Optom Vis Sci, 1995 May, 72(5), 312 - 9 Non-CMV infectious chorioretinopathies in AIDS; Litwak AB; Cytomegalovirus (CMV) retinitis is the most common posterior segment opportunistic infection and the leading cause of blindness in acquired immunodeficiency syndrome (AIDS) patients . CMV is not the sole agent that can infect the fundus of an immunocompromised patient . Disseminated herpes zoster (HZ), herpes simplex, toxoplasmosis, and Candidiasis are possible . Syphilis, Pneumocystis carinii, cryptococcosis, tuberculosis, and a host of other viruses, protozoa, bacteria, or neoplasms may invade the retina or choroid . The eye care practitioner must not only differentiate noninfectious retinopathy (AIDS retinopathy) from CMV retinitis, but also distinguish CMV retinitis from other posterior segment infections because the treatment modalities are different . This paper will review the clinical features of non-CMV infectious retinopathies and choroidopathies that occur in AIDS patients. J Med Vet Mycol, 1995 May-Jun, 33(3), 151 - 6 Iron acquisition by Cryptococcus neoformans; Vartivarian SE et al.; Iron is an essential element for the growth and metabolism of microbial cells . Most pathogenic microbes elaborate powerful iron chelating agents (siderophores) to mobilize iron from ferric ligands . The pathogenic yeast, Cryptococcus neoformans has not been found to produce siderophores and its mechanism of iron acquisition is unknown . This investigation explored an alternative pathway for iron acquisition by examining the interactions of iron with the cell surface . Iron uptake experiments were conducted utilizing radiolabelled ferrous iron and ferric iron chelates, with evidence for the presence of iron(II) receptors and the generation of ferrous iron by surface reduction . Hyperbolic kinetics were found when 59FeII was presented to the organism and uptake was blocked with bathophenanthroline sulphonate, an Fe2+ chelator . The yeast also acquired iron as {59Fe3+}-citrate and {59Fe3+}-pyrophosphate while bathophenanthroline sulphonate reduced the acquisition of these ferric ligands by 48% and 52% respectively . Pre-incubation with either ferric ligand also reduced iron acquisition by 50% . KCN inhibited uptake of iron(II) by 90% and uptake of {59Fe3+}-pyrophosphate and {59Fe3+}-citrate by 46% and 56% respectively; dinitrophenol had no effect on these processes . The data suggest that C . neoformans can (i) generate ferrous iron at the cell surface via a reduction of ferric chelates, with the subsequent acquisition of the ferrous iron, and (ii) acquire iron through the interaction of ferric chelates with a surface component. Antimicrob Agents Chemother, 1995 May, 39(5), 1077 - 81 Evaluation of water-soluble pneumocandin analogs L-733560, L-705589, and L-731373 with mouse models of disseminated aspergillosis, candidiasis, and cryptococcosis; Abruzzo GK et al.; The activities of the water-soluble pneumocandin derivatives L-733560, L-705589, and L-731373 were evaluated in mouse models of disseminated aspergillosis, candidiasis, and cryptococcosis and were compared with those of commercially available antifungal agents . Pneumocandins are inhibitors of 1,3-beta-D-glucan synthesis . In the aspergillosis model, L-733560 and L-705589 significantly prolonged the survival of DBA/2N mice challenged intravenously with Aspergillus fumigatus conidia . L-733560 and L-705589 exhibited efficacies comparable to that of amphotericin B (AMB) with 90% effective doses of 0.48, 0.12, and 0.36 mg/kg of body weight, respectively . Two mouse models of disseminated candidiasis were used to evaluate these compounds . In both models, mice were challenged intravenously with Candida albicans . In a C . albicans survival model with DBA/2N and CD-1 mice, the efficacy of L-733560 was comparable to that of AMB, while L-731373 and L-705589 were somewhat less active . In a previously described C . albicans target organ kidney assay, the pneumocandin analogs and AMB at doses of > or = 0.09 mg/kg were effective in sterilizing kidneys, while fluconazole and ketoconazole were considerably less active and did not sterilize kidneys when they were used at concentrations of < or = 100 mg/kg . Although orally administered L-733560 showed activity in both candidiasis models, its efficacy was reduced compared with that of parenterally administered drug . In a disseminated cryptococcosis mouse model that measures the number of CFU of Cryptococcus neoformans per gram of brain and spleen, L-733560 at 10 mg/kg was ineffective in reducing the counts in organs, while AMB at 0.31 mg/kg sterilized the organs.These results indicate that the pneumocandins may be beneficial as potent parenterally administered therapeutic agents for disseminated aspergillosis and candidiasis. Antimicrob Agents Chemother, 1995 May, 39(5), 1070 - 6 In vitro evaluation of the pneumocandin antifungal agent L-733560, a new water-soluble hybrid of L-705589 and L-731373; Bartizal K et al.; Lipopeptide L-733560 is a hybrid analog of L-731373 and L-705589 . All are water-soluble semisynthetic pneumocandin Bo derivatives . In vitro susceptibility testing of L-705589, L-731373, and L-733560 against more than 200 clinical isolates consisting of eight Candida species, Cryptococcus neoformans, and three Aspergillus species was performed by the broth microdilution methods . All three pneumocandins exhibited potent anti-Candida activity and moderate anti-C . neoformans activity . However, anti-Aspergillus activity was demonstrated only by an agar disk diffusion method . Antifungal agent-resistant Candida species and C . neoformans showed susceptibility comparable to that of susceptible isolates . Growth inhibition kinetic studies against Candida albicans revealed fungicidal activity within 3 to 5 h . Drug combination studies with pneumocandins and amphotericin B revealed indifferent activity against C . albicans and additive effects against C . neoformans and Aspergillus fumigatus . The activities of the compounds were not dramatically affected by the presence of serum . Resistance induction studies showed that the susceptibility of C . albicans MY1055 was not significantly altered by repeated exposure to subinhibitory concentrations of L-733560 . Erythrocyte hemolysis studies indicated minimal hemolytic potential with pneumocandins . Results from preclinical evaluations and development studies performed thus far indicate that the pneumocandins should be safe, broad-spectrum fungicidal agents and potent parenteral antifungal agents. Clin Infect Dis, 1995 May, 20(5), 1396 - 8 Cryptococcal empyema: case report and review; Mulanovich VE et al.; A 28-year-old male infected with the human immunodeficiency virus (HIV) developed a pleural empyema caused by Cryptococcus neoformans . He responded well to chest-tube drainage and antifungal therapy; he received fluconazole as maintenance therapy for 1 year and has not relapsed . We reviewed the English-language literature on cryptococcal pleural effusions in patients with and without AIDS . Only three other cases of empyema, one of them in an HIV-infected patient, have been reported . A pleural-fluid cryptococcal antigen test was diagnostic in our case and should be included in the diagnostic evaluation of unexplained pleural empyema/effusion in immunocompromised patients. Nihon Kyobu Shikkan Gakkai Zasshi, 1995 May, 33(5), 548 - 52 {A case of primary pulmonary cryptococcosis associated with pneumothorax}; Shibuya Y et al.; We report a case of primary pulmonary cryptococcosis . A 20-year-old woman was admitted to the hospital complaining of coughing, fever, and dyspnea on exertion . She had no underling disease or immunological abnormality . Chest X-ray film revealed bilateral diffuse infiltrative shadows, which were first believed to have been caused by a community-acquired pneumonia . Pulmonary cryptococcosis was diagnosed from the results of a transbronchial lung biopsy . After 2.5 years of anti-mycotic chemotherapy with amphotericin B and flucytosine, pneumothorax occurred in the left lung . Thoracotomy and open lung biopsy were done . Histological findings of the open lung biopsy specimens showed numerous broken cryptococcal organisms within alveolar macrophages . Diffuse fibrosis accompanied by multiple bullae may have punctured bullae or blebs and thus led to pneumothorax. Infect Immun, 1995 May, 63(5), 1810 - 9 Determination of antigen binding specificities of Cryptococcus neoformans factor sera by enzyme-linked immunosorbent assay; Belay T et al.; The competitive binding specificities of glucuronoxylomannan (GXM) and its derivatives to factor sera of Cryptococcus neoformans were studied by enzyme-linked immunosorbent assay . An effort was made to determine the epitope specificity of each factor serum . Despite the presence of antigenic factor 1 on all serotypes of C . neoformans, variations in inhibition ability were observed with different GXMs . The panspecific component of factor serum 1 (antibody 1) appeared to be due to the presence of more than one antibody component . The activity was dependent on the 6-O-acetyl substituent . GXMs of serotypes A and D inhibited factor serum 2 equally well, indicating a low titer for the antibody 7 component . Serotype B GXM was a poor inhibitor, and serotype C GXM did not inhibit factor serum 2 . The activity of factor serum 2 was 6-O-acetyl dependent . GXMs from typical serotype A and serotype D isolates were excellent inhibitors of factor serum 3 . GXMs from serotype B were poorly inhibitory and serotype C did not inhibit factor serum 3 . The activity of factor serum 3 was 6-O-acetyl dependent . The activity of factor serum 4 was due predominantly to antibody component 6 . The activity of factor 4 was directed mainly against serotype C, and it was independent of 6-O-acetyl substitution Factor serum 5 was specific for serotype B GXMs . The inhibitory effect was independent of 6-O-acetyl substitution, but the effect was diminished by reduction of the glucuronic acid . The GXMs with a typical serotype C structure inhibited antibody 6 . O deacetylation of the GXMs did not affect their inhibitory activity . However, reduction of glucuronic acid reduced factor serum 6 binding . Factor serum 8 was specific to serotype D; native GXMs of serotype A were slightly inhibitory . O deacetylation of the serotype D GXMs abrogated the inhibitory effect . O deacetylation alone abrogates the activity of antibody components 1, 2, 3, and 8 . Reduction of glucuronic acid reduces the inhibitory activity of the GXM to antibody components 4, 5, and 6 . Partial GXM structures and methyl glycosides did not effectively inhibit the activity of any of the factor sera. Clin Neuropharmacol, 1995 Apr, 18(2), 95 - 112 Therapy of fungal meningitis; Slavoski LA et al.; There has been an increase in recent years in the number of reported cases of meningitis and brain abscesses caused by fungi . This increase is due to the availability of better diagnostic techniques for fungal infections and the ever-increasing population of immunocompromised hosts (1,2) . The patients most susceptible to invasive fungal infections include those with hematologic malignancies; those receiving hyperalimentation, corticosteroids, or cytotoxic drugs; transplant recipients; injection drug abusers; and those with the acquired immunodeficiency syndrome (AIDS) . Although many fungi infect only immunologically impaired patients, some will infect normal hosts as well . The successful treatment of central nervous system (CNS) fungal infections is highly dependent on the underlying immune status of the host, as well as on the prompt initiation of appropriate antifungal therapy . However, the diagnosis of these infections may be difficult, and proper therapy often delayed . Furthermore, information on treatment regimens ranges from extensive, as in the case of cryptococcal meningitis, to scanty or nonexistent in the case of rare, opportunistic fungi . For > 3 decades, the standard antifungal agent for the treatment of CNS fungal infections has been amphotericin B . However, the effectiveness of amphotericin B is often eliminated by poor CNS penetration, fungal resistance, and toxicity (3) . Because of the problems associated with use of amphotericin B, newer azole antifungal agents have been developed, some of which are efficacious in the therapy of fungal meningitis . We give an overview of the antifungal agents currently available for clinical use and their utility in the treatment of fungal meningitis. Can J Microbiol, 1995 Apr-May, 41(4-5), 428 - 32 Reduced recovery of a Cryptococcus neoformans adherence mutant from a rat model of cryptococcosis; Merkel GJ et al.; Stable mutants of Cryptococcus neoformans (strain CSF-1) induced by treatment with ultraviolet light and nitrosoguanidine were isolated that demonstrated reduced adherence to glial cells in culture . Adherence of the mutants, as measured by a radiometric assay, was reduced by 50-70% of that attained for the parent CSF-1 strain . The adherence mutants appeared to be phenotypically similar to the CSF-1 strain . However, all but one mutant (designated as CSF-23) demonstrated slightly slower growth rates than the wild-type strain . The CSF-1 and CSF-23 strains were injected intravenously and intratracheally into normal rats and rats immunosuppressed by cyclophosphamide treatment, and the organ distribution and recovery of viable yeasts determined over 2-96 h . During this relatively short period of observation the majority of the yeasts were localized in the lungs . By either route of injection, the recovery of the CSF-23 adherence mutant was reduced by as much as 90% of that obtained for the wild-type strain . The results indicated that host cell adherence may be important for the persistence of cryptococci in tissue and that further studies with the adherence mutants are warranted. Rev Latinoam Microbiol, 1995 Apr-Jun, 37(2), 135 - 46 {Hematologic changes associated with infection of mice by Cryptococcus neoformans}; Velasco-Lezama R et al.; The pathogenicity of the L, P and E strains of C . neoformans was studied in 3-5 weeks old CD1 male mice . Cell suspensions containing the most (L), and the least (E) pathogenic strains were inoculated intracerebrally (IC), and intraperitoneally (IP) . After 14 days total and differential counts were made for erythrocytes, leukocytes and platelets, yeasts from infected organs were recovered in Sabouraud Dextrose Agar (SDA) . The capsular material from C . neoformans was used to stimulate in vivo and in vitro platelet production . Mice inoculated with the L strain, showed increase of neutrophils and platelets, decrease of lymphocytes, the yeast was recovered from spleen, liver and lungs and from brain of mice injected by the IC route . In contrast, strain E produced an increase of neutrophils, reduction of lymphocytes, and was only isolated from the brain of mice inoculated IC . The capsular material stimulated the production and maturation of megakaryocytes only in vitro . The development of the infection and the yeast dissemination were associated with increases in the number of platelets, probably as a result of the stimulant effect of the capsular material on the maturation of megakaryocytes. Infect Immun, 1995 Apr, 63(4), 1218 - 22 Biomolecular events involved in anticryptococcal resistance in the brain; Blasi E et al.; We have recently shown that intracerebral (i.c.) administration of heat-killed Cryptococcus neoformans (HCN) enhances mouse resistance to a subsequent local challenge with lethal doses of viable yeast cells . Here we show that i.c . administration of HCN is also effective in significantly delaying brain colonization of mice intravenously infected with viable C . neoformans . PCR analysis revealed that interleukin 6 (IL-6) and IL-1 beta gene expression occurs in brain of HCN-treated mice but not in brains of saline-treated controls . In contrast, no differences are observed in terms of tumor necrosis factor alpha and IL-1 alpha gene transcripts, which are slightly and highly detectable, respectively, in saline-treated mice and which remain such also following HCN treatment . Furthermore, i.c . administration of exogenous IL-6 or IL-1 beta, but not tumor necrosis factor alpha, before local challenge with viable C . neoformans results in significantly reduced microbial counts in the brain and blood and in increased mouse survival . Taken together, these observations provide initial evidence that brain anticryptococcal resistance involves elicitation of a local cytokine response, involving primarily IL-6 and IL-1 beta. J Clin Microbiol, 1995 Apr, 33(4), 995 - 7 Oxygen as limiting nutrient for growth of Cryptococcus neoformans; Odds FC et al.; In microbroth cultures with RPMI 1640 medium, the growth yield of seven Cryptococcus neoformans isolates was unaffected by augmentation of the normal (0.2%) glucose concentration in the medium to 2%, and the addition of other potential carbon, nitrogen, and vitamin sources to the medium also failed to produce large changes in growth yield . However, macrobroth cultures of C . neoformans in RPMI 1640 that were agitated by rotation in air gave turbidities 6 to 37 times greater than those in identical cultures incubated statically, and similar levels of increase were seen whether the medium contained 0.2 or 2% glucose . Incubation of microplates under an oxygen atmosphere or with agitation by rotation led to an increase of up to twofold in growth turbidity of the yeast . The maximum increase was achieved by incubation with rotation and was dependent on the brand of microplate used . The findings implicate oxygen as a growth-limiting nutrient for C . neoformans . Incubation of microbroth cultures under conditions that enhance oxygen availability for antifungal susceptibility testing purposes may increase the speed of such tests and enhance the determination of MIC endpoints. Microbiology, 1995 Apr, 141 ( Pt 4), 901 - 6 Phylogenetic analysis of the ballistosporous anamorphic genera Udeniomyces and Bullera, and related basidiomycetous yeasts, based on 18S rDNA sequence; Suh SO et al.; The small subunit nuclear ribosomal DNA (18S rDNA) sequence was determined for twelve species of basidiomycetous anamorphic yeasts, i.e . three species of Udeniomyces, seven species of Bullera, Cryptococcus albidus and Phaffia rhodozyma . For phylogentic analysis, these sequences were aligned with published sequences for 36 other fungal species . Molecular phylogenetic analysis of maximum likelihood and parsimony showed that the 44 species of basidiomycetes analysed were divided into three major lineages . The ballistosporous yeast genera Udeniomyces and Bullera were clearly separated . On the phylogenetic tree, Udeniomyces megalosporus, U . puniceus and U . piricola showed a very close relationship with one another, and composed a lineage with Mrakia frigida, P . rhodozyma and Cystofilobasidium capitatum at high bootstrap confidence level . On the other hand, eight species of Bullera made lineages with selected species of Tremella (Tremellaceae), Filobasidium and Filobasidiella (Filobasidiaceae), Cryptococcus albidus and Trichosporon cutaneum . The molecular phylogeny deduced from the 18S rDNA sequence showed a possibility of heterogeneity among the species of Bullera at the generic level. Indian J Med Res, 1995 Apr, 101, 134 - 41 Pathological lesions in HIV positive patients; Santosh V et al.; Pathomorphological features of 10 HIV positive individuals studied at autopsy and biopsy are described . Nine patients had evidence of neuro-AIDS and eight of them succumbed to various opportunistic infections . One surviving patient underwent a diagnostic lymph node biopsy which revealed tuberculous lymphadenopathy . Cryptococcal meningitis was the commonest CNS opportunistic infection, seen in five cases, with disseminated systemic cryptococcosis in two . The other opportunistic infections included toxoplasma encephalitis in two, with acanthamoeba infection in one patient . Pulmonary tuberculosis was noted in three patients while other bacterial infections such as meningococcal meningitis, pseudomonas septicaemia were observed in three and pneumocystis carinii pneumonia in one . One seropositive individual was clinically asymptomatic but succumbed to a road traffic accident . The brain in this case showed features of HIV associated early leucoencephalopathy . Bacterial infections caused by organisms other than Mycobacterium tuberculosis associated with AIDS are often underdiagnosed and should be considered, especially in developing countries . In cases of cryptococcal and tuberculous meningitis or multiple parasitic infections, the patients should be screened for associated HIV infectionPIP: Autopsy or biopsy findings in 10 human immunodeficiency virus (HIV)-positive persons from Bangalore, India, revealed a wide spectrum of pathological changes . Patients' mean age was 33.4 years and the mean duration between symptom onset and death was 27.13 days . Nine patients had evidence of neuro-acquired immunodeficiency syndrome (AIDS) and 8 of them succumbed to various opportunistic infections . Histologic examination showed diffuse cryptococcal meningitis in 5 cases; 2 cases showed disseminated systemic cryptococcosis . Pulmonary tuberculosis was present in 3 patients . Despite no signs of associated neurotuberculosis in any patient, 4 autopsied and 1 biopsied case showed evidence of systemic tuberculosis . Toxoplasma encephalitis was present in 2 cases; observed in this series was the first case, in India, of co-existent toxoplasma and acanthamoeba . Other bacterial infections such as meningococcal meningitis and psudomonas septicemia were found in 3 cases; pneumocystis carinii pneumonia was present in 1 case . Evidence of early HIV leukoencephalopathy was observed in the only asymptomatic HIV-positive individual (who died in a traffic accident) . AIDS-associated bacterial infections caused by organisms other than Mycobacterium tuberculosis are often underdiagnosed and should be considered in developing countries . In cases of cryptococcal and tuberculosis meningitis or multiple parasitic infections, patients should be screened for associated HIV infection . J Neuroimmunol, 1995 Apr, 58(1), 111 - 6 Role of nitric oxide and melanogenesis in the accomplishment of anticryptococcal activity by the BV-2 microglial cell line; Blasi E et al.; In the present paper, we investigated the involvement of cryptococcal melanogenesis and macrophage nitric oxide (NO) production in the accomplishment of anticryptococcal activity by microglial effector cells, using the murine cell line BV-2 . We demonstrate that the constitutive levels of anticryptococcal activity exerted by BV-2 cells is significantly enhanced upon interferon gamma plus lipopolysaccharide treatment . The phenomenon, which occurs with no enhancement of phagocytic activity, is associated with the production of high levels of NO and is abolished by addition of NG-monomethyl-L-arginine . Comparable patterns of results are observed employing either unopsonized or opsonized microbial targets, the latter microorganisms being markedly more susceptible to BV-2 cell antimicrobial activity . Furthermore, melanization of Cryptococcus neoformans significantly reduces its susceptibility to BV-2 antimicrobial activity, regardless of the fact that activated macrophages or opsonized microorganisms have been employed . In conclusion, our results provide evidence that NO-dependent events are involved in the fulfillment of anticryptococcal activity by activated microglial cells and that fungal melanization is a precious escamotage through which C . neoformans overcomes host defenses. J Leukoc Biol, 1995 Apr, 57(4), 657 - 62 Immune complexes increase nitric oxide production by interferon-gamma- stimulated murine macrophage-like J774.16 cells; Mozaffarian N et al.; Murine macrophage-like J774.16 cells were tested for changes in nitric oxide production upon incubation with immune complexes . Cryptococcus neoformans capsular polysaccharide and polysaccharide-specific monoclonal antibodies were added to J774.16 cells in the presence and absence of recombinant murine interferon-gamma (IFN-gamma) . The effect of immune complexes on nitrite synthesis was both concentration dependent and isotype dependent . In the presence of IFN-gamma, immune complexes of IgG1, IgG2, IgG2b, or IgG3 isotype increased nitrite levels, whereas complexes of IgM isotype did not . Immune complexes did not alter nitrite production by unstimulated macrophages . Antibody alone, antigen alone, and antigen with irrelevant IgG1 antibody did not augment nitrite formation, either in the presence or absence of IFN-gamma, indicating a requirement for Fc gamma R cross-linking . These results suggest that IgG isotypes may offer additional protection against pathogens by enhancing macrophage nitric oxide production. Bull Acad Natl Med, 1995 Apr, 179(4), 789 - 800; discussion 800-3 {A very up-to-date stage in the fate of infectious diseases: parasitic and fungal opportunistic infections}; Ambroise-Thomas P et al.; Opportunistic parasitosis and mycosis are becoming ever more widespread, mainly under the influence of major immunodeficiencies, either acquired (AIDS) or therapeutic . In this general overview, their main aspects, both clinical and epidemiological, are underlined . In terms of epidemiology, three types of phenomena have been observed: 1) emergence of human parasitosis unknown before (microsporidiosis due to Enterocytozoon bieneusi, Encephalitozoom hellem or Septata intestinalis); 2) among the human parasites already known, identification of very pathogenic strains (Toxoplasma gondii, Aspergillus fumigatus, Cryptococcus neoformans); 3) origin probably or certainly nosocomial of certain infections (pneumocystosis; toxoplasmosis and visceral leishmaniasis transmitted during bone-marrow or organ transplantations) . The development of deep mycosis (invasive aspergillosis) is particularly promoted by granulopenia and alterations in the phagocytosis . On the other hand, opportunistic protozoosis (toxoplasmosis and leishmaniasis) and helminthiasis (strongyloidosis due to Strongyloides stercolaris) are related, above all, to disorders in cellular immunity (deficit of CD4+, mainly) . Finally, several of these infections may be characterised by a variety of clinical pictures and outcome, depending on the contributory factors (immunodeficit or not) which led to the development of the infection. Rinsho Shinkeigaku, 1995 Apr, 35(4), 373 - 8 {A case of cryptococcal meningoencephalitis with the cerebral superficial cystic lesions detected on magnetic resonance imagings}; Kondo H et al.; The patient was a 35-year-old man with confusional state and headache . Analysis of cerebrospinal fluid (CSF) showed 1,383/mm3 cell count, the protein level of 300mg/dl and glucose level of 42 mg/dl . Cryptococcus neoformans was disclosed by India ink preparation . The cryptococcal antigen test was positive at 1:125 by latex agglutination . The diagnosis of cryptococcal meningoencephalitis was determined . Antifungal treatment with amphotericin B resulted in improvement of neurologic signs, CSF findings and cryptococcal antigen test . But two months later, brain MRI demonstrated low intensity areas on T1 weighted image and high intensity areas on T2 and proton weighted images in the cerebral cortical region . Gd-DTPA MRI showed enhanced areas in the cerebral leptomeninges . It was considered that these MRI lesions corresponded to pseudocysts and Gd-DTPA enhanced lesion indicated dilated vessels or destructed blood-brain barrier . After administration of larger doses of amphotericin B, these lesions on MRI disappeared . It is suggested that brain MRI is useful in diagnosis of cryptococcal meningoencephalitis to detect pseudocysts at the cortical region which may imply the early stage of procrastinating process. Semin Thorac Cardiovasc Surg, 1995 Apr, 7(2), 95 - 103 The endemic mycoses: surgical considerations; Johnson PC et al.; Surgical consultation is regularly requested for diagnosis and treatment of pulmonary complications of the endemic mycosis, Histoplasma capsulatum, Blastomyces dermatitidis and Coccidioidomycosis immitis, and the yeast Cryptococcus neoformans . All resemble pulmonary malignancies . Histoplasmosis causes pericarditis, mediastinal fibrosis and mediastinal granuloma, which can cause entrapment of vascular structures, the esophagus, and the trachea . Coccidioidomycosis can cause spontaneous pneumothorax and thin wall cavities that can be superinfected with tuberculosis and Aspergillosis . The pathogenesis, diagnosis, and treatment of these organisms are discussed with emphasis on the new oral therapies and complications encountered in persons with human immunodeficiency virus (HIV) infection. Aust N Z J Med, 1995 Apr, 25(2), 133 - 9 The role of bronchoscopy in the diagnosis and treatment of pulmonary disease in HIV-infected patients; Lewin SR et al.; BACKGROUND: Pulmonary disease is the most common reason for presentation and the major cause of death in HIV-infected patients . There has been an evolution in the optimal approach to the investigation of a pulmonary infiltrate in HIV-infected patients since the introduction of induced sputum for the diagnosis of Pneumocystis carinii pneumonia (PCP) . AIMS: To evaluate the usefulness of flexible fibreoptic bronchoscopy (FFB), bronchoalveolar lavage (BAL), transbronchial biopsy (TBB) and bronchial brushings (BB) in the diagnosis of pulmonary disease in HIV-infected patients and to examine the effect of FFB on changes in therapy and survival . METHODS: The histories of all HIV-infected patients referred to Fairfield Hospital for FFB between January 1990 and June 1993 were examined retrospectively . RESULTS: Forty-two FFB were performed on 41 patients (40 male and one female) . Definitive diagnoses made at FFB included Kaposi's sarcoma (KS) (n = 9), invasive aspergillosis (n = 5), PCP (n = 4), Mycobacterium avium complex (MAC) pneumonia (n = 2), cytomegalovirus (CMV) pneumonia (n = 1), Cryptococcus neoformans pneumonia (n = 1), microsporidium (n = 1) and Pseudomonas aeruginosa pneumonia (n = 1) . TBB and BB did not provide a diagnosis for diseases not seen macroscopically at FFB or diagnosed by BAL . FFB findings altered diagnosis in 21/42 (50%) presentations and changed therapy in 26/42 (62%) cases . CONCLUSIONS: FFB together with BAL altered the working diagnosis and changed therapy in a significant number of patients . TBB and BB should not be routinely performed in all patients as these procedures are of limited value in this setting. Zentralbl Bakteriol, 1995 Apr, 282(3), 244 - 54 Evidence of canary droppings as an important reservoir of Cryptococcus neoformans; Criseo G et al.; After preliminary results had shown the occurrence of Cryptococcus neoformans in canary droppings in southern Italy, the increasing epidemiological interest in cryptococcosis and the habitats of the agent led to more extensive studies . 180 samples of canary droppings were collected from pet shops and private households in two towns (Messina and Reggio Calabria) of southern Italy and culturally examined for C . neoformans . The examination was carried out with the help of the brown colour effect (BCE) specific of the C . neoformans colony on Guizotia abyssinica creatinine agar (Staib agar) . 48 samples (26.6%) were positive; of these, 32/108 (29.6%) were from pet shops and 16/72 (22.2%) from private households . The colony growth was not mucous, i.e . microscopically the blastospores were found to be little or not encapsulated . All C . neoformans strains tested by the auxanographic method showed a weak assimilation of creatinine . The variety status of the isolates was tested with canavanine-glycine-bromothymol-blue (CGB) agar; all strains tested (n = 420) were found to be C . neoformans var . neoformans . In the light of extensive studies on C . neoformans and the canary in the pre-AIDS era in Germany, the present observations in Italy ask for further basic research, epidemiological studies, and education of the public. Infect Immun, 1995 Apr, 63(4), 1298 - 304 Cryptococcus neoformans fails to induce nitric oxide synthase in primed murine macrophage-like cells; Naslund PK et al.; Nitric oxide (NO) is a microbiostatic gas generated by activated murine macrophages . Cytokine signals, gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) act synergistically to induce production of a macrophage nitric oxide synthase (NOS) . A variety of intracellular pathogens, when recognized by macrophages primed with IFN-gamma, induce NOS by eliciting TNF-alpha secretion, which then functions as a positive autocrine signal . In cell culture assays, a murine macrophage cell line (J774), primed with IFN-gamma, was tested for NOS induction upon challenge with virulent Cryptococcus neoformans . C . neoformans failed to induce macrophage NOS as measured by nitrite production . This was true irrespective of the C . neoformans-to-J774 ratio . Other nonpathogenic Cryptococcus species likewise failed to induce NOS, yet Saccharomyces cerevisiae, Histoplasma capsulatum, and Candida albicans were efficient inducers of NOS . Conditions which promoted attachment and/or phagocytosis of C . neoformans did not lead to NOS induction (including opsonization with specific antibodies against C . neoformans) . Assays for transcriptional repressors of NOS were negative . Tests for consumption of nitrite by measurement of additional products of NOS induction were negative . No TNF-alpha was detected by enzyme-linked immunosorbent assay in supernatants from C . neoformans-J774 cocultures . A mutant C . neoformans strain with a minimal, but visible, polysaccharide capsule also failed to induce NOS; however, several nonencapsulated mutants of C . neoformans did induce NOS . Failure of C . neoformans to act as an inducer of NOS may be related to the virulence of this pathogen in mice; C . neoformans is a unique example of a facultative intracellular pathogen which fails to induce NOS in primed macrophages . The mechanism appears to involve the failure of TNF-alpha secretion once the macrophage comes in contact with the fungus . The presence of the polysaccharide capsule appears to mask the signal necessary for TNF-alpha secretion and, ultimately, NOS induction. Wei Sheng Wu Xue Bao, 1995 Apr, 35(2), 97 - 102 {The phenoloxidase test and its application to identify Cryptococcus neoformans with various biological characteristics}; Li A et al.; Cryptococcus neoformans strains with various biological characteristics were examinated the phenoloxidase activity on the caffeic acid cornmeal agar (CACA) . Other medically important yeasts were also included in this research . Firstly, thirteen reference strains of Cryptococcus neoformans were confirmly found positive phenoloxidase production on the CACA medium . Then, in total 150 isolates of yeasts, forty three Cryptococcus neoformans strains were phenoloxidase positive, other than that 107 other yeast strains were all negative . It is suggested that Cryptococcus neoformans strains with different biological features specifically and uniquely produce phenoloxidase, thus the phenoloxidase test can be applied as a useful tool to identify this pathogenic yeast . Our results also show that the culture on the CACA medium is an effective method to test the phenoloxidase activity within 72 hours . It is further approved that the urease test will not be able to be a screening test for Cryptococcus neoformans in the clinical laboratory, but it is still valuable to identify urease negative Cryptococcus neoformans when the test is used in combination with the phenoloxidase test. N Engl J Med, 1995 Mar 16, 332(11), 700 - 5 A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection . NIAID AIDS Clinical Trials Group; Powderly WG et al.; BACKGROUND . Cryptococcal meningitis and other serious fungal infections are common complications in patients infected with the human immunodeficiency virus (HIV) . Fluconazole is effective for long-term suppression of many fungal infections, but its effectiveness as primary prophylaxis had not been adequately evaluated . METHODS . We conducted a prospective, randomized trial that compared fluconazole (200 mg per day) with clotrimazole troches (10 mg taken five times daily) in patients who were also participating in a randomized trial of primary prophylaxis for Pneumocystis carinii pneumonia . RESULTS . After a median follow-up of 35 months, invasive fungal infections had developed in 4.1 percent of the patients in the fluconazole group (9 of 217) and in 10.9 percent of those in the clotrimazole group (23 of 211; relative hazard, as adjusted for the CD4+ count, 3.3; 95 percent confidence interval, 1.5 to 7.6) . Of the 32 invasive fungal infections, 17 were cryptococcosis (2 in the fluconazole group and 15 in the clotrimazole group; adjusted relative hazard, 8.5; 95 percent confidence interval, 1.9 to 37.6) . The benefit of fluconazole was greater for the patients with 50 or fewer CD4+ cells per cubic millimeter than for the patients with higher counts . Fluconazole was also effective in preventing esophageal candidiasis (adjusted relative hazard, 5.8; 95 percent confidence interval, 1.7 to 20.0; P = 0.004) and confirmed and presumed oropharyngeal candidiasis (5.7 and 38.1 cases per 100 years of follow-up in the fluconazole and clotrimazole groups, respectively; P < 0.001) . Survival was similar in the two groups . CONCLUSIONS . Fluconazole taken prophylactically reduces the frequency of cryptococcosis, esophageal candidiasis, and superficial fungal infections in HIV-infected patients, especially those with 50 or fewer CD4+ lymphocytes per cubic millimeter, but the drug does not reduce overall mortality. Arch Intern Med, 1995 Mar 13, 155(5), 538 - 40 Initial therapy for acquired immunodeficiency syndrome-associated cryptococcosis with fluconazole; Nightingale SD; BACKGROUND: Published opinion has generally favored amphotericin B over fluconazole as initial therapy for acquired immunodeficiency syndrome-associated cryptococcosis, although data that support this recommendation are limited . METHOD: Retrospective review of 30 consecutive patients with acquired immunodeficiency syndrome-associated cryptococcosis seen at a single institution over a 1-year period and given fluconazole, 400 mg/d, as initial therapy . RESULTS: No patient died within the first 30 days of therapy, and none of the 14 patients who died within 1 year had clinically detectable infection when last seen or at death . Pretreatment blood cultures were positive in 26 of 27 patients; cerebrospinal fluid cryptococcal antigen titer was greater than 1:1024 in 12 of 23 patients; and five of 30 patients presented with altered mental status . The median CD4 count at diagnosis was 0.042 x 10(9)/L (42/microL) . Eight of 25 patients who were followed up for more than 30 days relapsed, as evidenced by a positive culture; all relapses were successfully treated with fluconazole, either by reinstitution of therapy or by increase of dosage . CONCLUSION: This experience supports the use of fluconazole as initial therapy for acquired immunodeficiency syndrome-associated cryptococcosis. Lancet, 1995 Mar 4, 345(8949), 548 - 52 Primary prevention of cryptococcal meningitis by fluconazole in HIV-infected patients; Quagliarello VJ et al.; To evaluate whether oral fluconazole reduces the risk of a first episode of cryptococcal meningitis in HIV-infected patients, we conducted a case-control study of patients cared for in a university teaching hospital and two urban HIV-outpatient clinics . Cases consisted of HIV-infected patients with CD4 cell counts less than 250/microL who developed a first episode of cryptococcal meningitis between July 1, 1990, and June 30, 1993 . For each case (n = 18), 4 control subjects were chosen from HIV-infected patients (CD4 count < 250/microL) whose cerebrospinal fluid was negative for cryptococcal antigen and culture, and who were matched by age, sex, and time of lumbar puncture . There were no significant differences between cases and controls in age, sex, insurance status, mean CD4 count, history of oral candidosis, presence of a previous AIDS-defining illness, the number of visits to the HIV-outpatient clinic, or use of antiretroviral therapy . In the 6 months before lumbar puncture, 2 of 18 cases (11%) and 26 of 72 controls (36%) were exposed to fluconazole, a finding that gives a matched odds ratio (adjusted for race, route of HIV infection, and CD4 count) of 0.08 (95% CI 0.01-0.84; p = 0.035) and indicates a 92% protective efficacy . We conclude that fluconazole reduces the risk of a first episode of cryptococcal meningitis in HIV-infected patients with a CD4 count less than 250/microL . Although the optimum dose and duration of fluconazole could not be determined, our results suggest that less than daily use was effective in the prevention of cryptococcal meningitis. Clin Exp Immunol, 1995 Mar, 99(3), 425 - 32 Antibodies to the Cryptococcus neoformans capsular glucuronoxylomannan are ubiquitous in serum from HIV+ and HIV- individuals; Deshaw M et al.; Murine MoAbs to the Cryptococcus neoformans capsular glucuronoxylomannan (GXM) polysaccharide are protective in mice in vivo and in vitro . The prevalence of protective anti-GXM antibodies in human serum is unknown . To provide further insight into the human antibody response to C . neoformans we determined the prevalence, isotype, and IgG subclass utilization of human anti-GXM antibodies in HIV+ and HIV- sera by a sensitive antigen capture FLISA assay . One hundred and twenty-three sera from the Bronx Municipal Hospital Centre serum bank were studied retrospectively . Seventy were from HIV+ individuals, 10 with a history of cryptococcal meningitis (CM), and 53 were from HIV- individuals . Serum GXM determinations were also performed on 61 HIV+ sera . Our results demonstrated that anti-GXM IgG, IgA, and IgM are ubiquitous in both HIV+ (including those with CM), and HIV- sera . Anti-GXM IgA titres and total serum IgA concentration were elevated in HIV+ sera . Anti-GXM IgG antibodies were almost exclusively isotype-restricted to the IgG2 subclass . Our data also demonstrated elevations of anti-bovine serum albumin (BSA) titres in HIV+ sera . Taken together, our findings confirm hypergammaglobulinaemia and expansion of anti-protein (BSA) antibodies in HIV+ individuals and isotype restriction of human anti-carbohydrate (GXM) antibodies to the IgG2 subclass . Our report of ubiquitous anti-GXM antibodies of the IgG and IgA isotypes suggests that anti-GXM antibodies exist before HIV infection. Infect Immun, 1995 Mar, 63(3), 770 - 8 Intravascular cryptococcal culture filtrate (CneF) and its major component, glucuronoxylomannan, are potent inhibitors of leukocyte accumulation; Dong ZM et al.; Disseminated cryptococcosis is characterized by high titers of cryptococcal polysaccharides in serum and minimal cellular infiltrates in infected tissues of patients . The main objective of this study was to determine whether the circulating cryptococcal polysaccharides could contribute to the lack of cellular infiltration into infected tissues . To assess this possibility, a gelatin sponge implantation model was used . We found that intravenous (i.v.) injection of mice with cryptococcal culture filtrate antigen (CneF) inhibited migration of leukocytes (neutrophils, lymphocytes, and monocytes) into the intrasponge sites of acute inflammation induced by CneF, tumor necrosis factor alpha, or formylmethionyl leucyl phenylalanine . In addition, i.v . administration of CneF inhibited leukocyte migration into the intrasponge sites of a cell-mediated immune reaction irrespective of whether the delayed-type hypersensitivity response was to CneF or the mycobacterial antigen purified protein derivative . Glucuronoxylomannan, a major constituent of CneF and a major cryptococcal antigen detected in the sera of patients with disseminated cryptococcosis, when given i.v . to mice, inhibited leukocyte migration into the sponges . Our results suggest that the minimal cellular infiltrates observed in infected tissues of cryptococcosis patients may be due, in part, to the circulating cryptococcal polysaccharide functioning as we have demonstrated in the mouse model . Furthermore, the high titers of cryptococcal antigen in the sera of patients may diminish leukocyte migration in response to stimuli other than Cryptococcus neoformans, a point that may be relevant in AIDS patients with cryptococcosis. Antimicrob Agents Chemother, 1995 Mar, 39(3), 586 - 92 Identification of the aminocatechol A-3253 as an in vitro poison of DNA topoisomerase I from Candida albicans; Fostel J et al.; The aminocatechol A-3253 is active against several pathogenic fungi, including Candida albicans, Cryptococcus albidus, and Aspergillus niger . A-3253 interferes with both the in vitro biosynthesis of (1,3)-beta-glucan and the activity of topoisomerases I isolated from Candida spp . It is likely that one or more of the enzymes involved in glucan biosynthesis rather than topoisomerase I is the primary intracellular target of A-3253, since a strain of Saccharomyces cerevisiae lacking topoisomerase I is as susceptible to A-3253 as cells containing wild-type levels of topoisomerase I . However, the interaction of A-3253 with topoisomerase I in vitro is of interest since the Candida topoisomerase is more susceptible to A-3253 than is the topoisomerase I isolated from human HeLa cells . A-3253 is both a reversible inhibitor of topoisomerase I catalysis and a reversible poison of topoisomerase I, and in both reactions the fungal topoisomerase I is more susceptible than the human topoisomerase I to A-3253 . In contrast, an earlier study found that the human topoisomerase I is more susceptible than the fungal topoisomerase to camptothecin (J . M . Fostel, D . A . Montgomery, and L . L . Shen, Antimicrob . Agents Chemother . 36:2131-2138, 1992) . Taken together with the response to camptothecin, the greater susceptibility of the Candida topoisomerase I to A-3253 suggests that there are structural differences between the human and fungal type I topoisomerases which can likely be exploited to allow for the development of antifungal agents which act against the fungal topoisomerase and which have minimal activity against the human enzyme. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi, 1995 Mar-Apr, 36(2), 131 - 5 Cerebral cryptococcosis in a child; Hung PC et al.; Reported is one case of cerebral cryptococcosis in a 12-year-old girl . The diagnosis was confirmed by the detection of Cryptococcus neoformans with both India ink preparation of the cerebrospinal fluid and Sabouraud's media culture . Clinical presentation included progressive severe headache, vomiting, left eye pain, diplopia, dizziness and unstable gait . Fever was absent as a symptom . Initial brain magnetic resonance imaging revealed a focal lesion over the right cerebellar hemisphere with better demonstration than contrast-enhanced computed tomography . The patient was treated with amphotericin B and 5-flucytosine with good final outcome . Early diagnosis and proper therapy are necessary in order to decrease the motality of cerebral cryptococcosis. J Child Neurol, 1995 Mar, 10(2), 93 - 9 A persistent biochemical marker for partially treated meningitis/ventriculitis; Katnik R; Regulation of circulating iron is important in bacterial, yeast, and fungal infections . In the present study, cerebrospinal fluid levels of ferritin, an iron-binding protein, were determined in controls and in patients with central nervous system pyogenic and viral infections . Among 441 controls, cerebrospinal fluid ferritin level was higher than 18 ng/mL in two relapsed patients with central nervous system leukemia, 12 with bacteremia or pneumonia, and one with hemorrhagic herpes simplex encephalitis . Cerebrospinal fluid ferritin levels were more than 18 ng/mL in 13 of 63 patients diagnosed with nonhemorrhagic aseptic meningitis/ventriculitis, when defined solely by negative cerebrospinal fluid culture . Conversely, cerebrospinal fluid ferritin exceeded 18 ng/mL in culture-proven meningitis (46 of 47 cases) and ventriculitis (five of five cases) . Cases of indolent cryptococcus and tuberculous meningitis showed modest increases despite traditional cerebrospinal fluid markers, at times, being normal . Cerebrospinal fluid ferritin levels did not correlate with cerebrospinal fluid neutrophil count, cerebrospinal fluid protein concentration, serum ferritin level, or patient age . In 16 of 19 cases monitored sequentially during ongoing antibiotic treatment, levels remained over 18 ng/mL (average, 15.0 days; range, 1 to 54 days) . This observation suggests that obtaining cerebrospinal fluid ferritin levels is helpful whenever traditional laboratory benchmarks normalize, as during acute or chronic antibiotic therapy, or create confusion with positive cultures stemming from sample contamination. Ceylon Med J, 1995 Mar, 40(1), 14 - 8 Raised serum IgE levels in chronic inflammatory lung diseases; Ray D et al.; OBJECTIVE: To study the serum IgE response in nonallergic subjects with chronic inflammatory lung diseases . SETTING: Christian Medical College Hospital, Vellore . SUBJECTS: Twenty six patients with bronchiectasis, five with pulmonary mycosis referred from all over India and 30 healthy subjects . MAIN OUTCOME MEASURES: Serum IgE value (determined by radioimmuno assay) above the upper limit of normal control range (136 to 948 iu/ml) was considered as raised level . RESULTS: Of the 26 patients with bronchiectasis 13 had pyogenic infections, six had pulmonary tuberculosis; in six patients sputum culture was sterile while another patient had herpes zoster . Five cases of mycosis included one each of actinomycosis, aspergillosis, blastomycosis, cryptococcosis and nocardiasis . The serum IgE levels were raised in 20 (65%) of the 31 patients . CONCLUSION: Associated bacterial, fungal and parasitic infections were probably responsible for inducing an hyper-IgE response in these non-allergic subjects. Am J Forensic Med Pathol, 1995 Mar, 16(1), 38 - 41 Disseminated cryptococcosis and sudden death . Report of an autopsy case; Zappi E et al.; We report a case of sudden death due to terminal cryptococcal pneumonia in a patient not suspected to have AIDS . The correct diagnosis was found only by microscopic examination and serologic workup, illustrating the hazards faced by forensic pathologists and their assistants working without adequate information about the bodies under study . This case illustrates the need for the highest levels of caution and compliance with universal precautionary measures during autopsy procedures in the present days of the AIDS epidemic. Radiographics, 1995 Mar, 15(2), 271 - 86 Thoracic mycoses from opportunistic fungi: radiologic-pathologic correlation; McAdams HP et al.; Fungi of the genera Aspergillus, Candida, and Cryptococcus and the class Zygomycetes are the most common causes of thoracic opportunistic mycoses in immunocompromised patients . Candidiasis and zygomycosis usually manifest as severe, often life-threatening, pneumonias . Aspergillus species are commonly implicated as the causative organisms in a broad spectrum of pulmonary disorders, ranging from hypersensitivity lung disease in atopic patients to invasive pneumonia in immunocompromised patients . Cryptococcus neoformans infects both immunologically normal and abnormal patients, with variable clinical and radiologic findings . The diagnosis of an opportunistic mycosis requires familiarity with the epidemiology of the disease, the various modes of clinical presentation, and the full spectrum of radiologic manifestations . Because many of these fungi may normally colonize in the upper respiratory tract, sputum cultures are considered diagnostically unreliable . Instead, definitive diagnosis hinges on either culture of the fungus from infected tissue or demonstration of the organism at microscopic examination. Clin Infect Dis, 1995 Mar, 20(3), 611 - 6 Cryptococcal disease of the CNS in immunocompetent hosts: influence of cryptococcal variety on clinical manifestations and outcome; Mitchell DH et al.; We performed a retrospective review of cases of cerebral cryptococcosis among patients admitted to 12 Australian teaching hospitals between 1985 and 1992 . Of 118 cases identified, 35 occurred in immunocompetent hosts . When cases due to Cryptococcus neoformans variety neoformans were compared with those due to Cryptococcus neoformans variety gattii, we found that the latter tended to occur in healthy hosts whose residence or job was located in a rural area, and cerebral mass lesions and/or hydrocephalus and pulmonary mass lesions were more common . For a subgroup of patients with infection due to C . neoformans variety gattii, multiple enhancing lesions were observed on cerebral computed tomograms, and papilledema, high CSF and serum cryptococcal antigen titers, and a worse prognosis (despite prolonged amphotericin B therapy and intraventricular shunt insertion) were also noted . No significant difference in clinical course or outcome in terms of variety of C . neoformans was noted for patients with cryptococcal meningitis whose computed tomographic scans appeared normal on presentation. J Clin Microbiol, 1995 Mar, 33(3), 765 - 8 Sensitivity of sandwich enzyme-linked immunosorbent assay for Cryptococcus neoformans polysaccharide antigen is dependent on the isotypes of the capture and detection antibodies; Mukherjee S et al.; Immunoglobulin M (IgM) and IgG1 monoclonal antibody isotype switch variants to Cryptococcus neoformans capsular polysaccharide were used to study the sensitivity of a double sandwich enzyme-linked immunosorbent assay (ELISA) . The most sensitive ELISA configurations used IgG1 monoclonal antibody absorbed on polystyrene plates or IgM immobilized with goat antisera for antigen capture. Pharmacotherapy, 1995 Mar-Apr, 15(2), 251 - 3 Flucytosine dosing in an obese patient with extrameningeal cryptococcal infection; Gillum JG et al.; A 31-year-old, obese woman with extrameningeal cryptococcal disease was admitted to the Medical College of Virginia for antifungal therapy . Various physiologic variables influence flucytosine pharmacokinetics, and there are no guidelines for dosing the agent in obese patients . This patient received a dosage based on her ideal body weight, and serum drug concentrations were monitored . She recovered without sequelae. Sarcoidosis, 1995 Mar, 12(1), 71 - 4 Pulmonary cryptococcal infection in an untreated patient with sarcoidosis; Shijubo N et al.; A 36-year-old housewife was referred to our hospital in March, 1993 . Her chest X ray films showed mediastinal and bilateral hilar lymphadenopathy . She was confirmed to have pulmonary sarcoidosis . We did not administer any medications for her . Four months after the diagnosis of sarcoidosis, opacities with cavitation appeared on the chest X ray . Histologic findings of lung biopsy specimens revealed granulomas with the existence of encapsulated Cryptococci . We administered an antifungal drug, itraconazole . The opacities were greatly improved by the medication . We report focal pulmonary cryptococcal infection in an untreated patient with sarcoidosis. Aust Vet J, 1995 Mar, 72(3), 93 - 7 Analysis of leucocytes and lymphocyte subsets in cats with naturally-occurring cryptococcosis but differing feline immunodeficiency virus status; Walker C et al.; Although cryptococcosis is a well-characterised disease of cats, the factors predisposing individuals to infection are unknown . As an indication of the immune status of an individual, lymphocyte subsets can be analysed . Reference ranges for feline lymphocyte subsets (Pan T+, CD4+, CD8+ and B cells) were established using a rapid whole blood technique and flow cytometry . There were no effects of age or sex on lymphocyte subset values . The numbers of circulating leucocytes and lymphocyte subsets were determined in FIV-positive and FIV-negative cats with cryptococcosis and compared with a group of healthy control cats . There were only minor differences in the numbers of lymphocyte subsets among the subgroups of cats examined in the study and the predisposition to cryptococcosis in cats could not be explained by deficiencies in lymphocyte subsets . There was a tendency for FIV-negative cats with cryptococcosis to have reduced numbers of circulating CD4+ cells and lower CD4:CD8 ratios compared with normal cats, although the interpretation of this finding was complicated by the wide reference range for normal cats . The extent to which this is the cause of the fungal infection was not determined . The only difference in leucocyte or lymphocytes subset values between FIV-negative cats with cryptococcosis and FIV-positive cats with cryptococcosis was that the CD4+ percentage was lower in the FIV-positive cats . The absolute CD4+ count was similar however, in FIV-positive and FIV-negative cryptococcosis cases . On the basis of this and other available information, the categorisation of cryptococcosis as a disease defining the AIDS phase of FIV infection may be incorrect. Indian J Cancer, 1995 Mar, 32(1), 1 - 9 Therapy for opportunistic fungal infections: past, present and future; Stevens DA; The field of antifungal chemotherapy is presently rapidly moving . It began in 1903, with the successful use of potassium iodide (KI) . Then there was little progress for 50 years, when in 1951, nystatin was introduced, the first useful polyene . Four years later amphotericin B followed, which is still the historical standard against which new systemic antifungals are compared . Except for the development of flucytosine, there was little progress until the early 1970s and the development of the azole drugs . The present era, which is characterized largely by the modifications of azole drugs, began with ketoconazole and brought agents which can be given orally and have increasing potency, decreasing toxicity and a broader spectrum of activity . Recent studies have examined ways to ameliorate the well-known toxicities of amphotericin B . A new approach has been to complex the drug with lipids or entrap it in liposomes . Itraconazole is a broad-spectrum oral triazole whose greatest advantages over the imidazoles are in its activity against aspergillosis and cryptococcosis, though it is also efficacious against the endemic deep mycoses . Fluconazole is a broad-spectrum triazole . It has been shown to be efficacious in various forms of superficial candidosis, including esophageal disease . We have shown in a randomized, double-blind, placebo-controlled study that maintenance therapy can completely prevent thrush in AIDS patients with recurrent thrush and possibly prevent all deep and superficial mycoses . Other studies have shown efficacy in cryptococcal meningitis in AIDS comparable to conventional therapy and with far less toxicity, and also in prevention of relapse of cryptococcal disease . Early diagnosis of fungal infections in cancer patients is problematic.(ABSTRACT TRUNCATED AT 250 WORDS) Mycoses, 1995 Mar-Apr, 38(3-4), 131 - 3 Cryptococcosis in a cat seropositive for feline immunodeficiency virus; Cabanes FJ et al.; A 5-year-old female Siamese cat was presented to the veterinary teaching hospital with a history of bronchopneumonia for 20 days . The cat had not responded to antibacterial chemotherapy and had developed a pronounced submandibular lymphadenopathy . Characteristically encapsulated yeast cells with narrow-necked buds were clearly seen in a fine-needle aspirate of the lymph node with an India ink preparation . Cryptococcus neoformans var . neoformans was identified . Susceptibility tests on the isolated strain were performed using antifungal tablets . The strain was sensitive to amphotericin B, fluconazole, itraconazole and ketoconazole and was resistant to 5-fluorocytosine . The cat was positive for feline immunodeficiency virus . Nevertheless, the cat was treated with ketoconazole for 3 months and apparently recovered . Three months later the animal was presented in a precomatose state . The owners refused to treat the animal and the cat was destroyed. J Immunol, 1995 Feb 15, 154(4), 1810 - 6 Isotype switching from IgG3 to IgG1 converts a nonprotective murine antibody to Cryptococcus neoformans into a protective antibody; Yuan R et al.; Passively administered mAbs to Cryptococcus neoformans capsular polysaccharide can alter the course of infection in mouse models . In preliminary studies of passive Ab efficacy, most IgM, IgA, and IgG1 mAbs were protective, but the few IgG3 mAbs tested did not confer significant protection . Because IgG3 is effective in pneumococcal infections, this phenomenon was examined more rigorously by generating an IgG1 switch variant from the non-protective IgG3 mAb 3E5 and comparing its protective efficacy in a murine model of i.v . infection by using strains of both the A and D serotypes . The 3E5 IgG3 mAb did not prolong survival or reduce organ fungal burden . Rather, the IgG3 decreased survival relative to controls . In contrast, the IgG1 switch variant of 3E5 significantly prolonged survival, reduced organ colony-forming units, and reduced serum polysaccharide Ag level in infected mice . The results establish that isotype is important for Ab efficacy against C . neoformans. Infect Immun, 1995 Feb, 63(2), 573 - 9 Antibodies to Cryptococcus neoformans glucuronoxylomannan enhance antifungal activity of murine macrophages; Mukherjee S et al.; Monoclonal antibodies (MAbs) to the capsular polysaccharide of the pathogenic fungus Cryptococcus neoformans can prolong survival and decrease organ fungal burden in experimental murine cryptococcosis . To investigate the mechanism of antibody-mediated protection, the interaction of C . neoformans and murine macrophage-like J774.16 cells was studied in the presence and absence of MAbs differing in isotype . Immunoglobulin G2a (IgG2a) and IgG2b isotype switch variants were isolated from an IgM hybridoma to complete the IgG subclass set . IgM, IgG1, IgG2a, IgG2b, IgG3, and IgA MAbs were studied for their ability to promote phagocytosis and reduce the number of CFU in C . neoformans and J774.16 cell cocultures . The MAbs in this set had similar if not identical fine specificities and were derived from a single B cell . All isotypes promoted phagocytosis; however, the IgG subclasses were more effective opsonins than IgM or IgA . All isotypes enhanced J774.16 anti-C . neoformans activity in vitro, as measured by a reduction in the number of CFU . The IgG1 MAbs were consistently more active in promoting opsonization and reducing the number of CFU . Addition of IgG1 MAb to C . neoformans and J774.16 cocultures resulted in rapid reduction in the number of CFU, which is consistent with fungal killing . Electron microscopy revealed that MAb-opsonized C . neoformans cells were internalized and appeared damaged . Administration of IgM, IgG1, IgG2a, and IgG2b isotype switch variant MAbs revealed that the IgG2a and IgG2b subclasses were the most and least effective isotypes, respectively, in prolonging survival in an intraperitoneal murine infection model . The results indicate that murine antibody subclasses differ in their ability to enhance macrophage anti-C . neoformans activity and suggest that antibody enhancement of macrophage function is a mechanism by which antibodies modify infection in vivo. Clin Neurol Neurosurg, 1995 Feb, 97(1), 23 - 7 An unusual case of central nervous system cryptococcosis; Schmidt S et al.; Opportunistic infections of the central nervous system (CNS) in immunocompromised patients often represent a diagnostic and therapeutic challenge due to the variety of possible infectious agents causing CNS disease . We report the case of a severely immunocompromised 43-year-old woman presenting with headache, confusion, abnormal CSF findings (cell count 237/mm3 with 50% eosinophils and elevated protein), multiple contrast enhancing lesions on CT and MRI in the basal ganglia, and serologic findings compatible with latent or reactivated toxoplasmosis with high IgA and IgG antibody titers against Toxoplasma gondii in whom a final diagnosis of CNS cryptococcosis was made . This case illustrates the considerable difficulties in the differential diagnosis of opportunistic CNS infection in the immunocompromised host . We conclude from our report that (1) the diagnosis of toxoplasma encephalitis should not be based on serological findings but rather be proven by either PCR, mouse inoculation or brain biopsy, (2) CNS cryptococcosis can be associated with marked CSF eosinophilia and multiple cryptococcomas, and (3) cryptococcomas can persist on CT and MRI despite successful antifungal treatment. Pharm Res, 1995 Feb, 12(2), 223 - 30 Efficacy evaluation of a novel submicron miconazole emulsion in a murine cryptococcosis model; Levy MY et al.; Submicron emulsions of miconazole were stabilized by using a combination of three emulsifiers comprising phospholipids, poloxamer, and deoxycholic acid (DCA) . The presence of DCA was vital for prolonged emulsion stability owing to its contribution to the elevated zeta potential of the emulsion . Further, the results by the phospholipid surface labelling colorimetric technique clearly suggested that poloxamer molecules interacted with phospholipid polar-head groups of the mixed DCA-phospholipid interfacial film, resulting in the stabilization of the emulsion by a steric enthalpic entropic mechanism . The plain emulsion vehicle was well tolerated up to a dose of 0.6 ml injected i.v . to BALB/c mice . The maximum tolerated dose of miconazole was 80 and 250 mg/kg in Daktarin i.v . (a marketed product) and emulsion, respectively, showing an improved safety ratio of 1 to 3 in favor of the emulsion . These results tended to confirm that the adverse effects associated with Daktarin i.v . injection should be associated with the vehicle rather than with the miconazole itself . In a murine cryptococcosis model, only one mouse out of ten remained alive by day 15 in the infected group treated with Daktarin i.v., while in the miconazole emulsion treated group, mice began to die from day 16 up to day 25 post inoculation . Thus, the multiple-dose treatment with the miconazole emulsions improved the protection offered to the infected mice . However, the therapeutic levels of miconazole that were reached in the target organ (brain) were lower than those required for complete eradication of Cryptococcus neoformans, which is known to multiply preferentially in the brain. Biosci Biotechnol Biochem, 1995 Feb, 59(2), 173 - 5 Biological activity of a heptaketide metabolite from Pleiochaeta setosa; Okeke B et al.; An uncommon heptaketide metabolite, setosol (2,8-dimethyl-4 methoxy-6,10,11-trihydroxy-benzo-oxaonin), was isolated from a liquid culture filtrate of the fungus Pleiochaeta setosa . The biological activity of the molecule was studied by using 12 microbial strains consisting of three bacteria, three yeasts and six fungi . The level of activity was compared with those of known antibiotics and antifungal agents . The metabolite exhibited antifungal and antibiotic activity against Drechslera oryzae, Gerlachia oryzae, Pyricularia oryzae, Cryptococcus neoformans, and Staphylococcus aureus . The acetylated derivative of setosol did not inhibit the growth of any of the target pathogens . Phytotoxicity studies on whole lupine leaves show that setosol is implicated in the pathogenesis of the brown spot disease of lupines since artificial inoculation of the leaves with the metabolite provoked lesions similar to the characteristic brown spots and lesions on lupine leaves infected by the fungus. Clin Infect Dis, 1995 Feb, 20(2), 263 - 6 Amphotericin B as primary therapy for cryptococcosis in patients with AIDS: reliability of relatively high doses administered over a relatively short period; de Lalla F et al.; Thirty-one consecutive AIDS patients with cryptococcal disease were enrolled in a study of the efficacy and safety of short-course primary treatment with a relatively high dose of amphotericin B (1 mg/{kg.d} for 14 days); 26 patients also received flucytosine (100-150 mg/{kg.d}, given either intravenously or orally) . Twenty-five patients had cryptococcal meningitis confirmed by culture, three had presumed cryptococcal meningitis, and three had disseminated extrameningeal cryptococcosis . After successful primary treatment, all patients were given oral itraconazole or fluconazole as suppressive therapy, and their lifelong clinical and mycologic follow-up was planned . Successful primary therapy was defined as the resolution of symptoms and the documentation of negative cultures of cerebrospinal fluid and/or blood 2 months after the initial diagnosis . Therapy was successful in 29 (93.5%) of all 31 cases and in 26 (92.8%) of the 28 cases of culture-proven or presumed cryptococcal meningitis . Nephrotoxicity developed as a result of amphotericin B administration in seven cases; this adverse reaction required a reduction of the dose in two cases and the discontinuation of therapy in five . No deaths due to cryptococcosis were documented during primary therapy . Treatment failed in two cases . During a mean observation period of 10.7 months, three relapses of the underlying infection occurred . Our results indicate that an aggressive approach to the primary treatment of cryptococcosis in AIDS patients, with the administration of a relatively high dose of amphotericin B for a relatively short period, is effective and well tolerated. Antimicrob Agents Chemother, 1995 Feb, 39(2), 295 - 300 In vitro antifungal and fungicidal spectra of a new pradimicin derivative, BMS-181184; Fung-Tomc JC et al.; A new pradimicin derivative, BMS-181184, was compared with amphotericin B and fluconazole against 249 strains from 35 fungal species to determine its antifungal spectrum . Antifungal testing was performed by the broth macrodilution reference method recommended by the National Committee for Clinical Laboratory Standards (document M27-P, 1992) . BMS-181184 MICs for 97% of the 167 strains of Candida spp., Cryptococcus neoformans, Torulopsis glabrata, and Rhodotorula spp . tested were < or = 8 micrograms/ml, with a majority of MICs being 2 to 8 micrograms/ml . Similarly, for Aspergillus fumigatus and 89% of the 26 dermatophytes tested BMS-181184 MICs were < or = 8 micrograms/ml . BMS-181184 was fungicidal for the yeasts, dermatophytes, and most strains of A . fumigatus, although the reduction in cell counts was less for A . fumigatus than for the yeasts . BMS-181184 was active against Sporothrix schenckii, dematiaceous fungi, and some members of the non-Aspergillus hyaline hyphomycetes . BMS-181184, however, was not fungicidal against members of the family Dematiaceae . BMS-181184 lacked activity or had poorer activity (MICs, > or = 16 micrograms/ml) against Aspergillus niger, Aspergillus flavus, Malassezia furfur, Fusarium spp., Pseudallescheria boydii, Alternaria spp., Curvularia spp., Exserohilum mcginnisii, and the zygomycetes than against yeasts . The activity of BMS-181184 was minimally (twofold or less) affected by changes in testing conditions (pH, inoculum size, temperature, the presence of serum), testing methods (agar versus broth macrodilution), or test media (RPMI 1640, yeast morphology agar, high resolution test medium) . Overall, our results indicate that BMS-181184 has a broad antifungal spectrum and that it is fungicidal to yeasts and, to a lesser extent, to filamentous fungi. Lancet, 1995 Jan 7, 345(8941), 17 - 20 Plasma (1-->3)-beta-D-glucan measurement in diagnosis of invasive deep mycosis and fungal febrile episodes; Obayashi T et al.; (1-->3)-beta-D-glucan is a characteristic fungal cell-wall constituent . To assess the clinical usefulness of this glucan in screening for invasive fungal infection or fungal febrile episodes, we measured the plasma concentration at the time of routine blood culture in 202 febrile episodes by means of factor G, a horseshoe-crab coagulation enzyme that is extremely sensitive to this polysaccharide . With a plasma cut-off value of 20 pg/mL, 37 of 41 episodes of definite fungal infections (confirmed at necropsy or by microbiology) had positive results (sensitivity 90%) . All of 59 episodes of non-fungal infections, tumour fever, or collagen diseases had concentrations below the cut-off value (specificity 100%) . Of 102 episodes of fever of unknown origin, 26 had plasma glucan concentrations of more than 20 pg/mL . With those 102 cases taken as non-fungal infections, the positive predictive value of the test was estimated as 59% (37/63), the negative predictive value as 97% (135/139), and the efficiency as 85% (172/202) . The positive predictive value should improve if there were a sensitive gold standard that could discriminate fungal from non-fungal infections . Causative fungi included candida, aspergillus, cryptococcus, and trichosporon . Determination of plasma (1-->3)-beta-D-glucan with factor G is a highly sensitive and specific test for invasive deep mycosis and fungal febrile episodes, and will substantially benefit immunocompromised patients. Acta Microbiol Pol, 1995, 44(2), 181 - 9 Yeasts and yeast-like organisms isolated from fish-pond waters; Slavikova E et al.; Fifteen genera and 29 yeast species were found in the water of three fish-ponds located in the area of the Lowland Zahorie (Slovakia) . The fish-ponds were sampled in summer and autumn . Aureobasidium, Sporobolomyces, Candida, and Cryptococcus species occurred the most frequently . The composition of yeast species was more heterogeneous in summer than in autumn, but the number of yeasts observed in autumn was 5.5 times higher than those isolated in summer . Some species of the genus Candida, Hyphopichia burtonii, Aureobasidium pullulans, Hansenula anomala and Cryptococcus laurentii were frequently isolated in summer in high counts . The occurrence of the "black yeasts" A . pullulans increased in autumn and together with red yeasts Sporobolomyces roseus represented approximately 70% of the yeast population. J Clin Lab Immunol, 1995, 47(1), 41 - 7 Low levels of LTB4 in cerebrospinal fluid of AIDS patients with cryptococcal meningitis; Froldi M et al.; In this study we evaluated the release of leukotriene B4 (LTB4) in the cerebrospinal fluid (CSF) of 12 patients with Acquired Immunodeficiency Syndrome (AIDS), which disease was complicated by Cryptococcal Meninigitis and in CSF of 12 control subjects with inflammatory and degenerative pathologies of the Central Nervous System (CNS) . We obtained low levels of LTB4 in all the AIDS patients (mean 60.5 pg/ml), while the HIV negative subjects with degenerative and inflammatory pathologies of CNS showed a mean of 91.5 pg/ml . The finding of low levels of this inflammatory reaction mediator agrees with the limited clinical symptoms of cryptococcal meningoencephalitis in patients affected by AIDS. Ann Dermatol Venereol, 1995, 122(11-12), 775 - 6 {Cutaneous and lymphatic cryptococcosis after transient lymphopenia in an immunocompetent patient}; Gil H et al.; INTRODUCTION: Cryptococcosis is an opportunistic infection, that rarely occurs in immunocompetent patients . CASE REPORT: We report a case of a 82 year-old woman who suffered from a bacterial pneumonia associated with lymphopenia . During the hospitalisation, she developed a cutaneous and ganglionnary cryptococcosis . No other cause of immunosuppression was found . The lymphopenia disappeared with the healing of the pneumonia treated with systemic antibiotics . Treatment with fluconazole was effective in 2 months on the cryptococcosis . COMMENTS: To our knowledge, this is the first case of cryptococcosis after a transitory lymphopenia, occurring in a immunocompetent patient. Trans Am Ophthalmol Soc, 1995, 93, 623 - 83 Ocular manifestations of HIV infection; Jabs DA; OBJECTIVE: To evaluate the frequency of ocular complications and the clinical outcomes of these complications in patients with various stages of HIV infection . METHODS: Retrospective review of all HIV-infected patients seen in an AIDS ophthalmology clinic from November 1983 through December 31, 1992 . RESULTS: Eleven-hundred sixty-three patients were seen for ophthalmologic evaluation . Of these, 781 had the acquired immune deficiency syndrome (AIDS), 226 had symptomatic HIV infection (AIDs-related complex {ARC}), and 156 had asymptomatic HIV infection . Non-infectious HIV retinopathy was the most common ocular complication, affecting 50% of the patients with AIDS, 34% of the patients with ARC, and 3% of the patients with asymptomatic HIV infection . Cytomegalovirus (CMV) retinitis was the most common opportunistic ocular infection, affecting 37% of the patients with AIDS . Other opportunistic ocular infections, including ocular toxoplasmosis, varicella zoster virus retinitis, and Pneumocystis choroidopathy were all much less common, each occurring in < or = 1% of the patients with AIDS . Treatment of CMV retinitis with either foscarnet or ganciclovir was successful in initially controlling the retinitis . However, relapse represented a significant problem and required frequent re-inductions . As a consequence of the retinal damage associated with relapse, loss of visual acuity occurred . The median time to a visual acuity of 20/200 or worse for all eyes with CMV retinitis was 13.4 months, and the median time to a visual acuity of 20/200 or worse in the better eye was 21.1 months . At last follow-up, 75% of the patients had a final visual acuity of 20/40 or better in at least one eye . Retinal detachments were a frequent ophthalmologic complication of CMV retinitis with a cumulative probability of a retinal detachment in at least one eye of 57% at 12 months after the diagnosis of CMV retinitis . Herpes zoster ophthalmicus developed in 3% of the overall series and was seen in all stages of HIV infection . Fifty-six percent of the cases of ocular toxoplasmosis had simultaneous toxoplasmic cerebritis . Ocular toxoplasmosis responded to standard anti-microbial therapy . Varicella zoster virus retinitis, when manifested by the acute retinal necrosis (ARN) syndrome, responded to intravenous acyclovir therapy . Conversely, in a limited number of patients with the progressive outer retinal necrosis syndrome, the disease responded poorly to intravenous acyclovir therapy, but appeared to respond to combination foscarnet and acyclovir therapy . Neuro-ophthalmic lesions were present in 6% of the patients with AIDS . The most common cause of a neuro-ophthalmic lesion was cryptococcal meningitis, and 25% of the patients with cryptococcal meningitis developed a neuro-ophthalmic complication . CONCLUSIONS: Ocular manifestations are common in patients with AIDS . CMV retinitis represented a major vision-threatening problem in these patients . While available therapy was successful in initially controlling the retinitis, the phenomenon of relapse resulted in some degree of long-term visual loss . Preservation of the patient's visual acuity in at least one eye was generally successful . Other opportunistic ocular infections were substantially less common than CMV retinitis but require aggressive therapy. Ann Dermatol Venereol, 1995, 122(10), 688 - 91 {Cryptococcal whitlow in a HIV positive patient}; Verneuil L et al.; INTRODUCTION: Cutaneous cryptococcosis is a systemic fungal disease; it is commonly observed in immunocompromised patients . OBSERVATION: We report the case of a cryptococcal whitlow in an HIV positive patient . The mycologic culture of the cutaneous lesion was positive for Cryptococcus neoformans serotype D . The detection of the blood antigen was positive but there was no pulmonary nor central nervous system involvement . The lesions cured with fluconazole (400 mg/day during 2 months and 200 mg/day after) . DISCUSSION: This unusual clinical presentation of cutaneous cryptococcosis has never been reported in an HIV positive patient . As the dermatologic manifestations of cryptococcosis are polymorphous mycologic examination of skin lesions is very important. Mycopathologia, 1995-96, 132(3), 133 - 41 Deactivation of macrophage oxidative burst in vitro by different strains of Histoplasma capsulatum; Ikeda T et al.; It was previously reported that Histoplasma capsulatum (Hc) yeast not only failed to stimulate a murine macrophage oxidative burst (OB), but they also blunted or abolished OB stimulation by a subsequent encounter with potent stimuli such as zymosan or phorbol 12-myristate 13-acetate (PMA) . The present studies show that macrophage deactivation is proportional to the time of incubation and the dose of Hc yeast that induce the deactivated state . Hc yeast derived from a virulent strain (G217B) are more efficient inducers of macrophage deactivation than similar preparations derived from the avirulent Downs Hc strain . Yeast cells of two other pathogenic fungi, Candida albicans and Cryptococcus neoformans are shown to stimulate rather than deactivate a macrophage OB. Trop Geogr Med, 1995, 47(5), 224 - 6 Cryptococcal meningitis and confusional psychosis . A case report and literature review; Sa'adah MA et al.; A previously healthy and immuno-competent 22-year-old man presented in confusional psychosis . Cryptococcal meningitis was later found to be the underlying cause as proven by culturing Cryptococcus neoformans serotype A from the cerebrospinal fluid . Combined antifungal therapy with amphotericin B and 5-fluorocytosine resulted in sustained improvement of all mental and physical functions . Cryptococcosis has rarely been reported from the Middle East . This represents the second case from Kuwait. J Acquir Immune Defic Syndr Hum Retrovirol, 1995 Jan 1, 8(1), 75 - 82 Incidence proportion of and risk factors for AIDS patients diagnosed with HIV dementia, central nervous system toxoplasmosis, and cryptococcal meningitis; Wang F et al.; We undertook this study to determine the incidence proportion of and risk factors for AIDS patients diagnosed with human immunodeficiency virus (HIV) dementia, central nervous system (CNS) toxoplasmosis, and cryptococcal meningitis . A historical cohort of 487 consecutive inpatients with AIDS treated by San Francisco General Hospital inpatient and outpatient services entered the study . We abstracted all available records for demographic information, diagnoses, and dates of death and estimated the incidence proportion of AIDS patients diagnosed with major CNS complications using the Kaplan-Meier method . We used the Cox proportional hazards model to analyze the effect of demographic factors on the hazard (risk per unit time) of diagnosis with these CNS conditions . The estimated incidence proportion of patients diagnosed with HIV dementia within 1 and 2 years of AIDS diagnosis increased from 0.10 to 0.18 . Corresponding proportions were 0.10 and 0.19 for CNS toxoplasmosis and 0.10 and 0.14 for cryptococcal meningitis . Only HIV dementia was independently associated with increasing age at AIDS diagnosis (relative hazard {RH} of 2.75 for ages 41-50 {95% confidence interval, 1.08-6.98}; RH of 4.73 for ages > 50 {95% confidence interval, 1.41-15.87}) and with injection drug use (RH of 2.03; 95% confidence interval, 1.19-3.47) . HIV dementia, CNS toxoplasmosis, and cryptococcal meningitis are about equally common complications in patients with AIDS, but only HIV dementia is associated with increasing age at AIDS diagnosis and injection drug use. Virchows Arch, 1995, 427(4), 407 - 14 Improved detection of medically important fungi by immunoperoxidase staining with polyclonal antibodies; Fukuzawa M et al.; This study was performed to identify pathological fungi of eight species {Aspergillus fumigatus, Candida albicans, Torulopsis (Candida) glabrata, Cryptococcus neoformans, Fusarium anthophilum, Rhizopus oryzae, Sporothrix schenckii and Trichosporon beigelii} in formalin-fixed, paraffin-embedded tissue sections by indirect immunoperoxidase staining . Mature albino rabbits were immunized with formalin-killed organisms . Antibodies were prepared by precipitation . Immunoperoxidase staining was applied to the paraffin-embedded tissue sections of experimentally infected mice and human autopsy and surgical specimens . Although the cell walls of each fungus stained clearly, many cross-reactivities appeared . However, it was possible to obtain specificity for the eight species by absorption and dilution of the antisera. Retina, 1995, 15(4), 300 - 4 An unusual case of cryptococcal endophthalmitis; Custis PH et al.; BACKGROUND: Cryptococcal endophthalmitis is a rare disorder, almost invariably diagnosed after enucleation or at postmortem examination . There are therefore few guidelines as to its identification or treatment . METHODS: A case of culture-positive cryptococcal endophthalmitis in a patient with chronic uveitis was diagnosed by vitreous biopsy at the time of retinal detachment repair . The patient was treated with oral fluconazole for 5 months . All reported cases of cryptococcal endophthalmitis were reviewed and compared . RESULTS: After oral fluconazole therapy, the patient was culture negative on repeat tap . Despite conversion to culture-negative status, however, visual acuity declined to hand motions because of hyphema and hypotony . The organism was successfully identified as a non-neoformans species, Cryptococcus laurentii, previously unreported as an ocular pathogen . CONCLUSION: This unique case demonstrates that cryptococcal disease can be diagnosed antemortem by vitreous biopsy, and should be added to the differential diagnosis in cases of chronic smoldering uveitis . A non-neoformans organism is also identified for the first time as a cause of ocular cryptococcosis . Fluconazole, used here for the only time of which we are aware to treat cryptococcal endophthalmitis, produced successful conversion to culture negativity and resolution of the uveitis. Scand J Infect Dis, 1995, 27(3), 235 - 7 Fluconazole for primary prophylaxis of AIDS-associated cryptococcosis: a case-control study; Ammassari A et al.; In order to verify whether fluconazole has a prophylactive effect against the occurrence of cryptococcosis in HIV-infected patients and to identify other factors capable of increasing or reducing the risk of this infection, we arranged a case-control study of 17 patients with cryptococcal infection . 34 controls were selected, matched by presence of an AIDS-defining event, CD4 cell count, and date of T-cell phenotyping . No significant difference in exposure to fluconazole, in total days of treatment, or in total dose administered was observed between cases and controls . However, control patients took a significantly higher average daily dosage of fluconazole and a linear tendency in risk reduction (p = 0.04) in relation to increasing dosage was observed . Antiretroviral therapy and an average daily fluconazole dose exceeding 150 mg both each reduced the risk of a cryptococcal infection. J Vet Intern Med, 1995 Jan-Feb, 9(1), 39 - 42 Itraconazole for the treatment of cryptococcosis in cats; Medleau L et al.; Itraconazole was used in 35 cats with cryptococcosis . Treatment response was determined by comparing clinical signs before, during, and after treatment . It could not be evaluated in 7 cats because they died during treatment from causes unrelated to cryptococcosis . Of the remaining 28 cats, treatment response was classified as success in 16 cats (57%), as improvement in 8 cats (29%), and as a failure in 4 (14%) . The failures were due to death or euthanasia from drug toxicity (1 cat), progressive fungal disease (2 cats), and relapse 1 year after treatment (1 cat) . The cats that improved did not undergo a 1-year posttreatment evaluation because they were lost to follow-up (3 cats), died or were euthanatized for other reasons (4 cats), or had a noncompliant owner (1 cat) . For the 16 cats in which treatment was successful, the median itraconazole dose was 13.8 mg/kg body weight daily (range, 10.9 to 26.7 mg/kg/d), and the median duration of treatment was 8.5 months (range, 4 to 16 months) . Five of these cats had previously been treated unsuccessfully with ketoconazole. Trop Doct, 1995 Jan, 25(1), 5 - 8 Bacterial meningitis in developing countries; Wright JP et al.; PIP: Hemophilus influenza, Streptococcus pneumoniae, and Neisseria meningitidis account for over 75% of all cases of bacterial meningitis . S . pneumoniae is the commonest causative organism in many developing countries, particularly in Africa . In developing countries overall case fatality rates of 33-44% have been reported, rising to over 60% in adult groups . S . pneumoniae accounts for the highest mortality worldwide . Sequela rates of 22-26% of survivors have been found in African studies, mostly of a neurological nature . There have been few reports of AIDS-related bacterial meningitis in the USA, and a recent study from Uganda found no association between HIV infection and meningococcal meningitis . Stronger associations have been found between opportunistic infections, both viral (cytomegalovirus, herpes virus) and non-viral (TB, Toxoplasma gondii, Cryptococcus neoformans) . A lumbar puncture and analysis of the cerebrospinal fluid should be performed on suspected cases unless there is suspicion of impending coning (decreasing consciousness or focal neurological signs) . The intramuscular administration of chloramphenicol alone is comparable with intravenous use, and can be given as a shorter course of therapy (2 or 3 days) followed by an oral course . The use of adjunct therapy with corticosteroids in children is now commonplace in the USA and Europe . It appears reasonable to use dexamethasone, given early and in high dosage (0.15 mg/kg 6 hourly for 4 days), in those patients who are severely ill . Rifampicin is effective for chemoprophylaxis (10 mg/kg twice daily for 2 days for meningococcal contacts, 20 mg/kg once daily for 4 days for hemophilus contacts, maximum 600 mg per dose) . The recent development and introduction of conjugate vaccines for H . influenza (HIB) has led to rapid reductions in the incidence of hemophilus meningitis in many European countries . An important step in improving prognosis is to increase awareness in both health workers and the public, to encourage early hospital referral, and early antibiotic therapy . J R Soc Med, 1995 Jan, 88(1), 24 - 7 Causes of death in renal transplant recipients: a study of 102 autopsies from 1968 to 1991; Reis MA et al.; A study was conducted on 102 patients submitted to renal transplant who died and were autopsied at the University Hospital, Faculty of Medicine of Ribeirao Preto, Brazil, from 1968 to 1991 . The cause of death, based on a review of medical records and autopsy reports, was assigned to one of the following categories: infectious (69.6%); cardiovascular (12.7%); gastrointestinal (7.8%); graft rejection (6.9%); tumoral (2.0%); and undetermined (1.0%) . Among the 71 cases of death caused by infection, 28 (39.4%) showed disseminated agents involving two or more organs . Isolated pneumonia involved 17 patients (23.9%), followed by acute pyelonephritis in the transplanted kidney in 10 patients (14.1%) . The most frequent agents were: bacteria (58.0%), divided into 'non-classified' (83.0%), Nocardia (10.6%) and Mycobacterium (6.4%); fungi (27.5%) represented by Cryptococcus (22.7%), Aspergillus, Candida and Pneumocystis carinii (18.1% each), Histoplasma (13.6%), Mucor and Paracoccidioides brasiliensis (4.5% each); viruses (6.2%) represented by Herpes simplex (60.0%); metazoa (5.0%, S . stercoralis), and protozoa (2.5%, T . cruzi) . Cytomegalovirus (CMV) was identified in the lungs of 12 patients and was not directly correlated with death but was associated with other agents . In conclusion, immunodepressed patients such as renal transplant recipients should be carefully monitored for infection due to the high mortality rate. J Clin Gastroenterol, 1995 Jan, 20(1), 57 - 60 Hepatic involvement culminating in cirrhosis in a child with disseminated cryptococcosis; Goenka MK et al.; A 7-year-old child had unusual manifestation of cryptococcosis; liver and lymph node involvement predominated . There was evidence of cryptococcal hepatitis, extrahepatic biliary obstruction, and subsequent cirrhosis of the liver . Despite widespread dissemination, underlying immune disturbance was not evident . The patient was treated with two courses of amphotericin and 5-flucytosine. Rev Clin Esp, 1995 Jan, 195(1), 12 - 5 {Central nervous system cryptococcosis in 10 patients with systemic lupus erythematosus}; Diaz Coto JF et al.; Central nervous system compromise is a major cause of morbidity and mortality in SLE . The clinical picture of cerebral cryptococcosis is non-specific and can be mistaken for lupic activity . A retrospective study was undertaken with 10 patients with SLE and cryptococcal meningitis compiled in a 23-year period . The most common symptoms were fever and headache . Lymphocyte counts ranged from 169 to 912 cells/mm . An average delay of 13.6 days in diagnosis was observed in patients with cryptococcal meningitis with no complications and an average delay of 52.4 days in patients with complications . Low lymphocyte counts, observed in all patients, was considered a possible risk factor for cerebral cryptococcosis . To note the association between the delay in the correct diagnosis and complications derived from cerebral cryptococcosis. J Neuroimaging, 1995 Jan, 5(1), 48 - 9 Infratentorial cerebral cryptococcosis; Borresen TE et al.; In a nonimmunocompromised patient with cerebral cryptococcosis, unique magnetic resonance findings included abnormalities limited to the posterior fossa and cerebellar hemispheric edema, gyriform enhancement of the vermis and cerebellar hemispheres, and infratentorial plaquelike enhancement . Magnetic resonance findings in central nervous system cryptococcosis are discussed. Am J Clin Pathol, 1995 Jan, 103(1), 48 - 51 Rapid method for detection of Aspergillus 5S ribosomal RNA using a genus-specific oligonucleotide probe; Montone KT et al.; Ribosomal RNA (rRNA) is present in all prokaryotic and eukaryotic cells . Although sequences are conserved, variations in nucleic acid composition are known to be species specific . Formalin or Bouin's fixed, paraffin-embedded tissue specimens from 17 cases of culture proven Aspergillus sp infections were studied by a rapid (< 30 minutes) in situ hybridization procedure using a biotinylated oligonucleotide DNA probe complementary to nucleic acids 1-22 of Aspergillus sp 5S rRNA sequence . Positivity was noted within fungal organisms in all 17 cases and was identified in both hyphal forms and within fruiting bodies . Signal was weak or absent within the center of Aspergillus abscess cavities with increasing signal located toward the periphery of the cavity, suggesting that rRNA in situ hybridization may detect viable fungal forms . In situ hybridization with the oligonucleotide probe on tissues containing several different organisms including Candida sp, Histoplasma capsulatum, Cryptococcus neoformans, Pneumocystis carinii, Pseudallescheria boydii, Fusarium sp, and Mucor were negative . Use of site specific oligonucleotide probes specific for a variety of rRNA sequences may aid in the diagnosis of several medically important bacterial, fungal, and protozoal pathogens. J Exp Med, 1995 Jan 1, 181(1), 405 - 9 Protective and nonprotective monoclonal antibodies to Cryptococcus neoformans originating from one B cell; Mukherjee J et al.; Two immunoglobulin M monoclonal antibodies (mAbs) derived from the same B cell recognize different epitopes on the capsular polysaccharide of the pathogenic yeast, Cryptococcus neoformans . Their respective epitopes are located in spatially distinct regions of the capsule . Passive administration of one mAb prolonged survival whereas the other mAb did not . The results indicate that specificity is an important determinant of antibody efficacy against C . neoformans and that somatic mutations occurring during the antibody response can affect the protective efficacy of antibodies to C . neoformans. J Exp Med, 1995 Jan 1, 181(1), 387 - 91 Interleukin 12 is effective treatment for an established systemic intracellular infection: experimental visceral leishmaniasis; Murray HW et al.; When administered at or near the initiation of experimental intracellular infection caused by Leishmania major, Toxoplasma gondii, or Cryptococcus neoformans, treatment with the immuno-regulatory cytokine interleukin 12 (IL-12), induces protective antimicrobial activity . In contrast, once infections are established, IL-12 exerts considerably less or no effect in the face of a suppressive Th2 cell-associated response (L . major) or rapidly progressive fatal infection (T . gondii) . To test the efficacy of IL-12 in an established intracellular protozoal infection but under quite different immunologic conditions (Th1 cell response, acquired resistance), L . donovani-infected BALB/c mice were treated starting 2 wk after challenge coincident with the onset of the Th1 cell response . In this environment, 7 d of IL-12 treatment reduced liver parasite burdens by 47%, an effect comparable to that induced by exogenous interferon (IFN) gamma . The in vivo mechanism responsive to IL-12 was complex, and required both CD4+ and CD8+ T cells as well as natural killer cells and the action of multiple endogenous antileishmanial cytokines (IFN-gamma, IL-2, tumor necrosis factor alpha) . Early treatment with IL-12 before the expression of the Th1 cell response was also effective and induced an accelerated, near-cure response via an IFN-gamma-dependent mechanism . These results extend the antimicrobial-inducing capacity of IL-12 beyond prophylaxis by indicating that IL-12 can exert clear-cut therapeutic activity in an established intracellular infection. Microbiol Immunol, 1995, 39(2), 135 - 43 T cell-dependent activation of macrophages and enhancement of their phagocytic activity in the lungs of mice inoculated with heat-killed Cryptococcus neoformans: involvement of IFN-gamma and its protective effect against cryptococcal infection; Kawakami K et al.; Previous investigations have demonstrated that macrophages play a critical role in the first-line cellular defense mechanism against infection with Cryptococcus neoformans . In the present study, to elucidate the way in which anticryptococcal activity of macrophages is regulated at the site of infection, pulmonary intraparenchymal macrophages were directly analyzed for expression of their surface molecules and their phagocytic activities against the organism, and the effects of depletion of T cells and endogenous IFN-gamma in vivo on these parameters were examined . In the lungs of mice intratracheally inoculated with heat-killed C . neoformans, macrophages were activated, as indicated by augmented expression of MHC class II, intercellular adhesion molecule-1 (ICAM-1) and Fc receptor (FcR), and about two-thirds of macrophages were found to have ingested an average of 3.77 +/- 0.12 yeast cells per macrophage . In mice depleted of both CD4+ and CD8+ T cells by injecting the specific monoclonal antibodies (mAbs) or anti-IFN-gamma mAb, not only augmentation of the expression of macrophage activation markers but also phagocytosis of C . neoformans was significantly reduced . These results suggest that anticryptococcal activity of macrophages is regulated by IFN-gamma endogenously produced by T cells . Additionally, treatment with IFN-gamma were shown to significantly prolong the survival time of mice infected with viable C . neoformans . Additionally, preimmunization with heat-killed C . neoformans significantly prolonged the survival time of mice which received the following infection. J Tongji Med Univ, 1995, 15(1), 41 - 4 Microcomputer system for automatic identification of the Cryptococcus neoformans and its clinical application; Zheng YC et al.; In this study, microcomputer image processing and pattern recognition technology, and the knowledge of morphology and optical characteristics of Cryptococcus neoformans were used for identification of Cryptococcus neoformans . Four groups of mice were lethally infected with standard strain, Wuhan strain, American B-2643 strain and Var . Shanghainesis of the Cryptococcus neoformans . The samples collected included mice brain, lung, kidney, liver, small intestine tissue and were observed under a light microscope . More than 600 images of the fungus were input into a microcomputer . A system of computer for automatic identification of the Cryptococcus neoformans was developed . The technique involved image preprocessing, image segmenting, coding of line-length on the edge, curve fitting, extracting of image feature, building of image library and feature data bank etc. . And then, 768 images of the clinical samples and other fungus samples whose morphological features tend to be confused with Cryptococcus neoformans were input into microcomputer and subjected to automatic identification . The Cryptococcus neoformans was accurately identified within 15 min, and the consistency rate with results of routine culture was 98%. Antonie Van Leeuwenhoek, 1995, 67(2), 217 - 9 Partial conversion of cinnamic acid into styrene by growing cultures and cell-free extracts of the yeast Cryptococcus elinovii; Middelhoven WJ et al.; Cultures of Cryptococcus elinovii CBS 7051 grown at the expense of cinnamic acid as the sole source of carbon and energy partially converted this substrate into styrene . The latter is toxic and eventually kills the culture . Cell-free extracts of cultures grown on cinnamic acid produced styrene from cinnamate . Other basidiomycetous yeasts tested did not produce styrene from cinnamic acid. Intern Med, 1995 Jan, 34(1), 54 - 7 Detection of Cryptococcus neoformans in bronchial lavage cytology: report of four cases; Maesaki S et al.; Four cases of pulmonary cryptococcosis were diagnosed by cytological detection of Cryptococcus neoformans in bronchial lavage . Three patients had underlying diseases, but not HIV infection . The chest X-rays showed 2 patients with nodular lesions and 2 with cavitary lesions . The cryptococcal antigen in the serum was positive in all four patients . In the cytology of bronchial lavage, Cryptococcus neoformans was detected after period-acid-Schiff (PAS) staining and was cultured in Sabouraud-dextrose agar . The cytology of bronchial lavage is useful for the rapid diagnosis of pulmonary cryptococcosis. J Clin Microbiol, 1995 Jan, 33(1), 99 - 102 Involvement of multiple Cryptococcus neoformans strains in a single episode of cryptococcosis and reinfection with novel strains in recurrent infection demonstrated by random amplification of polymorphic DNA and DNA fingerprinting; Haynes KA et al.; We compared the abilities of random amplification of polymorphic DNA and DNA fingerprinting, with oligonucleotide probes, to type five pairs of Cryptococcus neoformans clinical isolates recovered from five separate human immunodeficiency virus-positive patients in London, England . The two techniques had comparable discriminatory abilities when applied to these isolates . A total of eight different isolate types were demonstrated in these patients . No isolate type was observed in more than one patient . Two of the isolate pairs recovered from single episodes of cryptococcosis within 1 day of each other were genotypically indistinguishable by both methods . The other three pairs of isolates were all distinguishable . One of these isolate pairs was obtained from a single episode of cryptococcosis, while the other two were obtained from recurrent infections . These results indicate that multiple strains of C . neoformans may be responsible for a single episode of cryptococcosis and that recurrent infection may occur as a result of reinfection with a novel strain. Ann Pharm Fr, 1995, 53(3), 138 - 41 {Antifungal activity in vitro of Scutellaria baicalensis Georgi upon cutaneous and ungual pathogenic fungi}; Yang D et al.; The root of Scutellaria baicalensis Georgi (Lamiaceae) is one of the traditional drugs commonly used in the Far East . The extracts obtained by the successive exhaustion in chloroform and in ethyl acetat present clear fungistatic activities in vitro against to some cutaneous and ungual pathogenic fungi, and particularly upon strains of Candida albicans, Cryptococcus neoformans and Pityrosporum ovale . For each of these, its minimum inhibitory concentration is determined . The ethyl acetat extract appears the most interesting because of its efficiency and of its stability . An antifungal substance is found out as the baicalein. Med Trop (Mars), 1995, 55(1), 61 - 4 {Severe pulmonary and meningeal cryptococcosis in an immunocompetent Cambodian}; L'Her P et al.; A chest x-ray showing a large tumor-like opacity in the left lower lobe and endoscopy visualizing a budding mass suggested a diagnosis of bronchial carcinoma in a 55-year old, tobacco-smoking Cambodian who consulted for hemoptysis and altered general status . Histological study of bronchial biopsies allowed differential diagnosis of cryptococcosis . Serologic tests for human immunodeficiency virus were negative and there was no other cause of immunodepression . Left lower lobectomy was performed at the German hospital of the APRONUC in Phnom Penh . Examination of the surgical specimen confirmed massive bronchopulmonary cryptococcosis . Two months after the procedure the patient was readmitted for neuromeningial cryptococcosis that responded well to fluconazole . Another relapse occurred 5 months later and was treated using the same drug . The patient is currently in remission . An increasingly common deep mycosis that is serious but curable with proper treatment, cryptococcosis deserves the full attention of physicians working in Cambodia where, as in other tropical zones, it is likely that this infection will progress with the incidence of AIDS . Symptoms can be misleading, suggesting neuromeningial or pulmonary tuberculosis . The value of India ink smear which should be performed in all patients presenting lymphocytic meningitis with hypoglycorrhachia must be emphasized . In the present case bronchoscopy was useful to distinguish from bronchopulmonary cancer. Mycoses, 1995, 38 Suppl 1, 40 - 4 {HIV-associated mycoses}; Listemann H et al.; Candidosis, cryptococcosis, and histoplasmosis often occur as HIV-associated mycoses . However, aspergillosis can be observed quite recently . The morphology of the pathogen of HIV-associated mycoses in vivo and in vitro is demonstrated and discussed. Mycopathologia, 1995, 129(1), 25 - 8 Isolation of Cryptococcus neoformans var . neoformans from bird droppings, fruits and vegetables in Mexico City; Lopez-Martinez R et al.; The presence of Cryptococcus neoformans in various natural sources, such as bird droppings, fruits and vegetables, was investigated . A total of 711 samples were analyzed; C . neoformans var . neoformans was isolated from seven out of 74 bird droppings (9.5%), with parrots as one of the most significant sources . Fruits were positive in 9.5% of the 169 samples studied, specially citrus fruits, particularly grapefruit, in which the highest frequency was found . From the 468 vegetable samples, only 20 were positive (4.2%) . It is emphasized that five of the positive vegetables species are autochthonous to Mexico: avocado (Nectandra salicifolia), beet (Beta vulgaris var . quinopodiace), chayote (Sechium edule), stringbean (Cassia sp), and nopal (Opuntia ficus-indica). Verh K Acad Geneeskd Belg, 1995, 57(2), 133 - 56 Unraveling the secrets of Histoplasma capsulatum . A model to study morphogenic adaptation during parasite host/host interaction; Maresca B; Early in the developmental period of microbiology, Pasteur first observed the phenomenon of dimorphism in fungi when he noticed that the bread mold Mucor grew as a filamentous mold aerobically on the surface of broth cultures but at the bottom of the flask where the environment was anaerobic it reproduced as budding yeast cells . Several infectious fungal pathogens of humans, namely Histoplasma capsulatum, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Sporothrix schenkii, and Coccidioides immitis change from a multicellular filamentous form to an unicellular morphology when they invade tissues . The ability of pathogenic fungi to assume a different shape is referred to as dimorphism . This phenomenon has intrigued clinicians, and medical mycologists since its discovery at the turn of the century . The ability of pathogens to initiate infection, invade host tissues and survive in mammalian hosts is critically linked to the induction of specific gene products . In dimorphic fungi, developmentally regulated gene expression is particularly important, since they may exist in phylogenetically distinct hosts with different body temperatures . Using Histoplasma capsulatum as a model to study parasite-host interactions at the biochemical and molecular level, my laboratory has attempted to relate the clinical spectrum of disease to natural variations in the characteristics of this organism and to adaptations it must make as a saprobe and a parasite . Histoplasma capsulatum is the etiologic agent of histoplasmosis, a respiratory infection that is world-wide in distribution . As a saprobe in soil it is mycelial, but it becomes a budding yeast as a parasite in susceptible hosts . These morphological phases can be reversibly reproduced in vitro by shifting the temperature from 25 degrees C, at which it is mycelial, to 37 degrees C, when it becomes a budding yeast . The process of mycelial-to-yeast conversion is of particular interest since it is triggered by an increase in temperature and conversion to virulence . Viable mycelial fragments and conidia become airborne and enter the pulmonary tract by inhalation after which the fungus rapidly disseminates to other organs . Progressive disseminated histoplasmosis along with candidiasis, cryptococcosis, and invasive aspergillosis are opportunistic fungal infections in patients who are immunosuppressed or otherwise debilitated . Importantly, they are diagnostic hallmarks of acquired immunodeficiency disease syndrome (AIDS) . The clinical features of these infections and the genetic characteristics of the etiologic agents present unique parasite-host interactions that make them valuable research models to study . In the infected host, Histoplasma capsulatum encounters various environmental stresses to which it adapts by regulating the expression of specific genes.(ABSTRACT TRUNCATED AT 400 WORDS) Rev Med Chil, 1995 Jan, 123(1), 61 - 73 {Clinical characteristics and natural history of human immunodeficiency virus infection . Study in a Chilean population served at a multiprofessional pilot center}; Wolff M et al.; Four hundred and eighty six infected adults (90.7% men) were prospectively followed from 1988 to 1993 at a multiprofessional center in Santiago, Chile . 87.8% of male patients (pts)--84% of them homo/bisexual--and 64.4% of women acquired the infection sexually . At the beginning of the follow up (F/U) 51% of men and 71% of women were asymptomatic and 30% of the total group had AIDS . (AIDS definition: CDC 1993, excluded CD4 lymphocyte count < 200 x mm3) . 240/486 (49.4%) had developed AIDS at the end of the study (12/31/93) . AIDS defining events (ADE) were: interstitial pneumonia (confirmed or suggestive as caused by P . carinii {PCP}), 25%; tuberculosis (all forms), 22.1%; wasting, 13.8%; Kaposi Sarcoma, 9.2%; esophageal candidiasis, 6.7%; isosporiasis, 5.4% . Of all PCP cases, 72% were ADE, the rest, post.AIDS' . As expected, AIDS pts continued having major complications (mainly bacterial pneumonias, PCPs, esophagitis, tuberculosis and diarrhea due to I . belli and Cryptosporidium . Less frequently, but also observed, were toxoplasmic encephalitis and cryptococcal meningitis) . Known mortality (excluded abandonment of F/U) was 27% for the whole group and varied from 5.8%, 51.6% to 69.2% for the first, 4th and 6th year of F/U respectively . For II-III CDC pts the mortality was 5% and 57% and for IV CDC pts it was 38% and 100% during the first and 6th year of F/U respectively . 36%, 53%, 74% and 85% of the pts followed for 1, 3, 5 and 6 years respectively had developed AIDS by the end of 1993 . Multifactorial causes with either diarrhea, wasting or both were responsible for the death in half the pts in whom this was known, 15% died of respiratory complications and 5.7% of cryptococcal meningitis . 80% of AIDS pts survived their ADE . This study has provided information about the clinical profile of the HIV infection and natural history of the disease in Chile. Bull Soc Belge Ophtalmol, 1995, 255, 115 - 22 {Aids and chorioretinal opportunistic infections}; De Munck J et al.; Retrospective study of 19 cases of opportunistic infections of the chorioretina in patients with the Acquired