Commun Dis Rep CDR Rev, 1996 Apr 26, 6(5), R69 - 75 Fungal infections: a survey of laboratory services for diagnosis and treatment; Barnes RA et al.; A questionnaire on the services provided and the methods used for the diagnosis of fungal infections and for the support of antifungal chemotherapy was sent to members of the British Society for Medical Mycology (BSMM) and the British Society for Antimicrobial Chemotherapy (BSAC) . Ninety-five responses from general microbiology laboratories in the United Kingdom were analysed, and we compared services provided by laboratories that serve a transplant unit with those offered by other laboratories . We estimate that about 150 cases of cryptococcosis, 500 to 600 of candidaemia, and 300 to 400 of invasive aspergillosis are identified by laboratories in the United Kingdom (UK) each year . The clinical laboratories are aware of the importance of fungal infection, but rely heavily on reference services . In some laboratories, however, the degree of investigation of specimens and the procedures in use are inadequate for diagnosing systemic mycoses and determining the susceptibility of isolates to antifungal agents . The balance between reference and local services requires attention and external quality assurance needs to be applied effectively . In addition, effective methods for the diagnosis of systemic mycoses, and reliable and practicable methods for determining the susceptibility of isolates to antifungal agents, are needed urgently. J Clin Invest, 1996 Apr 15, 97(8), 1818 - 26 Urokinase is required for the pulmonary inflammatory response to Cryptococcus neoformans . A murine transgenic model; Gyetko MR et al.; Urokinase (uPA) is hypothesized to provide proteolytic activity enabling inflammatory cells to traverse tissues during recruitment, and it is implicated as a cytokine modulator . Definitive evaluation of these hypotheses in vivo has previously been impossible because uPA could not completely and irreversibly be eliminated . This limitation has been overcome through the development of uPA-deficient transgenic mice (uPA-/-) . Using these mice, we evaluated the importance of uPA in the pulmonary inflammatory response to Cryptococcus neoformans (strain 52D) . C . neoformans was inoculated into uPA-/- and control mice (uPA+/+), and cell recruitment to the lungs was quantitated . The number of CFU in lung, spleen and brain was determined to assess clearance, and survival curves were generated . By day 21 after inoculation, uPA-/- mice had markedly fewer pulmonary inflammatory (CD45+), CD4+, and CD11b/CD18+ cells compared with uPA+/+ controls (P<0.0007); pulmonary CFUs in the uPA-/- mice continued to increase, whereas CFUs diminished in uPA+/+ mice(P<0.005) . In survival studies, only 3/19 uPA+/+ mice died, whereas 15/19 uPA-/- mice died (p<0.001) . We have demonstrated that uPA is required for a pulmonary inflammatory response to C . neoformans . Lack of uPA results in inadequate cellular recruitment, uncontrolled infection, and death. Microbiology, 1996 Apr, 142 ( Pt 4), 937 - 43 Stress tolerance and pathogenic potential of a mannitol mutant of Cryptococcus neoformans; Chaturvedi V et al.; Cryptococcus neoformans produces large amounts of the acyclic hexitol mannitol in culture and infected animals, but the functional and pathogenic significance of mannitol production by this fungus is not known . We exposed C . neoformans H99 (Cn H99) to UV irradiation (1 x LD50) and screened survivors for mannitol production . A mutant, Cn MLP (Mannitol Low Producer), synthesized less mannitol from glucose (2.7 vs 8.2 nmol per 10(8) cells min-1 at 37 degrees C) and contained less intracellular mannitol (1 vs 11 mumol per 10(6) cells at 37 degrees C) than did Cn H99 . Cn MLP and Cn H99 were similar with respect to carbon assimilation patterns, rates of glucose consumption, growth rates at 30 degrees C, urease and phenoloxidase activities, morphology, capsule formation, mating type, electrophoretic karyotype, rapid amplification of polymorphic DNA (RAPD) patterns and antifungal susceptibility . However, Cn MLP was more susceptible than was Cn H99 to growth inhibition and killing by heat and high NaCl concentrations . Also, the LD50 values in mice injected intravenously were 3.7 x 10(6) c.f.u . for Cn MLP compared to 6.9 x 10(2) c.f.u . for Cn H99 . Moreover, 500 c.f.u . Cn H99 intravenously killed 12 of 12 mice by 60 d, whereas all mice given the same inoculum of Cn MLP survived . Classical genetic studies were undertaken to determine if these differences were due to a single mutation, but the basidiospores were nonviable . These results suggest that the abilities of C . neoformans to produce and accumulate mannitol may influence its tolerance to heat and osmotic stresses and its pathogenicity in mice. Emerg Infect Dis, 1996 Apr-Jun, 2(2), 109 - 16 Emerging disease issues and fungal pathogens associated with HIV infection; Ampel NM; Fungal diseases are increasing among patients infected with human immunodeficiency virus (HIV) type 1 . Infections due to Candida and Cryptococcus are the most common . Although mucocutaneous candidiasis can be treated with oral antifungal agents, increasing evidence suggests that prolonged use of these drugs results in both clinical and microbiologic resistance . The optimal therapy for cryptococcal meningitis remains unresolved, although initial treatment with amphotericin B, followed by life-long maintenance therapy with fluconazole, appears promising . Most cases of histoplasmosis, coccidioidomycosis, and blastomycosis occur in regions where their causative organisms are endemic, and increasing data suggest that a significant proportion of disease is due to recent infection . Aspergillosis is increasing dramatically as an opportunistic infection in HIV-infected patients, in part because of the increased incidence of neutropenia and corticosteroid use in these patients . Infection due to Penicillium marneffei is a rapidly growing problem among HIV-infected patients living in Southeast Asia . Although the advent of oral azole antifungal drugs has made primary prophylaxis against fungal diseases in HIV-infected patients feasible, many questions remain to be answered before the preventive use of antifungal drugs can be advocated. Rinsho Byori, 1996 Apr, 44(4), 373 - 8 {Studies on microtiter broth dilution method for antifungal susceptibility testing of yeast isolates from blood and cerebrospinal fluid}; Fujita S; Minimum inhibitory concentration (MICs) of amphotericin B (AMPH), fluconazole (FCZ), miconazole (MCZ), and flucytosine (5-FC) for five quality control (QC) strains, 135 Candida isolates from blood and 9 of Cryptococcus neoformans from the cerebrospinal fluid were determined by the microtiter broth dilution method . For FCZ, MCZ, and 5-FC, the MIC endpoints were defined at the concentrations of 50% (IC50), 80% (IC80), and 80% (IC80) growth inhibition in comparison with the growth control respectively . For AMPH, the MIC endpoint was at which concentration completely inhibited . The MICs were read after 24h incubation for C . albicans, C . tropicalis, C . glabrata and C . krusei, and 48h for C . guilliermondii, C . parapsilosis and C . neoformans . The MICs of four antifungal agents were determined 5 times each against the 5 QC strains, and the most MIC results ranged within the NCCLS QC range recommended . Four of 15 C . glabrata isolates (27%), four of 14 C . guilliermondii (29%) and three of 4 C . krusei (75%) were regarded to be resistant to FCZ (> or = 16 micrograms/mL), and one strain each of C . glabrata, C . guilliermondii and C . krusei were to MCZ (> or = 16 micrograms/mL) . On the other hand, all the isolates tested were inhibited at the concentration of < or = 1 microgram/mL of AMPH . Overall, no significant increase in antifungal resistance among the yeast isolates during the period from 1980 to 1994 was noted. Pancreas, 1996 Apr, 12(3), 308 - 12 Pancreatic fungal infections: a case report and review of the literature; Robbins EG 2nd et al.; Pancreatic necrosis as a consequence of acute pancreatitis usually implies a poor prognosis . Infection is the most common complication affecting mortality and appears to be increasing . While bacterial infections, particularly with coliforms, account for the majority of cases of infected necrosis, fungal infections are being more frequently documented . This may be due to increased recognition through improved laboratory techniques, more aggressive diagnosis by percutaneous aspiration, or the more widespread use of broad-spectrum antibiotics or parenteral nutrition . While the majority of documented fungal pancreatic infections have been with Candida species, recent reports have highlighted the importance of Torulopsis glabrata . This haploid yeast of the family Cryptococcaceae is a fungal commensal organism accounting for 16% of all human yeast isolates . Here we report the first case of T . glabrata infection complicating pancreatic necrosis and review the current knowledge of pancreatic fungal infections complicating acute pancreatitis . Superimposed infection, either bacterial or fungal, needs to be diligently sought in patients with pancreatic necrosis who fail to improve or deteriorate despite supportive care. J Clin Microbiol, 1996 Apr, 34(4), 912 - 7 Molecular subtype distribution of Cryptococcus neoformans in four areas of the United States . Cryptococcal Disease Active Surveillance Group; Brandt ME et al.; To improve understanding of the epidemiology of cryptococcal disease, we analyzed the multilocus genotype distribution of 358 Cryptococcus neoformans isolates obtained from 251 patients through active surveillance in four U.S . geographic areas from 1992 through 1994 . Isolates of the predominant enzyme electrophoretic type (ET), ET-1, were recovered in significantly greater proportion from Atlanta, Ga., Houston, Tex., and all major metropolitan areas of Alabama than from San Francisco, Calif . ET-2 and ET-7 complex (serotype AD) isolates were recovered predominantly from San Francisco . ET-3 was recovered less frequently from San Francisco than from the three other locations . These findings may reflect geographic differences in exposure to environmental strains or the identification of previously unrecognized C . neoformans clusters . Analysis by random amplified polymorphic DNA-PCR subtyping further divided 67 ET-1 isolates into 19 additional subtypes, none of which could be associated with a particular geographic region . Multiple isolates from the same patient always revealed the same multilocus enzyme electrophoresis and random amplified polymorphic DNA subtypes . No differences in subtype distribution were found when isolates from AIDS patients were compared with those from persons without or with another underlying disease, although one C . noeformans var . gattii isolate was obtained from an AIDS patient . When body site distribution was analyzed, ET-4 was disproportionately recovered from skin or surface body sites . Evidence for linkage disequilibrium in this fungal population suggests that virulent C . neoformans possesses a clonal population structure . Continued application of molecular subtyping methods will be useful in tracking the source, transmission, and relative virulence of different C . neoformans strains. J Clin Microbiol, 1996 Apr, 34(4), 848 - 52 Interlaboratory evaluation of Etest method for testing antifungal susceptibilities of pathogenic yeasts to five antifungal agents by using Casitone agar and solidified RPMI 1640 medium with 2% glucose; Espinel-Ingroff A et al.; An interlaboratory evaluation (two centers) of the Etest method was conducted for testing the antifungal susceptibilities of yeasts . The MICs of amphotericin B, fluconazole, flucytosine, itraconazole, and ketoconazole were determined for 83 isolates of Candida spp., Cryptococcus neoformans, and Torulopsis glabrata . Two buffered (phosphate buffer) culture media were evaluated: solidified RPMI 1640 medium with 2% glucose and Casitone agar . MIC endpoints were determined after both 24 and 48 h of incubation at 35 degrees C . Analysis of 3,420 MICs demonstrated higher interlaboratory agreement (percentage of MIC pairs within a 2-dilution range) with Casitone medium than with RPMI 1640 medium when testing amphotericin B (84 to 90% versus 1 to 4%), itraconazole (87% versus 63 to 74%), and ketoconazole (94 to 96% versus 88 to 90%) . In contrast, better interlaboratory reproducibility was determined between fluconazole MIC pairs when RPMI 1640 medium rather than Casitone medium was used (96 to 98% versus 77 to 90%) . Comparison of the flucytosine MICs obtained with RPMI 1640 medium revealed greater than 80% reproducibility . The study suggests the potential value of the Etest as a convenient alternative method for testing the susceptibilities of yeasts . It also indicates the need for further optimization of medium formulations and MIC endpoint criteria to improve interlaboratory agreement. Arzneimittelforschung, 1996 Apr, 46(4), 445 - 9 Clinical and pharmacokinetic evaluation of a new lipid-based delivery system of amphotericin B in AIDS patients; Villani P et al.; To evaluate the safety, tolerance and pharmacokinetics of a new formulation of amphotericin B (AmB; CAS 1397-89-3) 18 AIDS patients treated for different kinds of mycoses were studied: oropharingeal and/or esophageal azole-resistant candidiasis (9), CNS cryptococcosis (7) or aspergillosis (2) . Amphotericin B daily dose was infused in 100 ml of a lipid emulsion . The patients aged from 26 to 54 years with body weight ranging from 42 to 89 kg . Blood samples were collected at fixed intervals and plasma stored at -20 degrees C until tested by a specific HPLC assay . The individual kinetic analysis of plasma drug levels was performed by a two-compartment open model . The data were analyzed using P-Pharm, a computer program designed for population pharmacokinetic analysis that allows pooling of data . The effect of a variety of demographic factors on clearance and volume of distribution was investigated . The clearance and the apparent volume of distribution were, respectively, (mean +/- SD): 0.037 +/- 0.015 l/h/kg and 0.45 +/- 0.32 l/kg . The interindividual variability in AmB clearance and volume of distribution was modelled with proportional error with an estimated coefficient of variation of 40.6% and 70.9%, respectively . Clinical and biological tolerance was very good and no patient experience infusion-related adverse effects or hematologic and hepatic toxicity; a moderate renal failure occurred in only one patient. Clin Infect Dis, 1996 Apr, 22(4), 671 - 82 Cavitary pulmonary lesions in patients infected with human immunodeficiency virus; Gallant JE et al.; The differential diagnosis of cavitary pulmonary lesions in individuals infected with human immunodeficiency virus (HIV) is broad, especially in patients with advanced disease . In patients with Pneumocystis carinii pneumonia, cavitation is an uncommon manifestation of a common disease . It is unusual in patients with pulmonary cryptococcosis, coccidioidomycosis, and histoplasmosis but occurs frequently in patients with invasive pulmonary aspergillosis . In patients with pulmonary tuberculosis, cavities are more common during earlier stages of HIV disease, when cellular immunity is relatively preserved . Mycobacterium avium complex is an uncommon cause of lung disease and infrequently produces cavities . However, Mycobacterium kansasii, is often associated with cavitation . Cavities can complicate any bacterial pneumonia and are especially common with pneumonia due to Pseudomonas aeruginosa, Nocardia asteroides, and Rhodococcus equi . Noninfectious causes of cavitary lesions are rare, but cavitary lesions caused by pulmonary Kaposi's sarcoma and non-Hodgkin's lymphoma have been reported . Because of the broad differential diagnosis and because most cavities are caused by treatable opportunistic infections, a definitive diagnosis is essential. Cutis, 1996 Apr, 57(4), 229 - 31 Cutaneous cryptococcosis in a patient receiving chronic immunosuppressive therapy; Pineski R et al.; Cryptococcosis was diagnosed in an immunosuppressed patient . Topical treatment was ineffective and treatment with oral itraconazole was started . The lesion improved . Liver enzymes were monitored and, although their levels were raised before the start of itraconazole therapy, they did not increase further during treatment. Eur Respir J, 1996 Apr, 9(4), 837 - 9 Cryptococcosis: an unusual cause of endobronchial obstruction; Mahida P et al.; We report the case of a 43 year old male patient, with normal immune function, who presented with right middle and lower lobe collapse . At bronchoscopy, a white lobulated lesion was seen, completely obstructing the origin of bronchus intermedius . Bronchial washings and biopsy of the lesion demonstrated cryptococcal organisms . The patient responded clinically and radiologically to amphotericin B and flucytosine; however, repeat bronchoscopy revealed only partial resolution of the endobronchial lesion. J Nat Prod, 1996 Apr, 59(4), 431 - 5 Antifungal and molluscicidal saponins from Serjania salzmanniana; Ekabo OA et al.; An investigation of Serjania salzmanniana for biologically active substances has led to the isolation of two novel saponins, salzmannianoside A (3-O-{{beta-D- glucopyranosyl-(1-->4)}-{alpha-L-rhamnopyranosyl-(1-->2)}-alpha-L- arabinopyranosyl} gypsogenin) {3} and salzmannianoside B (3-O-{{beta-D-glucopyranosyl-(1-->4)}-{alpha-L- arabinopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)} -alpha-L-arabinopyranosyl} hederagenin) (4) . Two known saponins, pulsatilla saponin D (3-O-{{beta-D- glucopyranosyl-(1-->4)}-{alpha-L-rhamnopyranosyl-(1-->2)}-alpha-L- arabinopyranosyl} hederagenin) (1) and 3-O-{{beta-D-glucopyranosyl-(1-->4)}-{alpha-L-rhamnopyranosyl-(1-->2)}-a lpha-L- arabinopyranosyl} oleanolic acid (2) were also isolated from this plant . The structures of 3 and 4 were elucidated by FABMS and 2D NMR techniques . All these four saponins were mollusicidal, causing 70-100% mortality at 10 ppm against Biomphalaria alexandrina, a vector of Schistosoma mansoni in the Nile Valley . The saponins also showed antifungal activity against Cryptococcus neoformans and Candida albicans at minimal inhibitory concentrations of 8 and 16 micrograms/mL, respectively. J Exp Med, 1996 Apr 1, 183(4), 1905 - 9 Immunoglobulin G3 blocking antibodies to the fungal pathogen Cryptococcus neoformans; Nussbaum G et al.; Vaccination and infection can elicit protective and nonprotective antibodies to the fungus Cryptococcus neoformans in mice . The effect of nonprotective antibodies on host defense is unknown . In this study we used mixtures of protective and nonprotective monoclonal antibodies (mAbs) to determine if nonprotective mAbs blocked the activity of the protective mAbs . Antibody isotype and epitope specificity are important in determining the ability to prolong survival in mice given a lethal C . neoformans infection . Three different nonprotective immunoglobulin (Ig) G23 mAbs to cryptococcal capsular polysaccharide were used to study the interaction between the IgG3 isotype and protective IgG1 and IgG2a mAbs in murine cryptococcal infection . One IgG3 mAb reduced the protective efficacy of an IgG1 with identical epitope specificity . A second IgG3 mAb with different epitope specificity also reduced the protection provided by the IgG1 mAb . The protective efficacy of an IgG2a mAb was also dramatically decreased by still another IgG3 mAb . To our knowledge this is the first report of blocking antibodies to a fungal pathogen . The results have important implications for the development of vaccines and passive antibody therapy against C . neoformans. Aust Vet J, 1996 Apr, 73(4), 124 - 8 Combination chemotherapy of canine and feline cryptococcosis using subcutaneously administered amphotericin B; Malik R et al.; Six cases (3 cats, 3 dogs) of cryptococcosis were cured using combination chemotherapy that included amphotericin B . We developed a simple, practical and inexpensive method of administering amphotericin B as a subcutaneous infusion during the treatment of these patients . For this, the calculated dose of amphotericin B (0.5 to 0.8 mg/kg) was added to 400 mL, for cats, or to 500 mL, for dogs, of 0.45% saline containing 2.5% dextrose . These amounts were given subcutaneously 2 or 3 times weekly over several months, to a total cumulative dose of 8 to 26 mg/kg body weight . Subcutaneous infusions were generally well tolerated by the animals, although concentrations of amphotericin B in excess of 20 mg/L resulted in local irritation . This protocol enabled the administration of larger, and thus more effective, quantities of amphotericin B without producing marked azotaemia. APMIS, 1996 Apr, 104(4), 241 - 58 Diagnosis of systemic mycoses by specific immunohistochemical tests; Jensen HE et al.; Immunohistochemistry has proved to be a powerful tool for the accurate diagnosis of a number of important mycoses in humans and animals, such as aspergillosis, candidosis, cryptococcosis, blastomycosis, coccidioidomycosis, histoplasmosis capsulati and duboisii, paracoccidioidomycosis, fusariosis, pseudallescheriosis (scedosporiosis), sporotrichosis, trichosporonosis, penicilliosis, and zygomycosis (mucormycosis) . These techniques are also applicable to pneumocystosis and to non-mycotic infections caused by algae such as protothecosis . Apart from the specificity of immunohistochemistry, the application of fluorochromes is highly effective for the localization of typical or atypical fungal elements in lesions with only few organisms present . Occasionally, a dual aetiology of fungal infections may be suspected on the basis of morphological study, and dual staining techniques have the capacity for resolving this question by simultaneous and differential staining of two fungal species present in a tissue specimen. Am J Pathol, 1996 Apr, 148(4), 1275 - 82 Expression of inducible nitric oxide synthase in rat pulmonary Cryptococcus neoformans granulomas; Goldman D et al.; Rats, like humans, have extremely effective immune mechanisms for controlling pulmonary Cryptococcus neoformans infection . The mechanism(s) responsible for efficient immunity in rat experimental infection is unknown . Recently, induction of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) have been implicated as an important microbicidal mechanism by which activated macrophages effect cytotoxicity against microbes . In this report, we investigated the expression of iNOS in rat pulmonary cryptococcosis . Localization and regulation of NO production was studied by immunohistochemistry for iNOS in conjunction with immunohistochemistry for cell markers, cytokines, and cryptococcal capsular polysaccharide . iNOS immunoreactivity was detected in macrophages, neutrophils, vascular endothelium, and respiratory epithelium . Double-immunolabeling studies revealed that the most prominent iNOS immunoreactivity was localized to epithelioid macrophages (CD11b/c+) within granulomas; CD4+ and CD8+ T cells were numerous around granulomas but did not express iNOS . iNOS immunoreactivity was detected in a selective population of epithelioid macrophages within some granulomas but not others . iNOS- granulomas were identical to iNOS+ granulomas with respect to morphology and immunohistochemical profiles . Macrophage iNOS immunoreactivity was detected 1 week after infection in one out of four rats and was strongly expressed in all rats at 2 weeks (in up to 50 percent of the granulomas) but declined considerably by 25 days . iNOS expression coincided with granuloma formation and preceded a decrease in lung fungal burden, suggesting an anticryptococcal role for NO . By double labeling, cytokines that have been shown to promote (interferon-gamma, granulocyte/macrophage colony-stimulating factor) and inhibit (transforming growth factor-beta) macrophage iNOS expression were detected around iNOS+ granuloma . iNOS immunoreactivity was expressed in selected neutrophils (1 and 2 weeks) and endothelial cells (1 and 2 weeks and 25 days) in the inflamed lung . Airway iNOS immunoreactivity was limited to the luminal border of rare bronchiolar epithelial cells . iNOS immunoreactivity was not detected in uninfected rats . The present study provides the first evidence for association of iNOS expression with protective cellular responses to cryptococcal infection in vivo. Am J Pathol, 1996 Apr, 148(4), 1267 - 74 Immunohistochemical localization of capsular polysaccharide antigen in the central nervous system cells in cryptococcal meningoencephalitis; Lee SC et al.; Cryptococcal meningoencephalitis (CME) is caused by the encapsulated fungus Cryptococcus neoformans (CN) and is a major cause of mortality and morbidity in patients with AIDS . The polysaccharide capsule of CN is important for virulence, and soluble polysaccharide has the potential to cause immune modulation . To better understand the interactions of central nervous system cells and cryptococcal capsular polysaccharide (CNPS) in the pathogenesis of human CME, postmortem brain tissue from 21 patients with CME (13 AIDS and 8 non-AIDS patients) was analyzed . Histopathology and distribution of tissue CNPS antigen were analyzed using monoclonal antibodies against CNPS in combination with cell type-specific markers (glial fibrillary acidic protein for astrocytes, Ricinus communis agglutinin (RCA)-l for macrophage/microglia and endothelial cells; UCHL-1 for T cells, L26 for B cells) . The CN cells showed discrete capsular immunoreactivity as expected; however, diffuse and particulate cellular and tissue staining for CNPS was detected in the brain parenchyma and the meninges in all cases . By quantitative analysis, the CNPS immunoreactive area ranged from 0.1 to 88 percent of tissue cross sectional area, and tended to be higher in brains of AIDS (median values from two sections ranged from 1 to 57 percent; mean, 26 percent) than in non-AIDS (0.1 to 40 percent; mean, 9.6 percent) patients . The proportion of CNPS immunoreactive area was positively correlated with the estimated number of CN . None (0/13) of the AIDS patients displayed significant inflammatory responses to CN, whereas most (7/8) non-AIDS patients showed granulomatous inflammatory responses . The phenotype of infiltrating lymphocytes was UCHL-1+/L26-/RC4-, thus consistent with activated T cells, both in AIDS and non-AIDS patients . Double immunolabeling studies revealed that tissue CNPS immunoreactivity was most often localized in macrophages and microglia, less frequently in reactive astrocytes and endothelial cells, but not in lymphocytes . This study demonstrates that CNPS can be detected not only in the serum and cerebrospinal fluid (CSF) of patients, but also in the affected tissue, most often localized in cells of mononuclear phagocyte system . Potential implications of these findings for the pathogenesis of CME are discussed. J Antibiot (Tokyo), 1996 Apr, 49(4), 386 - 9 Relationship between structure and biological activity of novel R106 analogs; Rodriguez MJ et al.; The retro-aldol reaction at residue 8 of R106-1 produced a chemical handle, in the form of a sarcosine residue, that was amenable to classical aldol alkylation conditions . In vitro assay of several new hydroxylated analogs have shown that L isomers exhibit more potent antifungal activity than D isomers . However, all analogs exhibited a significant decrease in activity against Cryptococcus neoformans . By contrast, structural modifications of R 106 were tolerated by some Candida spp., but the potency of activity was diminished as compared to that of the natural product R106-1 . The full structure-activity relationship of the new R106 analogs has provided important information about the steric and electronic requirements of binding to target receptors . Furthermore, comparison of the structural differences between R106-1 and other derivatives, suggested that the potential for hydrogen bonding (at residue 8) was a key structural feature that was required to maintain activity against Cryptococcus neoformans. J Antibiot (Tokyo), 1996 Apr, 49(4), 340 - 4 YM-47522, a novel antifungal antibiotic produced by Bacillus sp . I . Taxonomy, fermentation, isolation and biological properties; Shibazaki M et al.; YM-47522, a novel antibiotic, was isolated from the culture broth of Bacillus sp . YL-03709B . The antibiotic was purified by centrifugal partition chromatography and ODS column chromatography . It exhibited potent in vitro antifungal activity especially against Rhodotorula acuta and Pichia angusta (MIC: 0.05 and 0.75 microgram/ml, respectively) . It also showed moderate or weak antifungal activity against Candida albicans and Cryptococcus neoformans (MIC: 25 and 6.25 micrograms/ml, respectively), whereas it was inactive against filamentous fungi and bacteria. Ann Intern Med, 1996 Apr 1, 124(7), 633 - 42 Natural history of opportunistic disease in an HIV-infected urban clinical cohort; Moore RD et al.; OBJECTIVE: To determine the effect of contemporary clinical care on the natural history of opportunistic disease in an urban population infected with human immunodeficiency virus (HIV) . SETTING: Urban university HIV clinic . DESIGN: Retrospective and prospective observational study . PATIENTS: 1246 HIV-infected patients with CD4+ counts of 300 cells/mm3 or less . MEASUREMENTS: Incidence rates and Kaplan-Meier estimates of the probability of developing opportunistic disease with time, distribution of the CD4+ counts at which opportunistic disease develops, survival after the development of opportunistic disease, and the association between preventive drug therapies and the occurrence of opportunistic infection . RESULTS: The most common opportunistic disease was Candida esophagitis, which had an incidence of 13.3 events per 100 person-years and a 3-year Kaplan-Meier probability of 0.30 . Pneumocystis carinii pneumonia, Mycobacterium avium complex bacteremia, cytomegalovirus, and the acquired immunodeficiency syndrome dementia complex occurred at rates of 5 to 9 events per 100 person-years and 3-year Kaplan-Meier probabilities of 0.15 to 0.22 . Toxoplasmosis, cryptococcal meningitis, herpes zoster, the wasting syndrome, and Kaposi sarcoma occurred at rates of about 2 to 4 events per 100 person-years and with 3-year Kaplan-Meier probabilities of 0.05 to 0.10 . Non-Hodgkin lymphoma, M . tuberculosis infection, progressive multifocal leukoencephalopathy, and cryptosporidiosis were the least common disorders, with an incidence of about 1 to 2 events per 100 person-years and a 3-year Kaplan-Meier probability less than 0.05 . Only the incidences of cryptococcal meningitis, secondary P . carinii pneumonia, and herpes zoster decreased (P < 0.05) between 1989-1992 and 1993-1995 . Fluconazole use was associated with a decreased relative rate of 0.49 (P = 0.06) for cryptococcal meningitis and a decreased relative rate of 0.61 (P = 0.005) for esophageal candidiasis . Rifabutin use was associated with a decreased relative rate of 0.37 (P = 0.002) for M . avium complex bacteremia, and trimethoprim-sulfamethoxazole use was associated with decreased relative rates of 0.33 (P = 0.02) for secondary P . carinii pneumonia and 0.55 (P = 0.08) for primary P . carinii pneumonia . Candidiasis, herpes zoster, and M . tuberculosis infection first occurred at a median CD4+ count greater than 100 cells/mm3, but all other opportunistic diseases first occurred at a median CD4+ count less than 50 cells/mm3 . Median survival after diagnosis varied from 35 days for non-Hodgkin's lymphoma to 680 days for herpes zoster . CONCLUSIONS: In the patients studied, the incidences of secondary P . carinii pneumonia, cryptococcal meningitis, and herpes zoster have declined in the past 5 years . The incidences of primary P . carinii pneumonia and Kaposi sarcoma appear to be declining compared with historical estimates . However, although these and other opportunistic diseases continue to be relatively frequent complications of HIV infection, they are first occurring at more advanced immunosuppression than in the past . Continued efforts are needed to develop effective strategies for preventing opportunistic disease in very advanced HIV infection. Carbohydr Res, 1996 Mar 22, 283, 95 - 110 Structure of the O-deacetylated glucuronoxylomannan from Cryptococcus neoformans Cap70 as determined by 2D NMR spectroscopy; Bacon BE et al.; Cryptococcus neoformans, an opportunistic pathogen, is the fourth leading cause of death among AIDS patients . The yeast's capsule is a major virulence factor, and serotype is related to the chemical structure of glucuronoxylomannan (GXM), its capsular polysaccharide . The GXM from Cap70, a hypocapsular mutant of serotype D isolate B-3501, was investigated by chemical analysis and 2D NMR spectroscopy . The assignment of 1H and 13C chemical shifts for the O-deacetylated polysaccharide was accomplished from the analysis of DQF-COSY, TOCSY, and gradient-enhanced HSQC spectra . The sequence and linkage positions of glycosyl residues were determined by NOESY and ROESY spectra . Two repeating polysaccharide components were identified as having the following structures in approximately equal proportions: {formula: see text} It is not known if these repeating units comprise a single or two separate polymer chains . Pentasaccharide 2 has been known to be the major GXM polymer of B-3501 and other serotype D isolates . Hexasaccharide 1 is identified for the first time although it has subsequently been identified in other C . neoformans isolates . The presence of 1 in the GXM of Cap70 is consistent with the extra xylose found relative to that in isolate B-3501 . The mannose:xylose:glucuronic acid:O-acetyl molar ratio of Cap70 GXM is 3.00:1.73:0.78:1.75, while the same ratio for B-3501 and other serotype D isolates is approximately 3.00:1.00:0.80:1.75 . Methylation analysis confirmed that the GXM of Cap70 contains unsubstituted, monosubstituted (2-linked), and disubstituted (2- and 4-linked) mannose in a ratio of 0.87:1.75:0.38 . Dot blot immunoassay indicates that Cap70 is a serotype D isolate like its parent strain. Med Clin (Barc), 1996 Mar 16, 106(10), 380 - 2 {Pleural cryptococcosis in patients with human immunodeficiency virus infection}; Mauri M et al.; Four cases of pleural cryptococcosis as the form of onset of cryptococcosis in patients with human immunodeficiency virus (HIV) infection are reported . In two out of the four cases cryptococci were simultaneously isolated in other localizations (blood and meninges) . In the two remaining patients the pleura was the only site of the disease, with serum determination of the cryptococci antigen being negative in one . The four patients evolved favourably, with three being exclusively treated with fluconazol . Pleuritis is an infrequent manifestation in cryptococcosis although it may be the form of onset and the only localization of the disease . Only 10 cases have been reported in patients with HIV infection . The present four cases represent 11% of the authors' series of cryptococcosis in AIDS patients . The diagnostic possibility of cryptococcosis should be considered in patients with human immunodeficiency virus infection presenting pleural effusion. Ann Intern Med, 1996 Mar 15, 124(6), 585 - 99 The laboratory evaluation of opportunistic pulmonary infections; Shelhamer JH et al.; The patient population at risk for opportunistic pulmonary infections has increased during the last decade . The spectrum of organisms causing opportunistic infections has also grown . With an ever broader list of potential diagnosis, a specific diagnosis of the cause of pulmonary disease becomes more important . Recent microbiologic advances have helped to facilitate the laboratory diagnosis of some of these agents . Immunoassays are available for the detection of antigen in nasopharyngeal secretions (respiratory syncytial virus, influenza) in serum (Cryptococcus species), and in urine (Legionella or Histoplasma species) . Rapid-culture techniques are available for the culture and detection of various viruses, including cytomegalovirus . Molecular probes can now assist in the rapid identification of Mycobacterium tuberculosis and some fungi . In the near future, polymerase chain reaction-based techniques may assist in the detection of Pneumocystis carinii and Legionella, Chlamydia, Mycoplasma, and Mycobacteria species . An expeditious evaluation of pulmonary disease requires an understanding of the differential diagnosis of likely causes of pulmonary disease in specific immunosuppressed patient populations, an understanding of the most appropriate specimens to process for these diagnoses, and an understanding of the limitations (sensitivity and specificity) of these diagnostic tests . An understanding of the most appropriate specimens and tests in a given institution should allow for early, relatively specific treatment of many potentially life-threatening infections. J Assoc Physicians India, 1996 Mar, 44(3), 178 - 80 Cryptococcal meningitis in AIDS--need for early diagnosis; Aquinas SR et al.; Cryptococcal meningitis is the most common opportunistic fungal infection in patients with Acquired Immunodeficiency Syndrome (AIDS) contributing to the increased morbidity and mortality . This important infection in AIDS seems to be under diagnosed in India . We discuss the clinical features, laboratory diagnosis and therapy of seven cases of cryptococcal meningitis detected in our hospital . Diagnosis was established in all cases by identification of the fungus in cerebrospinal fluid (CSF) by India Ink preparation and positive fungal culture in CSF and/or Blood . Six patients were treated with Amphotericin B and Flucytosine . Two were cured and have not relapsed on suppressive therapy . Two died during treatment . Two were lost to follow up . All the three patients who died had positive fungal culture in blood and CSF . Presence of Cryptococcemia in Cryptococcal meningitis is an indicator of poor prognosis . A high index of clinical suspicion and routine mycological surveillance essential to identify this infection. J Antimicrob Chemother, 1996 Mar, 37(3), 617 - 22 Combination of 5-flucytosine and capsule-binding monoclonal antibody in the treatment of murine Cryptococcus neoformans infections and in vitro; Feldmesser M et al.; The efficacy of combination therapy with 5-flucytosine and an IgG1 monoclonal antibody to Cryptococcus neoformans capsular glucuronoxylomannan was studied in vitro with J774 . 16 murine macrophage-like cells and in vivo in murine cryptococcal infection . The combination of 5-flucytosine and IgG1 was more effective in reducing the numbers of C . neoformans colony-forming units in vitro and in vivo than either agent alone. Clin Diagn Lab Immunol, 1996 Mar, 3(2), 239 - 41 Immunological characterization of a recombinant 27-kilodalton antigenic protein from Paracoccidioides brasiliensis; Ortiz BL et al.; We report the expression in Escherichia coli of a 27-kDa antigenic protein from Paracoccidioides brasiliensis . When analyzed by immunoblotting, this recombinant antigenic protein was recognized by antibodies present in the sera of 40 of the 44 paracoccidioidomycosis patients studied . No cross-reactions were observed with sera from patients with other mycoses (histoplasmosis, aspergillosis, cryptococcosis, sporotrichosis, and chromoblastomycosis) or with tuberculosis. Mikrobiol Z, 1996 Mar-Apr, 58(2), 8 - 12 {Yeasts contaminating salmon roe}; Nagornaia SS et al.; Quantitative and species compositions of yeast contaminating eggs, fry and fingerlings of Salmo gairdneri Rich under artificial breeding have been studied . Prevalence of species of genera Candida, Rhodotorula, Cryptococcus and Debaryomyces is noted . Yeast isolated from perished eggs and sick fry do not possess pathogenic properties . Certain strains of yeast make stimulating effect on the studied microorganisms. Mikrobiol Z, 1996 Mar-Apr, 58(2), 12 - 5 {The yeast flora of blood-sucking mosquitoes}; Ignatova EA et al.; Yeast flora composition has been studied in natural populations of blood-sucking mosquitoes of genera Aedes . Anopheles and Culex dwelling in the territory of Ukraine . The authors have distinguished 18 yeast species belonging to 7 genera . Species Candida famata, C . (Yarrowia) lipolytica as well as the yeast of genera Rhodotorula and Cryptococcus dominate on the larvae and imago of mosquitoes . The distinguished strains are the components of normal microflora of blood-sucking mosquitoes and take no pathogenic effect on the laboratory culture of mosquitoes Aedes aegypti. J Dermatol, 1996 Mar, 23(3), 209 - 13 Disseminated cryptococcosis with cutaneous lesions; Mostafa WZ et al.; A case of disseminated cryptococcosis in an HIV-negative patient presenting with cutaneous lesions is described for the first time in Egypt . The patient, a 16-year-old male, presented with cough, expectoration, loss of weight, and cutaneous lesions, mainly on the face and trunk . The lesions consisted of vegetating crusted plaques discharging purulent to sanguinous fluid and flattened, shiny, erythematous to brownish plaques . Anorexia, headache and personality changes soon followed . Histopathological examination of lesions was highly suggestive of a deep mycosis, particularly cryptococcosis . The fulminant disease advanced with central nervous system involvement . The progression was not arrested when systemic antifungal therapy was administered late in the disease course . Pathological examination of lungs, liver, pancreas and spleen revealed disseminated infection with no evidence of other underlying pathology . Disseminated cryptococcosis is a morbid infection, rare in an area where heightened awareness and raised index of suspicion will surely allow earlier diagnosis, management and better prognosis. Zentralbl Bakteriol, 1996 Mar, 283(3), 360 - 74 Cryptococcosis associated with HIV negative Indian patients and HIV positive Indian blood donors; Khan ZK et al.; Cryptococcosis, particularly cryptococcal meningitis (CM), has become an increasing problem globally in the AIDS era . In the present investigation we have made an effort for the first time to study Indian cases (100) both HIV-positive (23 cases, male, mostly Indian professional blood donors, PBDs') confirmed by an ELISA test and Western Blot but asymptomatic for CM and HIV-negative (77:49 male and 28 female) asymptomatic or symptomatic . These subjects were patients from the Lucknow hospitals admitted during the period between February, 1991 to February, 1994, for suspected cryptococcosis or CM . Of those cases, 10% were positive for cryptococcosis or CM . Meningoencephalitis was the dominant clinical manifestation in four (HIV-negative) cases of CM . CT scanning of the head of those cases revealed a noncommunicating hydrocephalus due to aqueductal stenosis (in 2 cases) and a communicating hydrocephalus with granuloma (by MRI) in another case . The latex agglutination test (LAT) of the sera was positive for Cryptococcus antigen in 6 (26%) of the (HIV-positive) patients and 4 (5%), of the HIV-negative cases . In the cases of CM, there was a lower antigen titre in CSF than in the pronase-treated sera . The LAT was found to be useful in diagnosis of cryptococcosis, especially in asymptomatic cases . The CSF of CM-positive cases revealed low levels of glucose, reduced cell count and high proteins . Among the HIV-negative cases, the onset of meningitis in 4 cases was preceded by the presence of encapsulated budding yeast cells in CSF India ink smear, or cryptococci in a direct urine smear in one case . The CSF culture of 3 cases was positive for mucoid Cryptococcus neoformans, showing brown colour effect (BCE) on Staib agar (syn . Guizotia abyssinica creatinine agar, bird seed agar) . The isolated yeast strains were identified as C . neoformans var . neoformans by physiological tests . The pathogenicity test of strains revealed virulence to BALB/c mice evidenced by a high mortality of mice and significantly (p < 0.05) high CN burden (> 4-5 mean log(10) cfu), in the brain followed by other visceral organs (lung, liver, spleen, kidney and heart) . The in-vitro susceptibility (MIC mu gmL(-1)) of strains. Antimicrob Agents Chemother, 1996 Mar, 40(3), 822 - 4 In vitro susceptibilities of clinical and environmental isolates of Cryptococcus neoformans to five antifungal drugs; Franzot SP et al.; A total of 53 Cryptococcus neoformans strains, including clinical and environmental Brazilian isolates, were tested for their susceptibilities to amphotericin B, 5-flucytosine, ketoconazole, fluconazole, and itraconazole . The tests were performed according to the National Committee of Clinical Laboratory Standards recommendations (document M27-P) . In general, there was a remarkable homogeneity of results for all strains, and comparable MICs were found for environmental and clinical isolates . This paper represents the first contribution in which susceptibility data for Brazilian C . neoformans isolates are provided. Antimicrob Agents Chemother, 1996 Mar, 40(3), 541 - 5 Susceptibility of melanized and nonmelanized Cryptococcus neoformans to the melanin-binding compounds trifluoperazine and chloroquine; Wang Y et al.; Cryptococcus neoformans is an opportunistic fungal pathogen which becomes heavily melanized in the presence of phenolic substrates such as L-dopa . Various drugs are known to bind to melanin with high affinity, including the antipsychotic agent trifluoperazine and the antimalarial agent chloroquine . We hypothesized that drugs which bind melanin may have different toxicities for melanized and nonmelanized C . neoformans cells . The effects of trifluoperazine and chloroquine or C . neoformans were determined by measuring cell viability after exposure to these drugs . Cell viability was measured by CFU determination and flow cytometry with propidium iodide staining . Melanized cells were more susceptible than nonmelanized cells to the fungicidal effects of trifluoperazine . Chloroquine had no fungicidal effect on either melanized or nonmelanized C . neoformans under the conditions studied . Flow cytometry of trifluoperazine-treated C . neoformans cells stained with the mitochondrial stain dihydrorhodamine 123 revealed fluorescence changes consistent with mitochondrial damage . Our results indicate that melanized and nonmelanized C . neoformans cells can differ in susceptibility to certain drugs and suggest that strategies which target melanin may be productive for antifungal-drug discovery. Mycoses, 1996 Mar-Apr, 39(3-4), 129 - 33 Effects of Aspergillus sulphureus mycotoxins on Cryptococcus neoformans; Vidotto V et al.; Many studies have evaluated the toxicity of mycotoxins to mammals, but there is little information on their action against fungal cells, even although mycotoxins are frequently active against fungi in nature . A crude extract of Aspergillus sulphureus was tested for its growth-inhibitory effect on Cryptococcus neoformans . The reduction in cell growth of Cr . neoformans caused by the extract was dose dependent . Using a liquid medium containing 2% A . sulphureus extract, the RNA content of Cryptococcus amounted to about 60% of that of non-treated cells . Capsule thickening, demonstrated biochemically and with cytological stains, occurred at doses that had minimal effect on cell growth and RNA content . Our results suggest that the virulence of Cr . neoformans may increase in cases of coenobiosis with A . sulphureus, which is theoretically possible in places where corn-fed pigeons are numerous. Arq Bras Cardiol, 1996 Mar, 66(3), 129 - 33 {Pathology of the heart in AIDS . Study of 73 consecutive necropsies}; Politi Okoshi M et al.; PURPOSE: To study the incidence and the etiology of the cardiac lesions in AIDS patients . METHODS: The autopsy protocols and the filled slides of the heart from 73 consecutive AIDS patients were reviewed . There were, at least, 2 slides of each heart stained by haematoxylin-eosin; when indicated, Ziehl-Nielsen, Gram and Gomori Grocott stains were used . RESULTS: No cause of death was assigned to the heart . There was involvement of the heart in 66 (90%) cases . Marked atrophy of cardiac fibers with or without lipomatosis was observed in 38 patients . Interstitial infiltrates of myocardium were present in 38 necropsies and in 13 of these cases a probable pathogen was demonstrated: cryptococcus neoforms in three cases and mycobacteria tuberculosis, atypical mycobacteria, toxoplasma' gondii, trypanosoma cruzi and cytomegalovirus in two cases each . Bacterial endocarditis was found in 4 autopsies and Kaposi sarcome in one . The pericardium was involved in 22 cases; in 12 there was only non specific mononuclear infiltration . CONCLUSION: Autopsy examination of the heart from AIDS patients revealed frequent pathologic involvement. J Med Vet Mycol, 1996 Mar-Apr, 34(2), 127 - 31 Natural habitat of Cryptococcus neoformans var . neoformans in decaying wood forming hollows in living trees; Lazera MS et al.; Cryptococcus neoformans var . neoformans was repeatedly isolated from decaying wood forming hollows in living trees growing in urban areas of Rio de Janeiro, Brazil . A new natural habitat for C . neoformans var . neoformans has been found that is not associated with specific trees. J Med Vet Mycol, 1996 Mar-Apr, 34(2), 83 - 90 Expression of PZ-peptidases by cultures of several pathogenic fungi . Purification and characterization of a collagenase from Trichophyton schoenleinii; Ibrahim-Granet O et al.; Peptidolytic activity was studied in the broken-cell extracts of 17 isolates of pathogenic fungi tested with phenylazobenzyloxycarbonyl-Pro-Leu-Gly-Pro-Arg (PZ-PLGPA) as a substrate . All the fungi studied except Candida spp., Cryptococcus neoformans and two actinomycetes hydrolyzed the substrate and therefore contained a so-called PZ-peptidase activity . Of all the positive strains, Trichophyton schoenleinii, a pathogenic fungus showed the highest activity and was therefore chosen as a source for PZ-peptidase purification . The four chromatographic steps, a 'negative' dye column, a 'positive' dye column, hydroxyapatite Ultrogel, and modified TSK (HW 55), gave a highly purified peptidase with a 12% overall yield . Inhibitor studies suggested that the 82 000 M(r) PZ-peptidase is a metalloproteinase . Moreover it cleaved native rat type I collagen . Partial peptide sequencing showed a strong sequence homology to regions of two metalloproteinases previously identified in the yeast Saccharomyces cerevisiae and in rat. Infect Immun, 1996 Mar, 64(3), 945 - 51 Effects of interleukin-10 on human peripheral blood mononuclear cell responses to Cryptococcus neoformans, Candida albicans, and lipopolysaccharide; Levitz SM et al.; Deactivation of mononuclear phagocytes is critical to limit the inflammatory response but can be detrimental in the face of progressive infection . We compared the effects of the deactivating cytokine interleukin 10 (IL-10) on human peripheral blood mononuclear cell (PBMC) responses to lipopolysaccharide (LPS), Cryptococcus neoformans, and Candida albicans . IL-10 effected dose-dependent inhibition of tumor necrosis factor alpha (TNF-alpha) release in PBMC stimulated by LPS and C . neoformans, with significant inhibition seen with 0.1 U/ml and greater than 90% inhibition noted with 10 U/ml . In contrast, even at doses as high as 100 U/ml, IL-10 inhibited TNF-alpha release in response to C . albicans by only 50% . IL-10 profoundly inhibited release of IL-1beta from PBMC stimulated by all three stimuli . TNF-alpha mRNA and release was inhibited even if IL-10 was added up to 8 h after cryptococcal stimulation . In contrast, inhibition of IL-1 beta mRNA was of lesser magnitude and occurred only when IL-10 was added within 2 h of cryptococcal stimulation . IL-10 inhibited translocation of NF-kappaB in response to LPS but not the fungal stimuli . All three stimuli induced IL-10 production in PBMC, although over 10-fold less IL-10 was released in response to C . neoformans compared with LPS and C . albicans . Thus, while IL-10 has deactivating effects on PBMC responses to all three stimuli, disparate stimulus- and response-specific patterns of deactivation are seen . Inhibition by IL-10 of proinflammatory cytokine release appears to occur at the level of gene transcription for TNF-alpha and both transcriptionally and posttranscriptionally for IL-1beta. Acta Cytol, 1996 Mar-Apr, 40(2), 363 - 70 Atypical cytomorphologic appearance of Cryptococcus neoformans: a report of five cases; Williamson JD et al.; BACKGROUND: Cryptococcus neoformans is not generally recognized as producing pseudohyphae . Although atypical morphologic forms have been described in the microbiology literature, we believe this is the first complete cytologic report describing this uncommon and unusual cytologic appearance of cryptococcal infection . CASES: In five cases of cryptococcal infection, C neoformans formed chains of budding yeasts, pseudohyphae and germ tube-like structures . The atypical forms of C neoformans were seen in cerebrospinal fluid, imprints and in histopathologic sections from multiple organs from two human immunodeficiency virus (HIV)-positive patients; in pleural fluid from a patient with non-Hodgkin's lymphoma; in crush smears from a stereotactic biopsy of the brain; and in a fine needle aspirate of a lung nodule in two patients with no known risk factors for HIV infection . CONCLUSION: Recognition of atypical cytomorphologic variants of C neoformans is important since there are potential diagnostic pitfalls for confusing these atypical-appearing organisms with a Candida-type species or fungal contaminants . Special stains for capsular material and culture can be helpful in making a correct diagnosis. Acta Cytol, 1996 Mar-Apr, 40(2), 205 - 10 Relationship between cytomegalovirus cells and survival in acquired immunodeficiency syndrome patients; Lemert CM et al.; OBJECTIVE: To determine whether cytopathic changes due to cytomegalovirus (CMV) in human immunodeficiency virus-infected patients are prognostic . STUDY DESIGN: Three-month mortality was compared in three groups: 36 patients with positive CMV cytology, 38 with negative cytology but culture positive, and 40 with no evidence of CMV . Bronchoalveolar lavage, Papanicolaou-stained cytocentrifuge smears were quantitated using an average of two slides per case . Additionally, coinfection with Pneumocystis carinii and Cryptococcus neoformans was evaluated . RESULTS: There was a statistically significant increase in mortality at three months in CMV cytology-positive patients versus those with no evidence of CMV . Ten patients had quantitative CMV counts of less than 2, with a median survival of 3.0 months (range, 0.3-13.0); seven patients had counts of 2 or 3, with a median survival of 5.5 months (0.4-13.5); and 11 patients had CMV counts greater than 3, with a median survival of 7.2 months (0.3-14.0) . There was no significant difference between the groups . Coinfection was P Carinii (12) or C neoformans (2) showed no difference from patients without coinfection (chi2 = 0.81) . CONCLUSION: The presence of CMV cytopathic changes is associated with poorer survival, but an increased number of CMV-infected cells is not related to higher mortality. J Infect Dis, 1996 Mar, 173(3), 754 - 8 Identification by random amplification of polymorphic DNA of a common molecular type of Cryptococcus neoformans var . neoformans in patients with AIDS or other immunosuppressive conditions; Chen SC et al.; Sixty clinical isolates of Cryptococcus neoformans var . neoformans were analyzed by random amplification of polymorphic DNA (RAPD) using 12- to 22-mer primers in pairs . Five major profiles, which clearly distinguished between serotypes A (profiles I-III), AD (profile IV), and D (profile V), were identified . Forty-two of 58 serotype A isolates were assigned to profile I, 13 to profile II, and 3 to profile III . Profile I compromised 5 subtypes (profiles Ia-Ie), with 37 to 42 isolates in profile Ia . Twenty-seven of 28 isolates from patients with AIDS belonged to profile Ia (P<.001), as did 7 of 10 isolates from otherwise immunocompromised patients . Isolates from immunocompetent hosts were broadly distributed (profile I, 8 isolates; profile II, 10 isolates; profile III, 2 isolates) . RAPD profiles were independent of body site and geographic origin of isolates . Isolates pairs from 3 patients produced identical profiles . A predominant genetic profile among serotype A strains from AIDS patients has not been reported previously. Clin Exp Immunol, 1996 Mar, 103(3), 436 - 41 Enhancing effect of oxygen radical scavengers on murine macrophage anticryptococcal activity through production of nitric oxide; Tohyama M et al.; We examined the roles of reactive nitrogen intermediates (RNI) and reactive oxygen intermediates (ROI) in interferon-gamma (IFN-gamma)-induced cryptococcostatic activity of murine peritoneal macrophages using N(G)-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of RNI synthesis, and superoxide dismutase (SOD) and catalase, oxygen radical scavengers . IFN-gamma-activated macrophages produced nitric oxide (NO) in a dose-dependent manner, as measured by increased nitrite concentration in the culture supernatant . IFN-gamma also enhanced the suppressive effect on cryptococcal growth in a similar dose-dependent manner . The induction of killing activity and NO production by an optimal dose of IFN-gamma (100 U/ml) was virtually suppressed by 500 microM L-NMMA . These results confirmed the importance of the RNI-mediated effector mechanism in anticryptococcal activity of macrophages . SOD and catalase significantly enhanced the cryptococcostatic activity of macrophages induced by a suboptimal dose of IFN-gamma (20 U/ml) . The augmenting effect of these reagents was mediated by NO, since they potentiated the production of NO by macrophages and their effects were totally blocked by L-NMMA . Our results indicate that the IFN-gamma-induced anticryptococcal activity of macrophages is dependent mostly on RNI, and suggest that the ROI system down-regulates the effector mechanism for cryptococcostasis by suppressing the RNI system. Am J Clin Pathol, 1996 Mar, 105(3), 364 - 6 Predominance of neutrophils in the cerebrospinal fluid of AIDS patients with cytomegalovirus radiculopathy; Granter SR et al.; Cytomegalovirus (CMV) radiculopathy has been associated with both viral cytopathic inclusions and an increased number of neutrophils in the cerebrospinal fluid (CSF) of patients with AIDS . The significance of these findings is unknown . To evaluate this, the authors reviewed all CSF cytology specimens from patients with a history AIDS or HIV infection over a 9-year period . Of 193 specimens identified, 42 (22%) had neutrophils present . Neutrophils were rare (<6 per slide) in the majority of specimens (57%) . Occasional neutrophils (<2/hpf) were observed in three patients; one with suspected CMV myelitis, one with bacterial meningitis, and one with cryptococcal meningitis . All 6 cases (3 patients) with numerous neutrophils (>10/hpf) had positive CMV CSF cultures and symptoms of radiculopathy . Definite viral inclusions were not seen . The prognosis was poor in all cases . The authors conclude that diagnostic CMV inclusions are quite rare . However, the presence of elevated numbers of neutrophils in the CSF of a patient with AIDS without an identified infectious agent is highly suggestive of CMV radiculopathy. Transplantation, 1996 Feb 15, 61(3), 396 - 401 Pulmonary infections in liver transplant recipients receiving tacrolimus . Changing pattern of microbial etiologies; Singh N et al.; Pulmonary infections are a significant cause of morbidity after liver transplantation; Gram-negative bacilli, cytomegalovirus, and Pneumocystis carinii were the usual pulmonary pathogens in the earlier studies in liver transplant recipients receiving cyclosporine . We prospectively assessed the impact of pulmonary infection in 101 consecutive liver transplant recipients receiving the new immunosuppressive agent tacrolimus (FK506) . Fifteen percent (15/101) of the patients had 19 episodes of pneumonia; 58% (11/19) of the pneumonias were bacterial, 37% (7/19) were fungal, and 5% (1/19) were protozoal (Toxoplasma gondii) . Twenty-seven percent of the bacterial pneumonias were due to Legionella . None of the patients had cytomegalovirus or P carinii pneumonia . Seven percent (7/10) of the study patients had fungal pneumonitis; 4% had invasive aspergillosis and 3% had cryptococcosis . Mortality was significantly higher (53%, 8/15) for patients with pneumonia than for patients without pneumonia (10%, 9/86, P = 0.0004) . Only fungal pneumonias were the direct cause of death; 63% (5/8) of the deaths were in patients with fungal pneumonitis . Our data suggest a changing pattern of microbial etiologies of pneumonitis in the era of modern immunosuppressive agents . We show that P carinii pneumonia and cytomegalovirus can be effectively curtailed with appropriate prophylaxis . Fungal infections, on the contrary, not only constituted a major proportion of the pneumonia, but also carried the highest pneumonia-associated mortality . Legionella infections can be overlooked unless specialized laboratory methodology (cultured on selective media, urinary antigen) are applied routinely on all cases of pneumonia . We recommend routine culture on the water supply for Legionella in all transplant centers. J Formos Med Assoc, 1996 Feb, 95(2), 119 - 25 Etiology of lymphadenopathy in patients with AIDS in Taiwan; Hung CC et al.; From 1986 to 1995, we retrospectively reviewed the records of 40 of 125 patients (32.0%) with acquired immunodeficiency syndrome (AIDS) who presented with extrainguinal lymphadenopathy . Most of the patients had an advanced stage of HIV infection with a mean CD4 lymphocyte count of 44/mm3 . AIDS-defining opportunistic infections and malignancies were present in most patients and the neck region was the most common site of involvement . The etiology of lymphadenopathy was established in 26 patients . Tuberculous lymphadenitis was the most common cause, followed by lymphadenopathic Kaposi's sarcoma, benign reactive hyperplasia, cryptococcal lymphadenitis and disseminated Mycobacterium avium complex infection . Characteristic histopathologic findings were detected in 19 patients and 7 had presumptive tuberculous infections . The remaining 14 patients had no definitive etiology for their lymphadenopathy . As the causes are variable and the number of HIV/AIDS cases is increasing in Taiwan, more patients with lymphadenopathy, especially in the early stages of HIV infection will be encountered . Therefore, it is essential that diagnostic histopathologic and microbiologic studies be performed for appropriate and timely treatment. Clin Infect Dis, 1996 Feb, 22(2), 322 - 8 Identification of patients with acute AIDS-associated cryptococcal meningitis who can be effectively treated with fluconazole: the role of antifungal susceptibility testing; Witt MD et al.; No method currently exists to predict which patients with acute AIDS-associated cryptococcal meningitis can be effectively treated with fluconazole . The objective of this study was to determine the relationship of cryptococcal susceptibility to fluconazole, along with clinical variables, to the risk of treatment failure for patients with acute AIDS-associated cryptococcal meningitis . Results of in vitro fluconazole susceptibility testing of cryptococcal isolates and data from two clinical trials were analyzed . Susceptibility to fluconazole was determined by means of both microtiter and macrobroth (M27-P) dilution methods . Treatment was defined as successful if the patient was alive at 10 weeks and if a cerebrospinal fluid culture was sterile at that time . Seventy-six patients receiving fluconazole +/- flucytosine were included; therapy failed for 19 . Patients whose therapy failed were more likely to have a positive blood and urine culture and a higher titer in serum and cerebrospinal fluid of cryptococcal antigen, and the MIC of fluconazole against their isolates (as determined by the microtiter method) was more likely to be higher; they were less likely to have received flucytosine . Logistic regression modeling revealed that a negative blood culture, a low MIC of fluconazole (per the microtiter method), and treatment with flucytosine were factors independently associated with successful treatment. Clin Infect Dis, 1996 Feb, 22(2), 315 - 21 Amphotericin B lipid complex compared with amphotericin B in the treatment of cryptococcal meningitis in patients with AIDS; Sharkey PK et al.; The study objective was to obtain preliminary information regarding the safety and efficacy of amphotericin B (AmB) lipid complex (ABLC) in the treatment of AIDS-associated cryptococcal meningitis . Of 55 patients randomly assigned to 6 weeks of therapy with ABLC (1.2-5.0 mg/{kg.d}, with ascending doses for three sequential cohorts) or AmB (0.7-1.2 mg/{kg.d}), 46 received > or = 12 doses . Transfusion requirements, mean decreases in hemoglobin level, and mean increases in creatinine level were significantly greater with AmB than with ABLC . The total number of adverse events, infusion-related events, and occurrences of hypomagnesemia and hypokalemia associated with each form of therapy were similar . Among 21 recipients of ABLC at a dosage of 5 mg/kg (daily for 2 weeks and then thrice weekly for 4 weeks), symptoms and signs resolved for 18 (86%) . Of those receiving > or = 12 doses of ABLC, cultures converted to negative for 8 (42%), were undeterminable for 3 (16%), and remained positive for 8 (42%) despite resolution of symptoms . Although preliminary, these data suggest ABLC has significant activity in patients with AIDS-associated cryptococcal meningitis . Because this formulation has less hematologic and renal toxicity than does AmB, further evaluation of ABLC is warranted. J Clin Microbiol, 1996 Feb, 34(2), 466 - 70 Serotyping of Cryptococcus neoformans by dot enzyme assay; Belay T et al.; A method is described for the serotyping of Cryptococcus neoformans based on direct analysis of culture supernatants for the major type-specific capsular antigen, glucuronoxylomannan . Factor sera prepared by absorption of polyclonal rabbit antisera (Iatron Laboratories, Inc., Tokyo, Japan) or selected anti-C . neoformans monoclonal antibodies were used in a dot enzyme assay to detect the presence of antigen. FEMS Immunol Med Microbiol, 1996 Feb, 13(2), 123 - 30 Contribution of interferon-gamma in protecting mice during pulmonary and disseminated infection with Cryptococcus neoformans; Kawakami K et al.; In the present study, the role of interferon-gamma (IFN-gamma) in the host resistance against Cryptococcus neoformans was examined using a murine model of pulmonary and disseminated infection . In this model, mice were infected intratracheally with live yeast cells, and the histological changes in the lungs and the number of microorganisms in the lung and brain were compared in mice treated and untreated with anti-IFN-gamma monoclonal antibody (mAb) to define the contribution of endogenously synthesized IFN-gamma in the natural course of infection . Administration of this mAb reduced the accumulation of inflammatory cells in the alveolar septa, peribronchial and perivascular areas, and promoted the expansive growth of microorganisms in the alveoli and destruction of alveolar structure . The neutralization of endogenous IFN-gamma by mAb increased the number of microorganisms in the lung and brain, and significantly shortened the survival time of infected mice . On the other hand, administration of IFN-gamma decreased the number of microorganisms in these organs, and significantly extended their survival time . Considered together, our results suggest that endogenous IFN-gamma protects mice from infection with C . neoformans by inducing a cellular inflammatory response, potentiating the clearance of microorganism from the lungs and preventing its dissemination into the central nervous system. Enferm Infecc Microbiol Clin, 1996 Feb, 14(2), 101 - 5 {Primary cutaneous cryptococcosis and bacterial pneumonia caused by Pseudomonas aeruginosa in AIDS: clinical case and review of the literature}; Dronda F et al.; BACKGROUND: Clinically symptomatic infection due to Cryptococcus neoformans is found in 5-10% of patients with AIDS . It usually appears as meningitis with or without associated blood stream infection . In the last years, severe Pseudomonas aeruginosa infections in HIV (+) patients, with a high morbidity and mortality, are increasingly reported . MATERIALS AND METHODS: A 27 year-old male HIV (+) patient, with previous opportunistic infections, was referred because of a nodular lesion on his left wrist, with an axillar homolateral lymph node of long-term evolution . Cryptococcus neoformans var . neoformans was isolated in pure culture from the lesion . Disseminated infection or affection of other organs was ruled out . Therapy with intravenous amphotericin B was initiated, but the patient developed an early nosocomial bacteremic pneumonia due to P . aeruginosa with a fatal outcome . A review of the literature about both complications in AIDS is carried out . RESULTS: The fungal clinical picture is compatible with primary cutaneous cryptococcosis that is a rare condition (12 clinical reports until 1993), of which only one case report in an AIDS patient has been described in 1994 . Since 1990 severe infections due to P . aeruginosa in HIV(+) patients are increasingly reported, and pneumonias, bacteremias, catheter-related sepsis, urinary tract infections, intraabdominal infections, central nervous system and othorrhinolaryngologic infections have been described in patients with AIDS in the English-language literature . CONCLUSIONS: Primary cutaneous cryptococcosis is another rare form of infection with C . neoformans in patients with AIDS . The increasingly reported cases of severe infections due to P . aeruginosa could have important implications in the therapy of patients with AIDS. J Antimicrob Chemother, 1996 Feb, 37(2), 265 - 73 Antifungal susceptibility testing using the E test: comparison with the broth macrodilution technique; Chen SC et al.; The National Committee for Clinical Laboratory Standards reference broth macrodilution method for antifungal susceptibility testing was compared with the E test by testing 86 clinical isolates of Candida spp . and Cryptococcus neoformans . The MIC agreement rates for the two methods for Candida spp . were 73-89% within +/-1 doubling dilution and 87-100% within +/-2 dilutions . For C . neoformans, agreement within +/-1 dilution was > 70% for all the agents tested except fluconazole for which agreement was 35% . Our data support the further evaluation of the E test as an alternative method for antifungal susceptibility testing . However, E test MICs of fluconazole for C . neoformans, particularly C . neoformans var . gattii should be interpreted with caution, as falsely elevated MICs may occur. J Clin Invest, 1996 Feb 1, 97(3), 689 - 98 Cryptococcal polysaccharides induce L-selectin shedding and tumor necrosis factor receptor loss from the surface of human neutrophils; Dong ZM et al.; High titers of cryptococcal polysaccharides in the serum and spinal fluid and the lack of cellular infiltrates in the infected tissues are hallmarks of disseminated cryptococcosis . Cryptococcal polysaccharides given intravenously to mice inhibit the influx of leukocytes into sites injected with inflammatory mediators . The purpose of this investigation was to determine if cryptococcal polysaccharides, i.e., glucuronoxylomannan (GXM), galactoxylomannan, and mannoprotein, affect expression of molecules on the surface of neutrophils that are important in extravasation . GXM in the absence of serum was shown to induce human neurophils to shed L-selectin, a molecule needed in the first step of neutrophil movement into tissues . In the presence of serum, GXM caused a further shedding of L-selectin . Shedding of L-selectin was evident by reduced amounts of L-selectin on the neutrophils treated with GXM and by increased levels of soluble L-selectin in the GXM-treated neutrophil supernatants . GXM also stimulated neutrophils to have reduced expression of TNF receptor . In contrast, GXM-treated neutrophils showed increased levels of CD15 and CD11b, and unchanged CD16 expression . In the absence of serum, galactoxylomannan and mannoprotein did not affect L-selectin, TNF receptor, CD15, CD11b, or CD16 on neutrophils but did induce loss of L-selectin in the presence of serum . Our results indicate that cryptococcal polysaccharides, especially GXM, can cause shedding of L-selectin from the surface of neutrophils, and this may prevent neutrophils from attaching to the endothelial cell surfaces . Blockage of this early step in cell migration from the vessels into tissues may be responsible in part for reduced cellular infiltration into infected tissues of individuals with disseminated cryptococcosis. Transplantation, 1996 Jan 15, 61(1), 146 - 9 Cryptococcal meningitis after liver transplantation; Jabbour N et al.; We present our experience with 10 liver transplant recipients in whom cryptococcal meningitis developed after liver transplantation . Disease developed a median period of 3.5 months (range, 2-36 months) after transplantation and patients were diagnosed a median period of 9 days (range, 2-90 days) after initial symptoms . Headache, fever, and mental status changes were the most frequent clinical presentations, while meningismus was found in only 30% of patients . Cerebrospinal fluid analysis was diagnostic in all cases . All patients were treated with amphotericin B and flucytosine . Immunosuppression was either decreased or discontinued during therapy . Five patients died, four as a direct result of cryptococcal infection and one as a result of chronic rejection . Three patients had long-term survival without any sequelae . One long-term survivor suffered blindness consequent to the disease . We conclude that cryptococcal meningitis is a rare complication in liver transplant recipients (0.25%), and has a high mortality rate (50%) . Early recognition, combination antifungal therapy, and decrease or discontinuation of immunosuppression are important for cure . No relapse has been seen in surviving patients. Mycopathologia, 1996-97, 136(3), 119 - 23 Phospholipase activity in Cryptococcus neoformans; Vidotto V et al.; Phospholipases have only been detected in a few fungi and yeasts, in particular in Candida albicans . Secreted phospholipases are considered by some researchers to be a potential factor of virulence and pathogenicity in C . albicans . Twenty-three Cryptococcus neoformans strains were tested in order to observe phospholipase production . Twenty-two of the 23 strains tested were able to produce phospholipases, and the ratio diameter of the colony to total diameter of the colony plus zone of precipitation (Pz) ranged between 0.271 and 0.949 . C . neoformans, just like C . albicans, can be divided on the basis of the Pz into different strains according to their virulence and pathogenicity . There also appeared to be a correlation between the phospholipase production and the size of the capsule in the strains isolated from AIDS patients . For this reason, further studies on C . neoformans phospholipase activity would be useful in evaluating the virulence of different strains. Mycopathologia, 1996-97, 136(2), 75 - 84 Purification and characterization of fatty acid synthetase from Cryptococcus neoformans; Mahmoud YA et al.; Fatty acid synthetase has been purified from Cryptococcus neoformans 450 fold to a specific activity of 3.6 units per mg protein with an overall yield of 23% . The purified enzyme contained two non-identical subunits, Mr approximately 2.1 x 10(5) and 1.8 x 10(5) . Under optimum conditions, 100 mM KCl and pH 7.5, apparent K(m) values for the substrates were: Acetyl CoA, 19 microM; Malonyl CoA, 5 microM; and NADPH, 6 microM . Product inhibition patterns were determined to be: CoA, competitive versus acetyl CoA and malonyl CoA, uncompetitive versus NADPH; NADP, competitive versus NADPH, uncompetitive versus acetyl CoA and malonyl CoA; Palmitoyl CoA, competitive versus malonyl CoA, noncompetitive versus acetyl CoA and NADPH; Bicarbonate, uncompetitive versus malonyl CoA . These product inhibition patterns are consistent with the multisite ping-pong mechanism previously proposed for the avian fatty acid synthetase complex . The cryptococcal fatty acid synthetase was inhibited by the polyanionic polymers, heparin and dextran sulfate, an effect never before demonstrated for a fatty acid synthetase . This inhibition exhibited a marked dependence on the length of the polymer chain, with dextran sulfate fractions with Mr of 6 x 10(5) and above having Ki values below 100 nanomolar . A model is presented that involves initial binding of the anionic polymer to the enzyme complex at a region of high positive charge density, followed by interaction of the end of the tethered polymer with the catalytic site . This study represents the first purification of fatty acid synthetase from a basidiomycete. Mycopathologia, 1996, 136(1), 21 - 3 A rapid urease test for presumptive identification of Cryptococcus neoformans; Canteros CE et al.; A rapid method to evidence urease activity is described . Urea hydrolysis and consequent production ammonia are detected by a chemical reaction producing a blue phenol compound (indophenol blue) . Three hundred and three yeast were tested . Out of 107 urease-positive organisms detected by Christensen's Urea Agar Test (CUAT) 102 were positive by our method . No false negatives were observed by this method when testing 87 Cryptococcus strains . Ths practical screening test for presumptive identification of Cryptococcus neoformans is simple, unaffected by pH changes and requires 15 minutes to be performed. Mycopathologia, 1996, 136(1), 1 - 8 Anticryptococcal activity by alveolar macrophages from rats treated with cortisone acetate during different periods of time; Gross NT et al.; The effect of cortisone acetate (CA) treatment on the anticryptococcal activity by rat alveolar macrophages (AM) was investigated . The animals received a weekly dose of 5 mg CA during 1, 2, 3 or 4 weeks . Following the final dose the AM were collected by lung lavage and challenged with Cryptococcus neoformans . Parallel experiments with silica particles of a similar size were performed . The phagocytic function was assessed using a fluorescence method that distinguishes between attached and ingested particles . The oxidative metabolism was studied by the nitroblue tetrazolium (NBT) reduction test . The accumulated attachment (a measure of the attachment process) of cryptococci and silica particles per AM was significantly depressed after the third and fourth week of CA treatment . The ingested fraction (a measure of the ingestion process) of cryptococci but not of silica particles showed a small but significant decrease after the fourth week . The NBT reduction of the unstimulated AM and those stimulated with either the cryptococci or silica particles for 24 h was significantly reduced after the fourth week of treatment . In conclusion, these results demonstrate that high dose CA treatment primarily affects the attachment of the cryptococci to the AM and to a lesser extent also the ingestion process . In addition, it decreases the NBT reduction by AM in response to the yeast . The impairment of the AM anticryptococcal activity by high doses of CA constitutes a risk of dissemination of C . neoformans from the lungs. Folia Microbiol (Praha), 1996, 41(1), 43 - 7 Production of extracellular beta-mannanases by yeasts and yeast-like microorganisms; Kremnicky L et al.; A new screening method for simultaneous detection of endo-beta-1,4-mannanase and endo-beta-1,4-xylanase producing microorganisms is described . Two differently dyed substrates Ostazin Brilliant Red-galactomannan and Remazol Brilliant Blue-xylan were incorporated into the same agar media . Decolorizing of one or both substrates around the cell colonies indicates secretion of the corresponding enzyme(s) . The method was used to screen 449 yeasts and yeast-like microorganisms belonging to 68 different genera . The secretion of endo-beta-1,4-mannanases and/or endo-beta-1,4-xylanases was found within 10 genera (42 positive strains out of 261 tested) . A low frequency of occurrence of endo-beta-1,4-mannanases was observed within the genera Cryptococcus (1 positive strain out of 15 tested), Geotrichum (1 of 6) and Pichia (1 of 35) . The highest frequency of occurrence of endo-beta-1,4-mannanases was found within the genera Stephanoascus (2 of 2) and Aureobasidium (14 of 14) . Strains hydrolyzing Ostazin Brilliant Red-galactomannan were cultivated in liquid media containing 1% locust bean gum . The best producers of extracellualr endo-beta-1,4-mannanases were found to be the strains of Aureobasidium pullulans. Mycopathologia, 1996, 135(2), 75 - 8 Serotypes of Cryptococcus neoformans isolated from patients prior to and during the AIDS era in Thailand; Sukroongreung S et al.; One hundred and eighty-seven strains of Cryptococcus neoformans isolated from patients in Thailand were characterized by biochemical varieties relating to serogroups . Canavanine-glycine-bromothymol blue (CGB) agar was used for differentiating the varieties of C . neoformans . Slide agglutination tests were performed with Crypto Check (Iatron, Inc., Tokyo) to determine their serotypes . Fifty-five percent (10 out of 18) of the pre-AIDS isolates were serotype B, 28% were serotype A, 5% were serotype D, and an unexpected 11% (2 out of 18) were serotype C . These are the first to be recorded in Asia . In contrast, among the 169 clinical isolates obtained between January 1993 and March 1995 (AIDS epidemic), serotype A was outstandingly predominant--93% (157 out of 169), serotype B was relatively low (3.6%) and both serotypes D and AD were 1.8% . The pattern of serotypes of the 59 isolates from known HIV-positive patients was closely similar to the total isolates during the AIDS epidemic . In determining the varieties of C . neoformans by CGB, only 1 of the 187 isolates gave a false reaction . On the basis of our findings, we believe that in the pre-AIDS era either C . neoformans var . gattii serotype B or serotype C were the common causative agents of cryptococcosis in Thailand . The advent of AIDS changed the pattern of serotypes with serotype A becoming predominant as has been reported world wide. Retina, 1996, 16(6), 510 - 2 Retinal vascular nonperfusion and retinal neovascularization as a consequence of cytomegalovirus retinitis and cryptococcal choroiditis; Saran BR et al.; BACKGROUND: Cytomegalovirus retinitis and cryptococcal choroiditis are opportunistic infections in patients with acquired immune deficiency syndrome . These infections are associated with a retinal vasculitis and vascular attenuation . METHODS: We present a case of retinal vascular nonperfusion and retinal neovascularization in a patient with acquired immune deficiency syndrome . RESULTS: Retinal vascular nonperfusion and retinal neovascularization were confirmed by fluorescein angiography . CONCLUSIONS: This is the first reported case of retinal neovascularization in a patient with acquired immune deficiency syndrome, ocular cytomegalovirus retinitis, and cryptococcal infection. Clin Neuropathol, 1996 Jan-Feb, 15(1), 30 - 3 Microglial nodule encephalitis: limited CNS infection despite disseminated systemic cryptococcosis; Edelman M et al.; A 28-year-old patient with AIDS was found at autopsy to have disseminated cryptococcal infection involving the lungs, spleen, lymph nodes, kidneys, gastrointestinal tract, thyroid, bone marrow, and liver . Despite widespread organ dissemination the patient did not have clinical or pathological evidence of meningitis . Microscopic examination of the brain showed cryptococci limited to the brainstem and basal ganglia; microglial nodules with multinucleate giant cells, a histological hallmark of HIV-1 encephalitis, were shown to contain Cryptococcus neoformans . This feature may suggest a form of synergism between HIV-1 and Cryptococcus neoformans . This case demonstrates an unusual form of cryptococcal neurotropism with limited CNS involvement. Mycopathologia, 1996, 134(2), 61 - 4 Cryptococcus neoformans var . gattii among patients with cryptococcal meningitis in Mexico . First observations; Lopez-Martinez R et al.; A retrospective study of 20 patients with cryptococcal meningitis and their isolated strains was performed . Cryptococcus neoformans var . neoformans was recovered from 14 (70%) cases, and var . gattii was recovered from six (30%) patients . Twelve patients had AIDS (all carrying var . neoformans), two had other diseases (one with var . neoformans and one var . gattii) and there was no identifiable underlying disease in six (one var . neoformans and five var . gattii) . Fourteen patients (11 var . neoformans and three var . gattii) resided in the Mexico City area, where a temperate climate is prevalent, and there were six cases (three var . neoformans and three var . gattii) from states with a tropical/subtropical climate . Although there was no significant statistical difference between the two varieties, the fatal outcome was higher in patients with var . neoformans . The disease caused by var . gattii strains was characterized by a higher opening pressure, more inflamatory changes of CSF and a longer clinical course (delayed clinical and mycological cure) . Cryptococcus neoformans var . gattii is a significant cause of cryptococcal meningitis in patients without underlying diseases in Mexico. Rev Med Panama, 1996 Jan-May, 21(1-2), 46 - 50 {Cryptococcus neoformans meningitis in patients with AIDS at the Saint Thomas Hospital}; Sierra LO et al.; The authors studied the clinical histories of 17 patients with AIDS who were hospitalized with the diagnosis of Meningoencephalitis . Laboratory studies showed the causative agent to be Cryptococcus neoformans . All patients had fever and most had localized headache . Some patients had nausea and vomiting, nuchal rigidity and convulsions . One each had blurred vision, photophobia, periods of disorientation, ataxia, lumbar or cervical pain . Cell count, chemical analysis, India ink preparation and culture of the cerebrospinal fluid confirmed the diagnosis and the etiologic agent . Blood cultures were negative in the few patients on whom it was performed . The best results of therapy were obtained in the patients who received Amphotericin B and Fluocytosine (80%) in dosages of 0.3 to 1 mg/k/day and 150 mg/day respectively, for 21 days. Rev Med Interne, 1996, 17(9), 754 - 60 {Epidemiology of invasive mycoses . Experience of a university hospital center in Paris}; Hennequin C; The incidence of opportunistic fungal infections have dramatically increased during the past decades . Data from a retrospective study conducted between January 1992 and December 1994 in Necker-Enfants Malades Hospital and a review of the literature were analyzed to assess the main epidemiological features of these infections . Candidiasis remained largely the most frequent: candidemia and invasive candidiasis were diagnosed in respectively 71 and 11 patients . Candida albicans was the agent the most frequently isolated from these infections . However, its percentage was not over 49.35% in our experience . In at least 13 of 27 cases, candidemia could be related to a colonized indwelling catheter . Though less frequent (24 cases), invasive aspergillosis is of major concern considering its mortality . A wider clinical spectrum was observed with sub-necrotizing aspergillosis reported in non-neutropenic immunocompromised patients (five cases) and invasive aspergillosis in AIDS patients (two cases) . Among the 14 cases of cryptococcosis, 11 were diagnosed in AIDS patients whereas the other three were observed in renal transplant recipients . Beside these three major fungal infections, deep immunosuppression, notably induced by bone marrow transplantation, favored the emergence of newly fungal opportunistic agents such as Fusarium sp (two cases), Scedosporium apiospermum (one case) and Trichosporon sp (one case). Adv Exp Med Biol, 1996, 404, 535 - 46 Saponins as antimycotic agents: glycosides of medicagenic acid; Zehavi U et al.; The continuous search for new antimycotic drugs is a consequence of the broad use of immunosuppressive drugs and broad-spectrum antibiotics, high number of AIDS patients, and widespread dermatophyte infections . The concern with increased resistance due to widespread and prolonged antifungal treatment, particularly with azoles, is noteworthy . Our efforts were focused on medicagenic acid derivatives isolated from alfalfa and on semisynthetic ones . In general, these materials exhibited potent fungistatic effects against several plant pathogens and human dermatophytes . Furthermore, they were fungicidal against medically important yeasts, showing a most impressive activity against Cryptococcus neoformans, the minimal fungicidal concentration (MFC) value of the gluco derivative of medicagenic acid, compound G2, is 4 micrograms/ml . The mode of action as well as the structure-activity relationships of these compounds were studied . Compound G2, when applied topically, was effective in curing skin lesions of guinea pigs infected with the dermatophyte Trichophyton mentagrophytes and good skin tolerance to the drug was noted . Furthermore, it had a life-prolonging effect on mice infected with C . neoformans and recently, liposomes containing compound G2 were used efficiently as a drug delivery system in treatment of murine cryptococcosis and candidiosis. Rev Clin Esp, 1996 Jan, 196(1), 4 - 8 {Fever of unknown origin in patients infected with the human immunodeficiency virus}; Carbonell Biot C et al.; BACKGROUND: To describe the clinical features and the final diagnosis of patients infected with human immunodeficiency virus who presented fever of unknown origin . METHODS: Retrospective study, from November 1989 to January 1994, of all patients infected with HIV who had fever of unknown origin and who were admitted to a community hospital in a Mediterranean area in Alicante (Spain) . Fever of unknown origin was defined as fever exceeding 38.3 degrees C lasting for at least three weeks with no diagnosis in the first three days of hospitalization after fulfilling clinical exam, three blood cultures, acid-fast bacilli stain in sputum and chest-X-ray . RESULTS: Of a cohort of 231 patients, 27 (12%) were evaluated because of fever of unknown origin during their follow-up . Patients' mean age was 31 years (interval, 22-75) and intravenous drug use (81%) was the most common risk factor for HIV infection . A total of 31 episodes of fever of unknown origin were reviewed . Twenty-three (74%) episodes occurred in patients with less than 200 CD4 lymphocytes/mm3 . A final diagnosis of fever of unknown origin was achieved in 24 (77%) episodes: visceral leishmaniasis (n = 11), tuberculosis (n = 9), non-Hodgkin's lymphoma (n = 1), CNS toxoplasmosis (n = 1), cryptococcal meningitis (n = 1) and drug adverse reaction (n = 1) . CONCLUSIONS: HIV-infected patients with fever of unknown origin very often show severe immunodeficiency . Cryptococcal antigen testing should be carried out in the initial evaluation of fever of unknown origin in HIV-infected patients . In our area, 64% of episodes of fever of unknown origin were caused by visceral leishmaniasis or tuberculosis. Mycopathologia, 1996, 133(3), 139 - 42 A vitamin-free minimal synthetic medium for Cryptococcus neoformans; Vidotto V et al.; The use of a simple synthetic medium is essential for study on the growth and physiology of Cryptococcus neoformans . In the present study, a minimal synthetic liquid medium (MSM) was tested for the growth of 23 C . neoformans strains . This medium contained a low concentration of glucose, ammonium sulphate and inorganic salts with a pH value of 4.5, but no amino acids or vitamins . The strains were starved for 4 days to eliminate nutrients which might have been carried over from their pre-culture medium . Then, they were inoculated in the MSM as an initial OD of 0.020 at 550 nm and incubated at 37 degrees C for 20 days . Cell growth was generally monitored daily by measuring the absorbance at 550 nm . The medium supported the growth of the strains tested and gave an average final OD of 0.500 . The results obtained indicate that C . neoformans may be autotrophic with respect to vitamins and in particular to thiamine . The MSM medium is easy to prepare and store . It is highly reproducible and useful for studies on the growth and physiology of C . neoformans. Drugs Exp Clin Res, 1996, 22(1), 25 - 8 Oral fluconazole in the treatment of pulmonary cryptococcosis in non-AIDS patients; Yew WW et al.; Four non-AIDS patients with pulmonary cryptococcus infection who could not tolerate amphotericin B treatment were given oral fluconazole at a dose of 600 mg once daily for 4-5 weeks followed by 400 mg once daily for 10-12 weeks resulting in cure . All patients did not have relapse of disease when followed-up for 8-24 months after cessation of treatment . The very good tolerance of oral fluconazole by these patients suggests that such effective monotherapy should be evaluated further in non-AIDS patients with pulmonary cryptococcosis. Clin Infect Dis, 1996 Jan, 22(1), 81 - 5 Lung abscess in patients with AIDS; Furman AC et al.; We identified 31 patients with human immunodeficiency virus (HIV) infection and lung abscess . All patients had advanced HIV disease, and the mean CD4 cell count was 17/mm3 (range, 2-50/mm3) . Twenty-two patients (71%) had previous opportunistic infections, and 24 (77%) had previous pulmonary infections . Symptoms at the time of presentation included fever (90% of patients), cough (87%), dyspnea (35%), pleuritic chest pain (26%), and hemoptysis (10%) . The microbiological etiology was established for 28 patients, and the pathogens recovered were bacteria (65%), Pneumocystis carinii (6%), fungi (3%), and mixed microorganisms (16%) . The pathogens included Pseudomonas aeruginosa (11), Streptococcus pneumoniae (6), P . carinii (5), Klebsiella pneumoniae (5), Staphylococcus aureus (4), Aspergillus species (3), viridans streptococcus (2), Haemophilus influenzae (1), Streptococcus milleri (1), Proteus mirabilis (1), and Cryptococcus neoformans (1) . Mycobacterium tuberculosis was not isolated; two patients for whom a microbiological etiology was not established responded to antituberculous therapy . Patients were treated for 2-12 weeks; 25% of the patients received > 4 weeks of therapy . The outcome was poor: 36% of the patients had recurrences, and 19% died . In patients with AIDS, lung abscess is associated with advanced HIV infection, is due to a broad spectrum of pathogens, responds poorly to antibiotics, and has a poor prognosis. Dermatol Clin, 1996 Jan, 14(1), 113 - 24 Yeast infections; Hay RJ; Yeasts are unicellular fungi that reproduce by the process of budding in which daughter cells are produced from parents by outpouching of the cell membrane and wall, migration of cytoplasm into the new structure thus formed, and then separation from the parent cell . Yeasts that are pathogenic in humans range in size from 2 to 12 microns in diameter; most, therefore, can be engulfed by phagocytic cells . These pathogens include many of the best known of pathogenic fungi, such as the Candida species, Cryptococcus neoformans, and the lipophilic yeasts of the genus Malassezia. Mycopathologia, 1996, 133(3), 149 - 58 Intravascular granuloma induced by intravenous inoculation of Cryptococcus neoformans; Yamaoka H et al.; In rodents an intravenous administration of viable Cryptococcus (C.) neoformans cells frequently resulted in attachment of intravascular cryptococcal granulomas to inner walls of the large to medium-sized veins of various organs, including the lungs, liver and spleen . In order to elucidate the pathogenesis of granulomatous changes, the cells composing the intravascular granulomas were observed by electron microscopic peroxidase (PO) cytochemistry . The granuloma composing cells could be divided into the following four types according to the pattern of endogenous peroxidase activity: exudate macrophage (M phi, type I), PO-negative M phi (type II), resident M phi (type III) and other inflammatory cells (type IV) . In the intravenous granulomas of the lung, the percentages of composed cells were 39.0% for type I, 57.9% for type II, 0% for type III and 3.1% for type IV . By contrast, in the interstitial granulomas in the lung, type III M phi s, possibly derived from alveolar M phi s, played a significant role in granuloma formation . This may indicate that the intravascular granuloma is almost composed of macrophages derived from monocytes rather than alveolar macrophages . The expression of ICAM-1 on endothelia of the pulmonary veins was examined by immunoelectron microscopy . An immunogold labeling index was significantly augmented on the surface of endothelia in response to intravenous challenge of C . neoformans . The intravascular granuloma demonstrates that the monocytes develop into the granuloma-composing macrophages and suppress the cryptococcal activities even in the peripheral blood resulting in an assistance of endothelial functions. Mycoses, 1996 Jan-Feb, 39(1-2), 25 - 30 Universal fungus-specific primer systems and group-specific hybridization oligonucleotides for 18S rDNA; Kappe R et al.; We designed two primer systems that amplify a fragment of the gene coding for the small ribosomal subunit (18S rRNA) . A broadly reactive, yet fungus-specific, primer cocktail comprises two previously published primers, TR1 and TR2, which specifically amplify dermatophytes, and two newly designed primers, CA1 and AF2, which specifically amplify Candida and Aspergillus respectively . This primer cocktail amplifies a DNA fragment of approximately 578 basepairs (bp) in length (from position 838 to 1415), which contains variable, possibly species-specific regions (V5, partly V7) . Another newly designed primer, UF1 (universal fungal primer 1), along with the eukaryotic primer S3 amplifies a 926-bp fragment (from position 263 to 1188) that includes the variable regions V3, V4 and V5 . Both primer systems amplified DNA from Saccharomyces cerevisiae, Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, Penicillium marneffei, Fusarium oxysporum and Trichophyton mentagrophytes, but not the DNA from Prototheca zopfii, Escherichia coli or humans . The previously published oligonucleotides TR and HC, which are specific for dermatophytes and Histoplasma respectively, and the newly designed group-specific oligonucleotides, CA and AF, hybridized with T . mentagrophytes, Histoplasma capsulatum, C . albicans and A . fumigatus respectively, but not with the other six fungi or with the three controls. J Med Vet Mycol, 1996 Jan-Feb, 34(1), 19 - 30 Cryptococcal capsular polysaccharide utilizes an antigen-presenting cell to induce a T-suppressor cell to secrete TsF; Blackstock R; A T-T hybridoma (F6.6.2) which secretes a T-suppressor factor (TsF) specific for cryptococcal capsular polysaccharide (glucuronoxylomannan, GXM) was tested to determine if antigen-presenting cells (APC) were necessary for activation of the hybridoma to secrete TsF . Normal, syngeneic spleen cells were required along with GXM before TsF could be detected in culture supernatants . Ts cells did not secrete TsF unless the APC were obtained from mice which were identical at the "so-called' I-J sublocus as defined by the difference between B10.A(3R) and B10.A(5R) mice . The APC was adherent and could be depleted from spleen cell suspensions by treatment with anti-I-J and complement but not anti-I-A and complement . Additionally, treatment with anti-T cell serum or anti-immunoglobulin and complement did not remove the APC function of the spleen cell population . A role for I-E antigens in the function of the APC was determined by blocking antigen presentation to the suppressor cell with anti-I-E antibodies . The polysaccharide was associated with splenic adherent cells as extensive washing of the APC after incubation with GXM did not eliminate the antigen presenting function of the population. Clin Diagn Lab Immunol, 1996 Jan, 3(1), 89 - 92 Production of agglutinating monoclonal antibody against antigen 8 specific for Cryptococcus neoformans serotype D; Ikeda R et al.; A hybridoma (clone CRND-8) that produced agglutinating monoclonal antibody (MAb) against Cryptococcus neoformans serotype D was established by using a soluble capsular polysaccharide-keyhole limpet hemocyanin conjugate for immunization . The isotype was immunoglobulin M(kappa) . Specificity was determined by cell slide agglutination and enzyme-linked immunosorbent assay (ELISA) . In both tests, the MAb reacted to serotypes D and A-D but not to serotypes A, B, and C . Furthermore, the specificity of the MAb determined by ELISA was the same as that of polyclonal antibody factor serum (PAb factor) 8, which showed high-level reactivity with serotypes D and A-D . These results supported the deduced specificity of the PAb-based antigenic factor 8 . A total of 15 isolates of serotypes D and A-D but no serotype A isolates reacted with the MAb in cell slide agglutination tests . CRND-8 MAb can be used in place of PAb factor 8 for serotyping C . neoformans isolates and for the analysis of the antigen 8 epitope. AJNR Am J Neuroradiol, 1996 Jan, 17(1), 110 - 3 Intraventricular cryptococcal cysts; Vender JR et al.; The case of a 55-year-old immunocompetent woman with central nervous system cryptococcosis and multiple intraventricular cysts is presented . The cysts did not enhance on MR and had signal characteristics similar to cerebrospinal fluid on T1- and T2-weighted images; their intensity was lower than cerebrospinal fluid on proton density-weighted images. Med Trop (Mars), 1996, 56(1), 63 - 5 {AIDS-related cryptococcal meningitis at the Bobo-Dioulasso Hospital Center: five case reports}; Ki-Zerbo GA et al.; The authors report five cases of Cryptococcus neoformans meningitis in HIV-positive patients hospitalized in the Souro Sanou National Hospital Center of Bobo-Dioulasso (Burkina Faso) . There were 3 men and 2 women with a mean age of 36 years (range: 29 to 47 years) . Presenting symptoms were persistent headache and/or mental confusion and neurosensory defects . Cerebrospinal fluid was clear with less than 20 lymphocytes/mm3 . Albumin concentration greater than 0.50 g/l was observed in only one case . India ink smear and culture demonstrated strains of Cryptococcus neoformans sensitive to amphotericin B in all five cases, flucytosin in 3 cases, and ketoconazole in two cases . Four patients died within 15 to 32 days after admission (mean 22.5 days) . Delayed diagnosis and inconsistent availability of systemic antifungal drugs are major limiting factors in the management of Cryptococcus neoformans meningitis in Burkina Faso. Mycoses, 1996, 39 Suppl 1, 113 - 7 {Studies on the ecological behavior of Cryptococcus neoformans}; Kielstein P; Tenacity studies of Cryptococcus neoformans in bird droppings originated from different ornamental birds and chickens showed that there is less chance for this fungus species to survive in non-sterile or bacteria-free droppings of large parakeets and chickens in comparison with droppings of small parakeets . Survival rates of Cr . neoformans in buffer solutions with pH-values ranging from 8.5-9.5 allow to conclude that this species is not alkali-sensitive . Therefore, the increase of pH is not regarded responsible for the survival of Cr . neoformans in bird droppings . Possibly fungistatic substances present in droppings are involved. Mycoses, 1996, 39 Suppl 1, 97 - 101 {Lethal meningeal encephalitis from Cryptococcus neoformans var . neoformans in a girl without serious immunodeficiency}; Wendisch J et al.; Case report on a lethal meningo-encephalitis due to Cryptococcus neoformans in a 14-year-old girl without serious immunodeficiency inclusive HIV-infection . The detection of high quantities of cells of Cryptococcus neoformans (about 10,000/ml) and high levels of Cryptococcus antigen (up to 1:2048) in the cerebrospinal fluid are remarkable . The patient was treated with a triple combination of amphotericin B, flucytosine and fluconazole . After 18 days the cerebrospinal fluid was sterile . Nevertheless considerable lesions of the brain arised . The patient died from the Cryptococcus infection on day 74 of the antimycotic therapy . Cryptococcosis should be included into the differential diagnosis of the chronic lymphocytic pleocytosis of the cerebrospinal fluid connected with symptoms of intracranial pressure and ocular symptoms. Mycoses, 1996, 39 Suppl 1, 94 - 6 {Osteomyelitis from Cryptococcus neoformans}; Hummel H et al.; A forty-three-year old patient suspected of having a bone tumor in his left femur, was submitted to the hospital . However, osteomyelitis caused by Cryptococcus neoformans has been demonstrated by culture . The history of the patient revealed a long-term therapy with corticosteroids due to sarcoidosis . The osteomyelitis was treated with fluconazole (200 mg daily p.o.) for three months . Under this therapy the infection resolved. Mycoses, 1996, 39 Suppl 1, 51 - 4 {Are there pathogenicity factors in fungi?}; Morschhauser J et al.; Since many years so-called pathogenicity or virulence factors of pathogenic bacteria have been studied intensively . Whereas these factors are produced especially by obligate but also facultative pathogenic bacteria, their presence and function in pathogenic fungi is still a matter of debate . In this minireview we summarize some data about possible pathogenicity factors of Cryptococcus neoformans, Aspergillus fumigatus and Candida albicans . The production of adhesins, proteases and capsules contributes to the virulence of these fungi . As fungal infections usually affect immunocompromised patients, the immune status of the host plays a decisive role in addition to the virulence factors produced by fungi. Mycoses, 1996, 39 Suppl 1, 26 - 9 {Fungi in the home and hospital environment}; Staib F; From the viewpoint of 40 years of experience in the field of medical mycology with the help of current topics the competence of the medical mycologist for evaluation of a presence of fungi in the home and hospital environment is commented . The topics considered are as follows: 1 . The HIV-infected person and the habitat of Cr . neoformans; the predisposition for cryptococcosis and the CD4 lymphocyte count . 2 . Invasive aspergillosis after heart transplantation; by exemplary cooperation between the heart surgeon and the medical mycologist it could be demonstrated that the frequently fatal invasive aspergillosis can be avoided . 3 . Attention is drawn to the currently most interesting habitats of fungi in the home environment, i.e., biological waste and compost . It has been shown that among the various fungi, the causative agents of systemic mycoses may also be found. Mycopathologia, 1996, 133(2), 71 - 7 Study of the role of iron in the anticryptococcal activity of human serum and fluconazole; Grover DD et al.; Anticryptococcal activity of human serum and apotransferrin in RPMI 1640 was studied in vitro . The effects of varying concentrations of FeCl3 on this activity was investigated . Possible synergy of serum and apotransferrin with fluconazole was also measured . The fungistatic activity of human serum, whether lyophilized, stored at 4 degrees C, fresh frozen or purchased from commercial sources vs . Cryptococcus neoformans was comparable . There was no significant loss of fungistatic activity after freezing and thawing the serum up to 10 times . The fungistatic activity of human serum was similar when tested in different tissue culture media with the exception of Medium 199 . The addition of apotransferrin (2.0 or 0.2 mg/ml) to RPMI 1640 had an inhibitory effect on cryptococcal growth . This effect was reversed by 20 microM, of FeCl3 at both apotransferrin concentrations . By contrast, addition of FeCl3 to human serum and RPMI 1640 did not reverse inhibition of growth . Fluconazole synergized with the human serum preparations described, but not with pooled commercial serum, for fungicidal activity . Synergistic activity of fluconazole and human serum was not affected by the addition of FeCl3 . Apotransferrin did not show any synergistic fungicidal activity with fluconazole. Mycopathologia, 1996, 133(2), 65 - 9 Cryptococcosis as an opportunistic infection in immunodeficiency secondary to paracoccidioidomycosis; Benard G et al.; We describe the case reports of two patients with immunodeficiency secondary to paracoccidioidomycosis (PCM) and opportunistic Cryptococcus neoformans infections . Secondary immunodeficiency likely occurred as a consequence of the intestinal loss of proteins and lymphocytes associated with malabsorption syndrome due to obstructed lymphatic drainage . Both patients had had severe abdominal involvement during the acute PCM disease . Immunological evaluation showed cellular and humoral immunity impairment . Cryptococcosis manifested as relatively well circumscribed lesions: osteolytic lesions of the skull in one patient, and pulmonary nodules in the other . The latter was treated surgically and with amphotericin B, whereas the other was treated with the combination amphotericin-B and flucytosine . Both patients had a good response to treatment with complete regression of the lesions . They have now 2 and 4 years of follow-up with maintenance therapy and no indication of reactivation of the infection . PCM also did not reactivate . The clinical and immunological characteristics of these patients are discussed and compared to the opportunistic C . neoformans infections of AIDS and transplant patients. J Clin Microbiol, 1996 Jan, 34(1), 218 - 21 D-mannitol in cerebrospinal fluid of patients with AIDS and cryptococcal meningitis; Megson GM et al.; Cryptococcal meningitis (CM) is associated with raised intracranial pressure which is linked with serious neurological sequelae . Cryptococcus neoformans produces D-mannitol in vitro and in experimental meningitis in rabbits . Mannitol present in the cerebrospinal fluid (CSF) of CM patients could exacerbate raised intracranial pressure and contribute to neurological damage . To link CSF mannitol to cryptococcal infection, levels of mannitol in the CSF of AIDS patients with CM were measured by gas-liquid chromatography . Mannitol was detected in 19 of 21 samples (range, 1.5 to 26.2 mg/liter), but there was no quantitative correlation between the mannitol concentration and the cryptococcal antigen titer. Br J Dermatol, 1996 Jan, 134(1), 159 - 63 Cutaneous Pneumocystis carinii and Cryptococcus neoformans in AIDS; Sandler B et al.; A patient with AIDS was found to have skin lesions which contained the organisms Pneumocystis carinii and Cryptococcus neoformans . Both organisms were identified using haematoxylin and eosin, Gomori methenamine silver, Giemsa and mucicarmine stains . Electron microscopy was performed and confirmed their presence . The clinical presentation, histopathology, differential diagnosis and treatment of cutaneous P . carinii and C . neoformans in AIDS is presented. Trans R Soc Trop Med Hyg, 1996 Jan-Feb, 90(1), 57 - 60 Meningitis caused by Cryptococcus neoformans var . gattii and var . neoformans in Papua New Guinea; Laurenson IF et al.; Eleven cases of cryptococcal meningitis were diagnosed and biotyped from September 1991 to August 1992 in Papua New Guinea (PNG) . Seven isolates were Cryptococcus neoformans var . gattii from paediatric and adult patients, one with diabetes mellitus and 4 were C . neoformans var . neoformans from adults, of whom 2 had human immunodeficiency virus type 1 (HIV-1) infection, and one each had tuberculosis and Plasmodium vivax malaria . Significant clinical findings were headache, fever, meningism, vomiting, photophobia, papilloedema and cranial nerve lesions . Five pa