Garden, New Delhi . The solitary positive Eucalyptus bark sample originated from Amritsar . The isolations of var . neoformans from decaying wood inside trunk hollows of B . monosperma and T indica constitute the first record of the natural occurrence of this pathogen in association with these trees . The observation reinforces the recent evidence for decaying wood inside trunk hollows of some trees to be a new natural habitat of the variety neoformans . Besides, in consonance with their essentially saprobic character, a number of other yeast-like fungi were sporadically isolated . This includes, Cryptoccus laurentii, Cryptococcus albidus, Candida lusitaniae, C . guilliermondii, C . krusei, C . tropicalis, C . zeylanoides, Trichosporon cutaneum, Rhodotorula mucilaginosa, R . glutinis, Geotrichum capitatum, G . klebahnii and Sporobolomyces salmonicolor . Cryptococcus neoformans var . gattii was not found in any of the 702 samples of plant materials, including the bark and detritus of Eucalyptus camaldulensis and E . tereticornis trees . A more extensive environmental survey, covering divergent climatic regions, is warranted to identify the natural reservoirs of var . gattii in India. Mycopathologia, 2001, 151(2), 53 - 6 Melanization decreases the susceptibility of Cryptococcus neoformans to enzymatic degradation; Rosas AL et al.; Cryptococcus neoformans is a free-living fungus that is primarily found in soils contaminated with avian excreta . Recent studies have shown that C . neoformans can synthesize melanins or melanin-like compounds in avian excreta . Melanization has been associated with protection of C . neoformans against harsh environmental conditions, such as ultraviolet radiation and extremes of temperature . In this study we examined whether melanization can protect C . neoformans against enzymatic degradation . Our results demonstrated that in vitro melanization decreases the susceptibility of C . neoformans to hydrolytic enzymes . This suggests a role for melanin in protection of C . neoformans against enzymatic degradation by antagonistic microbes in the environment. Infect Immun, 2001 Oct, 69(10), 6445 - 55 Both Th1 and Th2 cytokines affect the ability of monoclonal antibodies to protect mice against Cryptococcus neoformans; Beenhouwer DO et al.; Variable-region-identical mouse immunoglobulin G1 (IgG1), IgG2b, and IgG2a monoclonal antibodies to the capsular polysaccharide of Cryptococcus neoformans prolong the lives of mice infected with this fungus, while IgG3 is either not protective or enhances infection . CD4+ T cells are required for IgG1-mediated protection, and CD8+ T cells are required for IgG3-mediated enhancement . Gamma interferon is required for both effects . These findings revealed that T cells and cytokines play a role in the modulation of cryptococcal infection by antibodies and suggested that it was important to more fully define the cytokine requirements of each of the antibody isotypes . We therefore investigated the efficacy of passively administered variable-region-identical IgG1, IgG2a, IgG2b, and IgG3 monoclonal antibodies against intravenous infection with C . neoformans in mice genetically deficient in interleukin-12 (IL-12), IL-6, IL-4, or IL-10, as well as in the parental C57BL/6J strain . The relative inherent susceptibilities of these mouse strains to C . neoformans were as follows: IL-12(-/-) > IL-6(-/-) > C57BL/6J approximately IL-4(-/-) >> IL-10(-/-) . This is consistent with the notion that a Th1 response is necessary for natural immunity against cryptococcal infection . However, none of the IgG isotypes prolonged survival in IL-12(-/-), IL-6(-/-), or IL-4(-/-) mice, and all isotypes significantly enhanced infection in IL-10(-/-) mice . These results indicate that passive antibody-mediated protection against C . neoformans requires both Th1- and Th2-associated cytokines and reveal the complexity of the mechanisms through which antibodies modulate infection with this organism. Infect Immun, 2001 Oct, 69(10), 6256 - 63 Regulatory effects of macrophage inflammatory protein 1alpha/CCL3 on the development of immunity to Cryptococcus neoformans depend on expression of early inflammatory cytokines; Olszewski MA et al.; Macrophage inflammatory protein 1alpha (MIP-1alpha)/CCL3 prevents the development of eosinophilic pneumonia (EP) driven by a nonprotective T2-type immunity during infection with a highly virulent strain of Cryptococcus neoformans . The present study evaluated the interaction of MIP-1alpha with other innate immune system cytokines by comparing the immune responses that followed pulmonary infections with high- (C . neoformans 145A) and low (C . neoformans 52D)-virulence strains . In contrast to what was found for C . neoformans 145A infection, lack of MIP-1alpha in C . neoformans 52D infection did not cause the development of EP . C . neoformans 52D induced tumor necrosis factor alpha (TNF-alpha), gamma interferon (IFN-gamma), and MCP-1 in the lungs of infected wild-type (WT) and MIP-1alpha knockout (KO) mice by day 7 postinfection . Both WT and MIP-1alpha KO mice subsequently cleared this infection . Thus, the robust expression of early inflammatory cytokines in C . neoformans 52D-infected mice promoted the development of protective immunity even in the absence of MIP-1alpha . Alternatively, C . neoformans 145A-infected WT and MIP-1alpha KO mice had diminished TNF-alpha, IFN-gamma, and macrophage chemoattractant protein 1 (MCP-1) responses, indicating that virulent C . neoformans 145A evaded early innate host defenses . However C . neoformans 145A-infected WT mice had an early induction of MIP-1alpha and subsequently did not develop EP . In contrast, C . neoformans 145A-infected MIP-1alpha KO mice developed EP and had increased C . neoformans dissemination into the brain by day 35 . We conclude that, in the absence of other innate immune response effector molecules, MIP-1alpha is crucial to prevent the development of EP and to control C . neoformans dissemination to the brain. Infect Immun, 2001 Oct, 69(10), 6064 - 73 Interdependency of interleukin-10 and interleukin-12 in regulation of T-cell differentiation and effector function of monocytes in response to stimulation with Cryptococcus neoformans; Retini C et al.; We previously demonstrated that the principal component of capsular material of Cryptococcus neoformans, glucuronoxylomannan (GXM), induces interleukin-10 (IL-10) secretion from human monocytes . Here we report that encapsulation of the yeast with GXM is able to down-regulate interleukin-12 (IL-12) production by monocytes that would normally occur in the absence of encapsulation . This phenomenon appeared to be the result of inhibition of the phagocytic process by encapsulation with GXM as well as of negative signals such as IL-10 secretion produced by interaction of GXM with leukocytes . Decreased secretion of IL-12 correlated with decreased release of gamma interferon (IFN-gamma) from T cells, suggesting a role for encapsulation with GXM in hindering a T helper type 1 (Th1) response . This is supported by the ability of encapsulation with GXM to limit increased expression of B7-1 costimulatory molecules that otherwise might limit IL-10 secretion . Endogenous IL-10 played a critical role in modulatory activity associated with encapsulation with GXM . Blocking IL-10 with monoclonal antibody to IL-10 resulted in increased (i) IL-12 secretion, (ii) IFN-gamma release from T cells, and (iii) killing of C . neoformans by monocytes . These results suggest that encapsulation with GXM limits development of a protective Th1-type response, an inhibitory process in which IL-10 plays a critical role . Scavengers of GXM and/or IL-10 could be useful in a protective Th1-type response in patients with cryptococcosis. Trends Microbiol, 2001 Sep, 9(9), 445 - 51 Polysaccharides, mimotopes and vaccines for fungal and encapsulated pathogens; Pirofski LA; Vaccination is a rational alternative to treatment for Cryptococcus neoformans infections, as these infections are currently intractable in immunocompromised (including HIV-infected) individuals . Vaccines composed of the cryptococcal capsular polysaccharide glucuronoxylomannan (GXM), the key C . neoformans virulence factor, elicit protective antibodies in mice, although deleterious antibodies can also be induced . By contrast, polysaccharides are poor immunogens in HIV-infected humans and others with B-cell defects . Peptide mimotopes of GXM can induce protective immunity to C . neoformans in mice, however, our knowledge of the mechanisms of mimotope-induced protection is incomplete and further work is needed if polysaccharide- or mimotope-based vaccines are to be used to manage C . neoformans infection. Infection, 2001 Aug, 29(4), 213 - 7 Clinical, cerebrospinal fluid and pathological findings and outcomes in HIV-positive and HIV-negative patients with tuberculous meningitis; Schutte CM; BACKGROUND: The early diagnosis of tuberculous (TB) meningitis remains difficult . In South Africa, the HIV epidemic has shifted the spectrum of meningitis towards chronic infections (mainly tuberculosis {TB} and cryptococcosis) . This study aimed to analyze clinical, cerebrospinal fluid (CSF) and pathological findings and outcomes in TB meningitis to evaluate whether HIV infection significantly influences the characteristic findings . PATIENTS AND METHODS: 40 consecutive patients with TB meningitis presenting at the Pretoria Academic Hospital were evaluated clinically and chest X-rays (CXR), computerized tomography (CT) brain scans, CSF profiles, HIV and routine blood tests were analyzed . Postmortem examinations (PM) were performed in seven patients and outcomes were assessed after treatment . RESULTS: 20 patients were HIV-positive and 17 were negative (three not tested) . History and clinical findings were similar in both groups . The mean Glasgow Coma Scale (GCS) value on admission was 13 in both groups, while CXR showed abnormalities consistent with TB in 9/17 with HIV and 7/15 without, with abnormal CT brain scans in 15/19 patients with HIV and 12/16 without . Dilated ventricles and infarcts occurred more commonly in HIV-positive patients . The CSF results showed similar results in both groups . PM in three HIV-positive patients showed weakly formed granulomas and extensive endarteritis and infarcts . Outcomes were similar in the two groups, but a low GCS value on admission was a better prognostic indicator than the CD4-count in HIV-positive patients . CONCLUSION: HIV infection does not significantly alter clinical and CSF findings in TB meningitis in South Africa, but ventricular dilatation and infarcts are more frequent in HIV-positive patients . The GCS gives a better indicator of prognosis than the CD4-count. Appl Biochem Biotechnol, 1989, 20-21, 845 - 67 Rheologically interesting polysaccharides from yeasts; Petersen GR et al.; We have examined the relationships between primary, secondary, and tertiary structures of polysaccharides exhibiting the rheological property of friction (drag) reduction in turbulent flows . We found an example of an exopolysaccharide from the yeast Cryptococcus laurentii that possessed high molecular weight but exhibited lower than expected drag reducing activity . Earlier correlations by Hoyt showing that beta 1 --> 3, beta 2 --> 4, and alpha 1 --> 3 linkages in polysaccharides favored drag reduction were expanded to include correlations to secondary structure . The effect of sidechains in a series of gellan gums was shown to be related to sidechain length and position . Disruption of secondary structure in drag reducing polysaccharides reduced drag reducing activity for some but not all exopolysaccharides . The polymer from C . laurentii was shown to be more stable than xanthan gum and other exopolysaccharides under the most vigorous of denaturing conditions . We also showed a direct relationship between extensional viscosity measurements and the drag reducing coefficient for four exopolysaccharides. Mycologia, 1985 Jan-Feb, 77(1), 149 - 53 Cryptococcus friedmannii, a new species of yeast from the Antarctic; Vishniac HS; Cryptococcus friedmannii Vishniac sp . nov . from an Antarctic cryptoendolithic community is a psychrophilic basidioblastomycete characterized by cream-colored colonies of cells with smooth, layered walls, budding monopolarly, producing amylose and extracellular proteinase, utilizing nitrate and D-alanine (inter alia) as nitrogen sources and L-arabinose, arbutin, cellobiose, D-glucuronate, maltose, melezitose, salicin, soluble starch, trehalose, and D-xylose as carbon sources . This species differs from all other basidiomycetous yeasts in possessing the following combination of characters: amylose production (positive), assimilation of cellobiose (positive), D-galactose (negative), myo-inositol (negative), D-mannitol (negative), and sucrose (negative). Int J Syst Bacteriol, 1985 Jan, 35(1), 119 - 22 Cryptococcus socialis sp . nov . and Cryptococcus consortionis sp . nov., Antarctic basidioblastomycetes; Vishniac HS; New yeasts from the Ross Desert (dry valley area) of Antarctica include Cryptococcus socialis sp . nov . and Cryptococcus consortionis sp . nov . Cryptococcus socialis MYSW A801-3aY1 (= ATCC 56685) requires no vitamins, assimilates L-arabinose, cellobiose, D-glucuronate, maltose, melezitose, raffinose, soluble starch, sucrose, and trehalose, and may be distinguished from all other basidioblastomycetes by the combination of amylose production, cellobiose assimilation, and failure to utilize nitrate, D-galactose, myo-inositol, and mannitol . Its guanine-plus-cytosine content is 56 mol% . Cryptococcus consortionis MYSW A801-3aY92 (= ATCC 56686) requires thiamine, assimilates L-arabinose, D-glucuronate, 2-ketogluconate, salicin, succinate, sucrose, trehalose, and D-xylose, and may be distinguished from all other basidioblastomycetes by the combination of amylose production and failure to utilize nitrate, cellobiose, D-galactose, myo-inositol, and mannitol . Its guanine-plus-cytosine content is 56 mol%. Can J Microbiol, 1984, 30(5), 613 - 21 25S ribosomal RNA homologies of basidiomycetous yeasts: taxonomic and phylogenetic implications; Baharaeen S et al.; Genera, families, and possibly orders of basidiomycetous yeasts can be defined by 25S rRNA homology and correlated phenotypic characters . The teleomorphic genera Filobasidium, Leucosporidium, and Rhodosporidium have greater than 96 relative binding percent (rb%) intrageneric 25S rRNA homology and significant intergeneric separation from each other and from Filobasidiella . The anamorphic genus Cryptococcus can be defined by morphology (monopolar budding), colony color, and greater than 75 rb% intrageneric homology; Vanrija is heterogeneous . Agaricostilbum (Phragmobasidiomycetes, Auriculariales), Hansenula (Ascomycotera, Endomycota), Tremella (Phragmobasidiomycetes, Tremellales), and Ustilago (Ustomycota, Ustilaginales) appear equally unrelated to the Cryptococcus, Filobasidiella, and Rhodosporidium spp . used as probes . The Filobasidiaceae and Sporidiaceae, Filobasidiales and Sporidiales, form coherent homology groups which appear to have undergone convergent 25S rRNA evolution, since their relatedness is much greater than that indicated by 5S rRNA homology . Ribosomal RNA homologies do not appear to measure evolutionary distance. J Infect, 2001 Feb, 42(2), 134 - 9 The changing pattern of AIDS-defining illnesses with the introduction of highly active antiretroviral therapy (HAART)in a London clinic; Ives NJ et al.; OBJECTIVES: To quantify the progressive impact of combination antiretroviral therapy (ART) on the incidence of AIDS-defining illnesses (ADIs) over a 9-year period . METHODS: Retrospective cohort study . Eligible patients were 1538 AIDS-free, HIV-1-positive patients attending a large HIV clinic in west London who were at risk of developing AIDS because their CD4 count had declined to < or =350 x 10(6)/l cells during the period 1 January 1990 and 31 December 1998 . Incidence rates for the 12 most frequent ADIs were compared for two time periods, 1990-1995 (pre-HAART) and 1996-1998 (post-HAART), using Poisson regression methods . Multivariate Poisson regression models were used to examine the contribution of ART and HAART to any observed temporal trends in incidence rates . RESULTS: After a median follow-up of 35 months, 450 (29%) patients had developed AIDS . Between the two time periods there was a significant decrease in the incidence of Pneumocystis carinii pneumonia (PCP) by 35% (4.11 per 100 person-years in 1990-1995 vs . 2.67 in 1996-1998;P= 0.007), Kaposi's sarcoma by 34% (3.27 vs . 2.17;P= 0.022) and cryptosporidiosis by 60% (0.76 vs . 0.31;P= 0.029) . A non-significant reduction in incidence was observed for cryptococcosis by 45% (0.81 vs . 0.45;P= 0.11), oesophageal candidiasis by 29% (3.34 vs . 2.39;P= 0.053) and mycobacterium avium complex by 18% (1.58 vs . 1.29;P= 0.4), and a non-significant increase was observed for tuberculosis by 17% (0.62 vs . 0.73;P= 0.66) and non-Hodgkins lymphoma (NHL) by 51% (0.43 vs . 0.65;P= 0.31) . The incidence of cerebral toxoplasmosis, cytomegalovirus, recurrent bacterial chest infections and dementia remained stable . There was a clear stepwise reduction in the incidence of PCP, Kaposi's sarcoma and cryptosporidiosis with the use of non-H AART and HAART regimens relative to no ART . In a multivariate analysis, the use of ART and HAART explained the progressive decrease in incidence of PCP and Kaposi's sarcoma . CONCLUSIONS: The incidence of most ADIs has decreased over the last 9 years . The striking reduction in the inci-dence of PCP and Kaposi's sarcoma since 1996 can be attributed to the use of combination ART and particularly HAART . The non-significant increase in the incidence of NHL and tuberculosis needs confirmation in other patient cohorts. J Med Assoc Thai, 2001 Jun, 84 Suppl 1, S86 - 90 Childhood cryptococcosis: an increasing problem in the era of AIDS; Pancharoen C et al.; The authors reported 8 children with cryptococcosis from King Chulalongkorn Memorial Hospital from 1991 to 2000 . Five patients were older than five years . The two common underlying diseases were HIV/AIDS (5 cases) and systemic lupus erythematosus (2 cases) . Seven cases had been observed in the past four years, four of these in 2000 . One patient developed disseminated disease and two patients died . In the era of HIV/AIDS and due to the fact that HIV-infected children are tending to live longer, we may encounter a higher occurrence of this opportunistic fungus in children. J Med Assoc Thai, 2001 Jun, 84 Suppl 1, S1 - 17 Update on HIV/AIDS in Thailand; Ruxrungtham K et al.; Thailand experienced its first case of AIDS in 1984 . Approximately 800,000 Thais were infected with HIV in 1995 and 1 million Thais became infected by the year 2000 . There have been 5 major epidemic waves: among male homosexuals (started 1984-5), intravenous drug users (started 1988), female commercial sex workers (started 1989), male clients (started 1990), and housewives and the newborn (started 1991) . Approximately 96 per cent of HIV-1 infected Thais carried recombinant subtype A/E, the rest carried B' . In a male seroconvertors cohort of 235 cases, median time to show CD4 <200 cells/microL was 6.8 years . Five years survival was significantly lower than that of the other subtype B seroconvertors study, i.e., 82 per cent compared to 90 per cent . Interestingly, 13.5 per cent of seronegative Thais showed homozygous SDF1-3'A polymorphism, which suggests that approximately one-tenth of Thais may become long-term non-progressors after HIV-1 infection . Primary HIV infection syndrome is rare among Thai patients (1.1%) . In contrast, it was 50-90 per cent in Western cohorts . In early symptomatic patients, one-third developed pruritic pappular eruptions (PPEs) . In advanced stage, disseminated tuberculosis, Pneumocystis carinii pneumonia (PCP), cryptococcosis, and esophageal candidiasis are commonly found . In Northern Thailand, however, Penicillium marneffei infection or penicillosis is more common than cryptococcosis . The recent understanding of HIV pathogenesis suggests that HIV eradication is unlikely to be achievable with current strategies . Several National HIV treatment guidelines including the Thai guideline have been recommended treatment with triple antiretroviral regimen when patients become symptomatics or CD4+ <200 . Current development of antiretroviral therapy which includes new agents, new formulas, and pharmacokinetic enhancements, is directed to better potency, higher genetic resistant barrier, less pill burden, and once a day dosing . These will ultimately improve the adherence and the long-term effectiveness of antiretroviral treatment . In reality, however, although the cost of triple regimen is dramatically declining, many patients still can not afford it . Primary prophylaxis and early diagnosis and treatment of opportunistic infection should be considered in patients with CD4+ <200 cells/microL . Modified short course ZDV studies and donation campaigns for preventing mother-to-child transmission, clinical trials to investigate the best use of expensive anti HIV medications in a poor resource setting have been or are being conducted . Nine phase I/II HIV-1 vaccine trial protocols have been or are being tested . A phase III trial of gp120 subtype B/E (AIDSVAX, VaxGen) was started in 1999, a total of 2,500 volunteers will be enrolled, and interim analysis is planned for August 2002 . Thai investigators are also participating in pre-clinical development of recombinant BCG and DNA vaccines . Multidisciplinary and multi-level approaches, both by the government and private sectors, have had a positive impact on the HIV epidemic as shown by the declining seroprevalence of HIV infection in Thai male conscripts, and of major sexually transmitted diseases in men . Nevertheless, more effort at the grass roots level is needed to ensure further success and sustainability of the control of the HIV epidemic in Thailand. J Clin Microbiol, 2001 Sep, 39(9), 3365 - 7 Cryptococcus neoformans var . neoformans (serotype D) strains are more susceptible to heat than C . neoformans var . grubii (serotype A) strains; Martinez LR et al.; Cryptococcus neoformans var . neoformans (serotype D) and C . neoformans var . grubii (serotype A) differ in geographic prevalence and dermatotropism, with C . neoformans var . neoformans strains being more prevalent among isolates from temperate countries as well as from skin infections . Analysis of 19 strains from each serotype revealed wide variation in thermal susceptibility, with C . neoformans var . neoformans strains being more susceptible, on average, to heat killing . The results suggest a consistent explanation for the geographic differences between serotype A and D strains and for the dermatotropism of serotype D strains. AIDS Patient Care STDS, 2001 Aug, 15(8), 407 - 10 Fungemia in HIV-infected patients: a 12-year study in a tertiary care hospital; Garbino J et al.; Opportunistic infections caused by fungi are common in human immunodeficiency virus (HIV)-infected patients . We focused on severe infections as indicated by detectable fungemia . Medical charts available for patients having positive blood cultures with fungi at the University of Geneva Hospital were retrospectively (1989 to 2000) reviewed . Of 328 patients with fungemia during the study period, 315 (96%) medical charts were accessible . Of these 315 patients, 37 (12.2%) were HIV-positive, and 13 (35.1%) died within 6 months from their episode of fungemia . This was a lower mortality rate than for the HIV seronegative patients (45.8%) . The median and average age of the 34 HIV-positive patients was 37.2 years, and 24 (64.9%) were males . Cryptococcus neoformans (n = 14) and Candida albicans (n = 12) were the most frequently identified species, followed by Candida glabrata (n = 3), of which 3 were mixed C . albicans + C . glabrata, Histoplasma capsulatum (n = 2), and Penicillium marneffei (n = 2) . The frequency decreased significantly (p < 0.007) from the time period 1993 to 1996 (n = 21) to the period 1997 to 2000 (n = 6) . Fungemias in HIV-infected patients have declined significantly since 1996 . This coincides with the introduction of highly active antiretroviral therapy (HAART). Indian J Pediatr, 2001 Jul, 68(7), 655 - 68 Systemic antifungal agents; Abuhammour W et al.; Anti-fungal agents are classified under two major headings, systematic and topical agents . Only systematic anti-fungal agents will be discussed in this chapter . Since the discovery in 1955, amphotericin B has been the cornerstone of anti-fungal treatment . It is active against most species of fungi . However, Candida lusitaniae, Pseudallescheria boydii, and fusarium spp have primary resistance to amphotericin B . Recently, new liposomal preparations of amphotericin B have been developed . They are less nephrotoxic . The azole family of anti-fungal includes two broad classes: the imidazoles (clotrimazote, ketoconazote, miconazole) and the triazoles (flucouazole and itracouazole) . Imidazoles are still widely used for the treatment of superficial mycoses and vaginal candidiasis . The systematic triazoles are more slowly metabolized and have less effect on human synthesis than imidazoles, hence they are preferred for systemic therapy . Flucytosine is a fluorinated pyrimidine . Clinically, the principal use of flucytosine is as adjunctive therapy with amphotericin B in the treatment of candidial or cryptococcal diseases, Griseofuluin is derived from penicillium . It is fungistatic in vitro for species of dermatophytes . It is useful for the treatment of tinea capitis and tinea unginum. No To Shinkei, 2001 Jul, 53(7), 645 - 8 {A case of SLE presenting the features of antiphospholipid antibody syndrome during a treatment for complicated cryptococcal meningitis}; Izumi Y et al.; A 39-year-old woman had developed systemic lupus erythematosus(SLE) at the age of 29 . She had a long history of immunosuppressant therapies such as corticosteroid . On admission, she presented a headache due to the cryptococcal meningitis which was confirmed by lumbar puncture . Combined medications of amphotericin B and fluconazole were not effective, and combined amphotericin B and flucytosine were replaced . Prednisolone and methotrexate had been tapered gradually . Fifty days after the initial treatment for meningitis Cryptococcal neoformans was not observed in the cerebrospinal fluid . Sixty days after the treatment, thrombocytopenia was observed with positive lupus anticoagulant and anticardiolipin antibody . Following which, thrombophlebitis occurred in the left brachium . We suggest that the provoked pathoimmunological reaction such as antiphospholipid antibody syndrome during the treatment for meningitis needs to be cared during the course of SLE. AIDS, 2001 Jul 27, 15(11), 1438 - 9 Cessation of secondary prophylaxis in patients with cryptococcosis; Nwokolo NC et al.; Cryptococcal disease in HIV-positive individuals is usually a consequence of advanced immunosuppression . Treatment consists of long period of induction therapy followed by long-term secondary prophylaxis, usually with fluconazole . The introduction of highly active antiretroviral therapy has resulted in improvements in immunological function such that the cessation of primary and secondary prophylaxis against several opportunistic infections has become possible . We report our experience of the cessation of secondary antifungal prophylaxis in patients responding to highly active antiretroviral therapy. Proc Natl Acad Sci U S A, 2001 Aug 28, 98(18), 10422 - 7 Epub 2001 Aug 14. Molecular characterization of a mannoprotein with homology to chitin deacetylases that stimulates T cell responses to Cryptococcus neoformans; Levitz SM et al.; The fungus Cryptococcus neoformans is a major cause of morbidity and mortality in patients with impaired CD4(+) T cell function, particularly those with AIDS . To identify cryptococcal antigens that could serve as vaccine candidates by stimulating T cell responses, C . neoformans-reactive CD4(+) T cell hybridomas were generated by immunization of C57BL/6 mice and fusion of splenocytes with thymoma cells . The antigen that stimulated one of the hybridomas, designated P1D6, to produce IL-2 was purified to homogeneity by sequential anion exchange chromatography, hydrophobic interaction chromatography, and SDS/PAGE . Based on its apparent molecular mass of 98 kDa and mannosylation, the antigen of interest was named MP98 . MP98 was N terminal-sequenced, and the gene encoding the protein was cloned and sequenced . Recombinant MP98, expressed in Saccharomyces cerevisiae, stimulated P1D6 to produce IL-2 . Analysis of the derived 458-aa sequence of MP98 reveals an N-terminal cleavable signal sequence, a polysaccharide deacetylase domain found in fungal chitin deacetylases, and a serine/threonine-rich C-terminal region . Overall, there were 103 serine/threonine residues serving as potential O-linked glycosylation sites as well as 12 possible N-linked glycosylation sites . Thus, a C . neoformans mannoprotein has been characterized that stimulates T cell responses and has molecular properties of a chitin deacetylase. Drug Resist Updat, 1999 Aug, 2(4), 259 - 269 Drug resistance in Cryptococcus neoformans; Perfect JR et al.; Cryptococcus neoformans has become a major opportunistic fungal pathogen worldwide . Successful treatment of invasive disease with this fungus has used amphotericin B, flucytosine and various azoles . However, treatment failures continue to occur for a variety of reasons including direct antifungal drug resistance . Issues and mechanisms for antifungal drug resistance in Cryptococcus neoformans are reviewed . Furthermore, approaches and strategies for prevention and treatment of antifungal drug resistance are identified and these include host immune modulation, dose optimization, prophylaxis/empirical regimens, improved drug delivery systems such as lipid preparations of amphotericin B, surgery, combination antifungal treatments and development of new antifungal agents . Pol Merkuriusz Lek, 2001 Jun, 10(60), 456 - 9 {Cutaneous cryptococcosis in AIDS patient}; Gasiorowski J et al.; 45-year-old man with the Acquired Immunodeficiency Syndrome, on highly active antiretroviral therapy (HAART) resulting in rapid decline of HIV RNA and increase of CD4 T cells count, developed multiple skin umbilicated lesions (resembling molluscum contagiosum) on his face, ears, neck and chest . Histopathology and mycological cultures of a skin biopsy revealed Cryptococcus neoformans . Antigens of Cryptococcus was also identified in blood . During treatment with amphotericin B, the skin lesions regressed . This case demonstrates that skin lesions resembling molluscum contagiosum may be caused by cryptococcal infection . It is necessary to perform skin biopsy in HIV-infected persons with skin lesions to diagnose cutaneous cryptococcosis . The open question is if skin cryptococcosis may be the immune reconstruction disease. Antimicrob Agents Chemother, 2001 Sep, 45(9), 2420 - 6 In vitro and in vivo activities of syn2836, syn2869, syn2903, and syn2921: new series of triazole antifungal agents; Salama SM et al.; The in vitro and in vivo activities of four azole compounds belonging to a new series of 2(2,4-difluorophenyl)-3-(4-substituted piperazin-1-yl)-1-(1,2,4-triazol-1-yl) butanol antifungal agents is described . The compounds were selected from a library of azole compounds synthesized by our group . The in vitro activities of Syn2869, Syn2836, Syn2903, and Syn2921 against a panel of over 240 recently collected clinical isolates of yeast and molds were determined, and the results were compared with those obtained with fluconazole (FLC), itraconazole (ITC), and amphotericin B (AMB) . The MICs at which 90% of the isolates were inhibited (MIC(90)s) for the four test compounds for strains of Candida spp . ranged from <0.048 to 0.78 microg/ml . All compounds were also active against FLC-resistant Candida albicans and other Candida sp . strains . Moreover, MIC(90)s for strains of Cryptococcus neoformans, Aspergillus spp., Trichophyton spp., and Microsporum spp . were also low and ranged from <0.048 to 0.39 microg/ml . The test compounds produced a fungistatic pattern during the time-kill kinetic studies . In vivo studies indicated that all four test compounds have good efficacies against C . albicans in a murine systemic infection model and significantly improved the survival rates of the infected mice . The results for Syn2903 were similar to those for FLC, while the other compounds were slightly less effective but had ranges of activities similar to the range of activity of ITC . The compounds were also evaluated against an Aspergillus fumigatus systemic infection . Syn2903 was also superior to ITC, whereas the efficacy data for the other compounds were similar to those for ITC . It was concluded from the data generated for this new series of azole compounds in the studies described above that further pharmacokinetic and toxicologic evaluations are warranted prior to selection of a candidate compound for preclinical testing. Pharmacotherapy, 2001 Aug, 21(8 Pt 2), 149S - 164S Rationale for combination antifungal therapy; Lewis RE et al.; The relentless increase of invasive fungal infections and poor outcomes associated with available antifungal agents prompted the search for better therapeutic strategies . Combining antifungal drugs was recommended as a means to enhance efficacy in a variety of invasive infections including cryptococcosis, candidiasis, and aspergillosis . With the exception of cryptococcal meningitis, data from controlled clinical trials supporting such combinations are sparse . Moreover, little consensus exists regarding which combinations are synergistic or antagonistic in vitro and in vivo . Based on available data, several principles underlie these combinations. Pharmacotherapy, 2001 Aug, 21(8 Pt 2), 111S - 123S In vitro antifungal susceptibility testing; Hoffman HL et al.; With the rising frequency of fungal infections, as well as increasing reports of resistance to antifungal agents, it is imperative that clinically applicable antifungal susceptibility testing be available . In 1997 the National Committee for Clinical Laboratory Standards published standard guidelines for antifungal susceptibility testing of Candida sp and Cryptococcus neoformans with amphotericin B, flucytosine, fluconazole, itraconazole, and ketoconazole . Although the methods are standard, they are time consuming, can be difficult to interpret, and are approved only for testing limited organisms and drugs . Modifications to the methods and alternative approaches have been proposed to make these tests more convenient and efficient, applicable to a greater number of species, and appropriate for performing in the clinical laboratory. Folia Microbiol (Praha), 2001, 46(2), 147 - 50 Yeast-like microorganisms in eye infections; Dorko E et al.; The proportion of yeast species involved in eye infections in 11 patients was examined . The presence of yeast organisms as causative agents of endophthalmitis was found in corneal smears (n = 4), conjunctival swabs (4), and vitreous fluid (3) . Altogether 5 strains of Candida albicans, 2 strains of C . krusei and one strain each of C . guilliermondii, C . parapsilosis, C . tropicalis and Cryptococcus neoformans were isolated from the clinical material . The hematogenic origin of endophthalmitis was proved in 7 cases on the basis of positive blood samples and in 2 cases by the isolation of yeasts from the tip of an intravenous catheter . Endophthalmitis-supporting risk factors such as indwelling intravenous catheters, prolonged use of broad-spectrum antibiotics and chemotherapy, surgical intervention, diabetes mellitus, and malignancy were observed in the patients. Infect Immun, 2001 Sep, 69(9), 5589 - 96 Laccase of Cryptococcus neoformans is a cell wall-associated virulence factor; Zhu X et al.; Virulence is the outcome of an interaction between the host and a microbe and is characterized by a large array of opposing reactions operating at the host-pathogen interface . Cryptococcus neoformans is an important opportunistic pathogen in immunocompromised patients, including those with human immunodeficiency virus, and expresses a virulence-associated laccase which is believed to oxidize brain catecholamines and iron as a defense against host immune cells . In the present report, we investigated the cellular location of laccase to understand more fully how it contributes to cryptococcal virulence . A monoclonal antibody to the C . neoformans laccase was generated and used to show localization in the cell walls of representative serotype A (H99) and serotype D (B-3501) strains by immunoelectron microscopy . In addition, confocal microscopy was used to show a peripheral location of green fluorescent protein-tagged laccase expressed in live H99 cells . Biochemical studies showed that laccase could be released from intact cells or cell wall fractions with glucanase enzymes but was retained in the cell wall after sequential extraction with 1 M NaCl, 6 M urea, and 1% sodium dodecyl sulfate . The presence of a hydrolyzable bond linking laccase to the cell wall was suggested by removal of laccase from cell wall preparations after they were boiled in 1% sodium dodecyl sulfate, as was the presence of a disulfide or thioester bond by removal with dithiothreitol or beta-mercaptoethanol . These data show that laccase is present as a tightly associated cell wall enzyme that is readily accessible for interactions with host immune cells. Microbiology, 2001 Aug, 147(Pt 8), 2355 - 65 Dynamic changes in the morphology of Cryptococcus neoformans during murine pulmonary infection; Feldmesser M et al.; The pathogenesis of Cryptococcus neoformans infection has been studied extensively with respect to inflammatory and pathological changes, but very little information is available regarding the morphology of yeast cells during the course of infection . Electron microscopy of Cryptococcus neoformans in murine pulmonary infection revealed increased cell wall thickness with time, but this difference was only partially accounted for by increases in cell diameter . Cell walls of melanized cells were thicker than those of nonmelanized cells 2 h after infection, and the cell wall of yeast became blacker with time, suggesting that melanization contributes to the increased cell wall thickness . Heterogeneous cell populations emerged, with the appearance of giant forms . While for C . neoformans ATCC strain 24067 (serotype D) the full spectrum of cell sizes were observed, for strains H99 (serotype A) and 3501 (serotype D) cells were divisible into two populations, giant and micro forms . In contrast to cellular heterogeneity, the epitope recognized by a protective mAb on the capsular glucuronoxylomannan (GXM) was found at all times of infection . Immunoelectron microscopy using mAbs to GXM demonstrated reactivity with intracellular structures, suggesting that synthesis of capsular polysaccharide occurs, at least in part, in the cytoplasm . In summary, the results indicate that: (i) the infection is dynamic with respect to yeast cell morphology; (ii) giant cell forms arise in tissue during the course of infection; (iii) cell walls blacken and thicken during the course of infection, consistent with melanin synthesis during infection; and (iv) GXM epitopes are found in the capsule, cell wall and cytoplasm, consistent with intracellular polysaccharide synthesis . The results indicate that the population of C . neoformans cells in tissue is in a highly dynamic state, implying that the immune system must confront cells with varying characteristics during the course of infection. Microbiology, 2001 Aug, 147(Pt 8), 2029 - 36 A survey of heterobasidiomycetous yeasts for the presence of the genes homologous to virulence factors of Filobasidiella neoformans, CNLAC1 and CAP59; Petter R et al.; Among species of the heterobasidiomycetous yeasts, Filobasidiella neoformans is the only serious pathogen that causes fatal infections in both immunocompromised as well as immunocompetent patients . Three phenotypic characteristics, including growth at 37 degrees C, extracellular polysaccharide capsule and laccase activity, of F . neoformans are known to play major roles in the pathogenicity of the fungus . Several CAP genes involved in polysaccharide capsule formation, as well as the CNLAC1 gene encoding a laccase, have previously been cloned and characterized . To analyse the presence of these Cryptococcus neoformans virulence factors in other heterobasidiomycetous yeasts, numerous species of heterobasidiomycetous yeasts were screened for the presence of laccase activity and a polysaccharide capsule . Species exhibiting laccase activity and possessing a glucuronoxylomannan (GXM) capsule were screened for homologues of both the CAP59 gene and the CNLAC1 gene of F . neoformans . Southern blots of genomic DNA from GXM capsule-producing species exhibited no discernible hybridization to the CAP59 DNA sequence except for the two varieties of F . neoformans and Cryptococcus podzolicus . Although discernible, the hybridization band observed with the DNA of C . podzolicus was faint . Oligonucleotide primers constructed using the CAP59 gene sequence also failed to yield PCR products from DNAs of these yeasts except for the two varieties of F . neoformans . These results, coupled with the absence of a CAP59 homologue in the database, suggested the CAP59 gene to be unique to F . neoformans . C . podzolicus was the only species besides F . neoformans that possessed a capsule and expressed strong laccase activity on various media containing phenolic compounds . A CNLAC1 homologue was isolated from C . podzolicus while it was not detected in the species producing beige to faint tan colonies on media with phenolic compounds . Compared to the CNLAC1 sequence of four serotypes of F . neoformans, the CNLAC1 homologue of C . podzolicus showed the highest homology to that of serotype B/C strains and the lowest homology to that of serotype A strains. Rev Argent Microbiol, 2001 Apr-Jun, 33(2), 118 - 21 {AIDS-associated meningeal cryptococcosis in the Hospital Diego Paroissien from 1996-1999}; Monaco LS et al.; A total of 148 patients with a diagnosis of HIV infection were studied in order to evaluate the incidence of meningeal cryptococcosis, including epidemic, immunologic and diagnostic characteristics . The diagnosis of cryptococcosis was carried out by direct examination with India ink and culture in Sabouraud agar of CSF in 28 patients (93.3%) and by blood cultures (lysis-centrifugation) in 2 patients (6.6%) . All the isolated strains were identified as Cryptococcus neoformans . The incidence was 20.3% (30 patients) . The preponderant risk behavior was endovenous drug addiction, and it was observed in 18 patients (60%) . The symptomatology that prevailed was headache (87%) . The median age was 28 years . At diagnosis, the immunologic impairment was severe (CD4+ lymphocyte count < 200) in 90% of patients . We found that 86.7% of patients had not completed their primary studies and only 13.3% had completed secondary studies . Although the acute mortality was high (36.7%), it was observed that all the patients who survived (24%) had been treated with anti-retroviral drugs. Curr Treat Options Neurol, 2001 Sep, 3(5), 413 - 426 Cryptococcal Meningitis; Irizarry L; Cryptococcal meningitis, often seen in immunocompromised hosts, is also a disease of the immune-competent individual . The diagnosis of cryptococcal meningitis requires a lumbar puncture with measurement of the opening pressure, standard laboratory assessment including cell count, protein and glucose, fungal culture, and cryptococcal polysaccharide antigen . Serum cryptococcal antigen is of great diagnostic value in individuals infected with HIV . Hospital admission for initial therapy with amphotericin B desoxycholate is required . Adjuvant oral therapy with flucytosine for the first 2 weeks of therapy is strongly recommended . If flucytosine is not well tolerated, it may be discontinued with close monitoring and follow-up of cerebrospinal fluid (CSF) response to therapy . Good hydration and appropriate premedication concomitant to the use of amphotericin B are useful interventions preventing side effects . Occasionally, amphotericin B needs to be discontinued due to intolerance or side effects . After CSF sterilization is completed, therapy can be switched to oral fluconazole . Fluconazole is well absorbed orally . There is rarely a need to give intravenous fluconazole. Mycoses, 2001, 44(5), 137 - 40 First isolation of Cryptococcus neoformans var . gattii from a native jungle tree in the Brazilian Amazon rainforest; Fortes ST et al.; Cryptococcus neoformans var . gattii was isolated for the first time from decaying wood in a hollow of a native jungle tree Guettarda acreana, in a wild area of an Amazon rainforest island, in Brazil . The presence of this variety in a virgin environment without either anthropic action or introduced vegetation is discussed with regard to the common knowledge of Cr . neoformans ecology. Int J Food Microbiol, 2001 Jul 20, 67(1-2), 49 - 53 Comparison of dichloran 18% glycerol (DG18) agar with general purpose mycological media for enumerating food spoilage yeasts; Deak T et al.; Dichloran 18% glycerol (DG18) agar was originally developed to enumerate xerophilic foodborne moulds . However, some laboratories are using DG18 agar as a general medium to enumerate foodborne moulds and yeasts . A collaborative study, with the participation of seven laboratories, was undertaken to compare DG18 agar with dichloran rose bengal chloramphenicol (DRBC) agar, tryptone glucose yeast extract chloramphenicol (TGYC) agar, and plate count agar supplemented with chloramphenicol (PCAC) for enumerating 14 species of common food spoilage yeasts . Comparison of the mean values of populations of all yeasts recovered on each medium revealed no significant differences among DRBC agar, PCAC, and TGYC agar, while each of these media supported the development of significantly (P < or = 0.05) higher numbers of colonies than DG18 agar . However, differences were only 0.08 to 0.10 log10 cfu/ml, making the practical significance questionable . The overall coefficient of variation (CV) for within laboratory repeatability was 1.71%, while the CV for reproducibility of counts obtained among laboratories was 6.96% . Compared to DRBC agar, TGYC agar, and PCAC, yeast colonies were smaller on DG18 agar . Growth of Brettanomyces anomalus, Cryptococcus albidus, and Rhodotorula mucilaginosa was particularly retarded or inhibited on DG18 agar . Based on the performance of media in supporting colony development and ease of counting colonies, the use of DG18 agar as a general enumeration medium for foodborne yeasts cannot be recommended. Rinsho Shinkeigaku, 2001 Feb-Mar, 41(2-3), 154 - 6 {MRI finding of CNS cryptococcosis in an HIV-positive patient}; Mandokoro H et al.; We report an HIV-positive patient with CNS cryptococcosis, diagnosis of which was based on detection of Cryptococcus neoformans by Indian ink staining and culture of CSF . MRI displayed dilated Virchow-Robin space in bilateral basal ganglia which were hypointense on T1-weighted images, hyperintense on T2-weighted images, and enhanced by gadolinium administration . In addition cryptococcoma in the cerebellum was observed by MRI . This finding may suggest a progression from cryptococcal meningitis to intraparenchymal invasion, accompanied with breakdown of the blood brain barrier. Acta Cytol, 2001 Jul-Aug, 45(4), 589 - 92 Fine needle aspiration cytology in lymphadenopathy of HIV-positive cases; Saikia UN et al.; OBJECTIVE: To evaluate the role of fine needle aspiration biopsy (FNAB) material in 25 HIV-positive cases with lymphadenopathy . STUDY DESIGN: We selected 25 cases for the present study who were enzyme-linked immunosorbent assay positive for HIV (HIV-1) . FNAB was performed as a routine, outdoor procedure with informed consent of the patient . For each case, along with routine May-Grunwald-Giemsa and hematoxylin and eosin staining, Ziehl-Neelsen staining for acid-fast bacilli and periodic acid-Schiff staining for fungi were performed wherever necessary . RESULTS: A total of 28 sites were aspirated from 25 HIV patients . All these patients were heterosexual, and none had a history of drug abuse . FNAB was performed under ultrasound guidance in all four cases of a retroperitoneal group of lymph nodes . The most common FNAB diagnosis was reactive lymphoid hyperplasia (10), followed by tuberculosis (8) . There were three cases diagnosed as fungal infection (two, Cryptococcus; one, histoplasmosis) . FNAB of a case of lymph node was suggestive of tuberculosis . There was one case each diagnosed as non-Hodgkin's lymphoma and squamous cell carcinoma (metastatic) . One case of a small axillary lymph node did not yield representative material . CONCLUSION: FNAB is a relatively inexpensive initial investigative technique in the diagnosis and management of HIV-positive patients . It can obviate the need for surgical excision and enable immediate treatment of specific infections. Nippon Ishinkin Gakkai Zasshi, 2001, 42(3), 127 - 32 Atypical Cryptococcus neoformans isolate from an HIV-infected patient in Brazil; Uno J et al.; Cryptococcus neoformans is an important fungal pathogen in immunocompromised hosts . Capsulation, urease and melanin synthesis activity of the fungus are well known virulence factors . Although artificial melanin-deficient mutants of Cr . neoformans have been investigated, the clinical mutant is rare . We found a Cr . neoformans isolate in the cerebrospinal fluid of an AIDS patient which produced a light tan colony on a caffeic acid cornmeal agar (CACA) plate . The mycological feature of the isolate was as follows; normal capsulation, defective inositol assimilation ability, serotype A; urease-positive; mating type alfa; haploid; extremely slow growth in RPMI 1640 medium, Sabouraud dextrose broth, brain heart infusion broth and yeast nitrogen base; lower production of melanin with L-DOPA substrate; and low virulence to ddY mice . We also investigated the partial DNA sequence of CNLAC1 gene between the 3085th to 3623rd base . There were many substitutions, 3 insertions and 3 deletions in the isolate compared with GenBank accession number L22866 . The result indicated some functional disorder in the gene . Although the CACA plate is an excellent selective medium for Cr . neoformans, other identification methods should also be used. Clin Infect Dis, 2001 Sep 1, 33(5), 690 - 9 Epub 2001 Jul 26. Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy; Pappas PG et al.; We conducted a case study of human immunodeficiency virus (HIV)-negative patients with cryptococcosis at 15 United States medical centers from 1990 through 1996 to understand the demographics, therapeutic approach, and factors associated with poor prognosis in this population . Of 306 patients with cryptococcosis, there were 109 with pulmonary involvement, 157 with central nervous system (CNS) involvement, and 40 with involvement at other sites . Seventy-nine percent had a significant underlying condition . Patients with pulmonary disease were usually treated initially with fluconazole (63%); patients with CNS disease generally received amphotericin B (92%) . Fluconazole was administered to approximately two-thirds of patients with CNS disease for consolidation therapy . Therapy was successful for 74% of patients . Significant predictors of mortality in multivariate analysis included age > or =60 years, hematologic malignancy, and organ failure . Overall mortality was 30%, and mortality attributable to cryptococcosis was 12% . Cryptococcosis continues to be an important infection in HIV-negative patients and is associated with substantial overall and cause-specific mortality. FEMS Immunol Med Microbiol, 2001 Jul, 31(1), 59 - 64 Immunodiagnosis of tuberculous meningitis: rapid detection of mycobacterial antigens in cerebrospinal fluid by reverse passive hemagglutination assay and their characterization by Western blotting; Katti MK; Tuberculous meningitis (TBM) is one of the commonest chronic infections of the central nervous system (CNS) . Diagnosis of TBM has been a problem as it causes various clinical manifestations which can be confused with those of other chronic infections of the CNS such as neurocysticercosis (NCC), neurobrucellosis and cryptococcal meningitis, that are prevalent in many underdeveloped and developing countries . Differential diagnosis of TBM can be made by detecting circulating mycobacterial antigens in CSF by immunoassays . In this study, a reverse passive hemagglutination (RPHA) has been developed using rabbit antimycobacterial IgG for detection of circulating mycobacterial antigens in CSFs from chronic infections of the CNS in order to develop a rapid, simple, sensitive and cost-effective method . Circulating mycobacterial antigens were characterized by immunoblot assay . The sensitivity limit of RPHA was 400 ng ml(-1) . RPHA was specific as antimycobacterial IgG did not show any reaction with porcine Cysticercus cellulosae which was used as a control antigen . RPHA could detect mycobacterial antigens in CSF at a sensitivity level of 94.11% with a specificity of 99.0% . Immunoblot analysis of RPHA positive CSFs revealed predominantly 30-32 kDa and 71 kDa antigens whilst 6, 86, 120, 96 and 110 kDa showed varied degree of reactivity . Antigens of masses 30-32 and 71 kDa were absent in culture filtrate of Mycobacterium tuberculosis H37Rv grown in Proskeur-Beck liquid medium . RPHA is a rapid, simple and sensitive immunological method with a long shelf life of 6-8 weeks if stabilized coated erythrocytes are stored at +4 degrees C . RPHA could be used as an additional immunodiagnostic tool in both differential diagnosis and prognosis of TBM . Immunoblot results indicate that 30-32 kDa and 71 kDa antigens are cell wall derived. Recenti Prog Med . 2001 Jul-Aug;92(7-8):463. {Immune restoration syndrome}; Borre S et al.; A new syndrome, "immune restoration syndrome", has been described among patients with CMV retinitis, mycobacterial infections or cryptococcosis when HAART is initiated . The mechanism is most likely an enhanced immunologic reaction at the site of infection due to an improved T-lymphocyte function . The syndrome appears to be a rare event: the authors report a case of immune restoration syndrome in a patient with atypical mycobacteriosis. J Infect Dis, 2001 Aug 15, 184(4), 479 - 87 Epub 2001 Jul 13. In vivo clearance of glucuronoxylomannan, the major capsular polysaccharide of Cryptococcus neoformans: a critical role for tissue macrophages; Grinsell M et al.; Cryptococcus neoformans produces a life-threatening meningitis in patients who are immunocompromised by AIDS . A striking feature of cryptococcosis in AIDS is high serum levels of the major capsular polysaccharide, glucuronoxylomannan (GXM) . Soluble GXM has numerous biologic activities that may contribute to the pathogenesis of infection . The objective of the study was to further understand in vivo processing of GXM . Mice were injected intravenously with GXM, and the tissue distribution was determined . A macrophage suicide technique that used liposome-encapsulated dichloromethylene diphosphonate determined the role of macrophages . GXM was cleared from serum with a half-life of 24-48 h but was retained for an indefinite period in tissues rich in cells of the mononuclear phagocyte system . Ablation of macrophages decreased GXM in the liver and spleen and increased serum GXM . The results identify a key role for macrophages in the clearance of GXM from serum and identify macrophages as a long-term reservoir for storage. Curr Infect Dis Rep, 2001 Aug, 3(4), 365 - 370 Therapy of Cryptococcal Meningitis in non-HIV-infected Patients; Pappas PG; Cryptococcus neoformans is the most common cause of fungal meningitis in HIV and non-HIV-infected patients . The organism has a worldwide distribution, with cases typically occurring among patients with well-recognized specific underlying disorders associated with dysfunction of cell- mediated immunity . While the therapy for disease was studied extensively in the 1970s and the 1980s among non-HIV-infected individuals, most of the recently published data have concerned therapy for central nervous system cryptococcosis in HIV-infected patients . As a result, the current approach to therapy for central nervous system cryptococcosis in the non-HIV-infected patient represents a hybrid of the established "gold standard," which includes at least 6 weeks of combination therapy with amphotericin B and 5-flucytosine, and the more contemporary regimen, which consists of 2 weeks of induction therapy with an amphotericin B-containing regimen followed by fluconazole . Clearly, well-designed prospective studies are needed to define the best approach to therapy in these patients, but until then, we must rely on the results of the existing clinical trials and carefully interpret the results of the available retrospective data . At present, amphotericin B (deoxycholate or lipid-associated) is recommended as initial therapy for all non-HIV-infected patients with proven or suspected cryptococcal meningitis . Fluconazole plays an important role in consolidation therapy and among selected patients who require long-term chronic suppression . The potential role of the newer triazoles (voriconazole and posaconazole) is undetermined. Int J Infect Dis, 2001, 5(2), 78 - 85 Histopathology of cryptococcosis and other fungal infections in patients with acquired immunodeficiency syndrome; Shibuya K et al.; OBJECTIVE: To gain insight into the histopathologic characteristics of fungal infection in acquired immunodeficiency syndrome (AIDS) . METHODS: A review was conducted of the histopathology for 162 patients with evident fungal infection . RESULTS: The microscopic appearance of esophageal candidiasis that was common in patients with single organ involvement revealed necrotic debris containing proliferating hyphae at the site of mucosal erosions without fungal invasion of underlying tissue . The incidence of oral and esophageal candidiasis was followed by that of pulmonary aspergillosis and Candida infection . Eighteen patients had generalized cryptococcosis, representing the commonest generalized fungal disease . The essential histologic features of the disease consisted of yeast cell proliferation with a histiocytic response, but only minor lymphocytic and neutrophilic components . This was different from the manifestations of both Candida and Aspergillus infections . The two histologic patterns recognized in the pulmonary cryptococcal lesions could be graded with respect to the degree and type of inflammatory reaction . The milder one consisted of small scattered foci of intra-alveolar cryptococcal proliferation with a histiocytic response . Another pattern involved massive cryptococcal infection, which might be simply more extensive than that in the former . Capillary involvement of alveolar septa was an important common finding in all 18 patients. Int J Infect Dis, 2001, 5(2), 63 - 9 Seasonal variation in the etiology of bloodstream infections in a febrile inpatient population in a developing country; Bell M et al.; OBJECTIVES: Published data suggest that Streptococcus pneumoniae, non-typhi Salmonella species, and Mycobacterium tuberculosis are the predominant causes of bloodstream infection (BSI) in hospitalized populations in sub-Saharan Africa . This study was conducted during the wet season to ascertain the etiology and prevalence of BSI among febrile inpatients in a hospital where the dry season BSI profile in a similar study population had already been documented . METHODS: In the period from March to May 1998, consecutive febrile (> or = 37.5 degrees C) adult (> or = 14 y) patients presenting to a Malawi hospital were enrolled after providing informed consent . Following clinical evaluation, blood was drawn for culture (bacteria, mycobacteria, and fungi), human immunodeficiency virus (HIV) testing, and malaria smears . RESULTS: Of 238 enrolled patients, 173 (73%) were HIV-positive and 67 (28%) had BSI . The predominant wet season BSI pathogens were non-typhi Salmonella species (41%), M . tuberculosis (19%), and Cryptococcus neoformans (9%) (cf . the predominant dry season pathogen was S . pneumoniae) . Mycobacteremia was more likely in HIV-positive than in HIV-negative patients (13/173 vs . 0/65; P < 0.05) . A logistic regression model yielded clinical predictors of BSI that included chronic fever, oral candidiasis, or acute diarrhea . CONCLUSION: Pathogens causing BSI in febrile inpatients in a Malawi teaching hospital vary by season . Season- and country-specific studies, such as this one, provide data that may facilitate empirical therapy of febrile illnesses whose etiologies vary by season. Epidemiol Infect, 2001 Jun, 126(3), 397 - 414 Emerging trends in the epidemiology of invasive mycoses in England and Wales (1990-9); Lamagni TL et al.; Invasive fungal infections are becoming an increasing public health problem owing to the growth in numbers of susceptible individuals . Despite this, the profile of mycoses remains low and there is no surveillance system specific to fungal infections currently existing in England and Wales . We analysed laboratory reports of deep-seated mycoses made to the Communicable Disease Surveillance Centre between 1990 and 1999 from England and Wales . A substantial rise in candidosis was seen during this period (6.76-13.70 reports per million population/year), particularly in the older age groups . Rates of cryptococcosis in males fluctuated over the decade but fell overall (1.05-0.66 per million population/year), whereas rates of female cases gradually rose up until 1998 (0.04-0.41 per million population/year) . Reports of Pneumocystis carinii in men reduced substantially between 1990 and 1999 (2.77-0.42 per million population/year) but showed little change in women . Reports of aspergillosis fluctuated up until 1996, after which reports of male and female cases rose substantially (from 0.08 for both in 1996 to 1.92 and 1.69 per million population/year in 1999 for males and females respectively), largely accounted for by changes in reporting practice from one laboratory . Rates of invasive mycoses were generally higher in males than females, with overall male-to-female rate ratios of 1.32 (95% CI 1.25-1.40) for candidosis, 1.30 (95% CI 1.05-1.60) for aspergillosis, 3.99 (95% CI 2.93-5.53) for cryptococcosis and 4.36 (95% CI 3.47-5.53) for Pneumocystis carinii . The higher male than female rates of reports is likely to be a partial reflection of HIV epidemiology in England and Wales, although this does not fully explain the ratio in infants and older age groups . Lack of information on underlying predisposition prevents further identification of risk groups affected . Whilst substantial under-reporting of Pneumocystis carinii and Cryptococcus species was apparent, considerable numbers of superficial mycoses were misreported indicating a need for clarification of reporting guidelines . Efforts to enhance comprehensive laboratory reporting should be undertaken to maximize the utility of this approach for surveillance of deep-seated fungal infections. Curr Drug Targets, 2000 Nov, 1(3), 261 - 84 Membrane transporters and antifungal drug resistance; St Georgiev V; Over the last 30 years or so, the incidence of invasive fungal infections in man has risen dramatically . Patients that become severely immunocompromised because of underlying diseases such as leukemia or recently, acquired immunodeficiency syndrome or patients who undergo cancer chemotherapy or organ transplantation, are particularly susceptible to opportunistic fungal infections . Although Candida species continue to be the major pathogenic fungi in these patients, cryptococcosis, aspergillosis, and coccidioidomycosis, among others, have become increasingly important mycoses . Antifungal drugs currently being used in clinic include polyene antibiotics, azole derivatives and 5-fluorocytosine . With the exception of the latter, all other drugs possess mechanisms of action aimed at disrupting the integrity of the fungal cell membrane by either interfering with the biosynthesis of membrane sterols or by inhibiting sterol functions . However, one significant obstacle preventing successful antifungal therapy is the dramatic increase in drug resistance, especially against azole antimycotics . Among the major mechanisms by which fungi invoke drug resistance is the overexpession of extrusion pumps able to facilitate the efflux of cytotoxic drugs from the cell thus leading to decreased drug accumulation and diminished concentrations . Since the initial observations that azole resistance by fungi may be caused by overexpression of multidrug efflux transporter genes, significant advances have been achieved primarily with Saccharomyces cerevisiae and Candida albicans . The purpose of this review is to discuss various aspects of multidrug resistance in fungi such as antifungal drug mechanisms of action and fungal molecular genetics in the context of targeted drug discovery . The role that membrane transporter proteins play in drug resistance in various species of Candida, Aspergillus and Cryptococcus will be address in more detail, as will be their importance as selective drug targets in the design of novel antifungal agents. Clin Infect Dis, 2001 Aug 15, 33(4), 550 - 5 Epub 2001 Jul 11. Fungal infections in older adults; Kauffman CA; Invasive fungal infections have become an increasing problem in older adults . Infections with opportunistic fungi have increased because older patients are more likely to be considered for transplantation, receive aggressive regimens of chemotherapy for cancer, and take immunosuppressive drugs for nonmalignant diseases . In addition, healthy older adults are now more likely to travel extensively and to indulge in outdoor activities, which put them at risk for exposure to endemic mycoses . Although many of the clinical manifestations of fungal infections in older and younger adults are similar, there are aspects of histoplasmosis, aspergillosis, and cryptococcosis that are unique to older patients . Treatment of older adults with amphotericin B is difficult because of the intrinsic nephrotoxicity of the drug . Although they are less toxic, azoles must be used carefully for treatment of older adults, who are more likely to experience serious drug-drug interactions than are younger persons. Mol Microbiol, 2001 Jul, 41(1), 105 - 15 Spatial and temporal sequence of capsule construction in Cryptococcus neoformans; Pierini LM et al.; The pathogenic yeast Cryptococcus neoformans is distinguished by an extensive polysaccharide capsule, which impedes host defences and is absolutely required for fungal virulence . Despite the biological importance of the capsule, nothing is known about how it is assembled . Substantial capsule growth occurs in two distinct situations relevant to cryptococcal pathogenesis: formation of new buds and induction of capsule on mature cells . We developed pulse-chase protocols to examine these events in a dynamic way using a variety of microscopy techniques . We show that the capsule overlying buds is newly synthesized and differs physically from the corresponding parental material . New capsule formed by mature cells upon induction of synthesis is added at the inner aspect of the existing structure, displacing pre-existing material outwards . Surprisingly, new polysaccharide material is also deposited throughout the capsule, yielding a progressively denser structure . These results yield the first model of capsule synthesis and open new lines of investigation into the underlying mechanisms. Chest, 2001 Jul, 120(1), 177 - 84 Pulmonary fungal infection: emphasis on microbiological spectra, patient outcome, and prognostic factors; Chen KY et al.; STUDY OBJECTIVES: To investigate the microbiological spectra, patient outcome, and prognostic factors of pulmonary fungal infection . DESIGN: The medical and microbiological records of patients with pulmonary fungal infection were retrospectively analyzed . SETTING: A university-affiliated tertiary medical center . Patients and methods: From January 1988 to December 1997, all cases of pulmonary fungal infection were reviewed . The criteria for inclusion were obvious lung lesion shown on chest radiographs and one of the following: (1) the presence of fungi in or isolation of fungi from the biopsy specimen of open thoracotomy, thoracoscopy, transbronchial lung biopsy, or ultrasound-guided percutaneous needle aspiration/biopsy; or (2) isolation of fungi from pleural effusion or blood, with no evidence of extrapulmonary infection . RESULTS: A total of 140 patients were included . Ninety-four cases of pulmonary fungal infection (67%) were community acquired . The most frequently encountered fungi were Aspergillus species (57%), followed by Cryptococcus species (21%) and Candida species (14%) . There were 72 patients with acute invasive fungal infection, with a mortality rate of 67% . Multivariate logistic regression analysis showed that nosocomial infection (p = 0.014) and respiratory failure (p = 0.001) were significantly and independently associated with death of acute invasive fungal infection . CONCLUSIONS: Pulmonary fungal infection of community-acquired origins is becoming a serious problem . It should be taken into consideration for differential diagnosis of community-acquired pneumonia . Furthermore, acute invasive fungal infection is associated with a much higher mortality rate for patients with nosocomial infection or complicating respiratory failure . Early diagnosis with prompt antifungal therapy, or even with surgical intervention, might be warranted to save patients' lives. Diagn Microbiol Infect Dis, 2001 May-Jun, 40(1-2), 27 - 33 A two year global evaluation of the susceptibility of Candida species to fluconazole by disk diffusion; Liebowitz LD et al.; The in-vitro activity of fluconazole against 46,831 yeast isolates collected over a two-year period from 57 laboratories in 33 countries worldwide was assessed using a disc diffusion method . Candida albicans was the organism isolated most frequently, accounting for 68.6% of the total number of isolates . C . glabrata, C . tropicalis, C parapsilosis and C . krusei and Cryptococcus neoformans represented 9.9, 4.7, 4.3, 1.9, and 1.4% of isolates respectively during the 2 year period and rates varied markedly between countries . In 1999 data blood isolates represented 4.9% of all isolates and intensive care unit isolates represented 9.9% . In both the 1998 and 1999 data, 99% of C . albicans were fully susceptible (S) to fluconazole, and 95.6% of all species of yeasts tested were S or susceptible-dose dependent (S-DD) to fluconazole . No emerging trends of resistance were noted with any of the Candida spp . tested as 96% of all isolates retained susceptibility (S or S-DD) to this agent. Infect Dis Clin North Am, 2001 Jun, 15(2), 567 - 90 Central nervous system infections in the compromised host: a diagnostic approach; Cunha BA; The diagnostic approach to the compromised host with CNS infection depends on an analysis of the patient's clinical manifestations of CNS disease, the acuteness or subacuteness of the clinical presentation, and an analysis of the type of immune defect compromising the patient's host defenses . Most patients with CNS infections may be grouped into those with meningeal signs, or those with mass lesions . Other common manifestations of CNS infection include encephalopathy, seizures, or a stroke-like presentation . Most pathogens have a predictable clinical presentation that differs from that of the normal host . CNS Aspergillus infections present either as mass lesions (e.g., brain abscess), or as cerebral infarcts, but rarely as meningitis . Cryptococcus neoformans, in contrast, usually presents as a meningitis but not as a cerebral mass lesion even when cryptococcal elements are present . Aspergillus and Cryptococcus CNS infections are manifestations of impaired host defenses, and rarely occur in immunocompetent hosts . In contrast, the clinical presentation of Nocardia infections in the CNS is the same in normal and compromised hosts, although more frequent in compromised hosts . The acuteness of the clinical presentation coupled with the CNS symptomatology further adds to limit differential diagnostic possibilities . Excluding stroke-like presentations, CNS mass lesions tend to present subacutely or chronically . Meningitis and encephalitis tend to present more acutely, which is of some assistance in limiting differential diagnostic possibilities . The analysis of the type of immune defect predicts the range of possible pathogens likely to be responsible for the patient's CNS signs and symptoms . Patients with diseases and disorders that decrease B-lymphocyte function are particularly susceptible to meningitis caused by encapsulated bacterial pathogens . The presentation of bacterial meningitis is essentially the same in normal and compromised hosts with impaired B-lymphocyte immunity . Compromised hosts with impaired T-lymphocyte or macrophage function are prone to develop CNS infections caused by intracellular pathogens . The most common intracellular pathogens are the fungi, particularly Aspergillus, other bacteria (e.g., Nocardia), viruses (i.e., HSV, JC, CMV, HHV-6), and parasites (e.g., T . gondii) . The clinical syndromic approach is most accurate when combining the rapidity of clinical presentation and the expression of CNS infection with the defect in host defenses . The presence of extra-CNS sites of involvement also may be helpful in the diagnosis . A patient with impaired cellular immunity with mass lesions in the lungs and brain that have appeared subacutely or chronically should suggest Nocardia or Aspergillus rather than cryptococcosis or toxoplasmosis . Patients with T-lymphocyte defects presenting with meningitis generally have meningitis caused by Listeria or Cryptococcus rather than toxoplasmosis or CMV infection . The disorders that impair host defenses, and the therapeutic modalities used to treat these disorders, may have CNS manifestations that mimic infections of the CNS clinically . Clinicians must be ever vigilant to rule out the mimics of CNS infections caused by noninfectious etiologies . Although the syndromic approach is useful in limiting diagnostic possibilities, a specific diagnosis still is essential in compromised hosts in order to describe effective therapy . Bacterial meningitis, cryptococcal meningitis, and tuberculosis easily are diagnosed accurately from stain, culture, or serology of the CSF . In contrast, patients with CNS mass lesions usually require a tissue biopsy to arrive at a specific etiologic diagnosis . In a compromised host with impaired cellular immunity in which the differential diagnosis of a CNS mass lesion is between TB, lymphoma, and toxoplasmosis, a trial of empiric therapy is warranted . Antitoxoplasmosis therapy may be initiated empirically and usually results in clinical improvement after 2 to 3 weeks of therapy . The nonresponse to antitoxoplasmosis therapy in such a patient would warrant an empiric trial of antituberculous therapy . Lack of response to anti-Toxoplasma and antituberculous therapy should suggest a noninfectious etiology (e.g., CNS lymphoma) . Fortunately, most infections in compromised hosts are similar in their clinical presentation to those in the normal host, particularly in the case of meningitis . The compromised host is different than the normal host in the distribution of pathogens, which is determined by the nature of the host defense defect . In compromised hosts, differential diagnostic possibilities are more extensive and the likelihood of noninfectious explanations for CNS symptomatology is greater . (ABSTRACT TRUNCATED) J Chem Ecol, 2001 Apr, 27(4), 831 - 44 Butyl acetate and yeasts interact in adhesion and germination of Botrytis cinerea conidia in vitro and in fungal decay of golden delicious apple; Filonow AB; Butyl acetate is a volatile aroma and flavor compound in apple . Conidia of three strains of Botrytis cinerea, a fungus that causes decay of apple fruit in postharvest storage, had greater adhesion to and greater germination on polycarbonate membrane filters on water inside sealed 500 cc glass jars that were injected with 4 microliters butyl acetate than conidia not so exposed . Conidial germination was highly correlated with conidial adhesion . The yeasts Sporobolomyces roseus and Cryptococcus laurentii, but not Saccharomyces cerevisiae, reduced the adhesion and germination promoting effect of butyl acetate . Conidia did not readily utilize butyl acetate as a food source, as shown by lack of tetrazolium violet reduction, whereas S . roseus and C . laurentii, but not S . cerevisiae did . Butyl acetate added to suspensions of conidia increased the electrical conductivity of the suspensions and increased the loss of 14C from 14C-labeled conidia compared to conidia unexposed to butyl acetate . Uptake of {14C}glucose by conidia was not increased by butyl acetate . Wounds of Golden Delicious apples inoculated with conidia (strain F-J-4) in a dilute solution of butyl acetate had greater decay than unexposed wounds . S . roseus and C . laurentii, but not S . cerevisiae, added with the conidia decreased the incidence or size of decay . Results indicated that butyl acetate increased conidial adhesion, stimulating conidial germination, and some yeasts can reduce this effect. Scand J Infect Dis, 2001, 33(5), 388 - 9 Simultaneous occurrence of 2 HIV-related immunereconstitution diseases after initiation of highly active antiretroviral therapy; Legendre U et al.; The case of a 44-y-old woman with HIV infection and cytomegalovirus retinitis in whom antiretroviral therapy (HAART) revealed pulmonary cryptococcosis is presented . Pulmonary cryptococcosis occurred simultaneously with immune recovery uveitis after starting HAART, showing that complex clinical pictures may arise from immunreconstitution diseases. Transpl Infect Dis, 2000 Sep, 2(3), 101 - 11 Infections of the central nervous system in transplant recipients; Singh N et al.; Central nervous system (CNS) infections, accounting for 4-29% of CNS lesions in transplant recipients, are a significant post-transplant complication . Focal CNS infectious lesions or brain abscesses have been documented in 0.36-1% of the transplant recipients . Mycelial fungi, particularly Aspergillus, are by far the most frequent etiologies of post-transplant brain abscesses . Bacteria, with the exception of Nocardia, are rarely associated with brain abscesses in transplant recipients . Time of onset and concurrent extraneural lesions have implications relevant towards invasive diagnostic procedures in transplant recipients with brain abscesses . Meningoencephalitis in transplant recipients is predominantly due to viruses, e.g., herpesviruses, and less frequently due to Listeria monocytogenes, Toxoplasma gondii, and Cryptococcus . Despite a wide, and at times perplexing array of opportunistic pathogens that can cause CNS infections, the temporal association of the infection with the time elapsed since transplantation, risk factors, clinical manifestations, and neuroimaging characteristics of the lesion can allow a reasoned and rational approach towards the recognition, diagnosis, and appropriate management of CNS infections in transplant recipients. Transpl Infect Dis, 1999 Dec, 1(4), 247 - 61 Emerging fungal pathogens: evolving challenges to immunocompromised patients for the twenty-first century; Walsh TJ et al.; Opportunistic fungi have emerged during the past decade as important causes of morbidity and mortality in immunocompromised patients . Candida species constitute the third to fourth most common causes of nosocomial blood stream infections, and Aspergillus species have emerged as the most common infectious cause of pneumonic mortality in bone marrow/stem cell transplant recipients . Among HIV-infected patients, meningoencephalitis due to Cryptococcus neoformans ranks among the most common AIDS-defining infections . Hyaline septated filamentous fungi, such as Fusarium species, Acremonium species, Paecilomyces species, and Trichoderma species, are increasingly reported as causing invasive mycoses refractory to conventional therapy . Dematiaceous septated filamentous fungi, such as Pseudallescheria boydii, Bipolaris species, and Cladophialophora bantiana cause pneumonia, sinusitis, and CNS infection unresponsive to current therapy . An increasing number of different members of the class of Zygomycetes are reported as causing lethal infections, despite aggressive medical and surgical interventions . Yet the treatment for zygomycosis has not changed in approximately 40 years . The prevalence of the endemic mycoses, such as those due to Penicillium marneffei, Coccidioides immitis, and Histoplasma capsulatum, has been reported to expand rapidly in response to environmental exposures and increased numbers of vulnerable hosts in endemic regions of the world . Dermatophytoses are occurring with increasing prevalence and morbidity in elderly and immunocompromised patients . As we enter the next millennium, we may anticipate that emergent fungal infections will continue to develop in the settings of permissive environmental conditions, selective antifungal pressure, and an expanding population of immunocompromised hosts. Transpl Infect Dis, 1999 Dec, 1(4), 229 - 36 Epidemiology of fungal infections in solid organ transplant patients; Patterson JE; The epidemiology of fungal infection in solid organ transplant patients is of concern due to the high mortality associated with this complication . Rates of fungal infections vary by type of transplant recipient . Most of these infections occur two to six months after transplantation . Liver transplant recipients are more likely to have early fungal infection which is often due to Candida species . Exogenous and endogenous Candida infection may occur in the immunosuppressed patient in the intensive care unit . Patients with chronic rejection are more likely to have late infection (after six months) which may be due to Aspergillus or endemic fungi such as Cryptococcus . Lung and heart-lung transplant recipients are more predisposed to infection with Aspergillus and other filamentous fungi, due to exposure of the transplanted organ to the external environment . Preventative measures such as environmental controls and chemoprophylaxis may be beneficial in high-risk patients . Emerging fungal pathogens such as the dematiaceous fungi may cause skin or soft tissue infection, or more serious systemic infections . Fungal infection should be ruled out in the solid organ transplant patient with early brain abscess . Characteristic risk factors in high-risk types of solid organ transplant recipients should be recognized for early diagnosis and treatment of these infections associated with high morbidity and mortality. Transpl Infect Dis, 1999 Sep, 1(3), 213 - 7 Cryptococcal meningitis in renal transplant patients associated with environmental exposure; Kapoor A et al.; Fungal infections in renal transplant recipients are less common than bacterial infections; however, the morbidity from fungal infections is high . There is limited information in the literature concerning post-transplantation cryptococcal infection due to environmental exposure of patients living in high-risk areas . We report three patients who were diagnosed with cryptococcal meningitis after kidney transplantation . Cryptococcal titers prior to transplant surgery were negative in all three patients . These patients all lived in rural areas and demonstrated evidence of environmental exposure leading to subsequent cryptococcal meningitis . All patients had exposure to pigeon and chicken excreta and, after treatment, two patients are alive and well with excellent allograft function . The third patient has marginal renal function but is currently not on dialysis . Early diagnosis is essential for salvage from these potentially lethal infections . Intense headache was a prominent feature in the clinical presentation of our patients, and should signal the need for early sampling and culture of spinal fluid . Meningismus was not present in any of our patients, even when other systemic symptoms were identified . We recommend a high index of suspicion post-transplantation for all patients who may have environmental or occupational exposure to cryptococcus . If infection is detected quickly and treatment instituted promptly, patient recovery and allograft survival are possible . Long-term therapy with fluconazole, a non-nephrotoxic agent, should permit eradication of the infection with preservation of kidney function. J Thorac Imaging, 2001 Jul, 16(3), 139 - 48 The radiology of pulmonary cryptococcosis in a tertiary medical center; Lacomis JM et al.; Pulmonary cryptococcal infections occur in both immunocompetent and immunocompromised individuals, with a reported increased incidence of diffuse pulmonary disease in acquired immune deficiency syndrome (AIDS) patients . The authors observed no differences in the radiographic appearances of pulmonary cryptococcal disease between human immunodeficiency virus (HIV) patients and other immunocompromised individuals . Chest computed tomography (CT) contributes to a more comprehensive understanding of pulmonary cryptococcal infections. Yeast, 2001 Jun 30, 18(9), 865 - 80 The diversity of retrotransposons in the yeast Cryptococcus neoformans; Goodwin TJ et al.; We have undertaken an analysis of the retrotransposons in the medically important basidiomycetous fungus Cryptococcus neoformans . Using the data generated by a C . neoformans genome sequencing project at the Stanford Genome Technology Center, 15 distinct families of LTR retrotransposons and several families of non-LTR retrotransposons were identified . Members of at least seven families have transposed recently and are probably still active . For several families, only partial elements could be identified and these are quite diverse in sequence, suggesting that they are ancient components of the C . neoformans genome . Most C . neoformans elements are not closely related to previously identified fungal retrotransposons, suggesting that the diversity of fungal retrotransposons has been only sparsely sampled to date . C . neoformans has fewer distinct retrotransposon families than Candida albicans (37 or more), in particular fewer families represented solely by ancient and inactive elements, but it has considerably more families than either Saccharomyces cerevisiae (five) or Schizosaccharomyces pombe (two) . The findings suggest that elimination of retrotransposons is faster in C . neoformans than in C . albicans, but perhaps not as rapid as in S . cerevisiae or Sz . pombe . The identification of the retrotransposons of C . neoformans should assist in the molecular characterization of this important pathogen, and also further our understanding of the role played by retroelements in genome evolution . Radiology, 2001 Jul, 220(1), 122 - 8 Cryptococcomas distinguished from gliomas with MR spectroscopy: an experimental rat and cell culture study; Himmelreich U et al.; PURPOSE: To use magnetic resonance (MR) spectroscopy to characterize clinical isolates of Cryptococcus neoformans and a glioma cell line in culture and in experimental rats . MATERIALS AND METHODS: One- and two-dimensional hydrogen 1 MR spectra were acquired from fungi cultured in vitro (16 isolates of C neoformans, three of Candida albicans, three of Aspergillus fumigatus, three of Saccharomyces cerevisiae) and a C6 glioma cell line . Cerebral biopsy specimens were obtained from healthy rats and animals with experimental infections or gliomas (19 healthy brains, 20 cryptococcomas, and 19 gliomas) . Unequivocal signal assignment was performed for cell suspensions and tissue samples by using homo- and heteronuclear two-dimensional correlation spectra . RESULTS: MR spectra of C neoformans and cerebral cryptococcomas--but not of other fungi, healthy brains, or gliomas--were dominated by resonances from the cytosolic disaccharide alpha,alpha-trehalose . This spectral pattern was different from that of gliomas, which was dominated by lipids and an increased choline-creatine ratio, and that of healthy brain . CONCLUSION: A remarkably high concentration of alpha,alpha-trehalose in relation to other metabolites that are visible with MR spectroscopy is diagnostic of C neoformans . Cerebral cryptococcomas are an uncommon but serious manifestation of cryptococcosis in humans . Application of these results to the noninvasive diagnosis of cerebral cryptococcomas would help reduce the risk and expense of unnecessary surgery or biopsy and expedite patient treatment. Rev Mal Respir, 2001 Apr, 18(2), 125 - 35 {Respiratory infections during chemotherapy-induced aplasia}; Aoun M et al.; Damage to local and systemic host defenses of the lung makes the immunocompromised patient vulnerable to inhaled microorganisms . When a pulmonary infiltrate occurs, the array of possibilities is very large including conventional and opportunistic agents . The type of underlying disease and its associated immunodeficiency allow a high degree of accurate pathogen prediction . Neutropenia is associated with Gram-negative bacilli pn