J Clin Microbiol, 1998 Apr, 36(4), 883 - 6 Comparison of RapID yeast plus system with API 20C system for identification of common, new, and emerging yeast pathogens; Espinel-Ingroff A et al.; The ability to identify yeast isolates by the new enzymatic RapID Yeast Plus System was compared to the ability to identify yeast isolates by the API 20C system . A total of 447 yeast isolates representing Blastoschizomyces capitatus, 17 Candida spp., 5 Cryptococcus spp., Geotrichum spp., 2 Hanseniaspora spp., Hansenula anomala, Hansenula wingei, 3 Rhodotorula spp., Saccharomyces cerevisiae, Sporobolomyces salmonicolor, Trichosporon beigelii, and 2 Prototheca spp . were evaluated . Also, five quality control strains (Candida spp . and Cryptococcus laurentii) with well-documented reactivities by the RapID Yeast Plus System were used . Each isolate was evaluated by both methods with a 48-h culture grown at 30 degrees C on Sabouraud dextrose agar (Emmons modification) by following the recommendations of the manufacturers . The RapID Yeast Plus System enzymatic reactions were read after 4 h of incubation, and the API 20C carbohydrate assimilation identification profiles were obtained after 72 h of incubation . There was good (95.7%) agreement between the identifications obtained by the two methods with the eight common Candida spp . and with Cryptococcus neoformans . The agreement was lower when the emerging Candida spp . and other yeast-like pathogens were tested (79.1 and 75.2%, respectively) . These preliminary data suggest the potential utility of the RapID Yeast Plus System for use in the clinical laboratory for the rapid identification of common yeast pathogens as well as certain new and emerging species. Folia Neuropathol, 1997, 35(3), 133 - 43 Neuropathological syndromes in the course of full blown acquired immune deficiency syndrome (AIDS) in adults in Poland (1987-1995); Mossakowski MJ et al.; Morphological analysis of the brains from 100 cases of full blown AIDS patients observed in the course of 1987-1995 years was performed . The material comprised 96 males, 3 females and 1 infant, 11 months old . Early material consisted almost exclusively of homo- and bisexuals, while in the last years heterosexual drug addicts prevailed . Gross brain examination revealed focal changes in 25% of cases, most of them being connected either with opportunistic infections or primary proliferating malignancies . Brain atrophy with an evident regional differences was observed macroscopically in 35 cases . Microscopic examination allowed detection of pathological changes in the brains of 87 cases, although in the remaining 13 cases there occurred some slight abnormalities taking the form of non-specific neuronal degeneration and loss, considered as resulting from perimortal cardio-pulmonary insufficiency or bleeding . Specific HIV-related changes in the form of HIV-encephalitis, HIV-encephalopathy or coexistence of both and HIV-leptomeningitis as well as HIV-vasculitis were present in 35 cases . They were accompanied by HIV-associated changes (vacuolar myelopathy, vacuolar leukoencephalopathy and selective poliodystrophy) . Very seldom they appeared as independent pathological features and were characterized by very low frequency . Opportunistic infections composed the largest group of 59 cases . Proliferative malignancies occurred altogether in eleven cases, 10 of which were primary and secondary brain lymphomas . One case of Kaposi sarcoma completed the neoplastic series . Sixteen cases revealed various types of brain pathology such as hepatogenic encephalopathy, traumatic cortical scars, central pontine myelinolysis etc . The 59 cases of opportunistic infections consisted of a wide spectrum of viral and bacterial as well as fungal and protozoan infections . Among viral infections cytomegalovirus encephalitis was the most common, way ahead the progressive multifocal leukoencephalopathy . The second in frequency among opportunistic infections was brain toxoplasmosis and some fungal infections such as cryptococcosis and aspergillosis . Bacterial infections were in fact limited to tuberculosis, taking the form of granulomatous leptomeningitis with severe vascular pathology and/or tuberculoma formation . Many pathological processes appearing in a single case was characteristic feature of our collection . There was coexistence of HIV-specific CNS pathology and opportunistic infections, malignant neoplastic growth and other types of pathology . Various opportunistic infections coexisted without HIV-specific changes as well as malignant proliferation with opportunistic infections . Similarities and differences of our series were compared with data characterizing other, earlier collections of NeuroAIDS. FEMS Microbiol Lett, 1998 May 1, 162(1), 151 - 4 Isolation of dsRNA-associated VLPs from the strain Cryptococcus hungaricus CBS 6569; Pfeiffer I et al.; Double-stranded RNAs (dsRNAs) with molecular masses 1.7 and 5.0 kbp, respectively, were isolated from the strain Cryptococcus hungaricus CBS 6569 . The dsRNAs were copurified with eicosahedric virus-like particles, 29 nm in diameter . This strain produced a protease-sensitive 'toxin' which inhibited the growth of strain C . hungaricus CBS 4214 . The toxin had maximum activity at pH 3.7 . The highest toxin amount was attained after a culture period of four days. Ann Epidemiol, 1998 May, 8(4), 212 - 6 Surveillance of cryptococcosis in Alabama, 1992-1994; Thomas CJ et al.; PURPOSE: Although cryptococcosis is a significant opportunistic infection among patients with human immunodeficiency virus (HIV), there is conflicting information on rates of cryptococcosis among HIV-positive and HIV-negative patients . Precise state-wide epidemiologic data for cryptococcosis are not available in Alabama . METHODS: We conducted an active laboratory and hospital medical record-based surveillance for cryptococcosis in Alabama from October 1, 1992 to September 30, 1994 . A case of cryptococcosis was defined as a patient's initial episode of cryptococcal disease and based on either a positive culture for C . neoformans from any normally sterile site, a positive latex agglutination serologic test for cryptococcal antigen in CSF or serum, or histopathologic findings consistent with C . neoformans . RESULTS: Over the two year period, 153 cases were identified . The diagnosis was based on positive culture (37%), positive antigen (24%), positive autopsy culture (2%), and histopathologic findings (4%) . Further, 33% of the total cases were diagnosed from combined positive culture, antigen, or histopathology . Of the total 153 cases, 55% were in HIV-positive patients and 44% were in HIV-negative individuals and one case (1%) had an unknown HIV status . The overall annual incidence rate of cryptococcosis was 1.89 cases per 100,000 population . The incidence was 1638.7 per 100,000 in the HIV-positive population and 0.84 per 100,000 in the HIV-negative population . CONCLUSION: The first Alabama statewide active surveillance system for cryptococcosis confirms previous observations that rates of cryptococcosis are consistently higher in HIV-infected individuals than in their HIV-negative counterparts . In Alabama, cryptococcosis occurs more commonly in urban residents and in men . Cryptococcosis in HIV-positive persons is more likely to occur in the 20 to 44 year age group, whereas cryptococcosis in HIV-negative persons is more likely to occur in those greater than 45 years old. Am J Kidney Dis, 1998 May, 31(5), 780 - 5 Renal effects of amphotericin B lipid complex; Luke RG et al.; A study was conducted to compare the renal effects of amphotericin B lipid complex (ABLC), a lipid formulation of the widely used antifungal medication, with conventional amphotericin B (AmB) in the treatment of serious fungal infections, including invasive candidiasis, cryptococcal meningitis, and aspergillosis . The clinical experience of ABLC includes two types of open-label studies: randomized comparative (ABLC 5 mg/kg/d compared with AmB 0.6 to 1 mg/kg) and emergency use . In the comparative studies, changes in serum creatinine were evaluated three ways: doubling of the baseline value, an increase from < or = 1.5 mg/dL at baseline to > or = 1.5 mg/dL, and an increase from < or = 1.5 mg/dL at baseline to > or = 2.0 mg/dL . More patients in the AmB group reached these end points than in the ABLC group (P < or = 0.007), and the time needed to reach each of these end points was significantly shorter for the AmB group (P < or = 0.02) . Increased serum creatinine was reported as an adverse event more frequently by patients receiving AmB than by patients receiving ABLC . In the emergency use study, a steady and statistically significant decrease in serum creatinine was observed among patients who started ABLC treatment with serum creatinine greater than 2.5 mg/dL due to prior AmB treatment . ABLC offers the physician a valuable, less-nephrotoxic alternative to AmB for the treatment of patients with severe, invasive fungal infections. J Antibiot (Tokyo), 1998 Mar, 51(3), 359 - 67 Syntheses of antifungal aureobasidin A analogs with alkyl chains for structure-activity relationship; Kurome T et al.; The syntheses of aureobasidin A (AbA) derivatives with alkyl chains and their in vitro structure-biological activity relationships are discussed . The analogs replaced at positions 6, 7, or 8 of AbA with either L-glutamic acid, delta-hydroxy-L-norvaline, or delta-hydroxy-N-methyl-L-norvaline are prepared . The gamma-carboxyl or delta-hydroxyl group of these new amino acids was coupled with acids, alcohols, or amines with alkyl chains . While the analogs having L-glutamic acid residue at positions 6 or 8 showed weak activity, esterification of the gamma-carboxyl group with benzyl or shorter alkyl (C4 or C6) alcohols, significantly enhanced the activities . Introduction of longer alkyl (C14) chain to the same amino acids residues at positions 6, 7, or 8 resulted in total loss of antifungal activity . Among the lipophilic analogs in {L-Glu6} derivatives, the C6 alcohol ester showed the strongest antifungal activity against Candida spp . so far tested . None of the derivatives showed activity against Cryptococcus neoformans. J Fr Ophtalmol, 1997, 20(9), 689 - 92 {Cryptococcal chorioretinitis and acquired immunodeficiency syndrome}; Razavi S et al.; We report a case of cryptococcal chorioretinitis discovered at ophthalmological examination of a 68-year-old woman with acquired immune deficiency syndrome . This localization revealed cryptococcal septicemia, without involvement of the central nervous system unlike most cases reported . Therapy with fluconazole (400 mg per day) led to gradual regression of the chorioretinal lesion. J Assoc Acad Minor Phys, 1998, 9(1), 22 - 4 Recurrent central diabetes insipidus secondary to cryptococcal meningitis; Woredekal Y; Meningitis is often associated with hyponatremia due to inappropriate secretion of antidiuretic hormone, and diabetes insipidus is associated with bacterial meningitis . This article describes a patient with acquired immunodeficiency syndrome who experienced recurrent episodes of central diabetes insipidus in association with recurrent fungal meningitis . Desmopressin was effective in controlling the polyuria until the episodes of meningitis resolved. Pigment Cell Res, 1998 Apr, 11(2), 120 - 6 Chemical degradation of melanins: application to identification of dopamine-melanin; Ito S et al.; Melanocytes produce two chemically distinct types of melanin pigments, eumelanins and pheomelanins . These pigments can be quantitatively analyzed by acidic KMnO4 oxidation or reductive hydrolysis with hydriodic acid (HI) to form pyrrole-2,3,5-tricarboxylic acid (PTCA) or aminohydroxyphenylalanine (AHP), respectively . Dark brown melanin-like pigments are also widespread in nature, for example, in the substantia nigra of humans and primates (neuromelanin), in butterfly wings and in the fungus Cryptococcus neoformans . To characterize such diverse types of melanins, we have improved the alkaline H2O2 oxidation method of Napolitano et al . (Tetrahedron, 51:5913-5920, 1995) and re-examined the HI hydrolysis method of Wakamatsu et al . (Neurosci . Lett., 131:57-60, 1991) . The results obtained with H2O2 oxidation show that 1) pyrrole-2,3-dicarboxylic acid (PDCA), a specific marker of 5,6-dihydroxyindole units in melanins, is produced in yields ten times higher than by acidic KMnO4 oxidation, and 2) PTCA is artificially produced from pheomelanins . The results with HI hydrolysis show that dopamine-melanin produces a 1:1 mixture of 3-amino and 4-amino isomers of aminohydroxyphenylethylamine, while the isomer ratio is about 0.2 in melanins prepared from dopamine and cysteine . These results indicate that alkaline H2O2 oxidation is useful in characterizing synthetic and natural eumelanins and that reductive hydrolysis with HI can be applied to analyzing oxidation products of dopamine such as neuromelanin. Diagn Cytopathol, 1998 May, 18(5), 365 - 7 Pulmonary cryptococcosis and pituitary Cushing's disease; Drew PA et al.; Pulmonary cryptococcosis was diagnosed by examining smears obtained by fine-needle aspiration (FNA) in a patient with pituitary Cushing's disease . FNA allowed for rapid diagnosis and prompt treatment of a potentially serious infection . The patient fully recovered from her pulmonary disease . Although opportunistic infections may occur in patients with endogenous Cushing's syndrome, it is rare to see such infections in the subset of patients with pituitary Cushing's disease . Hypercortisolism associated with Cushing's syndrome appears to induce a transitory immune deficiency state and opens a window of opportunity for certain infectious agents such as Cryptococcus neoformans to exploit . To our knowledge, this is the third such case reported in this clinical setting, and the first diagnosed by FNA. Nippon Ishinkin Gakkai Zasshi, 1998, 39(2), 55 - 9 Extracellular phospholipases as universal virulence factor in pathogenic fungi; Ghannoum MA; Microbial pathogens use a number of genetic strategies to invade the host and cause infection . These common themes are found throughout microbial virulence factors . Secretion of enzymes, such as phospholipase, has been proposed as one of these themes which is used by bacteria, parasite, and pathogenic fungi . The role of extracellular phospholipase as a potential virulence factor in pathogenic fungi, including Candida albicans, Cryptococcus neoformans and Aspergillus has gained credence recently . In this address data implicating phospholipase as a virulence factor in Cryptococcus neoformans and Aspergillus fumigatus will be presented . This will be followed by a more detailed description of our molecular and biochemical approaches we used to more definitively delineate the role of phospholipase in the virulence of C . albicans . First, we purified the phospholipase B protein, the dominant phospholipase secreted by C . albicans, obtained the amino acid sequence of its N-terminus and an internal peptide fragment, and used this information to clone the gene encoding the protein using a PCR-based approach . Nucleotide sequence analysis revealed an ORF of 1818 bp that predicted for a pre-protein of 605 amino acid residues . The deduced amino acid sequences of the cloned gene (PLB 1) showed 42.3%, 45%, and 47.8% overall sequence identity, with the reported sequences of phospholipase B cloned from Penicillium notatum, Saccharomyces cerevisiae, and Saccharomyces rosei, respectively . Second, using targeted gene disruption, URA blaster, we created C . albicans null mutants which failed to secrete phospholipase B . Third, we tested the ability of these isogenic strain pairs to cause lethality using a murine model of hematogenously disseminated candidiasis . Our data demonstrate that the parent phospholipase-producing strain caused more fatality in mice, while the null phospholipase-deficient strain was avirulent . Importantly, the parent and null mutants had similar growth and germination rates . These data prove that phospholipase B is essential for candidal virulence, and pave the way for studies directed at determining the mechanism/s through which phospholipase modulate candidal virulence . Understanding phospholipase as a common theme in fungal pathogenicity is critical for developing new antifungal strategies based on anti-virulence. J Antimicrob Chemother, 1998 Mar, 41(3), 397 - 401 Antifungal pharmacodynamic characteristics of fluconazole and amphotericin B against Cryptococcus neoformans; Klepser ME et al.; The activity of fluconazole and amphotericin B against three isolates of Cryptococcus neoformans was evaluated, with fluconazole and amphotericin B MICs of 2.0-4.0 mg/L and 1.0 mg/L respectively, using time-kill curve methods . Fluconazole was fungistatic against all isolates tested (<99.9% decrease in cfu from initial inoculum) . The fungistatic activity of fluconazole was not enhanced by increasing the concentration of antifungal in solution . In contrast, amphotericin B was markedly fungicidal (> or = 99.9% decrease in cfu from initial inoculum) . Both the rate and the extent of amphotericin B activity were enhanced when drug concentration was increased. Am J Clin Pathol, 1998 May, 109(5), 634 - 41 Comparison of two rapid latex agglutination tests for detection of cryptococcal capsular polysaccharide; Jaye DL et al.; The Murex Cryptococcus Test was compared with the Cryptococcal Antigen Latex Agglutination System (CALAS) for detecting cryptococcal polysaccharide in 173 cerebrospinal fluid (CSF) specimens and 117 serum samples with 99% and 97% concordance, respectively . Eighteen CSF samples and 17 serum samples were positive in both assays, and 249 were negative . The sensitivity and specificity of the Murex relative to the CALAS were 90% and 100%, respectively, for CSF, and 81% and 100%, respectively, for serum . Six discrepancies were arbitrated by retesting, using a third analytic method, review of other laboratory and clinical data, or both . The reaction in 1 CSF specimen was considered false positive by the CALAS, and the reactions in 2 serum samples were false negatives by the Murex . For 3 patients with previous cryptococcal meningitis but no active disease, only the CALAS detected antigen, suggesting that the Murex has less analytic sensitivity in this context . Titer differences dictate that direct comparisons between the 2 tests are not feasible . There were no false-positive reactions in limited testing with either method using specimens from patients with concurrent noncryptococcal infections or in rheumatoid factor-positive serum samples . Infections caused by Cryptococcus neoformans serotypes A or AD were detected equally by both assays . Based on our study, we have elected to continue to use the CALAS for routine testing for cryptococcal antigen. J Clin Microbiol, 1998 May, 36(5), 1458 - 60 Rapid detection of species of the opportunistic yeast Trichosporon by PCR; Sugita T et al.; Trichosporon species are opportunistic pathogens, associated with a high mortality rate in immunocompromised patients . Oligonucleotide primers were used to amplify a 170-bp fragment of small-subunit ribosomal DNA of all species in the genus Trichosporon by PCR . The primers amplify DNAs of all species in the genus Trichosporon, including six causative agents of trichosporonosis . DNAs of other medically important yeasts, such as Candida albicans and Cryptococcus neoformans, are not amplified by this detection system. J Clin Microbiol, 1998 May, 36(5), 1450 - 2 Comparison of a 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-{(phenylamino)carbonyl}-2H-t etrazolium hydroxide (XTT) colorimetric method with the standardized National Committee for Clinical Laboratory Standards method of testing clinical yeast isolates for susceptibility to antifungal agents; Hawser SP et al.; MICs for clinical Candida and Cryptococcus isolates were determined by a method incorporating the colorimetric indicator 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-{(phenylamino)carbonyl} -2H-tetrazolium hydroxide (XTT), and the results were compared with MICs obtained by the National Committee for Clinical Laboratory Standards approved standard method (M27-A) . One hundred percent of all isolates demonstrated agreement within 2 dilutions between the MICs of amphotericin B, fluconazole, itraconazole, ketoconazole, and flucytosine obtained by the two methods . These data suggest that an XTT-based method could provide a useful means for the determination of antifungal susceptibility of yeasts. J Clin Microbiol, 1998 May, 36(5), 1330 - 2 Comparative evaluation of National Committee for Clinical Laboratory Standards broth macrodilution and agar dilution screening methods for testing fluconazole susceptibility of Cryptococcus neoformans; Kirkpatrick WR et al.; A simple screening method for fluconazole susceptibility of Cryptococcus neoformans using 2% dextrose Sabouraud dextrose agar (SabDex) with fluconazole was compared to the National Committee for Clinical Laboratory Standards (NCCLS) broth macrodilution method . By this method, fluconazole-susceptible C . neoformans isolates are significantly smaller on medium with fluconazole than on fluconazole-free medium . Isolates with decreased susceptibility have normal-size colonies on medium containing fluconazole . The 48-h NCCLS broth macrodilution MICs (NCCLS MICs) for isolates with normal-size colonies on 8- or 16-microg/ml fluconazole plates were predicted to be > or =8 or > or =16 microg/ml, respectively . On medium with 16 microg of fluconazole per ml, all strains (84 of 84) for which the NCCLS MICs were <16 microg/ml were correctly predicted, as were all isolates (7 of 7) for which the MICs were > or =16 microg/ml . Agar dilution appears to be an effective screening method for fluconazole resistance in C . neoformans. J Clin Microbiol, 1998 May, 36(5), 1176 - 9 Evaluation of BACTEC MYCO/F lytic medium for recovery of mycobacteria and fungi from blood; Waite RT et al.; The reliability of MYCO/F Lytic medium in the BACTEC 9240 blood culture system was evaluated by comparing its performance to that of the Isolator system for the recovery of fungi and to that of the ESP II system for the recovery of mycobacteria . Of 717 specimens of blood cultured for fungi, 24 were positive; 12 samples were positive with both systems, 7 samples were positive with the Isolator system only, and 5 samples were positive with MYCO/F Lytic medium only . Fourteen samples grew Histoplasma capsulatum; both systems detected H . capsulatum in seven samples but the Isolator system alone detected H . capsulatum in seven samples . The mean times to the detection of H . capsulatum were 8 days (range, 4 to 13 days) for MYCO/F Lytic medium and 9 days (range, 6 to 18 days) for the Isolator system; the mean times to identification were 20 days (range, 15 to 24 days) for isolates recovered with MYCO/F Lytic medium and 11 days (range, 6 to 18 days) for those recovered with the Isolator system (P < 0.05) . Cryptococcus neoformans was isolated from 10 fungal cultures; five isolates grew in both systems, and five isolates grew in MYCO/F Lytic medium only . The mean times to detection of C . neoformans were 4 days (range, 2 to 6 days) for MYCO/F Lytic medium and 7 days (range, 5 to 7 days) for the Isolator system (P < 0.05); the mean times to identification were 15 days (range, 7 to 27 days) for isolates recovered with MYCO/F Lytic medium and 8 days (range, 7 to 11 days) for those recovered with the Isolator system . Of the 687 samples of blood cultured for mycobacteria, 64 blood samples from 42 patients grew mycobacteria (58 grew Mycobacterium avium complex, 4 grew Mycobacterium kansasii, and 2 grew Mycobacterium tuberculosis); 42 isolates were recovered with both systems, 18 were isolated with MYCO/F medium only, and 4 were isolated with the ESP II system only alone (P < 0.05) . The mean time to detection of mycobacteria with MYCO/F Lytic medium was 14 days, whereas it was 17 days with the ESP II system (P < 0.05) . In summary, the combination of MYCO/F Lytic medium and the BACTEC 9240 instrument is an excellent blood culture system for the growth and detection of mycobacteria . A valid assessment of MYCO/F Lytic medium with regard to fungal isolation, however, was not possible due to the small number of isolates recovered. Infect Immun, 1998 May, 66(5), 2230 - 6 Isolation of the third capsule-associated gene, CAP60, required for virulence in Cryptococcus neoformans; Chang YC et al.; A polysaccharide capsule is one of the most important virulence factors for the pathogenic fungus Cryptococcus neoformans . We previously characterized two capsule-associated genes, CAP59 and CAP64 . To further dissect the molecular mechanism of capsule synthesis, 16 acapsular mutants induced by 4-nitroquinoline-1-oxide were obtained . The acapsular phenotype of one of these mutants was complemented . The cloned gene was designated CAP60, and deletion of this newly described capsule-associated gene resulted in an acapsular phenotype . The proposed 67-kDa Cap60p contains 592 amino acids and appears to have a putative transmembrane domain close to the N terminus . DNA sequence analysis revealed that CAP60 has similarity to CAP59 at the center portion of its coding regions . Contour-clamped homogeneous electric field blot analysis suggested that these two genes are on the same chromosome . CAP60 and CAP59, however, could not be functionally substituted for each other by direct complementation or by domain swap experiments . In addition, CAP60 is closely linked to a gene which is similar to a cellulose growth-specific gene of Agaricus bisporus, CEL1 . Immunogold electron microscopy studies of the epitope-tagged CAP60 gene revealed that Cap60p was primarily localized to the nuclear membrane . Animal model studies indicated that CAP60 is essential for virulence . Thus, CAP60 is required for both capsule formation and virulence. Drugs, 1998 Apr, 55(4), 585 - 612 Liposomal amphotericin B . Therapeutic use in the management of fungal infections and visceral leishmaniasis; Coukell AJ et al.; Incorporation of amphotericin B into small unilamellar liposomes (AmBisome) alters the pharmacokinetic properties of the drug, but allows it to retain significant in vitro and in vivo activity against fungal species, including Candida, Aspergillus and Cryptococcus, and parasites of the genus Leishmania . Used as prophylaxis against fungal infections in immunocompromised patients, liposomal amphotericin B appeared to reduce the incidence of both fungal colonisation and proven fungal infections, but did not affect overall survival . Empirical therapy with liposomal amphotericin B in immunocompromised adults or children with suspected fungal infections was at least as effective as therapy with conventional amphotericin B . In the largest noncomparative studies, liposomal amphotericin B produced mycological eradication in 40 and 83% of patients with proven Candida infections and 41 and 60% with proven Aspergillus infections; however, these studies included relatively few patients . Mycological eradication rates of 67 to 85% in patients with cryptococcal meningitis have been reported . Liposomal amphotericin B is an effective treatment for visceral leishmaniasis in immunocompetent adults and children, including those with severe or drug-resistant disease . The drug also produces good response rates in immunocompromised patients; however, relapse rates in these patients are high . Liposomal amphotericin B is generally well tolerated . Few patients require discontinuation or dose reduction of the drug because of adverse events . The most frequently reported adverse events are hypokalaemia, nephrotoxicity and infusion-related reactions; however, these occur significantly less often after liposomal amphotericin B than after the conventional formulation of the drug . The acquisition cost of liposomal amphotericin B is higher than that of conventional amphotericin B . Cost-effectiveness analysis did not clearly show an economic benefit for empirical liposomal amphotericin B antifungal therapy in adults; however, one model suggested that initial empirical therapy with the liposomal formulation in children may cost less per cure than initial therapy with the conventional formulation . Liposomal amphotericin B appears to be an effective alternative to conventional amphotericin B in the management of immunocompromised patients with proven or suspected fungal infections . Use of the drug is facilitated by its greatly improved tolerability profile compared with conventional amphotericin B . Because of this, liposomal amphotericin should be preferred to conventional amphotericin B in the management of suspected or proven fungal infections in immunocompromised patients with pre-existing renal dysfunction, amphotericin B-induced toxicity or failure to respond to conventional amphotericin B . Liposomal amphotericin B may also be considered for first- or second-line treatment of immunocompetent patients with visceral leishmaniasis. Chemotherapy, 1998 Mar-Apr, 44(2), 112 - 20 Antifungal activity of D0870 against murine infections and its mechanism of action; Yamada H et al.; We evaluated the in vivo antifungal activity of D0870, a new triazole agent, in comparison with that of fluconazole in two murine infection models . The therapeutic mechanism of D0870 in these models was also investigated in vitro . In a pulmonary infection with Cryptococcus neoformans in immunosuppressed mice, D0870 at 10-100 mg/kg significantly reduced viable counts in lungs infected with C . neoformans to 1/10-1,000 of the control on day 14, whereas fluconazole, only at 100 mg/kg, showed a significant reduction in the viable counts and was less active than D0870 at 10 mg/kg . D0870 at 3-30 mg/kg also showed excellent therapeutic efficacy against murine vaginal candidiasis and completely eliminated viable yeasts from the vaginal cavity, whereas positive cultures were found in 20% of mice treated with 30 mg fluconazole/kg . At pH 7 and 37 degrees C, D0870 was active against C . neoformans in synthetic amino acid medium, fungal or sabouraud dextrose broth . By reducing the pH of the medium, the in vitro anticryptococcal activity of D0870 was enhanced and found to be fungicidal under all culture conditions at pH 4-5 . D0870 also showed a stronger fungistatic activity against Candida albicans at pH 4 . These results suggest that D0870 may exhibit a potent activity against these two murine infections by exerting an excellent antifungal activity at the infection sites thought to be acidic environments. Antimicrob Agents Chemother, 1998 Apr, 42(4), 899 - 902 Comparison of fungizone, Amphotec, AmBisome, and Abelcet for treatment of systemic murine cryptococcosis; Clemons KV et al.; Three lipid-based formulations of amphotericin B have been approved for use in various countries . The aim of this study was to compare Amphotec (ABCD; Sequus), AmBisome (AmBi; Nexstar), Abelcet (ABLC; The Liposome Co.), and conventional deoxycholate amphotericin B (Fungizone; Bristol Meyers Squibb) for the treatment of experimental systemic cryptococcosis . A model was established in 10-week-old female CD-1 mice by intravenous (i.v.) injection of 6.25 x 10(5) viable Cryptococcus neoformans yeast cells . Therapy began 4 days later, with i.v . administration three times per week for 2 weeks . Mice received either no treatment, 1 mg of Fungizone per kg of body weight, or 1, 5, or 10 mg of ABCD, AmBi, or ABLC per kg . Ninety percent of control mice died between days 15 and 34 . All treatment regimens except ABLC at 1 mg/kg prolonged survival compared with no treatment (P < 0.01 to 0.001) . All mice receiving 5 or 10 mg of ABCD or AmBi per kg and 90% of mice given 10 mg of ABLC per kg survived, whereas < or =50% of those given other treatment regimens survived . Fungizone was the least effective of the four formulations, with 5 or 10 mg of ABCD, AmBi, or ABLC per kg resulting in a significantly better outcome than Fungizone (P < 0.001) . Among the three formulations, ABCD and AmBi were equally effective, both being better than ABLC at equal 5- or 10-mg/kg doses (P < 0.001) . Comparison of residual infectious burdens in various organs showed that each drug had some dose-responsive efficacy in three or more organs at escalating doses . In the brain, ABCD or AmBi at 5 or 10 mg/kg or ABLC at 10 mg/kg was more effective than Fungizone at 1 mg/kg or no treatment, while ABCD or AmBi at 1 mg/kg was as effective as ABLC at 10 mg/kg . Similar results were obtained for the kidneys and lungs . In the spleen, ABCD at 10 mg/kg cured all mice of infection and was superior to all other regimens . In the liver, AmBi at 5 mg/kg was superior to an equal dose of ABCD or ABLC . Overall, the efficacies of ABCD and AmBi were equal to that of Fungizone at 1 mg/kg and were about 10-fold better than that of ABLC, particularly in the brain; a comparative rank order of efficacies was ABCD approximately equal to AmBi > ABLC >> Fungizone . This is the first study that compared all four amphotericin B formulations. East Afr Med J, 1997 Dec, 74(12), 784 - 91 T-lymphocytopaenia, opportunistic infections and pathological findings in Ghanaian AIDS patients and their sexual partners; Ayisi NK et al.; Ninety-nine patients at Center for Disease Control (CDC) clinical stage IV were studied . Twelve (12.12%) of these patients turned out to be HIV seronegative . Ten out of the 12 HIV negative patients were immunocompetent whereas the other two had proportional decreases in both CD4+ and CD8+ T-lymphocytes . HIV-1, HIV-2, and dual infection, were detected in 51.5%, 2%, and 22.2% respectively of clinical AIDS patients . The other 12.12% of clinical AIDS patients were indeterminate for HIV antibodies . All HIV positive patients with the exception of two, were immunocompromised with respect to CD4+ and CD8+ T-lymphocyte counts . Two healthy spouses and three children of patients who died from the disease were seronegative for HIV antibodies . Herpes simplex virus type 2 (HSV-2) and cytomegalovirus (CMV) antibody titres were higher in HIV infected than uninfected blood . Patients with chronic diarrhoea, lymphadenopathy, pneumonia, and tuberculosis, either alone or in combination of two or more of such symptoms, were found to be more likely to be confirmed by serology and immunology as definitive AIDS patients in Ghana . In postmortem studies on 20 patients, pneumonia due to tuberculosis constituted the major cause of death . Toxoplasmosis, cytomegaloviral eosophagitis and enteritis, and cryptococcosis were the major opportunistic infections detected . Programmed cell death (apoptosis) was found by the DNA gel electrophoresis method to be an unlikely major mechanism of accelerated culture induced death of PBMCs from CDC stage IV AIDS patientsPIP: Since HIV infection was first diagnosed in Ghana in 1986, the incidence of HIV infection has increased steadily in the country over the years . Until 1990, most people infected with HIV in Ghana were infected with HIV-2 . However, in 1990, most people tested were found to be dually infected with HIV-1 and HIV-2, and recently, most HIV-infected people in Ghana are only HIV-1 positive . Findings are presented from the study of 99 US Centers for Disease Control and Prevention (CDC) clinical stage IV AIDS patients . Polymerase chain reaction assay identified 12 of these patients as HIV-seronegative . HIV-1, HIV-2, and dual infection were identified in 51.5%, 2%, and 22.2% of clinical AIDS patients, respectively, with the remaining patients being indeterminate for HIV antibodies . All but 2 HIV-positive patients were immunocompromised with regard to CD4+ and CD8+ T-lymphocyte counts . 2 healthy spouses and 3 children of patients who died from AIDS were seronegative for HIV antibodies . Herpes simplex virus type 2 and cytomegalovirus antibody titers were higher in HIV-infected than in uninfected blood . Patients with chronic diarrhea, lymphadenopathy, pneumonia, and tuberculosis (TB), either alone or in combination of 2 or more such symptoms, were more likely to be confirmed by serology and immunology as definitive AIDS patients in this study . Pneumonia due to TB was the major cause of death identified through postmortem studies conducted upon 20 patients . Toxoplasmosis, cytomegaloviral esophagitis and enteritis, and cryptococcosis were the major opportunistic infections detected . Programmed cell death was probably not a major mechanism of accelerated culture-induced death of peripheral blood mononuclear cells . J Neuroimaging, 1998 Apr, 8(2), 108 - 10 Intra-axial posterior fossa cryptococcosis: MRI findings; Wong DC; Two case reports of intra-axial posterior fossa cryptococcosis in immunocompetent patients are presented . Magnetic resonance findings of solitary abscesses with mildly irregular peripheral enhancement within the medulla, and irregular peripheral enhancement with a nodular component within the right cerebellum are described. J Eur Acad Dermatol Venereol, 1998 Mar, 10(2), 167 - 9 Primary cutaneous cryptococcosis in an immune competent patient; Handa S et al.; A 50-year-old female developed a swelling in the epigastrium which later ruptured to form a sinus . A diagnosis of primary cutaneous cryptococcosis was made with the help of histopathology and microbiological studies . Treatment with amphotericin-B and 5-flucytosine gave a good therapeutic response and the sinus healed within 2 months. Int J Antimicrob Agents, 1997 Jan, 9(3), 147 - 52 A broad-spectrum antifungal from the marine sponge Hyrtios erecta; Pettit RK et al.; Spongistatin 1, a macrocyclic lactone polyether from the marine sponge Hyrtios erecta, was fungicidal for a variety of opportunistic yeasts and filamentous fungi, including strains resistant to amphotericin B, ketoconazole and flucytosine . In broth macrodilution assays, MICs ranged from 0.195 to 12.5 microg/ml, and minimum fungicidal concentrations ranged from 3.12 to 25 microg/ml . Initial disk diffusion screens with six related macrocyclic lactone polyethers from H . erecta and Spirastrella spinispirulifera, revealed that these polyethers were also antifungal . The fungicidal activity of spongistatin 1 was confirmed in killing kinetics studies, where killing of Candida albicans and Cryptococcus neoformans occurred within 6 and 12 h, respectively . During the killing kinetics experiments, non-treated C . albicans maintained the yeast morphology . However, elongated forms resembling germ tubes were the predominant morphologic form in spongistatin 1-treated C . albicans cultures . The spongistatins show promise as potential antifungal agents and as probes to study fungal morphogenesis and nuclear division. J Formos Med Assoc, 1998 Mar, 97(3), 197 - 203 Ultrasound-guided fine needle aspiration biopsy in the diagnosis of pulmonary cryptococcosis; Kuo TH et al.; The purpose of this study was to assess the safety and reliability of ultrasound-guided fine needle aspiration biopsy (US-guided FNAB) combined with modified Papanicolaou's staining in the diagnosis of pulmonary cryptococcosis . The study included 10 patients (9 men, 1 woman, 28-70 yr) . Percutaneous US-guided FNAB was performed through a puncture probe with central channel guidance (n = 8) or in a 'free-hand' manner (2), depending on the size of the lesion and the experience of the operator . Sonography disclosed homogeneously hypoechoic lesions with air bronchograms over the peripheral or central portion in nine patients, and occasional heterogeneous echogenicity with necrotic tissue without air bronchogram in one . Thirteen lesions were found on the chest radiographs of the 10 patients; these could be divided into three patterns: infiltrates (2), nodules or masses (7), and consolidation (4) . Using US-guided FNAB and immediate modified Papanicolaou's stain, a diagnosis of pulmonary cryptococcosis was confirmed in nine of the 10 patients . The remaining case was proven by surgical resection . No major complications developed after US-guided FNAB . We conclude that this technique, combined with modified Papanicolaou's staining, provides a safe, rapid, and reliable method for diagnosing pulmonary cryptococcosis. Mycopathologia, 1997, 139(2), 93 - 5 Isolation of Cryptococcus neoformans from pigeon (Columbia livia droppings in northern Iran; Khosravi AR; Nine hundred and eighty three specimens of pigeon droppings, collected in different regions of northern Iran, were examined . Of these samples, 175 (17.8%) were positive for Cryptococcus neoformans . All isolates obtained were C . neoformans var . neoformans . Most of these isolates of C . neoformans were from pigeon shelters . There were significant differences in isolation frequency between pigeon shelters and the other collection sites. J Immunol, 1997 Dec 1, 159(11), 5528 - 34 IL-18 protects mice against pulmonary and disseminated infection with Cryptococcus neoformans by inducing IFN-gamma production; Kawakami K et al.; We examined the effects of a newly identified cytokine, IL-18, originally designated as IFN-gamma-inducing factor, in a mouse model of pulmonary and disseminated infection with a highly virulent strain of Cryptococcus neoformans . Administration of murine rIL-18 enhanced elimination of live micro-organisms from the lungs, prevented fungal dissemination to the brain, reduced the level of serum cryptococcal capsular polysaccharide Ags, and increased the survival rate of infected mice . Histologic examination of lung sections of infected and PBS-treated mice showed a poor cellular inflammatory reaction and a large number of multiplying C . neoformans yeast cells in alveolar spaces . In contrast, massive infiltration of inflammatory cells, consisting mainly of mononuclear cells, characterized sections of lungs of infected animals treated with IL-18 . Treatment with IL-18 also increased the level of serum IFN-gamma . In addition, the protective effect of IL-18 on cryptococcal infection was abrogated by administration of neutralizing anti-IFN-gamma mAb . Finally, we examined the effect of neutralizing anti-IL-18 Ab on cryptococcal infection to define the physiologic role of this cytokine in host defense using another weakly virulent strain of C . neoformans, which induced the expression of IL-18 mRNA in the infected lungs . Administration of this Ab exacerbated the infection, as shown by the increased lung burden . Our results indicate that IL-18 plays an important role in host defense against infection with C . neoformans. Am J Trop Med Hyg, 1998 Mar, 58(3), 273 - 6 The historical question of acquired immunodeficiency syndrome in the 1960s in the Congo River basin area in relation to cryptococcal meningitis; Molez JF; In Europe before the advent of the acquired immunodeficiency syndrome (AIDS), fatal cases of infection with Cryptococcus neoformans resembling acute meningitis were rarely described and never in young adults . However, rapidly fatal cryptococcal meningitis in young Africans has been known to exist in central Africa for at least 30 years, mainly in the lower area of the Congo River basin . Cases have been reported in this area since 1953, particularly in young patients during the 1950s . It is also known that central African AIDS patients frequently suffer from cryptococcosis, and there is a possibility that earlier clinical reports of encephalitis were actually fatal cases of AIDS in young Africans . It appears possible that the central part of the African continent is the area where human immunodeficiency virus originatedPIP: Rapidly fatal cryptococcal meningitis has existed in central Africa for more than 30 years, mainly in the lower area of the Congo River basin . Cases have been reported in that area since 1953, especially among young patients during the 1950s . People with AIDS in central Africa also often have cryptococcosis, and it is possible that earlier clinical reports of encephalitis were actually fatal cases of AIDS in young Africans . Before the advent of AIDS in Europe, fatal cases of infection with Cryptococcus neoformans resembling acute meningitis were rare and nonexistent in young adults . The available evidence suggests that HIV may have originated in central Africa, where it had long remained in a specific, but unknown and overlooked habitat . Cryptococcosis infection, cryptococcosis in the Congo River basin, the historical presence of HIV, and HIV in Haiti and among Haitians are discussed . Biochim Biophys Acta, 1998 Mar 2, 1379(3), 399 - 405 Peroxisomal localization of D-aspartate oxidase and development of peroxisomes in the yeast Cryptococcus humicolus UJ1 grown on D-aspartate; Kera Y et al.; The peroxisomal localization of D-aspartate oxidase (EC . 1.4.3.1) was demonstrated in the yeast Cryptococcus humicolus UJ1 cells grown in the medium containing D-aspartate as a nitrogen source . The conclusion is based on the identical behavior of the enzyme with those of peroxisomal marker enzymes, catalase and urate oxidase, during all steps of subcellular fractionations . Supporting evidence was provided by the morphometric analysis of the peroxisomes with electron microscopy, showing that the cells grown on D-aspartate contained more and larger peroxisomes than those grown on L-aspartate, consistent with the 500-fold and 3-fold, higher contents of D-aspartate oxidase and catalase activities, respectively, in the former cells than the latter. Yeast, 1998 Feb, 14(3), 233 - 8 Isolation and characteristics of yeasts able to grow at low concentrations of nutrients; Kimura Y et al.; Seven oligotrophic yeasts, which can grow in a 10(4)-fold dilution of malt-yeast-glucose-peptone medium (10(-4) YM), were mainly isolated from soil . These yeasts belong to the Cryptococcaceae . When inoculated at about 10(2) cells/ml in 10(-4) YM, the isolates grew to 1.4 x 10(3)-2.4 x 10(5) cells/ml after 3 days . Some culture collection yeasts fell into three groups according to their growth characteristics in 10(-4) YM, one group showing characteristics of the oligotrophic yeasts . The half-saturation values of uptake by the five isolated oligotrophic yeasts for D-glucose, L-leucine and L-amino acids were 6.0-25.0, 1.7-43.3 and 3.5-21.6 microM, respectively . The oligotrophic yeasts suspended in 10 mM-phosphate buffer (pH 6.0) had high tolerances for starvation, and remained more than 15% viable after 90 days of starvation. Pharmacotherapy, 1998 Mar-Apr, 18(2), 255 - 64 The association between cryptococcal variety and immunocompetent and immunocompromised hosts; Peachey PR et al.; The varieties of Cryptococcus neoformans serotypes are neoformans and gattii . Data suggest an association between cryptococcal variety and host immune status . In addition, the two varieties differ in their epidemiology and pathogenicity . Furthermore, symptoms, outcome, and response of cryptococcosis to antifungal therapy may vary . The two varieties also differ in immune-modulating effects . Sparse clinical data suggest var . gattii is more virulent and may be more recalcitrant to antifungal therapy . Also, its infections produce more sequelae . A better understanding of how cryptococcal variety influences the clinical course and response to the treatment of cryptococcosis is needed . Clinicians should be aware of the association, especially in patients with refractory disease . It may be useful to type the isolate to the variety level and administer prolonged antifungal therapy. Eur J Clin Invest, 1998 Feb, 28(2), 164 - 73 A functional defect in hereditary haemochromatosis monocytes and monocyte-derived macrophages; Moura E et al.; BACKGROUND: Hereditary haemochromatosis (HH) is a disease of the metabolism of iron characterized by increased iron absorption and heavy parenchymal iron deposition, but with the presence of little iron in the mononuclear phagocytic system (MPS) . METHODS: To investigate the role of the MPS, the phagocytic ability of HH monocytes (MNs) and in vitro monocyte-derived macrophages (MDMs) was studied . HH patients with different degrees of iron accumulation were chosen . RESULTS: We observed that HH patients' MNs and MDMs have a significantly decreased ability to phagocytose rabbit red blood cells (RRBCs) and that HH MNs possess a significantly decreased capacity to phagocytose Staphylococcus aureus (S . aureus) . The decrease in the ability to phagocytose S . aureus, however, was kinetic in nature, explaining the absence of increased prevalence of bacterial infections among HH patients . Both RRBCs and S . aureus were preopsonized with heat-inactivated serum . No alteration in the complement-dependent phagocytosis of Cryptococcus neoformans was demonstrated when normal human serum was used . The phagocytosis defect was observed in 100% of HH patients and was independent of the magnitude of iron overload, age or liver damage, and affected the antibody-mediated uptake of bacteria and (R)RBCs. Clin Exp Rheumatol, 1998 Mar-Apr, 16(2), 169 - 71 Cryptococcal meningitis presenting concurrently with systemic lupus erythematosus; Mok CC et al.; Cryptococcal meningitis is a rare but well recognized complication of systemic lupus erythematosus (SLE) . Since in all previously reported cases in the medical literature the patients developed this opportunistic infection as the result of immunosuppressive therapies, whether the intrinsic immunological abnormalities of SLE per se contribute to the susceptibility remains controversial . We report on a patient who presented concurrently with cryptococcal meningitis and cryptococcaemia at the time of her diagnosis of active SLE . This highlights the possibility that intrinsic immunological defects of SLE may be directly responsible for the predisposition to fungal infections . In addition, when SLE patients present with neurological symptoms, the possible presence of central nervous system (CNS) infection must be checked for, even if immunosuppressive treatment is not being considered. J Antibiot (Tokyo), 1998 Jan, 51(1), 41 - 9 Isolation and characterisation of an antifungal antibiotic (GR135402) with protein synthesis inhibition; Kinsman OS et al.; A novel antifungal antibiotic GR135402 has been isolated from a fermentation broth of Graphium putredinis which inhibited protein synthesis in Candida albicans but not rabbit reticulocytes . The spectrum of activity included C . albicans and Cryptococcus neoformans but not some other Candida species or Aspergillus species . Therapeutic efficacy in a mouse model of systemic candidosis was attained following parenteral dosing. Infect Immun, 1998 Apr, 66(4), 1547 - 53 Bivalency is required for anticapsular monoclonal antibodies to optimally suppress activation of the alternative complement pathway by the Cryptococcus neoformans capsule; Kozel TR et al.; Encapsulated cells of Cryptococcus neoformans are potent activators of the alternative complement pathway . Previous studies found that monoclonal antibodies (MAbs) specific for the major capsular polysaccharide, termed glucuronoxylomannan (GXM), can markedly suppress the ability of the capsule to accumulate C3 from normal human serum via the alternative pathway . The present study examined the abilities of F(ab)2 and Fab fragments of three MAbs (MAbs 439, 3C2, and 471) to mediate the suppressive effect . The results showed that F(ab)2 fragments of all three MAbs suppressed activation and binding of C3 via the alternative pathway in a manner similar to that of intact antibodies . In contrast, Fab fragments of MAb 439 and MAb 3C2 showed no suppressive activity, and Fab fragments of MAb 471 were markedly reduced in suppressive activity . Indeed, there was an earlier accumulation of C3 on encapsulated cryptococci in the presence of the Fab fragments . Study of subclass switch families of MAb 439 and MAb 471 found that MAbs of an immunoglobulin G (IgG) subclass with increased flexibility in the hinge region (IgG2b) had less suppressive activity than MAbs of IgG subclasses with less flexibility (IgG1 or IgG2a) . Taken together, these results indicate that cross-linking of the capsular matrix is an essential component in suppression of the alternative complement pathway by anti-GXM MAbs. Infect Immun, 1998 Apr, 66(4), 1538 - 46 Characterization of anticapsular monoclonal antibodies that regulate activation of the complement system by the Cryptococcus neoformans capsule; Kozel TR et al.; Incubation of the encapsulated yeast Cryptococcus neoformans in human serum leads to alternative pathway-mediated deposition of C3 fragments in the capsule . We examined the ability of monoclonal antibodies (MAbs) specific for different epitopes of the major capsular polysaccharide to alter the kinetics for classical and alternative pathway-mediated deposition of C3 onto a serotype A strain . We studied MAbs reactive with capsular serotypes A, B, C, and D (MAb group II); serotypes A, B, and D (MAb group III); and serotypes A and D (MAb group IV) . The MAb groupings are based on antibody variable region usage which determines the antibody molecular structure . When both the classical and alternative pathways were operative, group II MAbs induced early classical pathway-mediated binding of C3 but reduced the overall rate of C3 accumulation and the amount of bound C3 . Group III MAbs closely mimicked the effects of group II MAbs but exhibited reduced support of early classical pathway-facilitated accumulation of C3 . Depending on the antibody isotype, group IV MAbs slightly or markedly enhanced early binding of C3 but had no effect on either the rate of C3 accumulation or the amount of bound C3 . When the classical pathway was blocked, group II and III MAbs markedly suppressed C3 binding that normally would have occurred via the alternative pathway . In contrast, MAbs of group IV had no effect on alternative pathway-mediated C3 binding . These results indicate that anticapsular antibodies with different epitope specificities may have distinct regulatory effects on activation and binding of C3. Am J Med, 1998 Feb, 104(2), 123 - 8 The yield of bone marrow biopsy and culture compared with blood culture in the evaluation of HIV-infected patients for mycobacterial and fungal infections; Kilby JM et al.; PURPOSE: To compare the clinical utility of bone marrow biopsy and culture specimens with blood cultures for mycobacterial and fungal infections among human immunodeficiency virus (HIV)-infected patients . PATIENTS AND METHODS: All bone marrow biopsies obtained from HIV-infected patients at the University of Alabama at Birmingham (UAB) Medical Center during 1993 to 1995 were blindly reviewed in a standardized format . Bone marrow culture results and blood culture results obtained within 6 weeks of each bone marrow study were compiled . Medical records were reviewed to determine indications for performing bone marrow biopsies, empiric or prophylactic antimicrobial therapies preceding the biopsy, and CD4 counts . RESULTS: Eighty-two bone marrow studies were obtained from 76 patients . Most were performed during the evaluation of fever, cytopenia, or weight loss . Of 55 bone marrow mycobacterial cultures, 13 yielded Mycobacterium avium complex (MAC) and 2 yielded M tuberculosis (MTB) . Of 51 bone marrow fungal cultures performed, 2 yielded Cryptococcus neoformans and 1 Histoplasma capsulatum . All patients with a bone marrow culture positive for MAC had a CD4 count of 20 cells/mm3 or less . The mean CD4 count in this group (+/-95% confidence interval) (8+/-3 cells/mm3) was lower than that of culture-negative cases (41+/-25 cells/mm3); P <0.015) . When bone marrow cultures and mycobacterial blood cultures were concurrently obtained, results were usually in agreement between the two sites . The mean time until the report of positive mycobacterial bone marrow cultures (22+/-5 days) was similar to that for blood cultures (24+/-3 days) . Most (84%) patients with multiple mycobacterial cultures had completely concordant results (all positive or all negative) . When blood or bone marrow culture yielded mycobacteria, only 29% of the corresponding bone marrow examinations revealed stainable acid-fast bacilli (AFB) . In contrast, all 3 cases with positive fungal bone marrow cultures also had stainable organisms on histologic examination . CONCLUSIONS: The combined use of bone marrow biopsy and culture as well as blood cultures provide the maximum diagnostic yield when evaluating patients with AIDS for mycobacterial or fungal infections . However, when mycobacterial infections were diagnosed, bone marrow results seldom provided more immediate or specific information than lysis centrifugation blood cultures . A single lysis centrifugation blood culture should be the first step in the routine evaluation of HIV-infected patients when disseminated MAC infection is suspected. Antimicrob Agents Chemother, 1998 Feb, 42(2), 471 - 2 In vitro comparative efficacy of voriconazole and itraconazole against fluconazole-susceptible and -resistant Cryptococcus neoformans isolates; Nguyen MH et al.; In vitro susceptibility testing for 50 clinical isolates of fluconazole-susceptible or -resistant Cryptococcus neoformans was performed with itraconazole and voriconazole . Voriconazole was more potent than itraconazole for fluconazole-susceptible isolates and as potent as itraconazole for fluconazole-susceptible dose-dependent isolates and for fluconazole-resistant isolates . For fluconazole-resistant isolates, the voriconazole and itraconazole MICs ranged from 1 to 2 microg/ml. J Zoo Wildl Med, 1997 Dec, 28(4), 485 - 90 Pulmonary cryptococcoma and cryptococcal meningoencephalomyelitis in a king cheetah (Acinonyx jubatus); Berry WL et al.; A captive king cheetah (Acinonyx jubatus) was evaluated for a subacute onset of ataxia in all four limbs . The ataxia appeared to be spinal in origin, evidenced by apparent conscious proprioceptive deficits in all limbs, and there was no evidence of cerebellar involvement . Anesthesia was performed and survey spinal radiographs were normal . Cerebrospinal fluid analysis revealed an apparently sterile meningitis of unknown etiology . Although transient improvement was noted with glucocorticoid and antimicrobial therapy, the condition deteriorated subsequently and the animal became quadriparetic and paraplegic . Follow-up cerebrospinal fluid analysis and culture revealed the presence of Cryptococcus neoformans . Myelography demonstrated obstruction of the subarachnoid space at the level of the seventh cervical vertebra . Pathological examination following euthanasia revealed a solitary pulmonary cryptococcoma and confirmed cryptococcal meningoencephalomyelitis. P N G Med J, 1996 Mar, 39(1), 67 - 73 The management of cryptococcal meningitis in Papua New Guinea; Seaton RA; Cryptococcal meningitis is a difficult disease to treat and requires biochemical and haematological monitoring to detect the common adverse effects of treatment . Combination therapy with amphotericin B and flucytosine for at least 6 weeks is the best treatment so far evaluated . The role of azole drugs should become clearer as the results of large multicentre studies become available in the future . High case fatality and morbidity rates despite standard treatment suggest that other ancillary treatments such as corticosteroids and other treatments directed at lowering raised intracranial pressure may also be required in some patients. Clin Diagn Lab Immunol, 1998 Mar, 5(2), 146 - 59 Cryptococcus neoformans chemotyping by quantitative analysis of 1H nuclear magnetic resonance spectra of glucuronoxylomannans with a computer-simulated artificial neural network; Cherniak R et al.; The complete assignment of the proton chemical shifts obtained by nuclear magnetic resonance (NMR) spectroscopy of de-O-acetylated glucuronoxylomannans (GXMs) from Cryptococcus neoformans permitted the high-resolution determination of the total structure of any GXM . Six structural motifs based on an alpha-(1-->3)-mannotriose substituted with variable quantities of 2-O-beta- and 4-O-beta-xylopyranosyl and 2-O-beta-glucopyranosyluronic acid were identified . The chemical shifts of only the anomeric protons of the mannosyl residues served as structure reporter groups (SRG) for the identification and quantitation of the six triads present in any GXM . The assigned protons for the mannosyl residues resonated at clearly distinguishable positions in the spectrum and supplied all the information essential for the assignment of the complete GXM structure . This technique for assigning structure is referred to as the SRG concept . The SRG concept was used to analyze the distribution of the six mannosyl triads of GXMs obtained from 106 isolates of C . neoformans . The six mannosyl triads occurred singularly or in combination with one or more of the other triads . The identification and quantitation of the SRG were simplified by using a computer-simulated artificial neural network (ANN) to automatically analyze the SRG region of the one-dimensional proton NMR spectra . The occurrence and relative distribution of the six mannosyl triads were used to chemotype C . neoformans on the basis of subtle variations in GXM structure determined by analysis of the SRG region of the proton NMR spectrum by the ANN . The data for the distribution of the six SRGs from GXMs of 106 isolates of C . neoformans yielded eight chemotypes, Chem1 through Chem8. Clin Diagn Lab Immunol, 1998 Mar, 5(2), 125 - 9 The different binding patterns of two immunoglobulin M monoclonal antibodies to Cryptococcus neoformans serotype A and D strains correlate with serotype classification and differences in functional assays; Cleare W et al.; Cryptococcus neoformans var . neoformans strains have historically been divided into serotypes A and D on the basis of reactivity with rabbit sera . Previously, we noted that two murine immunoglobulin M monoclonal antibodies (MAbs) to the capsular glucuronoxylomannan produced different indirect immunofluorescence (IF) patterns, described as annular and punctate, when bound to C . neoformans cells from different strains . In this study, we examined the reactivity of these two MAbs, known as 12A1 and 13F1, with 20 C . neoformans var . neoformans strains, of which 13 were serotype A and 7 were serotype D . For all strains, MAb binding was studied by IF and agglutination assays . In addition, we blindly tested the IF patterns of 22 C . neoformans var . neoformans strains . For selected strains, MAb binding was studied by flow cytometry (FACScan) and phagocytosis assays . The epitopes recognized by MAbs 12A1 and 13F1 were found in all of the strains . MAb 12A1 binding produced an annular IF pattern with all of the strains, irrespective of the serotype classification . MAb 13F1 binding produced annular binding with all of the serotype A strains and punctate binding with 19 of 20 serotype D strains . In general, the punctate IF pattern was associated with lower fluorescence intensity, a requirement for higher antibody concentrations to produce yeast cell agglutination, and lower opsonic efficacy . Our results provide strong support for the existing classification of two serological types for strains assigned to variety neoformans and indicate qualitative and quantitative antigenic differences among serotype A and D strains. AIDS, 1998 Feb 12, 12(3), 309 - 13 Profile of central nervous system pathology in patients with AIDS: an autopsy study from India; Lanjewar DN et al.; OBJECTIVE: To study the spectrum of neuropathological brain lesions in HIV/AIDS cases . DESIGN: Retrospective autopsy study between 1988 and mid-1996 at a tertiary level public hospital . METHODS: Eighty-five adult brains, with at least 21 sections from each, were examined using routine and special stains . RESULTS: Risk factors in 64 men (75%) and 21 women (25%) included heterosexual contact with multiple sexual partners (83 cases, 98%), homosexual behaviour (one case, 1%) and blood transfusion (one case, 1%) . Central nervous system (CNS) lesions were observed in 67 cases (79%) . Opportunistic infections were present in 33 cases (39%), which included toxoplasmosis (11 cases, 13%), tuberculosis (10 cases, 12%), cryptococcosis (seven cases, 8%), and cytomegalovirus infection (six cases, 7%) . Multifocal myelin loss was observed in 18 cases (21%), microglial nodules in 15 cases (18%), and angiocentric pallor in five cases (6%) . Infarcts/haemorrhages were present in 13 cases (15%), choroid plexitis in 21 cases (25%), lymphocytic meningitis without opportunistic infection in 21 cases (25%), and calcification in four cases (5%) . A dual infectious pathology was observed in one case (1%) . Multinucleated giant cells and primary CNS lymphoma were not found in any of our cases . CONCLUSIONS: Patient profile and risk factors for AIDS in India differ from those reported in industrialized countries . Although not reported from India in the pre-AIDS era, toxoplasmosis was the most frequently observed CNS opportunistic infection in our study . CNS tuberculosis is frequently observed in Indian AIDS cases compared with reports from industrialized countries where its occurrence is uncommon . Death due to systemic opportunistic infections may punctuate the course of HIV encephalitis and prevent its full-blown morphological expression. Antimicrob Agents Chemother, 1998 Mar, 42(3), 528 - 33 Amphotericin B colloidal dispersion combined with flucytosine with or without fluconazole for treatment of murine cryptococcal meningitis; Diamond DM et al.; Studies with animals and in vitro studies have demonstrated that flucytosine plus amphotericin B or fluconazole has significantly improved mycologic activity against meningitis caused by Cryptococcus neoformans compared to the activity of amphotericin B or fluconazole used alone . However, few doses have been tested in combination . This study evaluated the antifungal efficacy of amphotericin B colloidal dispersion (ABCD) combined with flucytosine with and without fluconazole in a murine model of cryptococcal meningitis . The following dosages were tested: ABCD at 0 to 12.5 mg/kg of body weight given intravenously 3 days/week, flucytosine at 0 to 110 mg/kg/day, and fluconazole at 0 to 50 mg/kg/day . Meningitis was established in male BALB/c mice by intracerebral injection of C . neoformans . Treatment with flucytosine with or without fluconazole dissolved in the sole source of drinking water was started on day 2; animals were sacrificed at 16 days, and the numbers of fungal colonies in the brain were quantified . A survival rate of 100% was achieved with ABCD plus flucytosine without fluconazole; however, the addition of fluconazole was required to prevent weight loss (P < 0.00001) and to achieve the maximum antifungal effect (P < 0.00001) . The only region of dose combinations for which the 99% confidence intervals were less than 100 CFU/g of brain was defined by ABCD at 5.0 to 7.5 mg/kg combined with flucytosine at 20 to 60 mg/kg/day and fluconazole at 30 to 40 mg/kg/day . The triple combination of ABCD plus flucytosine and fluconazole was necessary to achieve the greatest antifungal activity. J Exp Med, 1998 Feb 16, 187(4), 641 - 8 Antibody-mediated modulation of Cryptococcus neoformans infection is dependent on distinct Fc receptor functions and IgG subclasses; Yuan R et al.; Coupling of an antibody response to effector cells through the Fc region of antibodies is a fundamental objective of effective vaccination . We have explored the role of the Fc receptor system in a murine model of Cryptococcus neoformans protection by infecting mice deleted for the common gamma chain of FcRs . Passive administration of an IgG1 mAb protects FcRgamma+/- mice infected with C . neoformans, but fails to protect FcRgamma-/- mice, indicating that the gamma chain acting through FcgammaRI and/or III is essential for IgG1-mediated protection . In contrast, passive administration of an IgG3 mAb with identical specificity resulted in enhanced pathogenicity in gamma chain-deficient and wild-type mice . In vitro studies with isolated macrophages demonstrate that IgG1-, IgG2a-, and IgG2b-opsonized C . neoformans are not phagocytosed or arrested in their growth in the absence of the FcRgamma chain . In contrast, opsonization of C . neoformans by IgG3 does not require the presence of the gamma chain or of FcRII, and the internalization of IgG3-treated organisms does not arrest fungal growth. J Bacteriol, 1998 Mar, 180(6), 1570 - 2 Melanin biosynthesis in Cryptococcus neoformans; Williamson PR et al.; Pigment production by Cryptococcus neoformans is virulence associated . Dopamine- and 3,4-dihydroxyphenylalanine-melanin products were identified after acidic permanganate oxidation, alkaline hydrogen peroxide oxidation, or hydrolysis with hydriodic acid . These data provide direct chemical evidence for the formation of eumelanin polymers by catecholamine oxidation by laccase alone followed by oxidative coupling of dihydroxyindole. Neurol Neurochir Pol, 1997 Sep-Oct, 31(5), 959 - 69 {Neurological syndromes in HIV patients . Part III -- HIV-related diffuse diseases of the central nervous system}; Zielinski A et al.; The last part of the review of the neurological syndromes observed among people who are HIV-infected deals with AIDS Dementia Complex, viral (CMV, HSV, VZV) encephalitides and cryptococcal meningitis and other less frequent diseases . Clinical presentation, neuropathology, diagnostic procedures and treatments are described . Diagnostic algorithm for central nervous system diseases in people with HIV is included . The main purpose of the present reviews is to pursue the common ground regarding treatment and diagnostic procedures with consulting neurologists and neurosurgeons for future cooperation in a growing area of HIV related neurology. Mycopathologia, 1997, 139(1), 19 - 21 Immunoadjuvant effect of inactivated Cryptococcus neoformans; Hubalek Z; Cryptococcus neoformans disseminated into the central nervous system (CNS) of intraperitoneally inoculated adult ICR mice, but did not potentiate penetration of concurrently given Bhanja virus (Bunyaviridae) into the CNS . Likewise, Bhanja virus infection did not affect significantly the course of murine cryptococcosis . However, formalin-killed C . neoformans cells non-specifically increased production of antibodies against the virus infection in the animals. Mycopathologia, 1997, 139(1), 1 - 7 In vivo interaction between alveolar macrophages and Cryptococcus neoformans; Nessa K et al.; In vivo interactions of rabbit alveolar macrophages (AM) and Cryptococcus neoformans, a yeast pathogenic for humans, were studied . As a control, inert silica particles of a similar diameter (5-6 microns) were used . Of 16 rabbits, 6 were instilled intratracheally with fluorescein-labelled heat-killed C . neoformans, 6 with fluorescein-labelled silica particles and 4 with saline only . After 24 h, the AM were collected by lung lavage, and phagocytosis, oxidative metabolism, phagolysosomal pH and morphology were studied . The accumulated number of yeasts attached to the AM was almost the same for C . neoformans as for the silica particles . The ingested fraction of C . neoformans was even higher than that of the silica particles . Quantitative NBT reduction by the AM, reflecting their oxidative metabolism, was markedly increased by exposure to C . neoformans for 24 h . The phagolysosomal pH was on the average lower in phagolysosomes with C . neoformans than with the silica particles, although approximately 2% of the phagolysosomes with C . neoformans had neutral pH . Phagolysosomes with neutral pH was not observed for silica particles . Electron microscopy showed presence of C . neoformans in phagolysosomes of AM . The conclusion of this study is that the phagocytic activity, oxidative metabolism and phagolysosomal pH AM against C . neoformans are significant 24 h after the exposure. J Am Anim Hosp Assoc, 1998 Mar-Apr, 34(2), 145 - 51 A case of canine central nervous system cryptococcosis: management with fluconazole; Tiches D et al.; A three-year-old, female Labrador retriever was presented for acute generalized seizures . Disseminated cryptococcosis with central nervous system (CNS) involvement was diagnosed by serum and cerebrospinal fluid (CSF) fungal titers, histopathological examination, and magnetic resonance imaging (MRI) . Fluconazole therapy resulted in prolonged, substantial clinical improvement for a period of one year . This report documents the diagnosis of a case of cryptococcal meningoencephalitis and its management with the new antifungal agent, fluconazole. Curr Top Med Mycol, 1996 Dec, 7(1), 19 - 42 Virulence factors of Cryptococcus neoformans; Hamilton AJ et al.; Cryptococcus neoformans is an encapsulated yeast which causes cryptococcosis, a disease typified by an initial pulmonary infection which can disseminate to cause a life threatening meningoencephalitis . Although the disease may occur in individuals who show no evidence of immunosuppression it has had it most significant impact as an infection in patients with AIDS . Research into the potential virulence factors of this yeast has recently attracted particular attention . Capsule synthesis has been the focus of most interest and it is now established as a major virulence determinant . The mechanisms by which the capsule and capsular material effect the immune response have now largely been elucidated, and the genes underlying capsular synthesis are now under investigation . The isolation of mutants incapable of melanogenesis have implicated this process in the pathogenesis of C . neoformans infections, and evidence suggests that the production of melanin protects the yeast against oxidant induced damage . There is also some genetic evidence for the potential involvement of temperature tolerance and mating types in the virulence of this encapsulated yeast . The roles of other potential C . neoformans virulence determinants are more speculative; these include proteinase production, release of polyol metabolites, interaction with hormones, adherence and production of mannoproteins . The involvement of housekeeping enzyme systems in the maintenance of infection by C . neoformans is now also under active investigation. Transpl Int, 1998, 11(1), 63 - 5 Successful treatment of disseminated cryptococcosis in a liver transplant recipient with fluconazole and flucytosine, an all oral regimen; Singh N et al.; Amphotericin B, with or without 5-flucytosine, is currently the therapy of choice for cryptococcal infections . However, amphotericin B, is nephrotoxic and requires long-term venous access for parenteral administration . The combination of fluconazole and flucytosine is synergistic in vitro against Cryptococcus . To date, however, the efficacy of fluconazole and flucytosine for cryptococcosis in liver transplant recipients has never been reported . We report a 66-year-old liver transplant recipient with disseminated invasive cryptococcus (presenting as cryptococcal subcutaneous abscess, osteomyelitis, and serum cryptococcal antigen titer of 1:32) . The administration of amphotericin B for 3 weeks led to nephrotoxicity without any clinical response (persistent abscess without change in serum cryptococcal antigen titer) . Fluconazole, at a dosage equivalent to 800 mg/day administered orally, and flucytosine, also given orally, led to a clinical response and a steady decline in serum cryptococcal antigen titer, which became negative at 6 weeks of therapy . The patient remains well 18 months after therapy . No adverse effects have been attributed to fluconazole or flucytosine . This combination obviates the nephrotoxicity and the need for parenteral access required for amphotericin B infusion, and it can be administered orally . The combination of fluconazole and flucytosine warrants future controlled trials for the treatment of cryptococcal infection in liver transplant recipients. Clin Infect Dis, 1998 Feb, 26(2), 284 - 9 Cryptococcal meningitis in human immunodeficiency virus-infected patients in Harare, Zimbabwe; Heyderman RS et al.; A prospective observational study was conducted over a 10-month period to determine the clinical and laboratory manifestations of cryptococcal meningitis in Zimbabwe, a country where antifungal agents are not widely available . Eighty-nine patients with cryptococcal meningitis (median age, 34 years; range, 11-63 years; 56 males) were identified from 406 patients for whom a clinical diagnosis of meningitis had been made . All patients tested were positive for antibody to human immunodeficiency virus . Cryptococcal meningitis was the first AIDS-defining illness in 88% of patients . Typical presentations were headache, mental impairment, and meningism (median duration, 14 days; range, 1-180 days) . The median CD4+ cell count was 70/microL (range, 0-651/microL) . The cumulative median survival from the time of diagnosis was 14 days (range, 0-233 days); 22% of patients survived for >30 days . Independent indicators of a good prognosis were not identified . This study provides a unique basis for the development of novel management strategies for patients with cryptococcal meningitis who reside in resource-poor countries. Clin Exp Dermatol, 1997 Jul, 22(4), 195 - 7 Primary cutaneous cryptococcosis in an immunocompetent pigeon keeper; Micalizzi C et al.; We report the case of a pigeon keeper who presented with a post-traumatic lesion of his third right finger . Cryptococci were found in the lesion in the absence of any other underlying disorder . Treatment with oral itraconazole achieved clinical resolution of the lesion. Emerg Infect Dis, 1998 Jan-Mar, 4(1), 71 - 83 What makes Cryptococcus neoformans a pathogen? Buchanan KL, Murphy JW. Life-threatening infections caused by the encapsulated fungal pathogen Cryptococcus neoformans have been increasing steadily over the past 10 years because of the onset of AIDS and the expanded use of immunosuppressive drugs . Intricate host-organism interactions make the full understanding of pathogenicity and virulence of C . neoformans difficult . We discuss the current knowledge of the characteristics C . neoformans must possess to enter the host and establish progressive disease: basic growth requirements and virulence factors, such as the polysaccharide capsule; shed products of the organism; melanin production; mannitol secretion; superoxide dismutase; proteases; and phospholipases. Arch Biochem Biophys, 1998 Mar 1, 351(1), 123 - 34 Biochemical role of the Cryptococcus neoformans ADE2 protein in fungal de novo purine biosynthesis; Firestine SM et al.; Comparative studies of 5-aminoimidazole ribonucleotide (AIR) carboxylases from Escherichia coli and Gallus gallus have identified this central step in de novo purine biosynthesis as a case for unusual divergence in primary metabolism . Recent discoveries establish the fungal AIR carboxylase, encoded by the ADE2 gene, as essential for virulence in certain pathogenic organisms . This investigation is a biochemical analysis that links the fungal ADE2 protein to the function of the E . coli AIR carboxylase system . A cDNA clone of ADE2 from Cryptococcus neoformans was isolated by genetic complementation of a purE-deficient strain of E . coli . High-level expression of the C . neoformans ADE2 was achieved, which enabled the production and purification of AIR carboxylase . Amino acid sequence alignments, C-terminal deletion mutants, and biochemical assays indicate that the ADE2 enzyme is a two-domain, bifunctional protein . The N-terminal domain is related to E . coli PurK and a series of kinetic experiments show that the ADE2-PurK activity uses AIR, ATP, and HCO3- as substrates . The biosynthetic product of the ADE2-PurK reaction was identified as N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) by 1H NMR, thus confirming that the C-terminal domain contains a catalytic activity similar to that of the E . coli PurE . By using an in situ system for substrate production, the steady-state kinetic constants for turnover of N5-CAIR by ADE2 were determined and together with stoichiometry measurements, these data indicate that ADE2 has a balance in the respective catalytic turnovers to ensure efficient flux . Distinctive features of the PurE active site were probed using 4-nitro-5-aminoimidazole ribonucleotide (NAIR), an analog of the product 4-carboxy-5-aminoimidazole ribonucleotide (CAIR) . NAIR was shown to be a selective inhibitor of the ADE2-PurE activity (K1 = 2.4 microM), whereas it is a slow-binding inhibitor of the G . gallus enzyme which further distinguishes the fungal ADE2 from the G . gallus AIR carboxylase . As such, this enzyme represents a novel intracellular target for the discovery of antifungal agents. J Immunol, 1998 Mar 1, 160(5), 2393 - 400 IL-5 is required for eosinophil recruitment, crystal deposition, and mononuclear cell recruitment during a pulmonary Cryptococcus neoformans infection in genetically susceptible mice (C57BL/6); Huffnagle GB et al.; CBA/J (highly resistant), BALB/c (moderately resistant), and C57BL/6 (susceptible) mice displayed three resistance patterns following intratracheal inoculation of Cryptococcus neoformans 52 . The inability to clear the infection correlated with the duration of the eosinophil infiltrate in the lungs . The role of IL-5 in promoting the pulmonary eosinophilia and subsequent inflammatory damage in susceptible C57BL/6 mice was investigated . C57BL/6 mice developed a chronic alveolar, peribronchiolar, and perivascular eosinophilia following C . neoformans infection . This resulted in the accumulation of intracellular Charcot-Leyden-like crystals in alveolar macrophages by wk 4 and the extracellular deposition of these crystals in the bronchioles with associated destruction of airway epithelium by wk 6 . IL-5 mRNA was expressed in the lungs, and injections of anti-IL-5 mAb prevented eosinophil recruitment and crystal deposition but did not alter cryptococcal clearance . Depletion of CD4+ T cells (but not CD8+) ablated IL-5 production by lung leukocytes in vitro and eosinophil recruitment in vivo . Neutralization of IL-5 also inhibited the recruitment of macrophages, CD8+ T lymphocytes, and B lymphocytes by 47 to 57% . Anti-IL-5 mAb inhibited CD4+ T lymphocyte recruitment by 30% but did not affect neutrophil recruitment . Thus, the development of a chronic eosinophil infiltrate in the lungs of C . neoformans-infected C57BL/6 mice is a nonprotective immune response that causes significant lung pathology . Furthermore, IL-5 promotes the recruitment and activation of eosinophils, resulting in the recruitment of additional macrophages and lymphocytes into the lungs. J Eukaryot Microbiol, 1998 Jan-Feb, 45(1), 112 - 21 Identification and characterization of an endo/exonuclease in Pneumocystis carinii that is inhibited by dicationic diarylfurans with efficacy against Pneumocystis pneumonia; Hildebrandt E et al.; Dicationic diarylfurans and dicationic carbazoles are under development as therapeutic agents against opportunistic infections . While their ability to bind to the minor groove of DNA has been established, the complete mechanism of action has not . We demonstrate here that an effective diarylfuran, 2,5-bis{4-(N-isopropylguanyl)phenyl}furan, inhibits an endo/exonuclease activity present in Pneumocystis carinii, Cryptococcus neoformans, Candida albicans, and Saccharomyces cerevisiae . This activity was purified from the particulate fraction of P . carinii . The enzyme requires Mg++ or Mn++, and shows preferences for single-over double stranded DNA and for AT-rich over GC-rich domains . A panel of 12 dicationic diarylfurans and eight dicationic carbazoles, previously synthesized, were evaluated for inhibition of the purified nuclease and for efficacy against Pneumocystis pneumonia in rats . Among the diarylfurans, potency of nuclease inhibition, in vivo antimicrobial activity, and DNA binding strength were all strongly correlated (p < 0.001) . These findings suggest that one target for antimicrobial action of the diarylfurans may be a nucleolytic or other event requiring unpairing of DNA strands . Dicationic carbazoles which were strong nuclease inhibitors all displayed anti-Pneumocystis activity in vivo, but there were also noninhibitory carbazoles with in vivo efficacy. Ann Acad Med Singapore, 1997 Sep, 26(5), 694 - 700 Infections in systemic lupus erythematosus patients; Paton NI; Infection is a frequent problem in patients with systemic lupus erythematosus (SLE), especially in those hospitalised with complications of disease . Infections contribute greatly to the morbidity of patients and are one of the commonest causes of death . The high frequency and unusual spectrum of infections can be attributed to the multiple disturbances of immune function in SLE in combination with the effects of immunosuppressive therapy . High doses of corticosteroids are particularly implicated as a risk factor for infection, although cyclophosphamide may also play a role . The majority of infections where a pathogen can be identified are due to typical gram-positive and negative bacteria . However, there is increasing evidence to indicate that opportunistic infections make a large contribution to the infectious mortality in SLE . Opportunistic infections are considerably under-reported due to difficulties in diagnosis pre-mortem and the fact that they can mimic or be superimposed upon active lupus . The presenting features of tuberculosis, listeriosis, nocardiosis, candidiasis, cryptococcal meningitis, Pneumocystis carinii pneumonia and invasive aspergillosis in patients with SLE are discussed in this review, with particular attention to presentation in SLE patients in Asia . Heightened awareness of the potential for opportunistic pathogens to infect SLE patients, together with earlier investigation and appropriate therapy for such infections, are likely to make a significant contribution to decreasing the mortality in patients with SLE. Diagn Microbiol Infect Dis, 1998 Jan, 30(1), 33 - 5 Cryptococcal osteomyelitis: case report and review; Liu PY; Cryptococcosis is a disseminated infection of man and animals caused by Cryptococcus neoformans . The most commonly involved sites are the lungs and the central nervous system . Isolated osteomyelitis due to C . neoformans is a rare complication of disseminated cryptococcosis . Herein we report a case of isolated osteomyelitis due to C . neoformans . A review of the English-language literature has been made and shows 40 cases (including this present report) with detailed data available since 1956 . Most of the cases occurred between the ages of 21 and 59 . Seventy-five percent of cases involved only one single site of bone infection, with vertebrae being the most common site . Sarcoidosis is the most common underlying disease, followed by tuberculosis and previous steroid therapy . Most of the cases (> 60%) reported were treated successfully with medical treatment alone or the combination of medical treatment and surgical curettage. Infect Immun, 1998 Mar, 66(3), 1244 - 7 Specific antibody to Cryptococcus neoformans alters human leukocyte cytokine synthesis and promotes T-cell proliferation; Vecchiarelli A et al.; Addition of a monoclonal antibody which binds the Cryptococcus neoformans capsule to suspensions of human monocytes, T lymphocytes, and cryptococcal cells (i) enhances interleukin-1beta (IL-1beta), tumor necrosis factor alpha, and IL-2 production; (ii) reduces IL-10 secretion; and (iii) promotes T-cell proliferation . The ability of specific antibody to influence cytokine production and lymphoproliferation suggests a mechanism by which humoral immunity can influence cell-mediated immunity. Infect Immun, 1998 Mar, 66(3), 1057 - 62 Isotype switching increases efficacy of antibody protection against Cryptococcus neoformans infection in mice; Yuan RR et al.; The isotype and epitope specificities of antibodies both contribute to the efficacy of antibodies that mediate immunity to Cryptococcus neoformans, but the relationship between these properties is only partially understood . In this study, we analyzed the efficacy of protection of two sets of immunoglobulin G (IgG) isotype switch variants from two IgG3 monoclonal antibodies (MAbs) which are either not protective or disease enhancing, depending on the mouse model used . The two IgG3 MAbs 3E5 and 4H3 have different epitope specificities . Protection experiments were done with A/JCr mice infected intravenously with C . neoformans and administered with 3E5 IgG3 and its IgG1, IgG2a, and IgG2b switch variants . These experiments revealed that IgG1, IgG2b, and IgG2a were each more effective than IgG3 . For 4H3 IgG3 and its IgG1 and IgG2b switch variants, the relative efficacy was IgG2b > IgG1 >> IgG3 . The combination of 3E5 IgG3 and 4H3 IgG3 was more deleterious than either IgG3 alone . All IgG isotypes were opsonic for mouse bronchoalveolar cells, with the relative efficacy being IgG2b > IgG2a > IgG1 > IgG3 . These results (i) confirm that a nonprotective IgG3 MAb can be converted to a protective MAb by isotype switching, (ii) indicate that the efficacy of protection of an IgG1 MAb can be increased by isotype switching to another subclass, (iii) show that protective and nonprotective IgG MAbs are opsonic, and (iv) provide additional evidence for the concept that the efficacy of the antibody response to C . neoformans is dependent on the type of MAb elicited. J Am Soc Echocardiogr, 1998 Jan, 11(1), 83 - 5 Aspergillus fungal mass detected by transesophageal echocardiography; Alam M et al.; Cardiac fungal infections have become more prevalent and are being diagnosed with increasing frequency . The most common infective organism is Candida albicans, followed by Aspergillus fumigatus and Cryptococcus . Cardiac involvement is usually associated with endocarditis, myocarditis, pericarditis, or intracardiac fungal mass . Early diagnosis is imperative, as these patients have poor outcome once there is cardiac involvement . In this report we describe a patient in whom an intracardiac mass was detected with transesophageal echocardiography and confirmed to be aspergillus fungal ball at surgery. East Afr Med J, 1997 Sep, 74(9), 576 - 8 Detection rate of Cryptococcus neoformans in cerebrospinal fluid specimens at Kenyatta National Hospital, Nairobi; Odhiambo FA et al.; A ten-year retrospective review of laboratory detection of Cryptococcus neoformans in cerebrospinal fluid was undertaken using past laboratory and clinical records at Kenyatta National Hospital . A total of 1462 India-ink tests were carried out, 76 (5.2%) of these tested positive for C . neoformans . An increasing number of clinical requests for India-ink test mirrored by increasing number of patients with immunological disorders were noted over the study period although no obvious trend emerged in the detection pattern of C . neoformans . The use of a more sensitive test such as the latex agglutination technique is suggested. Immunology, 1997 Nov, 92(3), 334 - 9 Presentation of cryptococcal capsular polysaccharide (GXM) on activated antigen-presenting cells inhibits the T-suppressor response and enhances delayed-type hypersensitivity and survival; Blackstock R et al.; A hallmark of infection with Cryptococcus neoformans is depression of the immune system characterized by poor inflammatory responses and loss of delayed-type hypersensitivity (DTH) and antibody responses . T-suppressor cell (Ts) responses, elicited by the capsular polysaccharide (GXM) of the organism, are known to develop during infection . This study was undertaken to develop a method to inhibit the anti-GXM Ts response and thereby study the influence of the Ts response on immune responsiveness and survival in cryptococcosis . Antigen-presenting cells (APC), elicited with complete Freund's adjuvant (CFA), were treated in vitro with GXM (GXM-APC) . The GXM-APC were injected intravenously into normal mice . These mice were resistant to induction of anti-GXM Ts cells when soluble GXM was administered in tolerogenic doses or when animals were infected with C . neoformans . Inhibition of the anti-GXM Ts response was specific to GXM as levan-APC did not inhibit induction of anti-GXM Ts cells . Inhibition of the anti-GXM Ts response could not be attributed to increased clearance of GXM due to induction of anti-GXM antibodies or other mechanisms . Anti-cryptococcal DTH responses were lost in mice by the second week of infection . However, treatment with GXM-APC, but not levan-APC, allowed mice to maintain their DTH response . GXM-APC pretreatment enhanced survival of infected mice compared with mice pretreated with levan-APC . These results show that GXM-APC induces immune responses that inhibit the induction of Ts responses and enhances DTH responses in infected mice . These responses correlate with enhanced survival after cryptococcal infection. Eur J Immunol, 1998 Jan, 28(1), 114 - 21 Cryptococcus neoformans differently regulates B7-1 (CD80) and B7-2 (CD86) expression on human monocytes; Vecchiarelli A et al.; To induce a specific response in primary resting T cells, two signals must be provided by antigen-presenting cells (APC) . The first antigen-specific signal is mediated by formation of the T cell receptor major histocompatibility complex molecule ternary complexes . The second signal is delivered by interaction of either B7-1 or B7-2 expressed by APC with CD28 or CTLA-4 on T cells . In this study, we examined the modulation of B7-1 and B7-2 molecules on human monocytes exposed to encapsulated or acapsular Cryptococcus neoformans or Candida albicans . In our experimental system, C . albicans or acapsular C . neoformans are able to induce B7-1 expression while the encapsulated yeast is a poor stimulator . A modest increase of B7-2 expression was also observed after monocyte treatment with acapsular C . neoformans or C . albicans, while the encapsulated yeast was ineffective in inducing B7-2 molecules . Kinetic analysis showed the maximum expression of B7-1 after 24 to 48 h . Addition of the opsonic IgG1 mAb 2H1 to monocytes and C . neoformans significantly increased B7-1, but not B7-2, expression . The contribution of B7-1 and B7-2 co-stimulatory (CS) molecules to cryptococcal-specific T cell activation was analyzed and a substantial inhibition of T cell proliferation was observed . In this study we provide the first demonstration of fungal interference in the regulation of CS molecules . Our results suggest a potential mechanism for poor inflammatory responses observed in C . neoformans infections. Trop Doct, 1998 Jan, 28(1), 34 - 9 Cryptococcosis at the University Hospital, Kuala Lumpur; Doi SA et al.; We review our experience with 27 cases of pulmonary and meningeal cryptococcosis at the University Hospital, (Kuala Lumpar, Malaysia) where this is the most common cause of adult meningitis in patients without debilitating illnesses . Of the 27 cases analysed, six presented primarily with pulmonary symptomatology which usually were mainly cough, chest pain and low grade fever . The rest presented with primarily central nervous system (CNS) symptomatology of which headaches and fever were the most consistent symptoms although a third of these patients also had pulmonary lesions noted on chest radiographs . Treatment in all cases was with amphotericin B and 5-fluorocytosine and usually till a total cumulative dose of 1.5 g of amphotericin had been reached (an average of 10 weeks) . Primary pulmonary presentations, if symptomatic, were treated as per CNS cryptococcosis due to the high likelihood of CNS dissemination . Incidental pulmonary cryptococcoma found on routine chest radiographs were confirmed by biopsy under ultrasound or fluoroscopy guidance and booked for surgical resection . Death usually occurred early in patients who presented late . Once patients responded to therapy, mortality was usually avoided . The only cause of morbidity in survivors was visual impairment or blindness, and this was attributed mainly to intracranial hypertension with residual deficits determined by the measures taken to lower intracranial pressures . Our experience suggests that: (i) symptomatic patients should have combination therapy with 5-fluorocytosine and amphotericin B till at least a cumulative dose of 1.5 g amphotericin B is reached irrespective of whether they have primary CNS or pulmonary symptomatology; (ii) non-symptomatic pulmonary cryptococcoma could be treated primarily by surgical resection; (iii) visual failure or papilloedema should be treated aggressively; and (iv) prognosis is good with adequate therapy and early presentation. Schweiz Rundsch Med Prax, 1997 Dec 3, 86(49), 1949 - 54 Cryptococcosis, epileptic seizures and encephalopathy in a HIV-infected patient}; Tolnay M et al.; We report on a 32-year old HIV-infected male patient who was admitted to the hospital in a comatose state . A cryptococcus neoformans septicemia with meningoencephalitis was diagnosed . Intravenous treatment with amphotericin B was initiated and replaced three weeks later by fluconazole per os . With this therapy the patient recovered quite well . However, following two grand mal epileptic seizures he suddenly fell into a deep coma 22 days after admission to the hospital . The cause of the encephalopathy remained unclear, and the patient died 2 days later . Autopsy revealed a severe meningoencephalitis and a pneumonia due to cryptococcus neoformans . Departing from this case we discuss diagnosis, clinical presentation and treatment of cryptococcus meningoencephalitis. Rev Mal Respir, 1997 Nov, 14(5), 365 - 70 {Pulmonary cryptococcosis during HIV infection . 15 cases}; Balloul E et al.; We reviewed the records of 15 Human Immunodeficiency Virus (HIV) infected patients with pulmonary cryptococcosis (PC) . PC was the first AIDS-defining manifestation in nine patients . HIV infection was identified simultaneously with the onset of PC in 4 patients . The CD4+ lymphocyte count was low in all cases (median, 24/m3) . Chest radiography showed interstitial infiltrates in 13 instances, associated with pleural effusion in 5 cases and hilar adenopathy in 2 cases . In one case, chest-X-ray showed isolated pleural effusion and was normal in one patient . For 11 of 12 patients, bronchoalveolar lavage fluid culture was positive for Cryptococcus neoformans . Seven of 15 patients had evidence of extrapulmonary cryptococcal disease with positive cerebrospinal fluid culture . Serum cryptococcal antigen was detected in all 15 patients . Concomitant lung infection with Pneumocystis carinii was diagnosed in 4 patients . First-line regimen was fluconazole in 10 patients and amphotericin B in 4 patients . Fluconazole has been prescribed in 7 patients as a permanent suppressive therapy and should be continued indefinitely. Ophthalmology, 1998 Feb, 105(2), 377 - 81 Endogenous cryptococcal endophthalmitis; Sheu SJ et al.; BACKGROUND: Occurrence of cryptococcal endophthalmitis is rare and commonly is associated with widespread disseminated diseases . The authors report here a well-documented case of endogenous cryptococcal endophthalmitis without the preceding meningeal infection . METHODS: A 45-year-old female with a history of long-term use of systemic corticosteroid and cytotoxic drugs for systemic lupus erythematosus suffered from progressive visual loss in her left eye over 1 month . Large exudative retinal detachment and severe vitreous infiltration were observed . RESULTS: Histopathologic study of the retinal biopsy specimen established the diagnosis of cryptococcal endophthalmitis . Subsequent positive histopathologic study of the aspiration vitreous smear and epiretinal membrane confirmed the recurrence and persistence of the disease over 4 months after the initial presentation . Systemic amphotericin B-fluconazole and two doses of intravitreous amphotericin B injection eliminated the infection successfully . CONCLUSION: The authors report here a well-documented case of cryptococcal endophthalmitis and present the serial clinical and histopathologic pictures . The importance of retinal biopsy in diagnosis and the combined form of antifungal treatment also are shown. Front Biosci, 1998 Feb 01, 3, d136 - 51 Mechanism of action of antibody to capsular polysaccharide in Cryptococcus neoformans infection; Feldmesser M et al.; Cryptococcus neoformans is an encapsulated fungus that causes meningoencephalitis in 5-10% of patients with AIDS . While the immune response that controls infection is predominantly cell-mediated, Ab-mediated immunity is being studied for therapeutic use . mAbs to glucuronoxylomannan (GXM), the predominant constituent of the polysaccharide capsule are protective in a variety of murine infection models . However, the mechanism of Ab action in this infection is unknown . We review the literature on the effect of Ab in cryptococcal infection and potential mechanisms of action . The mechanism is likely multifactorial, involving enhancement at several branches of the immune response, including opsonization, antigen presentation and altered effector cell function . Removal of the toxic and immunosuppressive effects of GXM may be an important component of the mechanism of Ab action . Changes in pathology in response to monoclonal antibody (mAb) administration suggest that alterations in cytokine production may mediate mAb effects . In summary, specific Ab can modulate the course of cryptococcal infection to the benefit or detriment of the host, but significant questions remain concerning the mechanism of action and the relative importance of antibody-mediated immunity in normal and immunocompromised hosts. Mycoses, 1997 Nov, 40(7-8), 297 - 302 Prevalence of serotype D in Cryptococcus neoformans isolates from HIV positive and HIV negative patients in Italy; Tortorano AM et al.; Cryptococcus neoformans strains isolated from 207 HIV positive and HIV negative patients hospitalized in Northern Italy were serotyped by slide agglutination . One Brazilian HIV negative woman was infected by var . gattii serotype B and all the other patients by var . neoformans, serotype D in 71%, serotype A in 24.6% and serotype AD in 3.4% . No difference was observed between subjects with serotypes A and D in HIV coinfection, exposure categories for AIDS, age, sex, and CD4 count of HIV positive patients . Meningeal and respiratory tract involvements and prostatic reservoir occurred with comparable frequency in AIDS patients infected by serotypes A and D . Skin lesions were observed only in serotype D infections, occurring in 12.6% of HIV positive and 58.3% of HIV negative patients infected by this serotype . Serotype A was found less susceptible to fluconazole than serotype D: 53.7% of serotype A strains had a MIC > or = 25 micrograms ml-1 compared to 17.7% of the serotype D isolates . On the other hand, both serotypes were highly susceptible to itraconazole. Mycoses, 1997 Nov, 40(7-8), 267 - 77 High-dose therapy with fluconazole > or = 800 mg day-1; Duswald KH et al.; Fluconazole dosages greater than 800 mg day-1 have been reported in about 900 patients treated for candidemia, oropharyngeal candidiasis and cryptococcal meningitis in HIV-infected patients, and for initial therapy of endemic mycoses . In patients with life-threatening infections caused by Candida spp., Cryptococcus neoformans and Coccidioides immitis, results of a limited number of dose-finding trials with non-neutropenic and HIV-infected patients show dose-dependent responses . These study results indicate that higher daily doses of fluconazole than are currently approved for these indications are well tolerated and tend to provide better clinical efficacy in selected patient populations . An excellent safety profile of dosages up to 2000 mg day-1 and linear predictable pharmacokinetics up to 1600 mg day-1 appear to justify further clinical investigations to better determine the optimum dosage and duration of treatment. Mycoses, 1997, 40 Suppl 2, 13 - 5 Diagnosis of fungal infections; Fussle R; Fungal infections become more and more important due to their increasing incidence in immunocompromised patients . In these patients opportunistic fungi (Candida, Aspergillus, Cryptococcus) can cause life-threatening infections . Diagnosis of fungal infections is difficult . Clinical symptoms are uncharacteristic, and laboratory diagnosis is confronted with many problems and requires expert interpretation. Mycoses, 1997 Oct, 40(5-6), 203 - 7 Efficacy of a short-term amphotericin B + flucytosine combination therapy followed by itraconazole monotherapy in acute and chronic AIDS-associated cryptococcosis; Parisi A et al.; The authors report the clinical and microbiological findings of a 6-month follow-up of nine AIDS patients affected with cryptococcosis . Among these, seven patients suffered from meningoencephalitis and two from disseminated infection . The antifungal therapy during acute illness included the administration of amphotericin B at doses of 0.6 mg kg-1 day-1 i.v . plus flucytosine at doses of 100 mg kg-1 day-1 i.v . during the first 15 days followed by itraconazole at doses of 400 mg day-1 p.o . in the following 15 days . The maintenance treatment included itraconazole at doses of 200 mg day-1 p.o . indefinitely . During the 6-month follow-up, one patient died of hepatic failure related to C virus (HCV) hepatitis reactivation and another patient died of polymicrobial pneumonia . In two patients, the presence of multiple nodular lesions in the cerebral computerized tomography (CT) scan, related to cryptococcal granulomas, was associated with the persistance of fungi in the cerebrospinal fluid . In three patients with meningoencephalitis the three-drugs regimen was effective in eradicating the neurological infection, and relapses were not observed during the maintenance therapy with itraconazole during the 6-month follow-up . The two patients with haematogenous cryptococcosis did not relapse after the 6-month follow-up. J Acquir Immune Defic Syndr Hum Retrovirol, 1998 Feb 1, 17(2), 137 - 42 Management of elevated intracranial pressure in patients with Cryptococcal meningitis; Fessler RD et al.; BACKGROUND: The most important predictor of early mortality in patients with HIV-associated cryptococcal meningitis is mental status at presentation; patients who present with altered mental status have up to 25% mortality . Historically, cerebrospinal fluid (CSF) diversion in HIV-negative patients with cryptococcal meningitis and signs of elevated intracranial pressure (ICP) has improved survival . In an effort to affect survival and morbidity rates in patients with HIV-associated cryptococcal meningitis, we have initiated aggressive management of elevated ICP in patients with focal neurologic deficits, mental obtundation, or both . METHODS: We identified 10 patients with HIV-associated cryptococcal meningitis who presented with symptoms consistent with elevated ICP, including headache, mental obtundation, papilledema, and cranial nerve palsies . Elevated opening pressure was defined as > 20 cm CSF during lumbar puncture . In patients with elevated opening pressures who had focal neurologic deficits or mental status changes refractory to serial lumbar puncture, management consisted of immediate placement of lumbar drains for continuous drainage of CSF to maintain normal ICP (10 cm CSF) . Patients with persistent elevations of spinal neuraxis pressure following lumbar drainage underwent placement of lumbar peritoneal shunts . RESULTS: All patients returned to their baseline level of consciousness following normalization of ICP . Two patients were weaned from lumbar drainage . Eight patients eventually required placement of lumbar peritoneal shunts for persistently elevated ICP despite successful antifungal therapy . Follow-up ranged from 1 to 15 months . One shunt infection occurred, one lumbar peritoneal shunt was converted to a ventriculoperitoneal shunt, and one shunt was removed . CONCLUSIONS: Elevated ICP in patients with HIV-associated cryptococcal meningitis is a significant source of morbidity and mortality . The use of lumbar drainage and selective placement of lumbar peritoneal shunts in the management of elevated ICP in patients with HIV-associated cryptococcal meningitis can ameliorate the sequelae of elevated ICP. Mycoses, 1997 Dec, 40(9-10), 385 - 9 Isolation of specific DNA probes for detection of Cryptococcus neoformans; Wu J et al.; We report the construction of a genomic library and isolation of repetitive DNA probes from Cr . neoformans that are species- and variety-specific . The inserts of the genomic library were in a range of 0.3-1.8 kb, which were in normal distribution in length . Among 592 clones of the genomic library, there were 400(67.6%) clones inserted repetitive DNA sequence and 192(32.4%) inserted single copy DNA sequence of the Cr . neoformans genome . From the library, three specific probes were identified . Clone pCNIIA6 was serotype A-specific, pCNIIB5 species-specific, and pCNIIIG1 variety-specific (var . neoformans) . On the basis of the high specificity and sensitivity of the signals observed by hybridization, we suggest that these probes provide a means for both biotyping and early diagnosis of Cr . neoformans. Mycoses, 1997 Dec, 40(9-10), 381 - 3 A case of feline cryptococcosis treated with itraconazole; Kano R et al.; We successfully treated a feline case of cryptococcosis with itraconazole (ITZ) at a lower dosage . The patient was a 2-year-old castrated male Abyssinian cat weighing 4.1 kg and with two masses on the head . Clinical signs were sneezing and nasal discharge . The plasma cryptococcal antigen titer measured by the latex agglutination test was proved to be high (512) . The biopsy specimen from the masses disclosed yeast cells which were cultured and identified to be Cryptococcus neoformans . The cat was treated with ITZ 5 mg kg-1 given orally once a day with food . After 4 weeks, treatment of ITZ discontinued, because the cat was clinically normal and the antigen titer was low (128) . However, about 7 months later, a subcutaneous nodule was detected on the same area . The nasal discharge appeared again, and the cryptococcal antigen titer was 256 . ITZ treatment was continued again at the same dosage for 3 months until the antigen titer was negative (< 8) . Four months after discontinuation of ITZ, the cat did not relapse and the antigen titer was in the negative range . No side-effects of ITZ were detected by physical and laboratory examination. Mycoses, 1997 Dec, 40(11-12), 423 - 7 Comparison of broth macrodilution, broth microdilution and E-test susceptibility tests of Cryptococcus neoformans for fluconazole; Chryssanthou E et al.; Forty Cryptococcus neoformans strains isolated from cerebral spinal fluid specimens collected from 39 patients were included in the study . The MICs for fluconacole were determined by YNB macrodilution test, microdilution tests using both RPMI1640 and YNB medium and E-tests on solidified RPMI1640 medium, Casitone and YNB agar . In comparison with the reference macrodilution method NCCLS M27-P both the microdilution as well as the E-test techniques can be used for fluconacole susceptibility testing of Cr . neoformans. J Med Assoc Thai, 1997 Dec, 80(12), 767 - 70 Maintenance therapy with itraconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome; Chotmongkol V et al.; We conducted a prospective, open trial to establish the efficacy of itraconazole 400 mg/d as maintenance treatment for cryptococcal meningitis in AIDS patients . Between February 1996 and May 1997, 50 patients were included for analysis . After a mean follow-up of 326 days, 2 of 38 patients (5.3 per cent) had relapses of symptomatic cryptococcal meningitis . Hepatotoxicity occurred in 2 cases . In conclusion, maintenance therapy with itraconazole 400 mg/d is effective in preventing recurrent cryptococcal meningitis. J Med Vet Mycol, 1997 Nov-Dec, 35(6), 437 - 40 Cryptococcus neoformans in Papua New Guinea: a common pathogen but an elusive source; Laurenson IF et al.; Around Port Moresby, Papua New Guinea (PNG), the annual incidence of cryptococcal meningitis is estimated to be up to 42.8 per million population; Cryptococcus neoformans var . gattii is the predominant causative agent . In Australia and California, environmental isolations have established an ecological association of C . neoformans var . gattii with Eucalyptus camaldulensis, E . tereticornis, and more recently E . rudis and E . gomphcephala . In PNG few E . camaldulensis survive experimental planting, E . tereticornis is endemic and there are no records of planting of the non-endemic E . rudis and E . gomphcephela . Despite extensive sampling of eucalypt-associated and other sources, we were unable to identify the ecological niche of C . neoformans var . gattii and neoformans in this region. J Clin Microbiol, 1998 Feb, 36(2), 458 - 61 First identification of autochthonous